Abstract: Mucopolysaccharidosis IVA (MPS IVA; Morquio A disease) is an autosomal recessive lysosomal storage disorder caused by a genetic deficiency of the N-acetylgalactosamine-6-sulfate sulfatase (GALNS; E.C.3.1.6.4). GALNS is required to degrade keratan sulfate (KS) and chondroitine-6-sulfate (C6S). The accumulation of undegraded substrates in lysosomes of the affected tissues leads to a systemic bone dysplasia. Total urine glycosaminoglycans (GAG) in patients with MPS IVA are close to the normal range so it is difficult to distinguish this disease based on urine GAG excretion. Another potential disease marker could be KS levels in urine and plasma. Although the enzymatic diagnosis of affected patients with MPS IVA can be made, the detection of obligate heterozygotes by enzymatic measurement is less reliable because of a marked overlap of GALNS in fibroblasts or leucocytes from affected phenotype and normal controls. The genetic heterozygoty of MPS IVA has been facilitated by the isolation and characterization of the full lengh cDNA encoding human GALNS. Conventional therapy is symptomatic and limited to palliative procedures, which have virtually no impact upon mortality. To date, there is still no general consensus about the effectiveness of bone marrow transplantation. In the future, gene therapy could represent a great therapeutic improvement.

Abstract: The presence and role of heavy metals in urinary stones is debated. We investigated the distribution of trace heavy metals in 78 calculi of well-defined composition by means of microfluorescence X analysis using synchrotron radiation. Seven elements were identified, the most abundant being Zn and Sr which together accounted for 91% of the heavy metal content of stones. The other heavy metals were Fe, Cu, Rb, Pb and Se. Zn and Sr were virtually confined to calcium-containing stones, whereas only trace amounts were found in uric acid or cystine stones. Among calcium stones, Zn and Sr were more abundant in calcium phosphate than in calcium oxalate stones and, in the latter, in weddellite than in whewellite stones. Fe, Cu and Rb were much less abundant and also found mainly in calcium stones. Pb was significantly less abundant than in previous studies, thus suggesting a rarefaction of Pb in the environment, and appreciable amounts of Se were found only in cystine stones. In conclusion, the preponderance of Zn and Sr, both bivalent ions, in calcium-containing stones suggests a substitution process of calcium by metal ions with similar charge and radius rather than a contribution of the metals to stone formation. Further studies are needed to examine the relationships between urine concentration in calcium or other solutes and the amount of Zn and Sr in calcium stones.

Abstract: Drug-induced renal calculi represent 1-2% of all renal calculi. They include two categories: those resulting from the urinary crystallisation of a highly excreted, poorly soluble drug or metabolite, and those due to the metabolic effects of a drug. Indinavir, used in HIV-infected patients, sulfonamides, especially sulfadiazine, and triamterene, which is less prescribed today, are the most frequent. Besides these drugs, about twenty other molecules, among them silicate-containing drugs and some antibiotics have been reported in patients receiving high doses or long-term treatments. Calculi analysis by physical methods such as infrared spectroscopy or x-ray diffraction can demonstrate the presence of the drug or its metabolites inside the calculi. In those calculi due to the metabolic effects of a drug, diagnosis relies on both stone analysis and clinical inquiry. Incidence of such calculi is probably underestimated, especially those due to calcium/vitamin D supplements or carbonic anhydrase inhibitors. Drug-induced calculi occur more often during high-dose or long term treatments, but there are also patient-related risk factors in relation to urine pH, urine output and other parameters, which can provide a basis for preventive treatment of such calculi. A better knowledge of these lithogenic complications of treatments and of solubility characteristics of drugs should reduce the incidence of drug-induced nephrolithiasis, especially in patients with identified risk factors.

Abstract: This paper describes the opportunities given by the synchrotron radiation techniques regarding the structural characterisation of biological entities. After a short recall on the characteristics of the synchrotron radiation, are described the experimental devices based on fluorescence X, wide angle X-ray scattering and X-ray absorption spectroscopy, which may applied for biological samples, especially in the field of stone analysis. Recent progresses in medical research using synchrotron radiation will be also discussed.

Abstract: A larger body size has been shown to be associated with increased excretion of urinary lithogenic solutes, and an increased risk of nephrolithiasis has been reported in overweight patients. However, the type of stones produced in these subjects has not been ascertained. Based on a large series of calculi, we examined the relationship between body size and the composition of stones, in order to assess which type of stone is predominantly favoured by overweight. Among 18,845 consecutive calculi referred to our laboratory, 2,100 came from adults with recorded body height and weight. Excluding calculi from patients with diabetes mellitus, as well as struvite and cystine stones, the study material consisted of 1,931 calcium or uric acid calculi. All calculi were analysed by infrared spectroscopy and categorized according to their main component. Body mass index (BMI) values were stratified as normal BMI (< 25 kg/m2), overweight (BMI 25-29.9) or obese (BMI > or = 30). Overall, 27.1% of male and 19.6% of female stone formers were overweight, and 8.4 and 13.5% were obese, respectively. In males, the proportion of calcium stones was lower in overweight and obese groups than in normal BMI group, whereas the proportion of uric acid stones gradually increased with BMI, from 7.1% in normal BMI to 28.7% in obese subjects (P<0.0001). The same was true in females, with a proportion of uric acid stones rising from 6.1% in normal BMI to 17.1% in obese patients (P=0.003). In addition, the proportion of uric acid stones markedly rose with age in both genders (P<0.0001). The average BMI value was significantly higher in uric acid stone formers aged < 60 years than in all other groups, whereas it did not differ from other groups in those aged > or = 60 years. Stepwise regression analysis identified BMI and age as significant, independent covariates associated with the risk of uric acid stones. Our data provide evidence that overweight is associated with a high proportion of uric acid stones in patients less than 60 years of age, whereas beyond this limit, advancing age is the main risk factor.

Abstract: An increased prevalence of nephrolithiasis has been reported in patients with diabetes. Because insulin resistance, characteristic of the metabolic syndrome and type 2 diabetes, results in lower urine pH through impaired kidney ammoniagenesis and because a low urine pH is the main factor of uric acid (UA) stone formation, it was hypothesized that type 2 diabetes should favor the formation of UA stones. Therefore, the distribution of the main stone components was analyzed in a series of 2464 calculi from 272 (11%) patients with type 2 diabetes and 2192 without type 2 diabetes. The proportion of UA stones was 35.7% in patients with type 2 diabetes and 11.3% in patients without type 2 diabetes (P < 0.0001). Reciprocally, the proportion of patients with type 2 diabetes was significantly higher among UA than among calcium stone formers (27.8 versus 6.9%; P < 0.0001). Stepwise regression analysis identified type 2 diabetes as the strongest factor that was independently associated with the risk for UA stones (odds ratio 6.9; 95% confidence interval 5.5 to 8.8). The proper influence of type 2 diabetes was the most apparent in women and in patients in the lowest age and body mass index classes. In conclusion, in view of the strong association between type 2 diabetes and UA stone formation, it is proposed that UA nephrolithiasis may be added to the conditions that potentially are associated with insulin resistance. Accordingly, it is suggested that patients with UA stones, especially if overweight, should be screened for the presence of type 2 diabetes or components of the metabolic syndrome.

Abstract: INTRODUCTION: The prevalence of urinary stones runs parallel with the socioeconomic and health level of populations. Few data are currently available concerning the characteristics of urinary stones in Algeria. Based on our recruitment of stones derived from the main teaching hospital urology departments of Western Algeria, we defined the stone profile in this region of North Africa and its changes in relation to previous data. MATERIAL AND METHOD: A series of 1,354 stones derived from urology departments in Western Algeria was studied by IRTF spectroscopy. Analysis of the results concerned the crystalline composition and anatomical site of the stones and the age and gender of the patients. RESULTS AND DISCUSSION: Conventional surgery is the method of extraction most frequently used with 79.7% of operations contre 0.2% for extracorporeal lithotripsy. The male/female ratio has remained almost constant at 2.23. The anatomical site has changed with a predominance in the upper tract (77.4% of stones). The proportions of whewellite and weddellite have increased compared to our first series, from 48.1% to 50.3% and 13.1% to 16.7%, respectively, while phosphates decreased from 24.4% to 16.7%. The presence of struvite has not decreased over recent years, as 28.8% of stones contain this type of crystal. Anhydrous uric acid has slightly increased to 8.8% versus 6.2%. The proportions of ammonium urate and cystine have not changed (1.8% and 0.7%, respectively), but ammonium urate forms is less frequently the nucleus of stones than previously (2% versus 5.89%). The study of the nucleus showed that phosphates are predominant in 48.6% of cases versus 35.6% for oxalates. Carbapatite and struvite are more frequent in women, found in 50.8% and 6.7% of cases, respectively, than in man, found in 44.6% and 3.7% of cases, respectively. Calcium oxalate is predominantly found in the upper urinary tract (70.9%) rather than in the bladder (48.3%), regardless of gender. Calcium phosphate is more abundant in the upper tract of females with 23.7% of cases versus 10.7% in the bladder. It is equally distributed between the bladder and the upper tract in males (13.7% and 13.2%, respectively). Examination of the side affected by stones showed a predominance of the left side in both sexes. CONCLUSION: Analysis of these data shows that urinary stones in Western Algeria are tending to evolve in the same direction as in industrialized countries, but urinary tract infection remais a frequent cause of stones.

Abstract: The current concept of metabolic syndrome comprises abdominal obesity and cardiovascular risk factors (HT and metabolic disorders). Compared to a control group, individuals with metabolic syndrome have a fourfold higher risk of cardiovascular disease and an increased risk of diabetes. Apart from cardiovascular morbidity, these patients also appear to have an increased incidence of urolithiasis. Urologists must therefore recognize this syndrome in order to identify this particular subgroup of urolithiasis patients. The objective of this article is to review the metabolic syndrome in order to help urologists to recognize this syndrome so that they can identify patients requiring more specific management and medical follow-up.

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Abstract: BACKGROUND: Urinary crystal precipitation is the necessary initial step in kidney stone formation. However, clinical relevance of crystalluria in the evaluation of stone formers is disputed. METHODS: We serially determined crystalluria in first-voided morning urine samples, together with full 24-hour urine biochemistry, in 181 patients with idiopathic calcium nephrolithiasis who had formed at least one calcium-oxalate stone and were followed for at least 3 years under our care. All stone events which occurred prior to referral, then after entry in the study were recorded. RESULTS: As compared with 109 patients who had no evidence of stone recurrence during follow-up, the 72 patients who experienced >/= one recurrent stone event had a lower daily urine volume (1.74 +/- 0.06 vs. 2.26 +/- 0.05 L/day (mean +/- SEM) (P < 0.0001), higher urine calcium and oxalate concentrations, and daily calcium excretion, and they had more frequent crystalluria (68% vs. 23% of urine samples) (P < 0.0001). By multivariate Cox regression analysis, the hazard ratio for stone recurrence was 0.32 (95% CI 0.16-0.62) for 1 L increase in daily urine volume, 1.12 (1.09-1.24) for 1 mmol/L increase in urine calcium concentration, 1.24 (1.02-1.50) for 0.1 mmol/L increase in urine oxalate concentration and 27.8 (10.2-75.6) for crystalluria index. CONCLUSION: These data provide evidence that crystalluria, when repeatedly found in early morning urine samples, is highly predictive of the risk of stone recurrence in calcium stone formers. Serial search for crystalluria, a simple and cheap method, may be proposed as a useful tool for the monitoring of calcium stone formers, in addition to urine biochemistry.

Abstract: INTRODUCTION: A single stone analysis is necessary during the patient's clinical history in order to institute specific drug treatment and health and dietary measures to prevent stone recurrence. In practice, only one in every two stones is recovered for morpho-constitutional analysis. The objective of this study was to determine the place of double J stent encrustation analysis for indirect determination of stone composition. MATERIAL AND METHODS: Double J stents and stones from all patients treated in the same centre over 24 months were consecutively analysed by infrared spectrophotometry. The correlation coefficient 1, evaluating the concordance between the composition of stones and double J stent encrustation was estimated statistically by SPSS 12.0 software (0<1<1; 1=0: no concordance; 1=1: perfect concordance). RESULTS: 45 males and 27 females with a mean age of 45.3 years (range: 29-70) were included Double J stents were placed for: febrile obstruction (N=52; 72%), acute renal colic (N=15; 21%) and impaired renal function (N=5; 7%). Calculated values for 1 were: 0.78 for the concordance between the predominant constituent of the stone and the encrustation (N=72; p < 0.0005); 0.91 for the concordance between the nature of the encrustation of the upper loop and that of the lower loop of the stent (N=30, p < 0.0005). CONCLUSION: The composition of mineral encrustation of double J stents is a good marker of stone formation. This constitutes an alternative method that can be used by urologists when no stone is available for spectrophotometric analysis.

Abstract: Chronic renal failure (CRF) favors the development of atherosclerosis and excessive calcification of atheromatous lesions. CRF was induced in apolipoprotein E knockout (apoE(-/-)) mice to study (1) a possible acceleration of aortic atherosclerosis, (2) the degree and type of vascular calcification, and (3) factors involved in the calcification process. For creating CRF, 8-wk-old apolipoprotein E gene knockout (apoE(-/-)) mice underwent partial kidney ablation. Control animals underwent sham operation. Aortic atherosclerotic plaques and calcification were evaluated using quantitative morphologic image processing. At 6 wk after nephrectomy, CRF mice had significantly higher serum urea, cholesterol, and triglyceride concentrations than non-CRF controls. The serum levels of advanced oxidation protein products were elevated in the uremic group and were correlated with serum urea levels. Atherosclerotic lesions in thoracic aorta were significantly larger in uremic apoE(-/-) mice than in nonuremic controls. The relative proportion of calcified area to total surface area of both atherosclerotic lesions and lesion-free vascular tissue was increased in aortic root of uremic apoE(-/-) mice when compared with controls. The calcium deposits were made of hydroxyapatite and calcite crystals. In addition, plaques from uremic animals showed a significant increase in collagen content, whereas the degree of macrophage infiltration was comparable in both groups. There was no difference in mean arterial BP. These findings demonstrate that CRF aggravates atherosclerosis in apoE(-/-) mice. Moreover, CRF enhances arterial calcification at both atheromatous intimal sites and atheroma-free medial sites. We anticipate that this experimental model will be useful to test treatment strategies aimed at decreasing the accelerated atherosclerosis and arterial calcification in uremia.

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Abstract: INTRODUCTION: The incidence of diabetes, particularly non-insulin-dependent diabetes, is on the increase in industrialized and developing countries. The prevalence of renal stones in the diabetic population was recently estimated to be 21%, i.e. more than twice the prevalence of stones in the general population. Other studies have emphasized the high frequency of uric acid stones in this particular population. The present study was designed to verify whether diabetic patients present a particular type of crystalluria predisposing them to a high frequency of uric acid stones than other types of stones, which could allow detection of this risk and the proposal of therapeutic measures to prevent these stones. MATERIAL AND METHOD: The first morning urine of 208 diabetic patients was examined by polarized light microscopy to detect and identify crystalluria. Patients were distributed into 3 age-groups: less than 40 years, 40 to 59.9 years and 60 years or more. The results are expressed as the predominant crystalline species. RESULTS: The overall frequency of crystalluria was 29.8%, i.e. about one half that observed in calcium stones. However, the crystallogenic profile was very unusual, as 61.3% of cases of crystalluria consisted of purine. Uric acid crystalluria was twice as frequent in women than in men (66% vs 33.3%, p < 0.05). The mean pH of the urine of diabetic subjects was 5.5, i.e. significantly more acidic than that of normal subjects or patients with calcium stones. pH was negatively correlated with the patient's age, decreasing from 5.54 in patients younger than 40 to 5.3 in patients over the age of 60 (p < 0.05). The mean pH of crystalluric urine was significantly more acidic than that of crystal-free urine (pH 5.2 +/- 0.46 vs 5.5 +/- 0.67, p < 0.01). CONCLUSION: Diabetic patients have an acidic urinary pH which tends to decrease with age, predisposing to uric acid crystalluria, which is particularly frequent in women. The high prevalence of uric acid crystalluria and the high proportion of uric acid stones reported in diabetic women suggest that women are at greater risk than men of developing uric acid stones in the context of diabetes. The study of crystalluria could be useful to detect this risk and to propose preventive measures. Complementary studies are necessary to identify factors accounting for the increased risk of uric acid stones in diabetic women and to verify whether good glycaemic control can reduce the crystallogenic risk.

