Abstract: BACKGROUND/AIMS: Hyperphosphatemia is recognized as contributing to the increased risk of cardiac death in end-stage renal disease (ESRD) and hemodialysis (HD) patients. Currently available pharmacologic treatment for hyperphosphatemia is based on phosphate binders but, despite treatment, only half of the patients fall within the range for serum phosphorus of the K/DOQI guidelines. Therefore, there is a need to identify other therapeutic approaches in order to reduce serum phosphate. Salivary fluid contains phosphate which, if related to the daily salivary secretion (1,000-1,880 ml), may raise interest in order to identify further additive approaches to phosphorus removal in uremic patients, while data about salivary phosphate secretion in ESRD patients are controversial. METHODS: This study evaluates salivary phosphate secretion in 68 HD patients compared with 30 healthy subjects. Saxon's test confirmed normal salivary function in patients and controls. Salivary calcium and serum phosphate, calcium and PTH were also measured. RESULTS: HD patients had significantly higher salivary phosphorus levels compared with healthy controls: 30.35 (26.5-34.6) vs. 12.1 (10.58-14.73) mg/dl (p < 0.0001), and this significantly correlated (p < 0.0001) with serum phosphorus. Multiple regression analysis confirmed serum phosphorus as the only predictor (p < 0.0001) of salivary phosphorus. CONCLUSIONS: Given the functional secretive similarity between salivary glands and the kidneys, this increased salivary phosphate secretion might be interpreted as being compensatory in the presence of renal failure. Absorption of the increased salivary phosphate secretion, however, may worsen hyperphosphatemia; therefore, the binding of salivary phosphate might be considered as a further therapeutic approach to hyperphosphatemia in ESRD.
Abstract: We report the case of a 13-year-old male patient with beta-thalassemic trait who presented for a colic pain. An ultrasound of the abdomen revealed absence of the right kidney with a complex hypoechogenic pelvic mass causing mild pressure on the posterior bladder wall. Urography showed hypertrophy of the left kidney with moderate ureteral enlargement of the distal third due to an insertion defect in the bladder suggestive of a primary segmental nonobstructing megaureter. MR studies showed right multilocular seminal vesicle cysts. One year later an MR examination of the pelvis showed an increase in size of seminal vesicle cysts and open surgery was performed to remove the cystic retrovesical mass. Our case represents a very rare association of seminal vesicle cysts, unilateral renal agenesis and alteration in contralateral ureteral insertion in a patient with beta-thalassemic trait.
Abstract: AIMS: Hyperphosphoremia, main contributor to cardiovascular calcifications, has a major impact on the morbidity and mortality of chronic renal failure (CRF) patients. Phosphate binders and dietary phosphate limitation are not effective enough to abolish hyperphosphoremia-induced cardiovascular abnormalities, therefore, the identification of other and more timely approaches for serum phosphorous reduction is necessary. Salivary fluid contains phosphate which, if related to the daily salivary secretion (1,000 - 1,800 ml), deserves attention as a marker for an earlier start of pharmacologic treatment for phosphorous removal. In ESRD patients under dialysis we have shown increased salivary phosphate closely to be related with serum phosphorous and interpreted as compensatory. This study evaluates salivary phosphate secretion in 77 nondialyzed CRF compared with healthy subjects and its relationship with renal function. METHODS: Saxon's test confirmed normal salivary function in patients and controls. Serum phosphorous, creatinine and GFR were also measured. RESULTS: Salivary phosphorous was significantly higher in CRF patients compared with controls: 38.60 mg/dl (range 12.20 - 95.60) vs 16.30 (10.30 - 27.10), p < 0.0001; serum phosphate was also significantly higher: 3.70 (2.10 - 6.80) vs 3.50 (2.3 4.6), p = 0.013. In CRF patients, salivary phosphorous positively correlated with serum phosphorous (r - 0.45, p < 0.0001) and with serum creatinine (r = 0.72, p < 0.0001), while negatively correlated with GFR (r = -0.72, p < 0.0001). CONCLUSIONS: The results of our study show also in CRF patients increased salivary phosphate secretion, which is related with renal function. On this basis the use of salivary phosphate secretion as a marker for an earlier start of the abnormal phosphate, metabolism pharmacologic treatment could be proposed.
Abstract: Cardiovascular mortality is the leading cause of death in the uremic patient. Hyperphosphatemia is considered an independent risk factor associated with cardiovascular morbidity and mortality in dialysis patients. As phosphate control is not efficient with diet or dialysis, phosphate binders are commonly prescribed in patients with chronic renal failure. Aluminum salts, the first phosphate binders, even if effective, have several side effects due to their deposition in CNS, bone and hematopoietic cells. Calcium-containing phosphate binders, used in the last 15 years, increase total body calcium load and may exacerbate metastatic calcification, thus, increasing the risk of cardiovascular mortality. Recently two new compounds non-aluminum and non-calcium phosphate binders, sevelamer hydrochloride and lanthanum carbonate, have been introduced. Sevelamer, besides the effect on phosphate, has been associated with reduction of coronary and aortic calcification and with other pleiotropic effects especially on lipid metabolism. Lanthanum carbonate has similar phosphate control to calcium-based binders with less incidence of hypercalcemia but long-term clinical studies are needed for testing long-term exposure. Recently the authors found in dialysis patients, that salivary phosphorus correlated with serum phosphorus. Therefore, they supposed that the use of salivary phosphate binders could reduce its absorption and represent a chance for reducing the serum phosphate concentration in uremic patients.
Abstract: BACKGROUND: Sevelamer hydrochloride, a major phosphate binder for patients on maintenance hemodialysis (MHD) is associated with reduced serum bicarbonate concentration due to hydrochloric acid release in the gut and to the binding of short chain fatty acids in the large intestine. Since metabolic acidosis can be deleterious, a study was devised to compare the time course of serum bicarbonate concentration during treatment with sevelamer hydrochloride or calcium carbonate. METHODS: Sixteen well nourished patients on MHD who were in excellent clinical conditions and achieving target levels for blood pressure (BP) and hemoglobin (Hb), while on a protein intake of 1.1g/kg body weight (bw), were enrolled in the study. After a 2-week washout period, the patients were divided into two groups, each consisting of eight patients, and randomized either to 24 weeks of sevelamer followed by 24 weeks of calcium carbonate (group A) or to 24 weeks of calcium carbonate followed by 24 weeks of sevelamer (group B). Protein intake, n-protein catabolic rate (nPCR), serum concentrations of calcium, phosphate, calcium x phosphate (Ca x P) product, bicarbonate, intact parathyroid hormone (iPTH) and albumin were monitored. Time course changes in serum bicarbonate concentrations in relation to short and long dialytic intervals (48 vs. 72 hr) were also investigated. RESULTS: Both sevelamer and calcium carbonate effectively controlled serum phosphate and the Ca x P product. During calcium carbonate treatment plasma phosphate concentrations were significantly below those of patients on sevelamer. Plasma bicarbonate concentration fell within target DOQI values during calcium carbonate administration both in group A and in group B, a goal which was not achieved under sevelamer administration. After a long dialytic interval in patients on sevelamer, serum bicarbonate concentration averaged 17.3 +/- 1.1 mEq/L, whereas it averaged 21.1 +/- 0.7 mEq/L in patients on calcium carbonate (p<0.01). Finally, a 24-week sevelamer administration caused a statistically significant (p<0.05) reduction (0.8 g/dL) in serum albumin concentration, without affecting iPTH. Taken together, these results indicate that sevelamer worsens metabolic acidosis, which needs to be corrected.
Abstract: Retroperitoneal fibrotic is a fibrous process of the retroperitoneum and can result in ureteral obstruction. Although the pathogenesis is unknown, it is suggested that an immunological mechanism plays a role. It can occur as an isolated finding or be associated with several conditions such as malignancies, infections, connective tissue disease and the action of drugs. However, a few cases of retroperitoneal fibrosis, associated with systemic lupus erythematosus (SLE) have been reported. We describe a case of a 23-year-old female with lupus nephritis who presented with bilateral obstructive nephropathy due to retroperitoneal fibrosis. Treatment with steroids improved both conditions. Our case and previously reported cases of SLE and retroperitoneal fibrosis support the hypothesis that this association is not fortuitous, but reflects a common immunological mechanism.
Abstract: New knowledge on the physiologic role of L-carnitine and on the rationale of its use in patients on maintenance hemodialysis is provided. In particular, carnitine normalizes plasma and muscle carnitine levels and modifies both enzymatic pattern of muscle and morphology of single fibers, improving exercise tolerance. In addition, carnitine reduces erythropoietin requirements, the number of hypotensive episodes, improves ejection fraction, and decreases hospitalization.