Abstract: OBJECTIVES: To determine the value of mid-infrared spectroscopy (MIRS) of ureteral stent encrustations in predicting urinary stone composition. METHODS: A retrospective study analyzed the composition of stent encrustations and urinary stones by MIRS in patients who had had a stent for ureteral obstruction between 2001 and 2003. The overall correlation was evaluated. The correlation coefficient kappa for agreement between the proportions of each component was calculated. RESULTS: A total of 72 stents and 72 stones from 72 patients were analyzed. The mean stent indwelling time was 55.5 days (range 14 to 102). The stents had been placed for fever (52 cases, 72%), pain refractory to analgesics (15 cases, 21%), and impairment of kidney function (5 cases, 7%). The overall correlation between stone composition and stent encrustation was 71.4%, excluding biofilm analysis. The kappa value was 0.78 for the main component (n = 72; P < 0.0005), 0.61 for the secondary component (n = 72; P < 0.0005), and 0.91 for the agreement between the composition of encrustations at each end of a stent (n = 30; P < 0.0005). CONCLUSIONS: MIRS analysis of stent encrustations is a reliable method of predicting stone composition when the stone cannot be retrieved. Systematic MIRS analysis of stent encrustations is not recommended but can be very useful in clinical situations in which no stone is available.

Abstract: A 58 year-old woman developed an acute renal failure very quickly after ingestion of two 500 mg tablets of ciprofloxacin, without any other identifiable risk factor. Renal biopsy was performed. No sign of acute interstitial nephritis was observed but tubular lesions were found, accompanied by deposits of a brown-yellowish substance identified by infrared microscopy as a ciprofloxacin salt. The outcome was favourable. This observation gives the opportunity to remind the different forms of quinolone-induced renal injury and to discuss the possible ways for preventing renal side-effects related to the quinolone use.

Abstract: INTRODUCTION: Calcium oxalate is the leading cause of renal stones and is mainly due to hypercalciuria, hyperoxaluria and/or hypocitraturia. Citrate is considered to be an effective inhibitor of calcium oxalate crystallization and is therefore increasingly prescribed as maintenance therapy for patients with calcium stones, but no study has investigated the effect of urinary citrate levels on spontaneous calcium oxalate crystalluria in human urine. In this study, the authors examined the relationships between the calcium oxalate molar product, the urinary citrate concentration and weddellite (oxalate calcium dihydrate) crystalluria, the most frequent crystalline form of calcium oxalate in human urine. MATERIAL AND METHODS: Crystalluria analysis and calcium, oxalate and citrate assays were performed on a series of 10,222 first morning urine samples from 4,809 stone patients and 453 first morning urine samples from 317 control subjects. The frequency and characteristics of weddellite crystalluria were determined as a function of the calcium oxalate molar product (pCaOx) and urinary citrate concentration. RESULTS: 1,940 urine samples (18.2%) presented weddellite crystalluria, which was pure in 1,378 urine samples from stone patients (13.5%) and 43 urine samples (9.5%) from controls (p < 0.05). The crystalluria rate in stone patients ranged from 4% for pCaOx < 1 (mmol/l)2 to 81.3% for pCaOx > or = 3 (mmol/l)2 (p < 0.0001). Over the same interval of pCaOx, weddellite crystalluria ranged from 1.5% to 72.2% in control subjects. An increase of urinary citrate excretion from 0.5 to 5 mmol/l significantly lowered the frequency of crystalluria from 32.4% to 10.1% for a pCaOx between 1 and 2 (mmol/l)2 (p < 0.0001) and from 63% to 27.9% for a pCaOx between 2 and 3 (mmol/l)2 (p < 0.001). For pCaOx values > or = 3 (mmol/l)2, urinary citrate excretion no longer significantly influenced the frequency of crystalluria. The number of crystals and aggregates and the maximum dimensions of aggregates were only influenced by the urinary citrate concentration when the pCaOx product was < 2 (mmol/l)2. CONCLUSION: The main determinant of the frequency and characteristics of weddellite crystalluria is the pCaOx molar product. The beneficial effect of the urinary citrate concentration on the frequency of crystalluria is observed for pCaOx values < 3 (mmol/l)2, but only for pCaOx values < 2 (mmol/l)2 for the characteristics of crystalluria such as the number and dimensions of crystals and aggregates. This means that therapeutic measures designed to increase urinary citrate concentrations can only be effective when pCaOx has been previously lowered by increased diuresis or specific reduction of urinary calcium and/or urinary oxalate levels.

Abstract: Nephrolithiasis still remains a too frequent - and under-appreciated - cause of end-stage renal disease (ESRD), and this is all the most unfortunate since such an untoward course is now preventable in most cases. Among 1391 patients who started maintenance dialysis at Necker hospital between 1989 and 2000, nephrolithiasis was identified as the cause of ESRD in 45 of them, an overall prevalence of 3.2%. Infection stones accounted for 42.2% of cases, calcium stones for 26.7%, uric acid stones for 17.8% and hereditary diseases for 13.3%. The proportion of nephrolithiasis-associated ESRD declined from 4.7% to 2.2% from the 1989-1991 to the 1998-2000 period, as a result of the decreased incidence of ESRD in patients with infection and calcium nephrolithiasis. Based on our observations and on published reports, it emerges that most cases of nephrolithiasis-associated ESRD were due to sub-optimal management (especially in the case of infection or cystine stones) or to late (or erroneous) etiologic diagnosis, precluding early institution of appropriate therapeutic measures. In particular, several patients with primary hyperoxaluria or 2,8-dihydroxyadeninuria were diagnosed while already on dialysis or after unsuccessful kidney transplantation, due to wrong initial diagnosis. In conclusion, thanks to recent advances in diagnosis and management of stone formers, ESRD should now be prevented in the great majority of patients, at the condition of early etiologic diagnosis based on accurate morphoconstitutional analysis of calculi and metabolic evaluation, and early implementation of appropriate preventive medical treatment.

Abstract: Nephrolithiasis is a frequent disease that affects about 10% of people in western countries. The prevalence of calcium oxalate stones has been constantly increasing during the past fifty years in France as well as in other industrialized countries. Stone composition varies depending to gender and age of patients and also underlines the role of other risk factors and associated pathologies such as body mass index and diabetes mellitus. The decrease in struvite frequency in female patients is the result of a significantly improved diagnostic and treatment of urinary tract infections by urea-splitting bacteria. In contrast, the increasing occurrence of weddellite calculi in stone forming women aged more than 50 years could be the consequence of post-menopausal therapy. A high prevalence of uric acid was found in overweight and obese stone formers and in diabetic ones as well. Another important finding was the increased occurrence with time of calcium oxalate stones formed from papillary Randall's plaques, especially in young patients. Nutritional risk factors for stone disease are well known: they include excessive consumption of animal proteins, sodium chloride and rapidly absorbed glucides, and insufficient dietary intake of fruits and potassium-rich vegetables, which provide an alkaline load. As a consequence, an excessive production of hydrogen ions may induce several urinary disorders including low urine pH, high urine calcium and uric acid excretion and low urine citrate excretion. Excess in calorie intake, high chocolate consumption inducing hyperoxaluria and low water intake are other factors, which favour excessive urine concentration of solutes. Restoring the dietary balance is the first advice to prevent stone recurrence. However, the striking increase of some types of calculi, such as calcium oxalate stones developed from Randall's plaque, should alert to peculiar lithogenetic risk factors and suggests that specific advices should be given to prevent stone formation.

Abstract: The purpose of this study is to evaluate the effect of fluid and diet restriction in fasting on biochemical factors of stone formation. Our study concernes 90 patients divided in three groups: healthy fasting patient (GI), healthy non fasting patient (G2) and non fasting patient with calcium lithiasis (G3). The promotors (oxalate, calcium, uric acid, phosphates) and inhibitors (citrate, magnesium) are statistically significant between G1, G2 and G3, G2. Supersaturation of urine with oxalate, uric acid and brushite are the same for (G1) and (G3) and higher than (G2). Crystalluria is more important in lithiasis subjects compared with healthy non fasting patients (58% vs 11,4%). Oxalate monohydrate (Whewellite) and uric crystal don't exist in the healthy non fasting people but reached 4% and 12% respectively in the lithiasis patient. The crystalluria profil is the same in the heathy fasting patients and calcium lithiasis patients. However healthy patients have equilibria between promotors and inhibitors of crystal formation which minimize the risk of crystalluria and subsequent stone formation.

Abstract: We report a case of a 33 years old female with a history of paroxystic hemidystonia treated by acetazolamide, a carbonic anhydrase inhibitor (CAI), and who developed two years after the initiation of this treatment bilateral radio-opaque stones. Laboratory tests revealed a hyperchloremic acidosis, an elevated urinary pH, a hypercalciuria, a severe hypocitraturia and numerous granulations of amorphous carbonated calcium phosphates and brushite crystals on urinary microscopic examination, the whole suggests a diagnosis of acetazolamide-induced nephrolithiasis. We discuss in this article the lithogenetic process and the usual composition of the stones induced by CAI, and specific risk factors for developing drug-induced lithiasis which should be taken into consideration when prescribing long-term drug regimens.

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Abstract: Crystalluria is a marker of urine supersaturation present in both normal and pathological conditions. Indeed, nature and characteristics of the spontaneous crystalluria are of clinical interest for detecting and following biological disorders involved in renal diseases. Method. Crystalluria examination should preferably be performed on first morning urine or fresh fasting voiding samples by polarised microscopy in a Malassez cell. Urine samples must be stored at 37 degrees C or at room temperature and examined within two hours following voiding. Results and discussion. Crystalluria should be interpreted according to various criteria: 1) chemical nature of crystals for abnormal crystals such as struvite, ammonium urate, cystine, dihydroxyadenine, xanthine or drugs; 2) crystalline phase of common chemical species as calcium oxalates, calcium phosphates and uric acids; 3) crystal morphology (calcium oxalates); 4) crystal size (calcium oxalates); 5) crystal abundance (calcium oxalates, calcium phosphates, uric acids, cystine); 6) crystal aggregation (calcium oxalates); 7) frequency of crystalluria assessed on serial first morning urine samples, a very useful tool for long-term surveillance of patients. Within calcium oxalate crystalluria, presence of whewellite is a marker of elevated oxalate concentration (urine oxalate > 0.3 mmol/L); a crystal number > 200/mm 3 is highly suggestive of heavy hyperoxaluria of genetic or absorptive origin. Predominant weddellite crystalluria is most often indicative of an excessive urine calcium concentration (> 3.8 mmol/L); a dodecahedric aspect of the crystals is a marker for heavy hypercalciuria (> 6 mmol/L) while an increased crystal size (>or= 35 microm) is indicative of simultaneous hypercalciuria and hyperoxaluria. Calculation of the global crystal volume, especially when applied to calcium oxalates or cystine, is a clinically useful tool for the monitoring of patients suffering from primary hyperoxaluria or cystinuria. Lastly, presence of crystalluria in more than 50% of serial first voided morning urine samples is in our experience the most reliable biological marker for detecting the risk of stone recurrence in lithiasic patients. Conclusion. Crystalluria examination is an essential laboratory test for detecting and following pathological conditions, which may induce renal stone disease or alter kidney function due to urine crystals.

Abstract: BACKGROUND: The contribution of nephrolithiasis-related end-stage renal disease (ESRD) to patients requiring renal replacement therapy has never been specifically evaluated. METHODS: Of the entire cohort of 1,391 consecutive patients who started maintenance dialysis therapy at our nephrology department between January 1989 and December 2000, a total of 45 patients (21 men) had renal stone disease as the cause of ESRD and constitute the study material. Type and cause of renal stone disease was determined in the 45 patients, as well as the change in prevalence of nephrolithiasis-related ESRD with time during this 12-year period. RESULTS: The overall proportion of nephrolithiasis-related ESRD was 3.2%. Infection (struvite) stones accounted for 42.2%; calcium stones, 26.7%; uric acid nephrolithiasis, 17.8%; and hereditary diseases (including primary hyperoxaluria type 1 and cystinuria), 13.3% of cases. Women were predominant among patients with infection and calcium stones, whereas men were predominant among patients with uric acid or hereditary stone disease. The proportion of patients with nephrolithiasis-related ESRD decreased from 4.7% in the triennial period 1989 to 1991 to 2.2% in the most recent period, 1998 to 2000 ( P = 0.07). This tendency to a decreasing prevalence mainly was caused by a rarefaction of infection and calcium stones with time, whereas frequencies of uric acid and hereditary stone disease remained essentially unchanged. CONCLUSION: Severe forms of nephrolithiasis remain an underestimated cause of potentially avoidable ESRD and need for renal replacement therapy. These findings highlight the crucial importance of accurate stone analysis and metabolic evaluation to provide early diagnosis and proper therapy for conditions that may lead to ESRD through recurrent stone formation and/or parenchymal crystal infiltration.

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Abstract: Drug-induced calculi represent 1-2% of all renal calculi. The drugs reported to produce calculi formation may be divided into two groups. The first one includes poorly soluble drugs with high urine excretion that favours crystallisation in the urine. Among poorly soluble molecules, triamterene was the leading cause of drug-containing urinary calculi in the 1970s, and it is still currently responsible for a significant number of calculi. In the last decade, drugs used for the treatment of HIV-infected patients, namely indinavir and sulfadiazine, have become the most frequent cause of drug-containing urinary calculi. Besides these drugs, about twenty other molecules may induce nephrolithiasis in patients receiving long-term treatment or high doses. Calculi analysis by physical methods, including infrared spectroscopy or x-ray diffraction, is needed to demonstrate the presence of the drug or its metabolites within the calculi. The second group includes drugs that provoke urinary calculi as a consequence of their metabolic effects. Here, diagnosis relies on careful clinical inquiry because physical methods are ineffective to differentiate between urinary calculi induced by the metabolic effects of a drug and common metabolic calculi. The incidence of such calculi, especially those resulting from calcium/vitamin D supplementation, is probably underestimated. Although drug-induced urinary calculi most often complicate high-dose, long-duration drug treatments, there also exist specific patient risk factors in relation to urine pH, urine output and other parameters, which provide a basis for preventive or curative treatment of calculi. Better awareness of the possible occurrence of lithogenic complications, preventive measures based on drug solubility characteristics and close surveillance of patients on long-term treatment with drugs with lithogenic potential, especially those with a history of urolithiasis, should reduce the incidence of drug-induced nephrolithiasis.

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Abstract: New software (ScanLith) was developed to provide an automated procedure for identifying and quantifying crystalline species in urinary calculi. The first step was to strictly define operative conditions of sample preparation because they have a significant influence on the stability of various crystalline phases. Second, we determined the quantification coefficients of a polynomial curve required to develop the automated procedure. This was illustrated by the study of carbapatite and weddellite, as both constituents represent one of the most frequent associations found in stones analyzed in our laboratory. The following quadratic equation was obtained with a correlation coefficient r2 = 0.9997: Y = -0.5144x2 + 1.5239x - 0.0141, where Y is the absorbance ratio carbapatite/weddellite and x is the percentage of carbapatite in the mixture. The absorbance of carbapatite and weddellite was measured at 1035 cm(-1) and 1325 cm(-1), respectively. The third step was to validate the ScanLith procedure in routine analysis by comparing computed results with those of an expert. Concordance (r2 = 0.9824) was better than that previously reported using various computerized systems with a mean deviation of 4%. Algorithms developed in ScanLith to identify main and minor components found in urinary stones, even in complex mixtures containing up to seven constituents, allowed us to lower the detection threshold down to 1 to 10% depending on the main component.