Abstract: The prevalence of erectile dysfunction (ED) has increased dramatically worldwide in parallel with the aging of the population. In 1995, ED was estimated to be present in more than 150 million men. Considering population aging in Western countries, estimates predict that more than 300 million men will be affected by ED by the year 2025. ED is a common and often distressing side effect of renal failure. It is present in 30% of patients with chronic renal failure and in 50% of patients undergoing dialysis treatment. Uremic men of different ages report a high variety of sexual problems including sexual hormonal pattern alterations, reduced or loss of libido, infertility, and impotence, thereby influencing their well-being. The pathogenetic mechanisms include physiologic, psychologic, and organic causes. Since the release of sildenafil citrate, the relationship between ED and the presence of cardiovascular disease (CVD) has been evaluated in several studies. Many of the risk factors for ED are the same as those for cardiac disease. CVD and ED are closely interrelated disease processes. Indeed, ED can be considered a symptom of vascular endothelial damage. Therefore, it can be expected that impotence will appear along with CVD, and the presence of ED suggests the existence of CVD. An accurate evaluation of the sexual histories of all men who present to internists, cardiologists, and also nephrologists for early detection of ED may allow for early diagnosis and management of CVD.
Abstract: Defense mechanisms are automatic psychological processes that protect the individual against anxiety and from the awareness of internal or external dangers or stressors. The influence of defense mechanisms in patients on chronic hemodialysis treatment was studied. There were 53 uremic subjects (37 males and 16 females), aged between 22 and 88 years (mean age 60.11, SD 15.03), on chronic dialysis and 50 healthy subjects as controls have been enrolled in the study. According to the duration of dialysis, uremic patients were divided in two subgroups: 21 patients with less than 5 years and 19 patients with more than 10 years of dialytic treatment. Assessment was conducted using the Defense Mechanisms Inventory DMI. The inventory identifies five defensive styles: turning against the object (TAO), projection (PRO), principalization (PRN), turning against the self (TAS) and reversal (REV). Results showed DMI scores within the normal range both for uremics and controls with significant differences in TAO (t = -3.053, p = 0.003) and REV (t = 5.067, p < 0.0001) between groups. No significant differences in the use of defensive styles related to the duration of dialytic treatment were observed. Besides other psychological features, the assessment of defense mechanisms in patients with chronic and invalidating diseases may contribute to ameliorate the knowledge of the adjustment processes and of the psychological well-being of the patients.
Abstract: INTRODUCTION: Recently, the identification of the SEN virus as a possible etiological agent of parental transmission hepatitis led to the study of the prevalence of such pathogen agents, particularly SENV-H, in our population. This paper compares the rate prevalence in high-risk subjects, such as dialysis patients, and low-risk subjects, such as blood donors. MATERIAL AND METHODS: The study was carried out on SEN virus DNA extracted from serum of dialysis patients and blood donors, and the presence of viral genomes was performed by the nested PCR method. RESULTS: The results showed a higher prevalence in male blood donors, supporting the hypothesis of an epidemiological role for sexual and also parental transmission, as is clearly demonstrated by the high prevalence in dialysis patients. The result reduced the importance of the possible etiological role of the SEN virus due to the high percentage of positivity in healthy population, and it induces one to consider poorly significant the pathogenicity of such viral agents. CONCLUSION: For this instance, the authors, in agreement with the phylogenically related TT virus, described SEN viruses as absolutely not pathogens and considered them as "simple guests."
Abstract: We report a case of a relapse of Henoch-Schönlein Purpura (HSP) associated with intake of paracetamol (also known as acetaminophene) and codeine. A 69-year-old man presented with fever, gross hematuria, acute renal failure, palpable purpuric skin rash over the legs, feet and arms, arthralgias and abdominal discomfort. 1 week before he had started therapy with co-efferalgan (association of paracetamol and codeine) for cervical arthrosis. Blood test revealed increase in serum creatinine levels (2.6 mg/dl), CRP (375 mg/dl), with no thrombocytopenia or hypocomplementemia. Co-efferalgan was discontinued. Gross hematuria resolved in 2 days, purpuric rash disappeared in 10 days, renal function returned to normal after 2 weeks and abdominal pain and arthralgias improved on the following 2 - 3 weeks. An objective causality assessment in accordance with the Naranjo algorithm, revealed that the adverse drug reaction was probable between paracetamol/codeine and Henoch-Schönlein purpura. To our knowledge, and based on a medline search (up to 2005), we believe that this could be considered the first case of Henoch-Schönlein purpura, associated with intake of paracetamol and codein. Although this event could be considered rare, clinicians should to be aware of possible associations between HUS and the intake of paracetamol and/or codeine to provide an early therapeutic intervention and a close monitoring.
Abstract: ESRD patients have to deal with two choices: the first is related to the dialysis modality; the second concerns the type of dialysis unit (public vs private) where to undertake the treatment. Such a choice is related to unobservable factors, among which there might be patients' clinical factors as well as factors related to the characteristics of each unit. We employ a recursive bivariate probit estimation on a sample of ESRD Sicilian patients in order to evaluate the impact of these factors. Results can have important implications for Sicily in order to organize dialysis services: here, in fact, the number of private centres is higher than in other Italian Regions.
Abstract: Although hemodialysis (HD) has improved the life expectancy of patients with end-stage renal disease (ESRD), uremic patients continue to experience high morbidity and mortality. Two of the most important risk factors for morbidity and mortality are protein-energy malnutrition (PEM) and inflammation. The causes for PEM in ESRD are numerous. The use of materials for dialysis, especially of the dialyzer membrane, is reported as one of the recognized causes for chronic inflammation in hemodialysis. We performed a 6-month prospective study examining the influence of on-line predilution hemodiafiltration on the inflammatory and nutritional status in a population of male hemodialysis patients using ultrapure dialysis fluid and polyamide dialyzers. We evaluated serum C-reactive protein, albumin, and transferrin and some nutritional parameters such as body mass index (BMI), phase angle (phi), fatty mass (FM), and free fatty mass (FFM) using bioelectrical impedance (BIA). Results showed significant amelioration of BMI and the re-equilibrium of the acute phase protein after on-line predilution hemodiafiltration. These results support the hypothesis that on-line predilution hemodiafiltration, as convective extracorporeal treatment, may be used to treat malnourished hemodialysis patients and to prevent malnutrition in the ESRD patient at risk for malnutrition.
Abstract: In 1992, the definition of erectile dysfunction (ED) replaced the old term of impotence that had been used for many centuries, in order to avoid the general confusion existing until today in this field. In the past, the origin of impotence had been attributed to different causes such as psychological diseases, or witches and demons. In 1764, Fusanacci described impotence that can occur in the male as well as in the female, as a defect in reproduc-tion. The main causes responsible for impotence were identified as inability to achieve erection, a very fluid seminal ejaculation, a defective organ, dryness of testicles, and lack of copulative power after many sexual intercourses with healthy women. Some decades later in 1847, Beatty affirmed that one of the most remarkable changes that can be observed in the passage from childhood to maturity is the development of the sexual organs, followed by the appearance of new sensations. He distinguished impotence that occurs only in men from sterility that for him affects women, and divided the causes of impotence into 3 classes: organic, functional and moral (today defined as psychological). For Beatty, the progress of knowledge had taken away magic and sorcery from the human mind and now it was widespread only among the lowest and most ignorant classes of humble people. In this way, he shows the evolution of medical science in XIX century in accepting only the rational explanation of the human diseases.
Abstract: L-Arginine is an essential amino acid for infants and growing children, as well as for pregnant women. This amino acid is a substrate for at least 5 enzymes identified in mammals, including arginase, arginine-glycine transaminase, kyotorphine synthase, nitric oxide synthase, and arginine decarboxylase. L-arginine is essential for the synthesis of creatine, urea, polyamines, nitric oxide, and agmatine. Arginine may be considered an essential amino acid in sepsis, and its supplementation could be beneficial in this clinical setting by improving microcirculation and protein anabolism. Rats receiving arginine-supplemented parenteral nutrition showed an increased ability to synthesize acute phase proteins when challenged with sepsis. Finally, L-arginine exerts antihypertensive and antiproliferative effects on vascular smooth muscles. It has been shown to reduce systemic blood pressure in some forms of experimental hypertension. Endothelial dysfunction and reduced nitric oxide bioactivity are associated with increased incidence of cardiovascular diseases. A beneficial effect of acute and chronic L-arginine supplementation on endothelial derived nitric oxide production and endothelial function has been shown. In end-stage renal disease patients, the rate of de novo arginine synthesis seemed to be preserved. Our preliminary data on a group of dialysis patients showed that predialysis arginine levels were stable in a normal range during the dialysis session and that hypertensive patients had lower arginine-citrulline ratio than normotensive patients.