Abstract: The aim of this study was to evaluate the efficacy of helical CT using a combination of CT-attenuation values and visual assessment of stone density as well as discriminant linear analysis to predict the chemical composition of urinary calculi. One hundred human urinary calculi were obtained from a stone-analysis laboratory and placed in 20 excised pig kidneys. They were scanned at 80, 120 and 140 kV with 3-mm collimation. Average, highest and lowest CT-attenuation values and CT variability were recorded. The internal calculus structure was assessed using a wide window setting, and visual assessment of stone density was recorded. A stepwise discriminant linear analysis was performed. The following three variables were discriminant: highest CT-attenuation value, visual density, and highest CT-attenuation value/area ratio, all at 80 kV. The probability of correctly classifying stone composition with these three variables was 0.64, ranging from 0.54 for mixed calculi to 0.69 for pure calculi. The probabilities of correctly classifying calculus composition were: 0.91 for calcium oxalate monohydrate and brushite, 0.89 for cystine, 0.85 for uric acid, 0.11 for calcium oxalate dihydrate, 0.10 for hydroxyapatite, and 0.07 for struvite calculi. When the first two ranks of highest probability for the accurate classification of each calculus type were taken into account, 81% of the calculi were correctly classified. Assessment at 80 kV of the highest CT-attenuation value, visual density and the highest CT-attenuation value/area ratio accurately predicts the chemical composition of 64-81% of urinary calculi. When the first two ranks of highest probability for the accurate classification of each calculus type were taken into account, all cystine, calcium oxalate monohydrate and brushite calculi were correctly classified.

Abstract: Urinary stone incidence and composition have changed markedly over the past half-century in industrialized countries, in parallel with profound changes in living standards and dietary habits, with a dramatic increase in the incidence of calcium oxalate stones. However, studies evaluating the influence of age and gender on the distribution of the various types of urinary calculi are scarce. We report the results of a study based on 27,980 calculi (from 19,442 males and 8,538 females) analyzed by infrared spectroscopy between 1976 and 2001. The relationships between age and sex and stone composition were investigated using a multivariate approach, based on correspondence factor analysis (CFA). We found a male predominance for calcium oxalate and uric acid, a female preponderance for calcium phosphate and struvite stones, and an increasing prevalence of uric acid stones with age in both genders. CFA was able to reconstruct in blind the age curve from stone composition. The first two axes of the multidimensional classification, which correspond to age, included 86.9% of the total variance, indicating that age was the main factor involved in stone type. Superimposition of age classes and stone components showed a strong relationship between age and whewellite, weddellite, brushite, carbapatite, octacalcium phosphate and uric acid, while other substances (whitlockite, amorphous carbonated calcium phosphate, struvite, proteins, mucopolysaccharides, triglycerides or ammonium urate) appeared weakly related to age. In addition, CFA suggests the role of common lithogenic factors between weddellite, carbapatite and brushite, which clustered in the same area, whereas the various crystalline forms of phosphate stones segregated into two different clusters, suggesting distinct pathogenic factors. In conclusion, this study provides a picture of the present epidemiology of urinary stones in France. CFA helped to confirm: (1) an etiopathogenic distinction between weddellite and whewellite, (2) etiopathogenic associations between chemical compounds, which were only suspected on a clinical basis, and (3) suggested yet unrecognized associations, especially with respect to the heterogeneous group of phosphate stones.

Abstract: Morphoconstitutional analysis of urinary calculi, i.e. morphologic examination combined with Fourier transform infrared spectroscopy (FTIR), is of decisive interest for the diagnosis of rare but severe inherited or acquired stone diseases such as cystine, 2,8-dihydroxyadenine, xanthine, struvite, ammonium urate or drug-containing calculi as well as primary hyperoxalurias. In the absence of early diagnosis and proper management, these diseases may lead to progressive loss of renal function. Among common forms of calcium oxalate (CaOx) stones, predominant CaOx monohydrate (whewellite) is mainly associated with hyperoxaluric conditions whereas predominant CaOx dihydrate (weddellite) is mainly associated with hypercalciuria, and this distinction is of interest to orient metabolic evaluation and preventive measures. Crystalluria examination, also based on morphology and FTIR, is a valuable diagnostic method when no stone is available for analysis. Presence of specific crystals (cystine, 2,8-dihydroxyadenine, struvite, ammonium urate) is diagnostic by itself. In all types of nephrolithiasis, serial crystalluria determination appears as a simple, cheap and reliable method to evaluate the risk of stone formation and assess the effectiveness of preventive measures. Determination of urinary crystal volume was in our experience a useful tool in the management of patients with cystinuria or primary hyperoxaluria in the post-transplantation period. In conclusion, both accurate morphologic and FTIR analysis of stones and serial crystalluria determination should be more largely used, in view of their value in the diagnosis and management of renal stone formers.

Abstract: Up until relatively recently, renal stones in developing countries were considered to be very different from those observed in industrialized countries, essentially characterized by the predominance of phosphate and urate stones, while the predominant stones in industrialized countries are calcium oxalate stones. To verify whether this difference in the epidemiological profile is still observed today, we analysed renal stones collected in various regions of the globe and compared their composition to that of stones observed in France. MATERIAL AND METHOD: 1,042 stones were collected between 1991 and 2000 from 14 different countries or geographical zones: Sub-Saharan Africa (Cameroon, Mali, Senegal), North Africa (Algeria, Morocco, Tunisia), South America (Brazil, Paraguay), Asia Minor (Pakistan, Turkey), Far East (China, Laos, Vietnam) and French Polynesia (Tahiti). Stones were analysed by infrared spectrophotometry. The composition of these stones was compared to that of 24,706 stones collected in France over the same period and analysed according to the same protocol. RESULTS: Overall, the proportion of calcium oxalate stones was the same in adults in France and in developing countries (men: 75.7% contre 72%; women: 59.8% contre 56.3%), but was higher in children in non-industrialized countries (boys: 52.6% contre 31.8% in France; girls: 67.8% contre 48.8% in France, p<0.0001). The frequency of calcium phosphate stones was particularly low in boys in developing countries (8.3% contre 45.1% in France, p<0.0001) andfrequency of purine stones was higher in boys (21.3% contre 5.2% in France, p<0.0001) and in girls (13.6% contre 4.3% in France, p<0.05). Major differences were observed according to continent and region; struvite was present in 42.9% of stones in women in Sub-Saharan Africa contre 13% in South America and 2.7% in Asia Minor. Purines were 4 times more frequent in Tahitian men than in North African men. Calcium phosphate stones were 10 times less frequent in men in Asia Minor than in the Far East. CONCLUSION: The epidemiology of renal stones is continuing to change all over the world towards a predominance of calcium oxalate stones, which is now generalized. Major differences in the frequency of the other constituents, particularly purines and struvite, reflect particular eating habits and infectious risk factors specific to certain population.

Abstract: We report the case of a 65 year old man, with a history of recurrent urolithiasis, who was referred for an acute renal failure. Investigations deny obstructive or glomerular involvement. 2,8-Dihydroxyadeninuria was diagnosed with the help of crystalluria. This rare metabolic disease is due to a deficiency of adenine phosphoribosyltransferase, a purine salvage enzyme. Allopurinol, a low purine diet and high fluid intake made possible the nearly entire regression of renal failure.

Abstract: Clinical investigations of a patient with urolithiasis include a careful history and radiological and biochemical evaluation. Stone analysis by infrared spectrophotometry remains the most important step. These investigations are essential in order to understand why a patient developed urolithiasis and, most importantly, how to avoid its recurrence in the future. Simple exams are often enough in a patient with a single urolithiasis episode. But biochemical evaluation should be extensive in a child, or an adult with several urolithiasis episodes or with renal insufficiency.

Abstract:

Abstract: Urinary stone disease is frequent, and characterized by a high recurrence rate. Prevention of recurrent urolithiasis is possible using an appropriate diet with or without medications. Patients should be encouraged to have a high fluid intake. For an adult, urine volume should exceed 2000 ml/day. Diet modification should be done according to the various metabolic factors contributing to the formation of the stone (ie, hypercalciuria, hyperoxaluria, hypocitraturia, hyperuricuria, and so forth). Calcium intake should be around 1000 mg/day, protein intake limited to 1.2 g/kg/day, and salt intake kept to less than 100-150 mEq/jour. For uric acid urolithiasis, patient should limit uric acid intake to less than 500 mg/day. If these dietary manoeuvers fail, one can use thiazide diuretics to treat hypercalciuria, potassium citrate to correct hypocitraturia or sodium bicarbonate to alkalanize urine and prevent uric acid stone formation.

Abstract:

Abstract: We report the case of a 69-year-old woman, with a BMI of 42.9, suffering from bilateral struvite calculi and who raised end stage renal failure. Urease-synthesizing bacteria, leading to the hydrolysis of urea into ammonium and to an alkaline urine (pH > 7.2), are required for struvite stone formation in humans. Struvite component constitutes the majority of staghom calculi. Patients with struvite stones could lose renal function because of obstructive or pyelonephritic episodes and surgical interventions on the kidney. Therapeutic success needs a follow up by a specialized uro-nephrologist team as soon as possible.

Abstract: Primary hyperoxaluria type I is a rare inborn error of metabolism caused by a deficiency of a liver-specific peroxisomal enzyme. It manifests by increased oxalate production that ultimately results in kidney failure, due to urolithiasis and nephrocalcinosis, and finally induces systemic oxalosis and risk of premature death. Primary hyperoxaluria type 2 is mainly responsible of urolithiasis. Enteric hyperoxaluria is a commonly seen adverse event of Crohn disease or after extensive intestinal resection. These affections represent the main etiologies of massive hyperoxaluria. If not recognized very soon and adequately treated, these conditions can progress rapidly to end stage renal failure.

Abstract:

Abstract: We prospectively determined cystine crystal volume (Vcys) in urine specimens from all consecutive patients with cystine urolithiasis followed at our institution over the past decade, in order to assess its predictive value as to the risk of recurrent cystine stone formation. A total of 57 patients (29 males, 28 females) with homozygous cystinuria entered in the study between January 1990 and December 2000, including 15 children aged less than 15 years and 42 patients aged 15 years or more. The clinical and radiological course was followed until December 2001, for a total of 243 patient-years of follow-up. From study entry until the end of follow-up, we serially examined first voided morning urine specimens in all patients, with determination of the number of cystine crystals per mm3, and the average size of crystals, thus allowing us to calculate Vcys using a simple formula based on crystal geometry. Recurrence was diagnosed on the basis of serial radiographic examinations using X-rays and echography. Overall, cystine crystals were present in 179 (39%) of the 460 examined urine specimens. Cystine crystalluria was significantly more frequent among the 27 patients who developed new cystine stones (SF) than in the other 30 who remained stone-free (63.3 vs 25.5% of samples, P<0.001). The presence of crystals in > or =50% of serially examined urine samples was more frequently found in patients with recurrent stone formation than in non-recurrent patients (24/27 vs 2/30, P<0.001). The average Vcys value was significantly higher in recurrent SF than in stone-free patients (8,173 +/- 1,544 vs 233 +/- 150 micro3/mm3, P<0.001) and there was no overlap in the individual values of recurrent vs stone-free patients. A Vcys value > or =3,000 micro3/mm3 was observed at least once prior to each of the 63 stone recurrences observed in 27 patients (2.3 per patient on the average). In addition, Vcys reflected the efficacy of treatment, with Vcys mean values of 12,097 +/- 3,214 micro3/mm3 at baseline, falling to 2,648 +/- 658 micro3/mm3 on basic therapy (hyperdiuresis plus alkalinization) alone, 1,141 +/- 522 micro3/mm3 on tiopronin therapy (median dose 1,000 mg/day) and 791 +/- 390 micro3/mm3 on D-penicillamine therapy (median dose 900 mg/day) whereas captopril had no effect (5,114 +/- 2,128 micro3/mm3). Based on the results of the present study, cystine crystalluria appears to accurately reflect active stone formation in cystinuric patients. Determination of total Vcys provides a simple, cheap and accurate means of predicting the risk of cystine stone recurrence with a Vcys value > or =3000 micro3/mm3 as the threshold risk value. We propose that serial Vcys determination be performed simultaneously with the measurement of urine pH and specific gravity to optimally monitor the medical treatment of cystine patients.

Abstract: INTRODUCTION: More than ten per cent of stones are associated with a urinary tract abnormality. To verify whether the malformation influences stone composition, we studied the composition of stones observed in fifteen urological abnormalities. MATERIAL AND METHOD: This study is based on 1,461 stones associated with a clearly defined malformation analysed by infrared spectroscopy plus 402 bladder stones in men with benign prostatic hyperplasia. RESULTS: In this series of 1,863 abnormalities, 732 (39.3%) involved the kidney, 561 (30.1%) involved the ureter and 570 (30.6%) involved the lower tract. Whewellite stones were predominant in all renal abnormalities with the exception of cysts, which were mainly associated with uric acid. The main differences concerned the second constituent: weddellite in horseshoe kidneys, carbapatite in Cacchi-Ricci disease and caliceal abnormalities. Struvite was uncommon (<10%). Whewellite was the main component in ureteric abnormalities except for megaureter and reflux in which carbapatite was predominant. Struvite was present in 10% to 30% of stones. Vesicourethral abnormalities were accompanied by calcium and magnesium phosphate stones (90% of cases), and struvite was present in 58% to 90% of cases. The exception to this general rule was bladder stones associated with benign prostatic hyperplasia, in which the main component was uric acid. CONCLUSION: Significant differences in stone composition were observed as a function of anatomical abnormalities reflecting the fact that some abnormalities add infectious or metabolic risk factors to anatomical factors.

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Abstract: BACKGROUND AND OBJECTIVE: Some halogenated agents, especially methoxyflurane, because of a higher level of fluoride production, induce a renal concentrating defect that could be related to an ascending limb impairment. We investigated the mechanisms of fluoride toxicity on an immortalized cell line. METHODS: Cells were cultured for 2, 6 or 24 h in the presence of fluoride. Toxicity evaluation was based on: cell numbers, protein content, leucine-incorporation, lactate dehydrogenase (LDH) and N-acetyl-beta-glucosaminidase (NAG) releases, Na-K-ATPase and Na-K-2Cl activities, electron microscope studies. Infrared analysis and fluoride microdetermination allowed crystal components. RESULTS: At 5 mmol after 24 h, fluoride decreased cell numbers (-14%, *P < 0.05), protein content (-16%*), leucine incorporation (-54%*), Na-K-2Cl activity (-84%*), increased LDH (+145%*) and NAG release (+190%*). Na-K-ATPase was more sensitive and impaired from 1 mmol for 24h and after 2 h at 5 mmol. Crystal formation in mitochondria occurred after 6 h at 5 mmol. Infra-red analysis and fluoride microdetermination established that crystals contained sodium, phosphate and fluoride. CONCLUSIONS: The results suggest that the Na-K-ATPase pump is a major target for fluoride toxicity in Henle's loop.

Abstract: Urologists frequently advise a high fluid intake to their patients with calcium stones, but apart from this simple advice, they often have few convincing arguments. This article describes the various types of drinking water available in France (mineral water, spring water, tap water), the legislation concerning drinking water, and the ions that must be taken into account for long-term forced diuresis. After studying their composition and adapting the dietary advice (particularly concerning dairy foods) to this ionic composition, various types of water can be advised to patients, including tap water, most types of spring water, but not all mineral waters.

Abstract: We report the first case of acute cholecystitis due to indinavir-induced cholelithiasis in a patient infected with human immunodeficiency virus who had been receiving indinavir for 56 months. Infrared spectroscopy demonstrated that the gallstone was composed of indinavir monohydrate (50%), calcium bilirubinate (28%), calcium palmitate (10%), cholesterol (7%), and proteins (5%). The role of high-level chronic unconjugated hyperbilirubinemia coupled with high blood concentrations of indinavir is discussed.