Abstract: Increased serum levels of C-reactive protein (CRP) in uremic and dialysis patients are associated with low serum prealbumin and albumin concentrations and increased mortality and greater risk of cardiovascular disease. Proinflammatory cytokines may cause malnutrition by increasing protein catabolism. Many studies have shown that L-carnitine supplementation leads to improvements in several conditions seen in uremic patients, including cardiac complications, impaired exercise and functional capacities, muscle symptoms, increased symptomatic intradialytic hypotension, and erythropoietin-resistant anemia. L-carnitine therapy may either suppress the inflammatory response or act independently on both inflammation and appetite and/or anabolic processes. Moreover, L-carnitine may suppress proinflammatory cytokines in sick individuals without renal disease and may improve protein synthesis or nitrogen balance in patients without renal disease and in hemodialysis and peritoneal dialysis patients. In a pilot study, we provided preliminary evidence that treatment with L-carnitine, 20 mg/kg 3 times weekly at the end of each hemodialysis treatment, was associated with a reduction in serum CRP levels and improvement in anabolic status. The improvement or normalization of serum concentrations of serum CRP also was correlated with increased serum concentrations of albumin, transferrin, and blood hemoglobin. The possibility that some or all of these changes may have been caused by improved nutritional intake cannot be ruled out. Further randomized clinical trials will be necessary to confirm the role of L-carnitine as a modulator of inflammatory protein synthesis in hemodialysis patients.
Abstract: Several trials argued the possibility that hyperuricemia may have a direct effect on cardiovascular and renal disease. It has been shown that an elevated serum uric acid concentration is a predictor of cardiovascular events such as myocardial infarction. It also predicts the development of hypertension and in hypertensive patients, hyperuricemia is associated with increased cardiovascular morbidity and mortality. Hyperuricemia is a complication often seen in patients with chronic and acute renal disease. The relationship between serum uric acid level and the appearance or progression of renal dysfunction has been debated in the last years. During chemotherapy for hematological malignancies or more rarely for solid tumors, acute renal failure, secondary to a sudden marked increase in uric acid, is not such a rare complication. The therapeutic intervention includes hyper hydration, urinary alkalinization, and the use of uric acid decreasing agents such as allopurinol and rasburicase, a recent recombinant-urate oxidase. In our personal experience, patients with acute renal failure due to hyperuricemia, showed a better renal prognosis with rasburicase than allopurinol. Chronic hyperuricemia is also associated with chronic tubulo-interstitial disease with glomerular sclerosis, and renal dysfunction. Experimental trials showed that uric acid can affect kidneys through different mechanisms at glomerular, tubulo-interstitial and vascular level. Although allopurinol is often the drug of choice, caution must be used to avoid serious side effects. New therapeutic options, for treating hyperuricemia are needed in patients with renal dysfunction for slowing the progression to end stage kidney disease.
Abstract: Scattered reports indicate that L-carnitine may suppress proinflammatory cytokines in sick individuals without renal disease and may improve protein synthesis or nitrogen balance either in patients without renal disease or in maintenance hemodialysis (MHD) or chronic peritoneal dialysis patients. We conducted an experimental study in MHD patients to evaluate the effects of L-carnitine treatment on inflammatory and protein-energy nutritional status. MHD patients were assigned to receive intravenous injections of L-carnitine 20 mg/kg (n = 48) or placebo (n = 65) thrice weekly at the end of each hemodialysis treatment for 6 months. The carnitine-treated group showed a statistically significant decrease in serum C-reactive protein and increase in serum albumin and transferrin, blood hemoglobin, and body mass index. Conversely, in the placebo-treated group, a significant decrease was reported for serum albumin, serum transferrin, and body mass index, whereas the other considered measures did not change significantly. These preliminary findings suggest that in MHD patients, L-carnitine therapy may suppress inflammation, particularly among those patients with C-reactive protein > or =3 mg/dL, and may improve protein-energy nutritional status.
Abstract: In patients with chronic kidney disease (CKD), specialized nutritional therapy may help reduce the risk of electrolyte imbalances, vitamin deficiencies, and protein energy malnutrition. Protein-restricted diets may slow the progression of renal disease and decrease the risk of morbidity and mortality in patients with CKD. In this review, we discuss some of the major nutritional concerns in individuals with CKD and offer practical recommendations for dietary therapy.