Abstract: Twelve of the urine parameters, namely sodium, potassium, chloride, urea, creatinine, uric acid, calcium, phosphate, protein, microalbumin, amylase and glucose, routinely measured in a biochemistry laboratory were chosen to revalue their interest in clinical practice. For each parameter, urinary collection method, physiologic review and specific indications were set out. The clinical interest of chloride, urea, phosphate or uric acid measurement seem limited to specific pathological conditions. The measurement of urine amylase is out of interest.

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Abstract: Analysis of 22,510 urinary calculi between January 1991 to July 2000 performed by infrared spectroscopy allows for separation of drug-induced urolithiasis into two categories: first, the drugs physically embedded in the stone (n = 238; 1.0 per cent), notably indinavir monohydrate (n = 126; 52.9 per cent), followed by triamterene (n = 43; 18.1 per cent), sulphonamides (n = 29; 12.2 per cent) and amorphous silica (n = 24; 10.1 per cent); second, the category of metabolic nephrolithiasis induced by drugs (n = 140; 0.6 per cent), involving mainly calcium and vitamin D supplementation (n = 56; 40.0 per cent) and carbonic anhydrase inhibitors (n = 33; 23.6 per cent). Composition of the stone depended not only on the inducer drug but also on the metabolic state of the patient. Today, drug-induced stones comprise about 1.6 per cent of all calculi in France. Physical analysis and therapeutic history recall of such patients are the keys to diagnosis. Medical care is based on drug avoidance or dose adjustment with increased diuresis and, if necessary, change in urinary pH.

Abstract: BACKGROUND: Lipids play a significant role in the process of calcification of bioprostheses. We assessed whether lipid extraction by ethanol, ether, or a surfactant could mitigate calcification of glutaraldehyde-treated bioprostheses. METHODS: On 200 bovine pericardium samples pretreated with 0.6% glutaraldehyde, lipid extraction was carried out by ethanol, ether, or the tween 80 surfactant, and combinations thereof. The treated tissues were implanted subcutaneously in 50 juvenile rats for 4 and 6 months. Lipids were analyzed by Fourier transform infrared spectrophotometer and chromatography before implantation. Calcium content of implanted tissues was assessed by atomic absorption spectrometer. RESULTS: Ethanol, ether, or surfactant did mitigate calcification. The most efficient pretreatments were the combination of ethanol and surfactant (calcium content: 15.5+/-6.8 microg/mg dry tissue after 6 months implantation) or the combination of ethanol, ether, and surfactant (13.1+/-6.2 microg/mg dry tissue) when compared with surfactant alone (42.9+/-12.7 microg/mg dry tissue). CONCLUSIONS: Ethanol or the combination of ethanol and ether added to the currently used glutaraldehyde-surfactant treatment further mitigates calcification.

Abstract: OBJECTIVE: High urine volume is known to be an effective measure for preventing stone recurrence. However, only few studies have investigated its effects on crystalluria and spontaneous passage of calculi. The aim of the study was to assess the effects of high diuresis on stone expulsion and recurrence. PATIENTS AND METHODS: 219 patients were consulting for a first stone episode in Urology units in the Mostaganem area between September 1996 and December 1999. All stones were under 6 mm in size. The patients were divided in two groups: group I included 129 patients (68 males, 61 females) who agreed to be on a high water intake, at least 3 liters per day, over a two months period and to be followed periodically by crystalluria examination in the first morning urine; group II included 90 patients (63 males, 27 females) who declined diuresis advice and urine collection for crystalluria examination. First morning urine collected in patients of group I were examined before (2.95 voidings per subject) and while on diuresis course (2.84 voidings per subject). For each sample, the urine pH was measured and crystals were looked for by polarizing microscopy. Stones spontaneously passed were collected and analyzed by infrared spectroscopy. Group II represented the control group for stone passing and recurrence. RESULTS: Crystalluria was present in 52.4% of urine samples before starting diuresis and decreased at 22.9% of urine samples on high diuresis. Mean pH value increased from 5.73 +/- 0.46 before to 6.09 +/- 0.47 (p < 10-6) while on diuresis course in males and from 5.8 +/- 0.68 to 6.24 +/- 0.66 in females (p < 10-6). The most frequent crystalline species was weddellite. Over the study period, 98 patients (76%) in group I and only 13 patients (14.4%) in group II passed stones spontaneously (p < 10-6 contre group I). No stone recurrence was observed in group I while 37.8% of patients in group II presented at least one stone recurrence (p < 10-7). CONCLUSION: A high diuresis is an effective measure (1) to make easier the passing of stone under 6 mm in size; (2) to reduce the occurrence of crystalluria; (3) to reduce significantly, because of its favourable effect on urine pH, the formation of pH-dependent crystalline phases, thus decreasing heterogeneous nucleation process of calcium oxalate and stone recurrence.

Abstract: OBJECTIVE: To determine the composition of caculi and the predisposing factors for stone nucleation and growth in children from two regions of Cameroon. METHODS: This was a cross-sectional study involving 21 children, 17 from the northern and 4 from the southern region, over a 6-year period. Data on age, diet, residence, clinical presentation, location of stone, and results of stone analysis were collated following a preestablished proforma. A computerized analysis of the data was carried out. The constituents of stone sections and nidus were assembled so as to determine the principal causes of stone nucleation and growth. RESULTS: Pediatric urolithiasis was more common in the northern Sahelian belt of Cameroon. Males and rural dwellers were more commonly affected. Endemic (bladder) stone disease was found in the majority of the patients. All stones were mixed. The most frequent constituents of the stones were ammonium urate, struvites, and whewellite in descending order of percentage mean volume per stone. The nidus was available for study in only 10 stones, and its composition revealed heterogeneity of causes of nucleation. The commonest cause for stone formation and growth were infection and hyperuricosuria (malnutrition). CONCLUSIONS: Pediatric bladder stone disease is not uncommon in northern Cameroon. Many factors combined to predispose to stone nucleation and growth, but the level of socioeconomic development was preponderant. Stone composition indicated that urolithiasis in children was a heterogeneous disorder, but hyperuricosuria, insufficient diuresis, and infection associated with malnutrition seemed to be the most common causes.

Abstract: Calculi from 45 Moroccan children aged between 2 and 15 years underwent morphological and infrared spectrometric analysis. The stones were three times more frequent in males than females (M/F = 3.09). Whewellite was the main component in 51.1% of cases and in 44.4% of stone nuclei, wheddellite in 8.9% of stones and nuclei, carbapatite in 6.7% of stones and 8.9% of nuclei, struvite in 15.6% of stones and 11.1% of nuclei. Ammonium hydrogen urate and uric acid were predominant respectively in 8.9% and 6.7% of stones and in 15.6% and 11.1% of nuclei. In addition to whewellite, struvite and ammonium hydrogen urate were the main components of bladder stones from both sexes. With respect to their calculi, whewellite was present in 84.4% of cases and wheddellite in 26.7%. Purines were present in 46% of calculi, especially as ammonium urate (28.9%) and uric acid (15.6%). Calcium phosphates as the main components were infrequent. In contrast, they were frequently identified in urinary calculi from children, respectively 64.4% and 40% for carbapatite and amorphous carbonated calcium phosphate.

Abstract: PURPOSE: We evaluated long-term results of a contemporary medical therapeutic regimen in patients with cystinuria and analyzed factors predictive of therapeutic success. MATERIALS AND METHODS: A total of 27 adults with cystine urolithiasis were treated at our institution for 1.3 to 32 years (mean 11.6, overall 312 patient-years). We obtained data on the pre-referral period for 274 patient-years overall. Basic therapy included hyperdiuresis and alkalization. The thiols D-penicillamine or tiopronin were added when standard therapy failed to prevent new stones and stone growth or dissolve preexisting stones. X-ray and echography were performed every 4 months during the initial 2 years and every 6 months thereafter. RESULTS: In the pre-referral period 256 stone episodes occurred and 81 urological procedures were performed in 24 patients (0.93 and 0. 29 per patient-year, respectively). Nine patients were treated with added thiols. During the therapeutic period the incidence of stone episodes decreased to 66 (0.20 per patient-year, p <0.001), while the need for urological procedures decreased to 44 (0.14 per patient-year, p <0.001). No further urological procedures were required in 15 patients, including 4 treated with thiols. However, the remaining 12 patients, including 5 treated with thiols, underwent 1 to 7 procedures each (mean 0.26 per patient-year). In the 2 groups mean daily cystine excretion plus or minus standard deviation at baseline (863 +/- 253 versus 761 +/- 270 mg. daily) and mean urinary pH of about 7.4 did not differ significantly. However, daily urine volume was significantly higher in patients with arrested stone formation (3,151 +/- 587 versus 2,446 +/- 654 ml./24 hours, p = 0.006). CONCLUSIONS: Our study provides evidence that a regularly followed medical program based on high diuresis and alkalization with second line addition of thiols may arrest or markedly decrease cystine stone formation and preclude the need for urological procedures in more than half of the patients. However, patients poorly compliant with hyperdiuresis remain at risk for recurrence. We suggest that maintaining a daily urine volume of greater than 3 l. is essential for therapeutic success regardless of whether thiol derivatives are administered.

Abstract: Foscarnet nephrotoxicity has been reported to be associated with acute tubulointerstitial nephritis. Crystals in glomerular capillary lumens have also been observed in patients with acquired immunodeficiency syndrome who were treated with foscarnet for cytomegalovirus disease. We describe a kidney transplant recipient who developed a nephrotic syndrome with microscopic hematuria and nonoliguric acute renal failure within 15 days after starting foscarnet therapy for cytomegalovirus infection. A kidney biopsy specimen showed the presence of crystals in all glomeruli and in proximal tubules. Fourier transform infrared microscopy analysis demonstrated that crystals were made from several forms of foscarnet salts: mixed calcium and sodium salts, and unchanged trisodium foscarnet salts. Renal function and proteinuria spontaneously improved, and a second transplant biopsy performed 8 months after the first one revealed fibrotic organization of half of the glomeruli and of interstitial tissue, and crystal vanishing. We were thus able to provide proof of the possible precipitation of foscarnet in a transplanted kidney.

Abstract: BACKGROUND: Urine is supersaturated in calcium oxalate, which means that it will contain calcium oxalate crystals that form spontaneously. Their size must be controlled to prevent retention in ducts and the eventual development of a lithiasis. This is achieved, in part, by specific inhibitors of crystal growth. We investigated whether promoters of crystal nucleation could also participate in that control, because for the same amount of salt that will precipitate from a supersaturated solution, increasing the number of crystals will decrease their average size and facilitate their elimination. METHODS: Albumin was purified from commercial sources and from the urine of healthy subjects or idiopathic calcium stone formers. Its aggregation properties were characterized by biophysical and biochemical techniques. Albumin was then either attached to several supports or left free in solution and incubated in a metastable solution of calcium oxalate. Kinetics of calcium oxalate crystallization were determined by turbidimetry. The nature and efficiency of nucleation were measured by examining the type and number of neoformed crystals. RESULTS: Albumin, one of the most abundant proteins in urine, was a powerful nucleator of calcium oxalate crystals in vitro, with the polymers being more active than monomers. In addition, nucleation by albumin apparently led exclusively to the formation of calcium oxalate dihydrate crystals, whereas calcium oxalate monohydrate crystals were formed in the absence of albumin. An analysis of calcium oxalate crystals in urine showed that the dihydrate form was present in healthy subjects and stone formers, whereas the monohydrate, which is thermodynamically more stable and constitutes the core of most calcium oxalate stones, was present in stone formers only. Finally, urinary albumin purified from healthy subjects contained significantly more polymers and was a stronger promoter of calcium oxalate nucleation than albumin from idiopathic calcium stone formers. CONCLUSIONS: Promotion by albumin of calcium oxalate crystallization with specific formation of the dihydrate form might be protective, because with rapid nucleation of small crystals, the saturation levels fall; thus, larger crystal formation and aggregation with subsequent stone formation may be prevented. We believe that albumin may be an important factor of urine stability.

Abstract: A Search algorithm included in the Opus software of Bruker (Germany) was evaluated for analysis of urinary stones. Three reference libraries containing respectively 85 (single components), 1,059 (binary mixtures) and 4,565 (ternary mixture) digitized spectra were created and used to identify unknown spectra (n=320), applying the automatic procedure. Identification of the major component was correct in 83% of cases but the percentage of identification significantly decreased for the second and the third components. In cases of identification of the two first components, quantitative assessment was correct within tolerance limits +/- 15%. The computer results are judged unsatisfactory with regard to pathology because computer-aided identification is not sufficiently sensitive and specific to differentiate species with similar spectral pattern, even for the identification of main component, and also to detect minor components. It can be of assistance to guide spectral analysis, but it cannot replace human identification.

Abstract: The successful fragmentation of kidney stones by means of extracorporeal shock wave lithotripsy partly depends on stone composition. In case of incomplete or coarse fragmentation, multiple urological procedures following ESWL may be necessary for removal of obstructive fragments. It is difficult to be sure that a given stone will be successfully destroyed. X-ray examinations before treatment are useful to classify calculi as calcium stones or not. Nevertheless, such investigations are often not sufficient to identify the main crystalline phases which form the stone and that can make it either resistant or friable to ESWL. OBJECTIVE: The aim of this study was to compare crystalluria and stone composition in patients with kidney calculi. MATERIAL AND METHODS: Seventy-five untreated patients (54 males, 21 females) were included. Their first morning urine was collected three days before surgical removal of the stone. Urine samples were kept at 4 degrees C during 48 hours before examination. RESULTS: Crystalluria occurred in 97.3% of urine specimens. Weddellite was the most frequent crystalline species found in urine (66.2%), followed by carbapatite (33.1%) and whewellite (23.1%). When compared to stone composition, crystalluria was mainly made of weddellite in urines from 68% of patients with weddellite-rich calculi. Stones from patients presenting with whewellite crystals in urine were mainly composed of whewellite in 88.9% of cases. Struvite stones were associated with struvite and carbapatite crystalluria in 85.7% of cases. CONCLUSION: Crystalluria studies could be of clinical interest to predict the main crystalline phase of calcium-containing stones in order to define the best procedures for stone removal.

Abstract: Two proteins of 17 and 24 kDa, respectively, which were immunologically related to bikunin, were purified from urine of healthy men, using in the last step a trypsin CNBr-sepharose affinity column. These proteins strongly inhibited calcium oxalate (CaOx) crystallization in two in vitro models. In the first model, the presence of 8 microg/ml protein in a medium containing 0.76 mM CaCl2 (with 45Ca) and 0.76 mM ammonium oxalate inhibited the crystallization process by 80%, as estimated by supernatant radioactivity after 60 min of incubation. A similar inhibition was observed in the second turbidimetric model, where the CaOx crystallization kinetics were followed for 10 min at 620 nm in a medium containing 4 mM CaCl2 and 0.5 mM Na2Ox. These proteins were used as standard protein for the development of an enzyme-linked immunosorbent assay (ELISA) in urine. Mean (+/-SEM) urinary bikunin concentration in 18 healthy subjects was 5.01 +/- 0.91 microg/ml. This was a concentration range of strong inhibitory activity in vitro. Bikunin values were nearly 50% lower (2.54 +/- 0.42 microg/ml, P=0.007) in 31 CaOx renal stone formers (having weddelite crystals in their first morning urine) than in the healthy volunteers. A correlation was found between urinary bikunin and alpha-1 microglobulin concentrations in the control group (y=0.73x + 1.09, r2=0.8) while no such correlation existed in the lithiasis group. In conclusion, bikunin exerts a strong inhibitory action of CaOx crystallization in vitro. Its involvement in urinary CaOx crystallization of stone formers is highly probable, based on the significant decrease in its urinary concentration in the majority of stone formers studied.

Abstract: In the past few years, alpha-1-microglobulin (alpha1m) has been copurified from human urine with bikunin, a potent inhibitor of calcium oxalate (CaOx) crystallization in vitro. In this study, we have purified alpha1m without bikunin contamination and investigated its possible role in CaOx crystallization by in vitro and in vivo studies. Alpha-1m was purified with an anti-alpha1m antibodies CNBr-activated sepharose column. Two molecular species of alpha1m of respectively 30 and 60 kDa were purified. For each protein, two blots of 30 and 60 kDa cross-reacted with anti-alpha1m antibodies, suggesting that these two forms were derived one from the other. Both protein species inhibited CaOx crystallization in a dose-dependent manner in two in vitro tests. In the first test, the presence of alpha1m of 30 kDa (8 microg/ml) in a medium containing 0. 76 mM CaCl(2) (with (45)Ca) and 0.76 mM Ox(NH(4))(2) inhibited CaOx crystallization by 38% as estimated by supernatant radioactivity after 1 h of agitation. In the second test, CaOx kinetics were examined for 3 to 10 min in a turbidimetric model at 620 nm. The presence of alpha1m of 30 kDa in a medium containing 4 mM CaCl(2) and 0.5 mM Na(2)Ox inhibited CaOx crystallization by 41.5%, as estimated by the slope modification of turbidimetric curve. Alpha-1m can be considered as another inhibitor of urinary CaOx crystal formation, as shown by the present in vitro studies. Using an ELISA assay, we found that urinary alpha1m concentration was significantly lower in 31 CaOx stone formers than in 18 healthy subjects (2.95 +/- 0.29 vs 5.34 +/- 1.08 mg/l respectively, P = 0.01). The decreased concentration of alpha1m in CaOx stone formers could be responsible in these patients, at least in part, for an increased risk of CaOx crystalluria.

Abstract: Drug-induced urolithiasis are observed in 1.6% of the urinary calculi in France. Drugs crystals are identified in two thirds of these stones. Other drugs are responsible for stones which have an apparent metabolic origin (one third of the cases). Stone analysis using physical methods such as infrared spectroscopy is needed to unambiguously identify stones containing drugs. The inquiry is an important step to identify lithogenetic drugs which do not crystallize in the stones. The main substances which were identified in stones over the past decade were indinavir monohydrate (31.4%), triamterene (11.1%), sulphonamides (10.5%) and amorphous silica (4.5%). The main drugs involved in the nucleation and growth of metabolic stones were calcium and vitamin D supplementation (15%) and long-term treatment with carbonic anhydrase inhibitors (8%). Stone prevention is based on drug withdrawal or change in dosage with additional measures including an increase of diuresis and, if necessary, changes in the urine pH.

Abstract: The composition of urinary stones in children depends on socioeconomic conditions and hygiene, geographical area, and dietary habits. We analyzed urinary stones from 120 consecutive Tunisian children (81 males, 39 females) aged 5 months to 15 years. The stone was located in the upper urinary tract in 91 cases (76%). Stone analysis included both a morphological examination and an infrared analysis of the nucleus and the inner and peripheral layers. The main components of bladder calculi were whewellite (69%) and struvite (22%), whereas the main component of upper urinary tract calculi was whewellite (67%). The nucleus of bladder stones was composed of ammonium urate (45%), struvite (28%), cystine (10%), and carbapatite (7%). The nucleus of kidney and ureteral calculi was mainly composed of ammonium urate (38%), whewellite (24%), carbapatite (13%), or struvite (11%). Based on stone composition, urinary tract infection was involved in the nucleation or growth of a third of calculi. Endemic urolithiasis involving simultaneous nutritional, metabolic, and infectious factors, and defined by its nucleus composed of ammonium urate without struvite, represented 40% of cases. Exclusive metabolic factors - including genetic diseases such as primary hyperoxaluria, cystinuria, and hypercalciuria - were responsible for less than 25% of cases.

Abstract: Cystine urolithiasis is the only clinical expression of cystinuria, an autosomal recessive genetic defect of the transepithelial transport of cystine and other dibasic amino acids in the kidney. Stones form due to the increased excretion of cystine, which is poorly soluble at normal urine pH. Cystine stones are often resistant to extracorporeal shock wave lithotripsy, so that percutaneous surgery or ureteroscopy are the preferred techniques of stone extraction. Medical preventative treatment is based on high diuresis (>/=1.5 l/m(2) per day) well distributed throughout the day and night, and urine alkalinization up to pH 7.5 by means of sodium bicarbonate and/or potassium citrate. When these basal measures are ineffective at preventing stone recurrence or dissolving pre-existing stones, sulfhydryl agents such as D-penicillamine or tiopronin, which form highly soluble mixed disulfides with cystine moieties, are to be added to urine dilution and alkalinization, especially when cystine excretion is in excess of 750 mg/day (3 mmol/day). Frequent clinical and ultrasound follow-up is needed to encourage patient compliance and assess efficacy and tolerance of treatment.

Abstract: Phosphates are encountered as the main components in about 15% of urinary calculi. Except for struvite, no specific correlations have been found between the crystalline phase of the phosphates and the cause of nephrolithiasis. OBJECTIVE: The relationship between aetiological factors and crystalline phases or carbonate rate in calcium phosphate stones were assessed. MATERIAL AND METHODS: From a series of 1148 phosphate calculi, we investigated the relationship between composition and aetiological factors. RESULTS: Carbapatite was the most frequent crystalline phase (74.0%). It was associated with many possible causes, including hypercalciuria, hypocitraturia, primary hyperparathyroidism, tubular acidosis, medullary sponge kidney and chronic urinary tract infection. The carbonate rate of carbapatite may be of clinical interest because carbonate rates above 15% are frequently related to urinary tract infection with urea-splitting bacteria. Conversely, the carbonate rate was commonly less than 10% in cases of carbapatite induced by metabolic disorders. Among other phosphates, brushite was found in hypercalciuric states and primary hyperparathyroidism and whitlockite in cases of urinary tract infection by non-urease-producing bacteria. CONCLUSION: Identification of crystalline phases and measurement of carbonate rate in calcium phosphate calculi is of clinical interest for identifying stone aetiology.

Abstract: Primary hyperoxaluria type I (PH I) is a congenital error of metabolism that can be manifested by an increased oxalate production, and ultimately result in kidney failure. After a combined liver/kidney transplantation, children with PH I have persistent excretion of oxalate that causes crystal formation in the urinary tract, and could result in systemic oxalosis and eventual graft failure. We speculated that crystalluria may be predictive of this nephrolithogenic tendency and thus investigated the effect of an intensive therapeutic strategy to prevent crystal formation in 13 children at our hospital. Oxalate crystal volume (OCV) measurements were performed at regular intervals for 36 months, and compared with urine supersaturation measurements. We found that crystalluria with the OCV measurement is non-invasive, easily performed, and gives feedback on the efficacy of PH I therapy within one hour. Further study is needed to determine whether this method is a better predictor of nephrocalcinosis than is supersaturation alone.

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Abstract: Twenty male Wistar rats, weighing 150 g, were placed in metabolic cages on a 30% sucrose diet for 7 days, before allocation to two groups: a control group (n = 5) and a lactose group (n = 15). They received respectively a 30% sucrose diet or a 30% lactose diet for 8 weeks, each containing 0.67% calcium and 0.38% phosphorus. After 4 (T1) and 8 (T2) weeks, the serum calcium (Ca) and citrate levels were significantly (P < 0.01) higher in rats fed the lactose diet. Serum alkaline phosphatase activity was increased in the lactose group (P < 0.01) at T1 and T2. The lactose-rich diet induced an increase in urinary Ca excretion at T1 and T2; citrate excretion was only enhanced at T2 (P < 0.001). No difference between the two groups was observed in urinary oxalate (Ox) excretion or creatinine clearance. Crystalluria analysis revealed a marked number (>300/mm3 at T1 and T2) of calcium oxalate dihydrate crystals (COD) in rats fed the lactose-rich diet, whereas no COD crystals were observed in sucrose-fed control rats at any time point. The formation of COD crystals in lactose-fed rats was related to an increase in calcium oxalate (CaOx) product (pCaOx), which was respectively 12.6 vs 3.9 at T1 and 10.5 vs 1.8 at T2, and an increase in CaOx ratio (Ca/Ox), which was 99.1 vs 7.5 and 67.5 vs 18.5 at T1 and T2, respectively. The high pCaOx and Ca/Ox ratios in the lactose group were due to hypercalciuria, in agreement with the number and the type of crystals. The present experimental model confirms that the ingestion of a 30% lactose diet increases urinary Ca excretion without changing urinary Ox excretion and shows for the first time that it induces a stable and marked crystalluria composed of COD. Such a non-nephrotoxic and stable model is of interest for the study of CaOx crystal formation secondary to hypercalciuria, and thus afterwards eventually for CaOx nephrolithiasis.

Abstract: Primary hyperoxaluria (PH) is a severe inherited disease induced by an enzymatic deficiency responsible for high endogenous production of oxalate. Oxalate ions are excreted by the kidney where they can form an insoluble salt with calcium ions, thus inducing urinary stones, crystal deposition in the tubular lumen and renal parenchyma leading to nephrocalcinosis and renal failure. Eighty-seven calculi from 63 PH patients with primary hyperoxaluria were analyzed and compared to 24,130 calculi from unselected consecutive stone formers referred to our laboratory between January 1977 and December 1996. All stones were analyzed according to a protocol including morphological examination of both surface and cross-section, and sequential infrared identification of the crystalline phases. A typical aspect of both surface and section corresponding to morphological type Ic according to our proposed classification (Daudon et al. Scanning Microsc 1993, 7:1081-1106) was observed in all patients but two whereas only two type Ic stones were observed among patients without primary hyperoxaluria. The latter two patients suffered from severe inflammatory bowel disease and developed heavy hyperoxaluria following extensive ileal resection. We conclude that evidence of type Ic morphology is a simple, cheap and fast tool to detect diseases with heavy hyperoxaluria such as primary hyperoxaluria.

Abstract: BACKGROUND: The methods currently used to analyze the process of calcification of bioprostheses give only global information on calcium deposition. We investigated the potential advantage of infrared spectroscopy, which makes it possible to analyze the various components of the calcification process, ie, lipids, proteins, and calcium deposits. METHODS: Sixty porcine aortic leaflets were fixed in 0.6% glutaraldehyde and then subsequently implanted in 10-day-old Wistar rats. The valve leaflets were removed 2, 7, 14, 21, 35, and 56 days after implantation. RESULTS: Before implantation infrared spectroscopic analysis revealed the presence of proteins only. On day 2 after implantation, all valves showed minor lipid deposits. On day 7, amorphous calcium phosphate was detected. Between days 7 and 14, crystalline forms of calcium phosphate appeared and amorphous calcium phosphate progressively changed into carbapatite over the 56-day period. CONCLUSIONS: Infrared spectroscopy yields valuable additional information on the nature and kinetics of the various components of glutaraldehyde-treated tissues after implantation. It may prove to be important in the evaluation of new techniques of calcium mitigation.

Abstract: Three acquired immune deficiency syndrome patients given foscarnet to treat cytomegalovirus retinitis developed renal failure with crystal deposits within the renal glomeruli. We identified these crystals as a mixture of sodium salt, calcium salt, and a mixed salt containing both sodium and calcium ions. This composition has not been previously reported. Foscarnet can complex available ionized calcium and secondarily precipitate in glomeruli. The percentage of complexing depends on calcium concentration in serum and the poor calcium salt solubility.

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Abstract: We analyzed a series of 61 stones from children aged 3 to 14 years old using Fourier transform infrared spectroscopy. The calculi were collected from urology departments of the University Hospitals of Oran, Sidi-Bel-Abbès and Mostaganem in West Algeria. This series is the first investigation concerning the composition of stones in children based on infrared analysis. Calculi were more frequent in males (75.4%) and mainly localized in the bladder (55.8%). Upper urinary tract calculi were more frequent in children over the age of 10 years, and the sex ratio was about 1. Calcium oxalate monohydrate was present in 70.5% of stones and was the main component in 50.8% of cases both in whole stones and nuclei. In contrast, calcium oxalate dihydrate was the main component in only 9.8% of calculi although it was present in 75.4% of stones. Ammonium urate was detected in 29.5% of stones and was always the main component of nuclei. Uric acid, observed in 31.1% of calculi, was the major constituent in 14.7% of stones and 19.7% of nuclei. Magnesium ammonium phosphate was observed in 24.6% of stones as a consequence of urinary tract infection by urea-splitting bacteria. Our observations emphasized that the anatomical location of stone and their composition were in accordance with those previously reported in other countries.

Abstract: We report on 24 children (10 girls) presenting with primary hyperoxaluria. The mean age at diagnosis was 6.3 years (range: 3 months-14.8 years). The mean interval between initial symptom and diagnosis was 1.3 year. The average follow-up period was 22 months (range: 1-60 months). At the time of diagnosis the renal function was normal in 6 children, moderately altered in 1 and severely in 17. During the follow-up the renal function remained stable in 6 patients, improved in 2, deteriorated in 4. The 12 patients with end-stage renal disease at diagnosis remained unchanged. Urolithiasis were present in all patients older than 2 years, and in 1 among the 5 infants. Medullary nephrocalcinosis was observed in 3 patients in whom the renal function was preserved. Diffuse nephrocalcinosis was present in all patients with end-stage renal failure. Improvement of renal function was secondary to stone removal in 2 patients. Extracorporeal shock wave lithotripsy performed in 7 patients was efficient only in 3. In 10 patients oxalate bone disease was correlated with both renal function and dialysis duration, whereas retinal involvement noted in 6 patients was not.

Abstract: OBJECTIVE: To confirm epidemiological studies showing a continuous progression of calcium oxalate nephrolithiasis in western countries, we investigated some aspects of the evolution of stone disease in France. METHODS: Calculi collected from 1977 to 1993 in 10,438 adult French patients were analyzed by infrared spectroscopy. Only 8,631 well-documented cases were available. The anatomical location, the removal mode of calculi, and the time evolution of stone composition were studied. RESULTS: The stones were more often retained in the upper urinary tract in females than in males and needed urological removal. Uric acid stones were more frequently observed on the left side in both sexes (p < 0.0001). Extracorporeal shock wave lithotripsy seems to have been used for a time in calculi which would have been spontaneously discharged. Calcium oxalate stones were preponderant, but their proportion did not change in both sexes. A significant decrease of the proportion of calcium phosphate stones was observed in females (p < 0.0001), probably responsible for the increase of the male/female sex ratio from 1.7 to 2.4. CONCLUSIONS: From our observations and from the evolution of dietary habits in France, it can be deduced that urolithiasis trends to a plateau.

Abstract: OBJECTIVE: To report the results of a comparative study of in vitro encrustation of five different types of JJ stents in human urine. MATERIALS AND METHODS: Samples of five JJ stents (polyurethane, silicone, Percuflex, C-Flex and hydrogel-coated C-Flex) were immersed for 24 h at 37 degrees C in fresh human urine supplemented with urease, and the surface photographed and dried. The crystals formed on the stents were dissolved in hydrochloric acid and the calcium and magnesium concentrations determined. RESULTS: Large crystals were deposited on the surface of the hydrogel-coated C-Flex stent and significantly higher levels of calcium and magnesium salts were obtained after acidic dissolution. There were no differences in crystal deposition among the remaining stents. CONCLUSION: Hydrogel-coated stents have an higher risk of becoming encrusted in vitro than do uncoated stents made of the same substrate polymer or made of different materials. These results emphasize the need for the regular follow-up of patients with hydrophilic stents in place.