Abstract: In the last twenty years, several systems have been proposed to codify renal allograft rejection. The Banff classification for kidney allograft pathology, introduced in 1993, started a new era in the standardization of criteria for rejection and for allowing uniform reporting. This consensus on allograft grading proposed a scheme to guide therapy in transplant patients and to help establish an objective rejection end point in clinical trials. This scheme, modified during 1993-1997 to address many of the criticisms, was substantially improved. Another important system of classification of allograft renal biopsies was the Cooperative Clinical Trials in Transplantation (CCTT) classification which was published in 1997. The aim of this system was to develop a schema that would be practical to implement, easy to describe to unfamiliar personnel, reproducible, with high rates of sensitivity and specificity and clinically informative (predictive of course and/or response to therapy). In March 1997, a fundamental revision of the Banff classification for acute rejection was achieved by a consensus conference for incorporating many of the strengths of the CCTT system. Some of these were the importance of vascular damage (endoarteritis, endothelial activation, fibrinoid necrosis) and interstitial hemorrhage, but not the interstitial infiltrate or tubulitis, which correlated with response to anti-rejection therapy and/or 1 year clinical outcome. The most recent modification concerns the addition of C4d-positive acute humoral rejection and the emphasis on differences between cell-mediated and antibody-mediated rejections. Future refinements of these classifications and findings of new molecular markers of allograft rejection, such as fas-ligand or granzyme-B, will help to improve diagnosis and therapy in renal transplant patients.
Abstract: BACKGROUND: The Dialysis Outcomes and Practice Patterns Study (DOPPS) is an international prospective, longitudinal, observational study examining the relationship between dialysis unit practices and outcomes for hemodialysis (HD) patients in seven developed countries France, Germany, Italy, Spain, United Kingdom, Japan and the United States. Results of the DOPPS in Italy are the subject of this report. METHODS: A national representative sample of 20 dialysis units (21 in Germany) was randomly selected in each of the European DOPPS countries (Euro-DOPPS). In these units, the HD in-center patients were included on a facility census, and their survival rates continuously monitored. A representative sample of incident (269 in Italy, 1553 in the Euro-DOPPS) and prevalent (600 in Italy, 3038 in the Euro-DOPPS) patients was randomly selected from the census for more detailed longitudinal investigation with regard to medical history, laboratory values and hospital admission. RESULTS: Comparing the Italian and Euro-DOPPS cohorts we found comparable mean age for prevalent patients (61.4 vs. 59.5 yrs), but incident patients were older in Italy. Italian prevalent patients had less cardiovascular disease, more satisfactory nutritional status and more frequent use of native vascular access. These data were associated with a comparable mortality (15.7 vs. 16.3 deaths/100 patient yrs), but morbidity was lower in Italy. Kt/V levels were comparable in the two cohorts (1.32 vs. 1.37), but 35% of Italian patients showed a Kt/V below the recommended target. Moreover, hemoglobin levels were below 11 g/dL in 60% of Italian patients. CONCLUSIONS: The DOPPS results bring to light several positive aspects and the opportunity for further possible improvements for Italian patients, but at the same time highlight some critical points that could represent a risk for dialysis quality.
Abstract: Carnitine is a small water-soluble molecule that is present in almost all animal species. It plays an indispensable role in fatty acid metabolism, where it is involved in the transport of activated fatty acids between different cellular compartments. Uremic patients, as well as patients with chronic renal failure, appear to have abnormal renal handling of carnitine leading to dyslipidemia, lethargy, muscular weakness, hypotension, cardiac dysfunction and arrhythmias, and recurrent cramps. It often is difficult to distinguish these symptoms from similar ones related to uremia and dialysis. Many investigators have advocated L-carnitine supplementation in an attempt to alleviate carnitine deficiencies, and good results from this therapy have been reported. Moreover, several studies have shown that L-carnitine supplementation improves the response to erythropoietin. Chronic inflammation is another particular aspect affecting these patients. Anti-inflammatory properties of L-carnitine in hemodialysis patients have been shown by our group. Treatment with L-carnitine (20 mg/kg, given intravenously at the end of each dialysis session for 6 mo), significantly decreased serum C-reactive protein (CRP) levels, a proinflammatory cytokine known to inhibit erythropoiesis. Moreover, data from published literature are indicative of L-carnitine modulation of the immune system by the activation of glucocorticoid receptors and the modulation of the transcription of glucocorticoid-responsive genes. Our study showed that in these patients, treatment with L-carnitine has been able to improve their body mass index, likely by promoting a positive protein balance. This aspect is strictly correlated with the status of insulin resistance, which is well described in patients with renal diseases. Many studies showed that carnitine allowed mitochondrial fatty acid usage to link to the rate of glucose usage, thus improving insulin resistance. In conclusion, clinical beneficial effects of L-carnitine treatment on patients suffering from renal diseases are supported by molecular evidence involving both inflammatory and metabolic aspects of the disease.