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Abstract: BACKGROUND: It is always of importance to define the cause of urinary calculi disease in children to prevent recurrence and possible impairing of renal function. Nevertheless, etiology is not always easy to prove and must be deduced from both clinical and biological arguments. PATIENTS AND METHODS: The aim of this prospective study including 39 Tunisian children with urinary stones was to identify etiology and stone risk factors and detail the part of clinical and biological data and results of physical analysis of stones in determining the cause of the stone. RESULTS: In 31 cases among 39, clinical and biological data were not sufficient to identify clearly the stone etiology. When considering the structure and stone composition, the cause of the stone could be determined in 97.4% of the cases. An inherited disease was found responsible for the stone in 11 children, urinary tract infection in 13 cases, idiopathic hypercalciuria in nine cases and a nutritional deficiency disease in seven cases. In one case, polycystic kidney disease with metabolic risk factors could explain the stone process. No precise etiology was found in one case. Among infection stones, struvite stones could be related to urea-splitting bacteria while other calculi, containing whitlockite and protein matrix could be related to other micro-organisms. Earlier severe chronic diarrhoea episodes were noted in six among seven children presenting stones with a nucleus mainly composed of ammonium urate. CONCLUSION: Clinical data, biological data from both urine and blood of the patients and also the structure and composition of the stones are needed to identify the cause of urinary calculi. Such a procedure could provide the stone etiology in most cases.

Abstract: OBJECTIVES: Anti-proteases, a new class of anti-HIV drugs used in combination with reverse transcriptase inhibitors have led to spectacular improvement in the patients' clinical status. Since April 1996, indinavir is the most widely prescribed anti-protease in France. PATIENTS AND METHODS: From July 1996 to July 1997, we analyzed 46 spontaneously expulsed stones in 45 HIV+ patients (35 men and 10 women; age range 25 to 64 years) given indinavir in combination with other drugs since one week to ten months. Only six patients were known to have a past history of renal lithiasis. RESULTS: Forty-one calculi contained indinavir monohydrate (INDM) identified by mass spectrometry and infrared spectrophotometry. INDM was the only component excepting proteins in 39/45 calculi. In the 12 others, other compounds were also identified. Among the 114 urine samples collected 2 to 3 hours after an 800 mg dose of indinavir, 38 (33%) monohydrate indinavir crystals, identified by infrared microscopy. Mean urinary pH was significantly higher than in samples without INDM crystals (6.53 +/- 0.68 versus 5.96 +/- 0.71, p < 0.001). CONCLUSION: Two measures could possibly reduce the risk of crystalization: administration of urine acidifiers and increased fluid intake to raise diuresis. Alkalinisation is not indicated. Long-term increased fluid intake should be preferred over acidification which could be reserved solely for the treatment of drug-induced lithiasis.

Abstract: Numerous studies of calcium oxalate crystal formation have been carried out in the past two decades. In the present study, experiments were carried out to validate a turbidimetric method allowing to assess the calcium oxalate crystallization process. This method is quick and reproducible and can be used to quantify the inhibition of calcium oxalate crystal growth by various compounds. An experimental method of validation has been developed, which consisted in filtering solutions pure or containing modifiers at given crystallization times, photographing the filters used on scanning electron microscopy and analyzing the images using mathematical methodology. The results obtained through image analysis, namely crystal density (mean particle number per unit volume) and mean area, were correlated with the turbidimetric parameters. This finding was consistent with the qualitative examination of the photographs. Moreover, the morphological differences in crystals observed on the photographs were confirmed by the calculated length/width ratio. One can therefore assume that inhibition of calcium oxalate crystal growth is at least, partly explained by surface adsorption phenomena, which may add to complex formation.

Abstract: Oxalosis is the final stage of primary hyperoxaluria type I (PHI) when reduction of GFR produces oxalate accumulation. It involves bones, arteries, eyes, heart, nerves, etc. The management of oxalosis starts with prevention of nephrocalcinosis and renal failure by diluting urine and by inhibiting oxalate crystal formation either by increasing the urinary citrate or the urinary pyrophosphate. At endstage renal disease (ESRD) there is no dialysis modality for avoiding the progression of oxalosis. Combined liver/kidney transplantation (LKT) represents the most effective approach. The European PHI transplant registry recently reported 64 LKT with a five-year patient survival of 80% and progressive healing of oxalosis. Four children who received LKT in our unit are reported, all of whom are alive with a follow-up of three months to five years. Bone disease completely healed in one case after three years, but retinal deposits persisted despite improvement of visual acuity. A special perioperative protocol must be applied for protecting the graft from oxalate released from the stores. Laboratory follow-up including oxalemia and urinary crystal volume helps to adjust the individual prescriptions. This intensive management must be continued as long as oxalate stores persist.

Abstract: BACKGROUND AND AIM OF THE STUDY: The mechanism of valvular bioprostheses calcification is still unknown, but early studies showed increased Gla-protein content in calcified valves. Using an experimental model, which reproduces the clinical process, we therefore analyzed the role of minerals and proteins in bioprosthetic valvular calcification. METHODS: Glutaraldehyde pretreated porcine valves were studied before and after implantation in rats by X-ray, calcium (Ca) and phosphorus (P) measurement, Fourier Transform Infrared (FTIR) spectroscopy, SDS-PAGE and 45Ca ligand blotting of the extracted proteins. RESULTS: Before implantation, there was no X-ray calcification with very little Ca and P content. After implantation, X-ray calcifications appeared on day seven with increased Ca and P up to day 35 (p < 0.05, ANOVA). FTIR revealed structural proteins alone before implantation, plus minor proportions of lipids on day two, which always preceded Ca and P appearance. Ca and P increased up to day 35, first as amorphous and changed in carbapatite over time. SDS-PAGE before implantation revealed two proteins (66-kD and 54-kD) alone, which were sustained up to day 35. The 66-kD had 45Ca affinity. On day two, many other proteins appeared on SDS-PAGE, four of which (52, 45, 14 and below 14-kD) with 45Ca affinity. Protein pattern did not change from day two to 35. CONCLUSIONS: Valvular bioprosthesis calcification is associated with progressive increase in Ca and P content and at least five calcium-binding proteins: one intrinsic valvular protein, pre-existing to implantation, plus four other, extrinsic valvular proteins adsorbed within the tissue after implantation.

Abstract: During about ten years, nephrocalcin was considered the main calcium oxalate crystal growth inhibitor. Today, it appears only a urinary protein inhibitor among other ones such as non polymerized Tamm-Horsfall protein, uropontin or crystal matrix protein (CMP), a protein derived from prothrombin. All these molecules are able to inhibit either crystal growth or aggregation of calcium oxalate in urine. Another protein, named renal lithostathine, was also reported to be a potent inhibitor of secondary nucleation and growth of calcium carbonate crystals. A new urinary inhibitor of calcium oxalate formation was isolated from the urine of healthy subjects using chromatographic procedures. It is a macromolecule with a molecular weight (MW) of approximately 35 kDa as estimated by polyacrylamide gel electrophoresis. Its carbohydrate content represents an average of 8.5% of its MW. Glutamic and aspartic acids represent 24% of total amino acids. This protein is called Uronic-Acid-rich Protein (UAP) because of its uronic acid content. The same protein isolated from the urine of stone formers showed less inhibitory activity than that purified from the urine of healthy subjects. Structural modifications may explain this diminution of its inhibitory activity. This protein was also purified from rat urine using same procedures. Human and rat UAP exhibit similar biochemical characteristics and strongly inhibit calcium oxalate crystallization in vitro. Partial amino acid sequence analysis showed a homology with inter-alpha-trypsin inhibitor (ITI), confirmed by the immunological results on Western blot. Nevertheless, various chemical and enzymic treatments revealed that UAP and ITI are not identical molecules. Consequently, urine contains several macromolecular substances belonging to ITI superfamily which are involved in the inhibition of calcium oxalate crystallization. UAP takes place among the most efficient macromolecular substances known as inhibitors in calcium oxalate nephrolithiasis.

Abstract: The presence of crystal deposits in tissues is associated with various pathologies. Sometimes their identification is useful for understanding the etiology or the mechanism of the disorder. The authors applied Fourier transform infrared microscopy (FTIRM) to the molecular characterization of crystal deposits in tissue and compared the results with those provided by histologic studies using polarized light microscope and histochemical reactions. Twenty-five biopsies were investigated. In 10 cases, the results were in good agreement. In 15 cases only FTIRM could precisely identify the crystals. In three cases, this technique allowed to characterize dihydroxyadenine crystals revealing an adenine phosphoribosyltransferase deficiency previously undiagnosed in patients presenting severe chronic renal failure. In three cases, crystal deposition was related to drug therapy. In other cases, crystal identification was useful to understand the mechanism of the pathology responsible for tissue damage and crystal deposition.

Abstract: Our aims were to analyze the protein composition of the organic matrix of urinary stones and to investigate the role of albumin in its constitution. Five different morphological types of stones were studied. Proteins extracted from the stone were submitted to sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and analyzed by immunoblotting with antibodies to 13 urinary proteins. Nine of the 13 proteins were found in all types of stone: human serum albumin (HSA), alpha 1-acid glycoprotein (alpha 1-GP), alpha 1-microglobulin (alpha 1-M), immunoglobulins (Igs), apolipoprotein A1 (apo-A1), transferrin (Tr), alpha 1-antitrypsin (alpha 1-T), retinol-binding protein (RBP) and renal lithostathine (RL). The beta 2-microglobulin (beta 2-M) was present only in calcium oxalate and uric acid stones. In contrast, ceruloplasmin, haptoglobin and Tamm-Horsfall protein (THP) were detected in none of them. Because HSA appeared as the major protein component in all stones, we wondered whether it might play a specific role in the constitution of the stone matrix. Association of HSA with urinary proteins that were present in stones was demonstrated by showing that proteins present in the matrix comigrated with HSA on gel filtration, whereas proteins that were absent did not. Moreover, HSA induced the binding of stone matrix proteins to an albumin-specific affinity column. Finally, we evidenced HSA binding to calcium oxalate monohydrate (COM) crystals in a solution similar to urine.(ABSTRACT TRUNCATED AT 250 WORDS)

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Abstract: Fifty-five Tunisian children with urinary stones, between the ages of 8 months and 15 years, underwent morphological and infrared spectrophotometric analysis of their stones. This study provides an approach to the aetiological profile of urinary stones in Tunisian children. The nucleus of the stones was composed of acidic ammonium urate in 48% of cases with a morphology suggestive of phosphorus deficiency associated with a history of diarrhoea. In 24% of cases, the nucleus contained struvite indicating the presence of urinary tract infection by urease-positive bacteria. The main growth factors of urinary stones were hyperoxaluria and urinary tract infection. In 5 cases, the stones were due to a hereditary lithogenic metabolic disease : cystinuria in 1 case and primary hyperoxaluria in 4 cases.

Abstract: We report our local experience of two patients with type 1 primary hyperoxaluria (PH1) who received successful isolated cadaver kidney transplantation. The indication of isolated renal transplantation exists for PH1, but it must probably be restricted to the less severe forms of this disease. Recipient and donor selection is crucial.

Abstract: OBJECTIVE: Measuring specific gravity of urine is a simple means of self-monitoring for urolithiasis patients. METHODS: We evaluated the reliability of two test strips (N-Multistix and Combur-Stix) and determined the relationship between urine specific gravity and crystal formation in first morning urine in 179 patients with calcium oxalate lithiasis. Urine hydrometry was used as the reference method. RESULTS: There was a good correlation between urine density read on the test strips and hydrometry (r = 0.733 for N-Multistix and 0.697 for Combur-Stix). Hydrometry showed little pH effect but the test strips gave results correlated with urine pH (r = 0.764 and 0.813 respectively). When urine pH was below 6.5, the specific gravity of the urine was overestimated; inversely for pH > 7, it was underestimated. Correction factors were obtained by comparing test strip values with specific gravity measurements for pH level between 4.5 and 8. There were crystals in 66% of the urine samples with a density > or = 1012 g/l. In contrast, 75% of the samples below this value were crystal free. There was a close relationship between 24-hour urine volume and specific gravity (n = 124; r = 0.778): a specific gravity of 1.012 corresponded to 2100 ml urine output. For 24% of the patients, specific gravity of the morning urine was > or = 1.012 despite a 24-h urine output > or = 2100 ml, indicating insufficient urine dilution during the night. CONCLUSION: Measurement of specific gravity with test strips with correction for pH can be a simple way to measure the specific gravity of urine and assess whether urine dilution is sufficient to reduce the risk of crystal formation, the main risk factor in urolithiasis patients.

Abstract: A series of 10 617 calculi were analyzed by stereomicroscopy and infrared spectroscopy. This first study of French calculi was compared with large series in the literature. That the frequency of pure calculi was the lowest ever observed can be related to the methodology routinely used in our laboratory, which includes microsampling. We described more than 70 components among the 10 617 calculi. The overall sex ratio male to female patients was high (2.27) and increased over the period 1981-1993. Calcium oxalate was the most frequent component (86.48%), followed by calcium phosphate (79.75%) and purines (18.64%). We found a low occurrence of "infection" stones. The sex ratio was related to stone composition and differed according to the main component. For instance, calcium oxalate dihydrate (COD) was more frequent in men than in women, with a sex ratio of 4.97 versus 2.57 for calcium oxalate monohydrate (COM). On the contrary, calcium phosphate was more frequent in female patients (sex ratio 0.72 versus overall ratio). The high frequency of COD calculi (23.17%) suggests that hypercalciuria is particularly frequent in French patients susceptible to stone formation. For each main component, a specific profile was observed in relation to the sex and age of the patients with stones.

Abstract: Despite nearly a half-century of study, the clinical value of spontaneous crystalluria (Cx) examinations in calcium stone formers (CaSF) is still uncertain. The analytical complexity of urine particle study is largely responsible for this situation. As a result, there is no consensus regarding technical methods in Cx with several techniques for urine sampling and three different instruments currently used for particle study, namely, particle counting (PC), light microscopy (LM) and petrographic microscopy (PM). In this work, we first examined urine sampling and instrument methods regarding their appropriateness for Cx studies. Then we performed a comparative analysis of Cx studies in CaSF. Despite many technical and clinical discrepancies, several studies agree that the frequency of "all particles" and of the weddellite and whewellite calcium oxalate (CaOx) crystalline phases are increased in CaSF as compared to normal subjects (NS). Particle sizes and aggregation ratio are also often increased. Altogether, these results reinforce the need for an efficient method for Cx studies in these patients. Examining each technique leads us to conclude that most particle parameters can be studied by "direct LM" observation of freshly voided urine samples, i.e., urine samples without any separation steps. For clinical applications, several examinations should be performed, first to define the specific Cx characteristics in a patient, then for the study of treatment efficiency on Cx control, and finally, during the patient follow-up. Due to Cx variability in each patient, the frequency of Cx examinations during each phase needs to be determined in longterm comparative prospective studies of CaSF.

Abstract: Forty adult male Wistar rats were placed in metabolic cages on a Ca-deficient diet (0.1%) for 7 days and then on a Ca-deficient, Na-oxalate (NaOx) enriched diet (20 mg/100 g) for another 14 days. The animals were subdivided into three groups receiving three different types of mineral water: group I (n = 13), Badoit (Ca 222 mg/l); group II (n = 14), Contrexéville (Ca 467 mg/l); and group III (n = 13), Evian (Ca 78 mg/l). Another series of 25 rats (group I, n = 9; group II, n = 8; group III, n = 8) underwent the same study protocol, except that they received a normal Ca diet (1%). On the low-Ca diet, urinary Ca-Ox monohydrate (COM) crystals were observed only under the Na-Ox diet, with a mean crystal number significantly greater in group III (16.7 +/- 4.5 crystals/mm3) than in group I or II rats (2.5 +/- 1.5 or 4.1 +/- 1.5 crystals/mm3, respectively). Urinary Ca concentrations decreased in all groups (P < 0.001) under the Na-Ox diet, while urinary oxalate concentrations increased in all groups (P < 0.001). On the normal Ca diet, COM crystal excretion was observed only with the Na-Ox-enriched diet, but in this case feeding the Na-Ox diet did not modify urinary oxalate excretion. Ca/Ox ratio was significantly lower under 0.1% Ca diet than under normal Ca diet, related with the type and the number of crystals observed, demonstrating that assessment of crystalluria can provide an index of disease severity. Moreover, the hardness of the drinking water influences urinary COM crystal excretion only under a low-Ca, oxalate-rich diet, suggesting that the total calcium intake rather than the water calcium content is an important factor in the occurrence of Ca-Ox nephrolithiasis.

Abstract: We recently reported that human urine contains a newly identified urinary glycoprotein acting as a potent inhibitor against calcium oxalate crystallization. This inhibitor is a uronic-acid-rich protein (UAP) with a molecular weight of approximately 35 kDa. In the present study, UAP was isolated from urine of stone formers and of subjects without a stone history, and its inhibitory activity was tested in a calcium oxalate crystallization system in vitro. Our results show a weaker inhibitory activity of UAP extracted from the urine of stone formers than that extracted from the urine of healthy subjects. Preliminary analyses of amino acid and carbohydrate content showed some differences between the two groups. The main difference was the reduction in sialic acid in UAP isolated from the urine of stone formers. We suggest that UAP contributes significantly to total urinary inhibitory activity of calcium oxalate crystallization and that the decrease in this activity in the urine of recurrent stone formers is due, in part, to the weak inhibitory activity of UAP. A structural abnormality of UAP could explain the diminution of its inhibitory activity in the urine of stone formers.

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Abstract: We report a case of adenine phosphoribosyltransferase deficiency in which the initial presentation was chronic renal failure. Diagnosis was made after infrared microscopy analysis of microcrystalline deposits on a kidney allograft biopsy specimen. This type of presentation is rarely seen, the most frequent manifestation of this disease being urolithiasis. This is the first report of recurrence of the microcrystalline nephritis in a kidney transplant with subsequent loss of allograft function.

Abstract: A calcium oxalate crystal growth inhibitor was isolated from human urine using DEAE-Sephacel gel followed by Sephacryl S-300 chromatography and FPLC column. The isolated inhibitor was a uronic-acid-rich protein (UAP). It was found to be a glycoprotein with a molecular weight of 35,000 Da as determined by SDS-polyacrylamide gel electrophoresis. Inhibitory activity was demonstrated using a calcium oxalate crystallization system. In addition UAP, nephrocalcin (NC) or nephrocalcin-like (NC-like) activity was an effective inhibitor in this system. However, the inhibitory activity of UAP appeared to be higher than that of NC or NC-like activity. This finding suggests that NC or NC-like activity is not only urinary protein with strong inhibitory activity. UAP and probably other proteins also play a role in the control of urinary crystal growth.

Abstract: Lithostathine is a protein of pancreatic secretion inhibiting calcium carbonate crystal growth. Antibodies to lithostathine were used to identify a related protein in urine and kidney stones. Western blot analysis of proteins extracted from concentrated normal urine or kidney stones demonstrated the presence of a protein with an apparent molecular weight of 23 kDa. The same antibodies were used in immunolocalization experiments on fresh human nephrectomy specimens cryosections. A positive signal was observed in the cells of proximal tubules and thick ascending limbs of Henle's loop. Protein extracts of renal stones inhibited calcium carbonate crystal growth. Because of its structural and functional similarities with pancreatic lithostathine, it was called renal lithostathine.

Abstract: The nucleation and crystal growth of calcium oxalate (CaOx) were studied at pH 5.5 using turbidimetric measurements at 620 nm of suspensions produced by mixing calcium chloride and sodium oxalate (initial conditions: Ca, 3 x 10(-3) M; Ox, 0.5 x 10(-3) M). CaOx crystallization kinetics were defined first by the induction time ti and then by the slope of turbidity as a function of time during the interval corresponding to a correlation coefficient r2 > 0.99. The technique described requires only a small amount of material, is quick, convenient, and can be used to study inhibitors of CaOx crystallization by comparing ti and the rate of crystal growth in the presence and absence of inhibitors. The effects on CaOx crystal growth of several low molecular weight compounds, i.e. di- and tricarboxylic acids, were examined. The majority of these compounds were inhibitors of crystal growth, the greatest effect being seen with citric acid (50% inhibition in the presence of 1.5 x 10(-3) M citric acid), isocitric acid (50% inhibition in the presence of 0.75 x 10(-3) M isocitric acid) and pyrophosphate (30% inhibition in presence of 0.15 x 10(-3) M pyrophosphate). The inhibitors' behaviour regarding the medium was studied without any assumptions about their possible mechanisms of action. Measurements of ionized calcium before and after the reaction, as well as the observation of crystals by scanning electron microscopy, allowed us to formulate the hypothesis that the effect of citric acid and tartaric acid can be attributed mainly to ion pairing, in contrast to that of pyrophosphate and the other carboxylic acids.

Abstract: In order to assess the influence of dietary protein and salt intake on urinary calcium excretion in calcium stone formers, we simultaneously determined 24 hour urinary excretion of Urea (UU) and sodium (UNa) together with that of calcium (UCa) in 184 patients (112 males) with idiopathic calcium nephrolithiasis studied on free diet. Mean (+/- SEM) values expressed as mmol/kg BW/day of both UU and UNa were higher in hypercalciuric (UCa > or = 0.1 mmol/kg/d, mean 0.15 +/- 0.01) male patients, respectively 6.63 +/- 0.25 and 2.71 +/- 0.13, than in normocalciuric males, respectively 5.33 +/- 0.22 (p < 0.001) and 2.36 +/- 0.15 (p = 0.06), while the latter did not differ from healthy controls. Similar findings were made in female stone formers. Linear regression analysis on the whole series showed a positive but weak correlation between UU and UCa (r = 0.47, p < 0.001) and between UNa and UC a (r = 0.33, p < 0.001), but the slope of the relation UCa/UU was increased only in hypercalciurics, whereas it did not differ between normocalciurics and controls. By multiple regression analysis, variations of UU and UNa altogether accounted only for 22% of variation in UCa. We conclude that in both sexes hypercalciuric stone formers have a higher protein and sodium intake than normocalciurics, and for a given urinary urea output, their mean urinary calcium excretion is higher, thus suggesting that hypercalciuric stone formers are electively sensitive to the hypercalciuric effect of high protein intake.

Abstract: Uronic-acid-rich protein (UAP) is a new urinary macromolecule which strongly inhibits calcium oxalate crystal formation. It is a glycoprotein with a molecular weight of about 35,000 Da, and its carbohydrate content is 8.5%. This inhibitor is composed of two polypeptidic chains crosslinked by chondroitin sulfate. It exhibits partial structural homology with alpha 1-microglobulin. The inhibitory activity seems to be supported by peptidic chains as determined by enzymatic assay.

Abstract: Current physical and chemical methods available for urinary stones analysis are critically reviewed. No one method is sufficient to provide all the clinically useful information on the structure and composition of the stones. We show that a combination of refined morphological and structural examination of stone with optical microscopy, complemented by compositional analysis using infrared spectroscopy of the core, cross-section and surface of calculi, provides a precise and reliable method for identifying the structure and crystalline composition, and permits quantification of stone components while being highly cost effective. Using such morphoconstitutional studies leads to a classification of urinary stones in seven distinctive types and twenty-one subtypes among monohydrate (whewellite) and dihydrate (weddellite) calcium oxalates, phosphates, uric acid, urates, protein, and cystine calculi. Furthermore, all of the recognized sub-types exhibit correlations with specific pathophysiologic conditions. We conclude that such morphoconstitutional refined analysis and classification of urinary calculi is of interest to properly identify the type of stone disease and provides clues to etiopathogeny.

Abstract: The authors report a case of silica-containing urinary stones in a child. This drug-induced urinary stone was secondary to absorption of Gelopectose and its composition was confirmed by infrared spectrophotometry. Other cases have been diagnosed but have not yet been published. Patients with such urinary stones should be investigated for possible hypercalciuria or a disorder of H+ metabolism in the context of distal tubular acidosis, which may be incomplete and/or transient.

Abstract: Glaphenine is an analgesic drug derived from anthranilic acid. We report the analytical procedures for stone analysis in three cases of common bile duct stones containing glaphenic acid, which developed in arthrosic patients treated for 13.7 +/- 5 years with glaphenine. Stone analysis was performed by infrared spectroscopy, high performance thin layer chromatography, scanning electron microscopy and energy dispersive X-ray analysis. Mechanisms of lithogenesis are discussed. These observations emphasize the possibility of radiolucent gallstones mainly composed of drug compounds.

Abstract: In order to reduce the relapse of the disease lithiasis, it is very important to have a very good idea about the growth process of the urinary stone. The greatest concern is the recuperation and the profound analysis of the nucleus and the peripheral layers. The preceding morphological study of the stone fragments in combination with the infrared spectrometry is the only manner to know all about the urinary calculus. Many information is lost if only an overall infrared spectrum of the sample is taken.

Abstract: Human calculi of various compositions were automatically identified by using near-infrared excitation Fourier-transform Raman spectrometry. After having built a 150-compound Raman library as a first step, we used a commercial software for infrared spectra (program BIRSY, from Brüker) to determine the composition of different calculi. Good results were obtained for both classical Raman laser and Raman laser fiber optics spectroscopies. With the use of a natural biological medium, e.g., urine, to mimic as closely as possible clinical in vivo conditions, the automatic search correctly identified the calculus composition with relatively good test quality; in some mixtures, however, the results can only be considered semi-quantitative at present, even after smoothing of the spectra.

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Abstract: Renal stones from 30 chronic hemodialysis patients were subjected to morphological study by means of microscopic examination and to constitutional analysis with infrared spectrophotometry. In 29 patients calculi could be classified into 3 main types: 1) protein stones made of pure proteins or with a protein core and less than 30% calcium oxalate (9 cases, or 30%)--they were observed predominantly in patients with primary glomerular disease, 2) oxalo-protein stones with a core of calcium oxalate and a total stone content of more than 30% calcium oxalate (15 cases, or 50%)--they appeared to be related to metabolic factors, such as high urinary oxalate and low urinary citrate concentration, and to iatrogenic factors, namely vitamin D3 and calcium salt supplementation, and 3) aluminum-magnesium urate stones, probably induced by aluminum overload (6 cases, or 20%). Thus, our study indicates that a significant proportion (70%) of stones formed by hemodialysis patients may be due to metabolic and iatrogenic factors. Our data suggest that accurate analysis of such stones provides useful information on pathogenetic factors and consequently may give clues to their prophylaxis.

Abstract: Pancreatic juice is supersaturated in calcium carbonate. CaCO3 crystal growth is controlled by lithostathine, a secretory protein synthesized by pancreatic acinar cells, first described as a constituent of pancreatic stones. It was recently reported that, in the thin descending limb of the Henle's loop, urine was supersaturated in CaCO3 (Coe FL, Parks JH: Defenses of an unstable compromise: crystallization inhibitors and the kidney's role in mineral regulation. Kidney Int. 1990: 38, 625-631. This observation suggested the presence in kidney of a similar inhibitor. In this study, we show that a protein immunologically related to lithostathine is actually present in urine of healthy subjects and in renal stones. Immunocytochemistry of kidney sections localized the protein to cells of the proximal tubules and thick ascending limbs of the Henle's loops. Protein extracts of renal stones inhibited CaCO3 crystal growth in vitro and this inhibition was significantly lifted by incubating the extracts with antibodies to lithostathine. The protein is not immunologically related to nephrocalcin. Because of its structural and functional similarities with pancreatic lithostathine, it was called renal lithostathine.

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Abstract: Numerous methods can be used for the analysis of urinary stones, but few of them provide information on the structure, chemical composition and crystal phases of these stones. In a good urinary stone analysis the stone is first examined through a binocular magnifying glass, for instance, to detect its structural features including umbilication. Randall's plaque, bracketing faces and individualized or non-individualized nucleus. Morphological typing is important as it points to one pathology or another irrespective of composition. Composition must be determined quantitatively, with differentiation of crystal phases, and this requires global physical methods such as X-ray microdiffractiometry or infrared spectrophotometry. Urinary crystals can be identified by polarized light microscopy supplemented, if necessary, by infrared microscopy when the crystals are few and of unusual morphology. Studying crystalluria is a simple and efficient means of following up lithiasic patients, provided their urine is collected and stored under adequate conditions. In interpreting the results various criteria, and particularly the nature, abundance, size, facies, aggregation and frequency of crystals, must be taken into account.

Abstract: Although crystalluria is generally considered a normal finding, sometimes it gives evidence of renal disturbance. Thus, detection and identification of urinary crystals may provide useful data for understanding the etiology of mechanism of the disorder. Light microscopy may be not sufficient to accurately identify the crystals. We investigated the ability of Fourier transform infrared microscopy (FTIRM) to identify isolated crystals of clinical interest. Twenty-five urine samples presenting crystalluria were tested because of their unusual aspect. We successfully identified 16 compounds and showed that crystals with the same apparent morphology can be composed of different substances. Moreover, an unexpected structure may be an insoluble phase of a drug metabolite. We conclude that FTIRM is a good technique for investigating urinary crystals of clinical interest.

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Abstract: Hyperoxaluria type I (HPI) is a metabolic disorder secondary to liver alanine glyoxylate aminotransferase deficiency. Renal failure occurs due to the excessive production and precipitation of oxalate in the kidney. Combined liver-renal transplantation is the correct treatment for this condition when end-stage renal failure occurs as with renal transplantation alone the risk of recurrence of the same pathology in the transplanted kidney would be high. We report the case of a 4 year-old child with HPI suffering from terminal renal failure in whom a hepato-renal transplantation was performed: six months later, creatinine clearance was 62 ml/min/1.73 m2 and liver function tests were normal.

Abstract: Idiopathic hypercalciuria (IHC) is defined by an urinary calcium excretion greater than or equal to 0.10 mmol/kg body weight/day on a free diet in the absence of hypercalcemia. Pak's classification into absorptive and renal forms of IHC is no longer accepted as such. The now proposed "operational" classification of IHC separates dietary IHC, where calcium excretion falls below 0.07 mmol/kg BW/day on moderate dietary calcium restriction, from true IHC, where urinary calcium excretion remains above this value while on a 600 mg Ca diet, with renal and absorptive "presentations". Etiopathogenic mechanisms of IHC are revisited and appear to be multifactorial. They involve endogenous factors, such as disorders of calcitriol biosynthesis (or receptors), bone resorption and/or calcium membrane transport, whose phenotypic expression is enhanced by extrinsic factors, mainly nutritional, such as high animal protein and salt intake. A protocol of laboratory investigation based on these recent data is proposed, together with a stepped therapeutic approach involving a readjustment of nutritional habits combined, when needed, with thiazide diuretics.

Abstract: 200 in vitro shots were performed with an EDAP LT 01 system in order to test the sensitivity of the various urinary stones to lithotrity and to study the action of the various shot parameters. All calculi do not have an equally favorable reaction to lithotrity. The deciding factor is neither their hardness, nor their chemical composition, nor their crystallizing shape, but rather the architecture ruling the arrangement of the crystallins forms in the calculus. The most important shot parameter is the power of the system, which conditions its efficiency. However, the shooting method, and more specifically the setting of the shot rate, allows adjusting the shots according to the desired results. The lithotriters will only be improved, ie. made more effective and less traumatic, if these experiments are continued.

Abstract: The morphological and constitutional analysis of renal stone fragments expelled after extracorporeal shock wave lithotripsy enables the structure and morphological type of stones to be reconstructed in 92.8 per cent of the cases as regards surface and section and in 74.5 per cent of the cases down to the core. A study of the molecular and crystalline composition of such fragments demonstrated the preponderance of whewellite in both sexes (men 85.4 per cent; women 72.4 per cent). The frequency of weddellite was 1.6 times higher in men (73.8 per cent) than in women (44.8 per cent), and the frequencies of struvite and ammonium urate were 2.8 and 2.6 times respectively higher in women than in men, despite a significant fall in frequency as compared to a previous series. Correlations between morphological type of stone and biochemical data (when available) could be established in 84 per cent of the cases. This made it possible to initiate treatments aimed at preventing recurrences, the cost of these treatments in the long term being lower than that of the curative urological treatments, including extracorporeal shock wave lithotripsy.