Abstract: The Italian Registry of Dialysis and Transplantation (RIDT) was born in 1996 under the aegis of the Italian Society of Nephrology, and it is organized as a federation of regional registries. This study aimed to completely revise the epidemiological data collected during the first 5 yrs (1996-2001) of RIDT activity to evaluate the trends of the main epidemiological features. During this period, regional registries were not always able to assure complete and exhaustive information according to RIDT requirements, owing to different levels of organization and functioning. To avoid any possible error in data analysis, information inadequately assessed was refused. The incidence of end-stage renal disease (ESRD) patients on renal replacement therapy (RRT) in Italy has increased from 114 pmp in 1996 to 139 pmp in 2001, that means an increase of 3.5%/yr, corresponding to 5718 patients during 1996 and 8000 patients during 2001. Primary renal diseases (according to the EDTA) in incident ESRD patients are vascular and diabetic nephropathy. Main dialysis modality in incident patients was hemodialysis (HD) (85%), while peritoneal dialysis (PD) was only 15%; pre-emptive transplantation was a very unusual modality. The prevalence of ESRD patients at 31 December was 693 pmp in 1996 and 827 pmp in 2001; among dialysis patients, the corresponding rates were 575 pmp and 657 pmp, respectively. Consequently, the number of dialyzed patients increased, respectively, from 28892 to 37919. The prevalent dialysis modality was bicarbonate dialysis in 74% of cases, followed by hemodiafiltration (HDF) in 15%, continuous ambulatory peritoneal dialysis (CAPD) in 7% and APD in 3%. The gross mortality rate in dialyzed patients was stable during this period, at approximately 14%, the main causes of death being cardiovascular diseases and cachexia.
Abstract: Erectile dysfunction (ED) is a common and often distressing side effect of renal failure. Uremic men of different ages report a high variety of sexual problems, including sexual hormonal pattern alterations, reduced or loss of libido, infertility, and impotence, thereby influencing their well-being. The pathogenic mechanisms include physiologic, psychologic, and organic causes. To determine the contribution of morphologic factors to impotence we studied the ultrastructure of the corpora cavernosa in 20 patients with end-stage renal disease who were treated with chronic dialysis and compared the findings with 6 individuals with no clinical history of impotence. Our results indicated that in male uremic patients with sexual disturbances there were major changes in smooth muscle cells. This was characterized by reduction of dense bodies in the cytoplasm, thick basement membranes, and increased interstitial collagen fibers with resultant reduction of cell-to-cell contact. In addition, there was thickening and lamination of basement membranes of endothelial cells and increased accumulation of collagen between nerve fibers. These alterations were more evident in patients with longer time on dialysis and were independent of type of primary renal disease. We hypothesize that ED in dialysis patients is not related to the primary disease but to the uremic state.