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Abstract: Nine renal stones were separated into 5 fragments of similar weight and size. One fragment was analyzed chemically and the other 4 fragments were submitted to treatment by piezoelectric shock waves according to the following modalities: 3,000 shock waves at firing frequencies of 1.25, 2.5, 5 and 10 shock waves/s. In the case of hard stones, better quality fragmentation was obtained with low frequencies than with high frequencies. With friable stones, using only 800 shock waves, the result was the same regardless of the frequency used. Treatment of hard stones by shock waves for 20 min at various frequencies revealed that a slightly better result was obtained with a frequency of 5 shock waves/s, although the result was not significantly better. In conclusion, slow frequencies of 1.25 or 2.5 shock waves/s allow better fragmentation of hard stones at the cost of a longer mean treatment than at high frequencies. High frequencies do not give significantly better results than low frequencies when the same firing time is used. In the clinical situation, it is therefore preferable to use low frequencies which allow treatment without anesthesia or analgesia and without admission to hospital.

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Abstract: All urinary stones should undergo detailed studies to identify those related to drug therapy. Among 520 stones analyzed by infrared spectrophotometry, we found 13 drug-induced stones (13/520: 2.5%). Drug-induced stones were caused by glafenine in 7 cases, piridoxylate in 4 cases, triamterene in one case and an unknown organic compound in one case. Glafenine stones appear to develop more readily in infected urine. Triamterene stones are often associated with uric acid disorders. Piridoxylate induces the formation of glyoxylate which is responsible for hyperoxaluria and formation of oxalocalcium stones.

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Abstract: We studied crystalluria in healthy subjects and in calcium oxalate stone formers using polarization microscopy and infrared spectroscopy, in freshly voided urine and after 48 h urine storage at +4 degrees C. 412 urine specimens from 39 normal subjects and from 172 stone formers were examined. In the latter, 90 voidings were obtained while on free diet, 61 on moderately calcium restricted diet, 34 in the fasting state and 136 while on thiazide therapy. In the normal subjects, all 91 voidings were obtained while on free diet. Crystalluria was more frequent in urine specimens collected on free diet in stone formers (48.9%) than in normal subjects (13.9%, p less than 0.001) and slightly decreased in patients on thiazide therapy (41.2%). Crystalluria increased following +4 degrees C urine storage in all groups. The most frequent crystalline phase was weddellite. Comparison of crystalline phases of calcium oxalate observed before and after +4 degrees C storage showed that crystallization spontaneously progressed to weddellite whatever the calcium oxalate phase initially present. On thiazide therapy we observed, in addition to lower calcium content, a decreased frequency of urate crystallization especially in +4 degrees C stored urine, in parallel with a decrease in urate concentration.

Abstract: Since stones are the only objective elements of lithiasis, the cause of this disease can only be determined by an accurate analysis of the morphology and composition of the stones. To identify the crystal phases and the distribution of constituents between superficial and central structures such efficient techniques as scanning electron microscopy, X-ray diffraction or infrared spectroscopy are required. At least two complementary techniques must be combined to obtain enough information on the morphology as well as on the molecular and crystalline composition of the stones. The importance of morphological typing for the aetiological evaluation of the disease is demonstrated by examples which clearly show that each stone must first be examined optically. The different techniques used for the study of stones are reviewed and their relative efficiency and adaptability to routine analysis is discussed.

Abstract: Various analytical methods are available to help identify the presence of drugs in urinary calculi. Using infrared spectrophotometric analysis, nonmetabolized flumequine was identified in a protein calculus from a patient who had taken the drug for a urinary tract infection. Free flumequine can precipitate in an acidic environment.

Abstract: We have created a library of 497 digitized infrared spectra of 58 components of urinary calculi and of their usual binary and ternary mixtures. We tested the operation of the "Birsy" search program (Bruker Analytische Messtechnik) with this library for the interpretation of infrared spectra of 50 urinary calculi, selected from both classical and difficult cases. This program correctly identifies the two first components 98% of the time and the third (minor) component 70% of the time. Using this program, those without training or experience in infrared analysis can routinely use the infrared method of analysis of urinary calculi.

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Abstract: During the last 4 years we collected 27 specimens of calcium oxalate nephrolithiasis in patients receiving long-term treatment with piridoxilate, a drug composed of an equimolar combination of glyoxylate and pyridoxine. The mean duration of treatment was 3.6 years (range 4 months to 10 years) and the mean daily dose was 580 mg. piridoxilate, which contained 160 mg. glyoxylate. Calculi often recurred, with an average number of 9.9 per patient, and an open operation, shock wave lithotripsy or percutaneous nephrolithotomy was required in 22 patients (81 per cent). Oxalate excretion was 727 +/- 246 mumol. per day while on the drug and 382 +/- 201 mumol. per day after the drug was withdrawn. Whewellite was the major component of calculi in all cases but the stones exhibited a peculiar morphological arrangement, with multiple small indentations and a fine mamillary structure. Freshly voided urine specimens contained unusual crystals, which on infrared spectroscopy were composed of calcium oxalate trihydrate, a variety of crystal never observed previously in human urine. Piridoxilate-induced calcium oxalate nephrolithiasis is a new variety of metabolic drug-induced nephrolithiasis. Our observations suggest that even large doses of pyridoxine may be unable to prevent the excessive production of oxalate from glyoxylate.

Abstract: We investigated the application of diffuse reflectance infrared Fourier transform spectroscopy to analysis of urinary calculi and compared its operation with that of older sampling techniques (pellet, mull, and attenuated total reflectance). The new method requires shorter sample preparation time and less sample (30 micrograms). Quantitative measurements are easier. Because of the additivity of the Kubelka-Munk functions, a quasi-exhaustive collection of infrared spectra of mixtures of possible components of stones can be compiled, facilitating a computerized intrepretation of infrared spectra of urinary calculi.

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Abstract: Medicinal crystalluria is often difficult to recognize and identify. Whether due to therapeutic overdoses or individual susceptibility, the diagnosis is always important. 70% of the drugs involved in crystalluria can induce kidney stones or promote their growth. In addition, approximately one medicinal crystalluria out of ten is clinically or biologically accompanied by kidney failure. On the basis of 59 cases of medicinal crystalluria, the means of identification, the molecules involved and the frequency of these iatrogenic crystalluria is discusses.

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Abstract: The occurrence of different hydrate forms derived from a single chemical compound results from the selective conditions of crystallization. Identification of the crystalline phases and the structural types of stones may provide the physician with important data concerning the etiopathogenesis of the complaint. The authors have studied the crystallization of calcium oxalate in an aqueous solution and the process of spontaneous crystalluria. They noted that whewellite resulted, in many cases, from a concentration of oxalate, and weddellite from a concentration of calcium. This article discusses the correlations between morphological types of oxalate stones, the localization of the stones in the urinary tract, the biological disorders noted, and the sex of the patients.

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Abstract: From 3000 urinary calculi analysis, a morphological classification allowed us to appoint 7 structural types of oxalate stones, dependent on whewellite or/and weddellite. We observed evidence for correlations between biological data and these structural types, mainly between types I and hyperoxaluria, types II and hypercalciuria, types II + IV or IV and hyperparathyroïdism, as well as between whewellite and hyperuricuria. We determined in vitro calcium and oxalate concentrations ranges to crystallize various hydrate forms of calcium oxalate and we observed that whewellite form is almost the only one fitted for crystallizing in renal papilla. From this various data, it results that, in vivo, whewellite is dependent on oxalate concentration whereas weddellite is rather dependent on calcium concentration. Otherwise, differences in occurrence of morphological types of oxalate calculi were observed as a function of the patient' sex, the urinary tract localisation of calculi, or the crystalluria.

Abstract: 6 100 specimens of urine were examined according to classical cytobacteriological techniques for the presence of crystals and the possible correlations with the bacteria identified and the sex of the patients. When crystals were present, the urine was centrifuged and the deposit was dried in a filter with low porosity, scraped away and incorporated in a tablet of potassium bromide and then examined by infra-red spectrophotometry. Positive crystalluria was found in 6.4% of urines from patients without lithiasis and in 59% of cases with lithiasis. Only 50% of cases had a pure mineral type. Struvite was the most common (34.3%), then weddellite (33.1%), carbapatite (23.1%), amorphous calcium phosphate (22.7%) and ammonium urate (18.3%). Any of these compounds could be found pure or in combination with others. The other constituents were appreciably less common. All in all, 76 types of crystalluria were demonstrated. Important differences in crystallurias and the bacteria identified were detected as a function of the sex of the patients. Positive correlations were found between a number of bacteria and the crystals with which they are associated. The distribution and the composition of the cases of crystalluria were compared with those of urinary calculi.

Abstract: The role of glafenine in certain cases of acute renal failure was described several years ago, but very little work has been done on the intratubular precipitates generally responsible for these manifestations. We have been able to study 6 cases of acute poisoning and 5 cases of glafenine renal stones which have shown that several mechanisms are likely to be involved. In 4 cases, the acute poisoning resulted in reversible oliguria which resolved after several days. In 3 of the 5 cases of renal stones, variable amounts of glafenine were found in the zone of nucleation. Infrared spectrophotometric and chromatographic examination of the first urine after the return of diuresis in the oliguric subjects and in the patients with renal stones, revealed that several metabolites of glafenine could be implicated in the development of these renal precipitates. In the different cases, free metabolites and conjugated derivatives were found to be responsible. The authors discuss the relationship between the products detected and the clinical manifestations observed.

Abstract: Drug-induced calculi are often mis-diagnosed because of inadequate analysis of the urinary calculi. These stones can only be characterized unambiguously by global physical methods like infra-red spectrophotometry. From a series of 2,000 calculi analysed under infra-red, we identified 22, i.e. 1.1% of cases, which contained, partly or entirely, drug products. Ten other cases are still being studied. Amongst the products identified we found metabolites of glafenine (Glifanan) in 7 cases, triamterene and its derivatives (Cycloteriam) in 7 cases, metabolites of phenazopyridine (Pyridium) in 4 cases, sulphonamides in 2 cases : N-acetylsulphamethoxazole hydrochloride (Bactrim) and N-acetylsulphaguanidine (Guanidan), flumequine (Apurone) in 1 case and calcite (Cal-Mag-Na) in 1 case. The authors estimate that about 100,000 calculi are excreted in France each year and that at least 1,000 of these potentially contain drugs and are not diagnosed. Early recognition of drug induced stones is essential in order to protect the patient from recurrences, the risks of renal complications or, more simply, from useless therapeutic or dietetic regimes.

Abstract: Infrared spectrophotometry and Raman spectroscopy, thanks to the laser molecular microsond (MOLE), are two analytical techniques particularly well suited to a precise analysis of the composition and structure of urinary calculi. They both showed noteworthy efficiency in their ability to recognize the various crystalline or amorphous mineral and organic species. The MOLE permits analysis of crystals 1 mu in size, demonstrating its usefulness in the study of calculi nuclei as well as in the study of urinary crystals. These analyses are a very important source of information about conditions of crystalline nucleation and growth as well as about ions and molecules which can take place in the formation and the evolution of the diverse crystalline phases. On the clinical level, these data can contribute to a better comprehension of the formation of every stone.

Abstract: All urinary calculi should be thoroughly examined. Among 2 000 calculi analyzed by infra-red spectrophotometry, some were found to contain rare constituants and drugs which might be held responsible for urinary stone formation. These included glafenine, triamterene, co-trimoxazole, sulphaguanidine, allopurinol, phenazopyridine, flumequine and anti-acid powders containing aluminium, calcium and magnesium trisilicates and/or carbonates or bicarbonates. Considering that these drugs are widely used, the incidence of drug-induced urinary calculi appears to be very low.

Abstract: Various studies have demonstrated a relationship between nephrolithiasis and the ingestion of certain drugs. We are particularly interested in the effects of triamterene. Five published case studies on patients of both sexes between 43 and 60 years of age have proven that a regular consumption of normal doses of triamterene has a direct effect upon the formation of renal stones. The stones analysed by infra-red spectrophotometry during the above observations contained from 20 to 100% of triamterene and it's metabolite hydroxytriamterene, following a daily consumption of 150 to 350 mg during a period of 6 to 38 months. It has been confirmed that triamterene and it's metabolite hydroxytriamterene are very poorly soluble and super-saturate the urine for a brief period following the ingestion of the drug. Triamterene might also intervene in the initial phenomena of nucleation. It is therefore recommended that triamterene be used with caution in those patients presenting a history of nephrolithiasis. The existence of drug induced nephrolithiasis reinforces the importance of the technique of renal stone analysis, and the necessity of a systematic study of all renal stones found. This will allow us to develop the study of the correlations between the different episodes of renal stone disease, the nature of the treatment undertaken and the systematic analysis, layer by layer, of the stone.

Abstract: The authors report the detailed analysis of 4 calculi containing triamterene observed between 1979 and 1981. The composition of drug layers is almost the same in the 4 calculi and shows a mixture of triamterene (estimated at 35% of iatrogenic components) and 7 metabolites among them p-hydroxy-triamterene (5-10%) and mainly p-hydroxytriamterene estersulfate (40-55%). The authors hypothesize a metabolic or physicochemical relation between triamterene and uric acid which are frequently associated in these calculi that represent 0.4% of all lithiasis. An estimated 150 to 200 calculi with triamterene are probably eliminated though not detected every year in France. The interest of a fine analysis of calculi by appropriate physical methods, such as infrared spectrometry, is emphasized.

Abstract: Two women aged 62 and 69 years who had been taking glafenine at normal dosage over a period of 4 years developed a renal calculus. In the first case, 6 small slightly radioopaque stones were extracted by pyelotomy, presenting a crystalline surface and yellow, soft, and amorphous section. They consisted of 50% calcium oxalate, 33% glafenic acid, and 10% proteins. In the second case, pyelography showed a sizable round and radiotransparent defect in the renal pelvis. At pyelotomy, a large, soft, and greenish stone was extracted, presenting a yellow and amorphous section, without calcium, but consisting of 75% glafenic acid, and 25% proteins. Through IR spectrography, glafenine metabolites found in the stones represented 33% in our first case and 75% in our second case. Through other methods, such as UV spectrophotometry and chromatography, 26% and 61% are respectively found. The metabolites are glafenic acid and hydroglafenic acid, in an identical proportion of 9 to 1 in both cases.

Abstract: The analysis of 322 urinary calculi in adults by microdissection, infrared spectromorphometry and microchemistry has shown that stones could be classified in several groups according to their morphology and composition: 8 morphological types have been defined (2 for the oxalic, 2 for the uric, 2 for the phosphatic and 2 for the cystinic stones). Correlations between morphology and composition have been established dividing the calculi into 10 categories, 4 for the pure forms and 6 for the mixed forms; the total includes approximately 94% of the calculi analyzed. An 11th category gathering various lithiases (rare or with multiple components) represents 6% of the cases. Moreover, the study of the localization of the component in stones emphasizes the high frequency of Ca phosphates in the nucleus of oxalic lithiases: 80% in mixed forms, in which the oxalate is the main constituent.

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Abstract: Numerous clinicians criticise the insufficiency and imprecision, and the incoherency of the analyses of biological calculations by the usual clinical methods and thus frequently avoid prescribing such an examination. The authors propose the application of a physical method, infrared spectrophotometry for the qualitative and semi-quantitative determination of the composition of stones of all origins. They recall the often heterogeneous structure of the stones and emphasise the importance which they attribute of differential analysis by separate zones during careful dissection, the results of which may orient the therapeutic attitude of the clinician. The differentiation of a few crystalline structures and the study of complex mixtures are dealt with in the form of characteristic infrared spectra. The advantages and limits of the method compared with other technics of analysis are discussed.

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