Abstract: L-carnitine (LC) plays an essential metabolic role that consists in transferring the long chain fatty acids (LCFAs) through the mitochondrial barrier, thus allowing their energy-yielding oxidation. Other functions of LC are protection of membrane structures, stabilizing a physiologic coenzyme-A (CoA)-sulfate hydrate/acetyl-CoA ratio, and reduction of lactate production. On the other hand, numerous observations have stressed the carnitine ability of influencing, in several ways, the control mechanisms of the vital cell cycle. Much evidence suggests that apoptosis activated by palmitate or stearate addition to cultured cells is correlated with de novo ceramide synthesis. Investigations in vitro strongly support that LC is able to inhibit the death planned, most likely by preventing sphingomyelin breakdown and consequent ceramide synthesis; this effect seems to be specific for acidic sphingomyelinase. The reduction of ceramide generation and the increase in the serum levels of insulin-like growth factor (IGF)-1, could represent 2 important mechanisms underlying the observed antiapoptotic effects of acetyl-LC. Primary carnitine deficiency is an uncommon inherited disorder, related to functional anomalies in a specific organic cation/carnitine transporter (hOCTN2). These conditions have been classified as either systemic or myopathic. Secondary forms also are recognized. These are present in patients with renal tubular disorders, in which excretion of carnitine may be excessive, and in patients on hemodialysis. A lack of carnitine in hemodialysis patients is caused by insufficient carnitine synthesis and particularly by the loss through dialytic membranes, leading, in some patients, to carnitine depletion with a relative increase in esterified forms. Many studies have shown that LC supplementation leads to improvements in several complications seen in uremic patients, including cardiac complications, impaired exercise and functional capacities, muscle symptoms, increased symptomatic intradialytic hypotension, and erythropoietin-resistant anemia, normalizing the reduced carnitine palmitoyl transferase activity in red cells.
Abstract: Lipoxins (LX) are lipoxygenase-derived eicosanoids with potent anti-inflammatory activities and vascular bed-dependent vasodilatory actions. LX can be formed in vitro and in vivo in a number of conditions, and we have reported that immunoreactive LXA(4) (iLXA(4)) is physiologically excreted with human urine. Using a recently developed LX extraction method coupled to an ELISA, we examined whether iLXA(4) excretion was modified by strenuous exercise, which is known to trigger potential LX-forming events. Maximal exertion significantly increased iLXA(4) urinary excretion in nine healthy volunteers (0.061 +/- 0.023 vs. 0.113 +/- 0.057 ng/mg creatinine; P = 0.028). iLXA(4) levels returned to baseline after 6 h and increased, although at a smaller extent, after 24 h. A significant correlation (r = 0.988) was denoted between iLXA(4) ELISA measurements and reversed-phase high-performance liquid chromatography quantitation of a previously described urinary tetraene, confirming its LXA(4)-related nature. These findings show for the first time that an increase in excretion of LXA(4)-related compounds can be observed in response to strenuous exercise. This may be the reflection of an enhanced LX biosynthesis, which may represent a safeguard mechanism that keeps the inflammatory reaction triggered by physical stress under control.
Abstract: Carnitine, gamma-trimethyl-beta-hydroxybutyrobetaine, is a small molecule widely present in all cells from prokaryotic to eukaryotic. It is an important element in the beta-oxidation of fatty acids. A lack of carnitine in hemodialysis patients is caused by insufficient carnitine synthesis and particularly by the loss through dialytic membranes, leading in some patients to carnitine depletion with a relative increase of esterified forms. The authors found a decrease in plasma-triglyceride and increase of high-density lipoprotein cholesterol (HDL-Chol) in dialysis patients during carnitine treatment. Many studies have shown that L-carnitine supplementation leads to improvements in several complications seen in uremic patients, including cardiac complications, impaired exercise and functional capacities, muscle symptoms, increased symptomatic intradialytic hypotension, and erythropoietin-resistant anemia, normalizing the reduced carnitine palmitoyl transferase activity in red cells. In addition, carnitine supplementation may improve protein metabolism and insulin resistance. Recently, carnitine supplementation has been approved by the US Food and Drug Administration not only for the treatment, but also for the prevention of carnitine depletion in dialysis patients. Regular carnitine supplementation in hemodialysis patients can improve their lipid metabolism, protein nutrition, antioxidant status, and anemia requiring large doses of erythropoietin, It also may reduce the incidence of intradialytic muscle cramps, hypotension, asthenia, muscle weakness, and cardiomyopathy.
Abstract: Several studies suggest the distinctive advantages of ACE-inhibitors and calcium-channel blockers in protecting the residual renal function in hypertensive patients. Pre-clinical and clinical studies have shown rare adverse events in the treatment with manidipine, which is commonly used as antihypertensive drug. We therefore decided to compare the effects of manidipine and nifedipine, on blood pressure, and renal function. One hundred and one hypertensive patients with chronic renal failure were randomly assigned to receive either manidipine 20 mg daily or nifedipine 60 mg daily, respectively. Patients were assessed every two weeks during the active treatment period with the final follow-up after three months. The primary endpoint was the achievement of DBP < or = 90 mmHg or a 10 mmHg DBP reduction from the baseline values, whilst the secondary endpoints was the improvement of the renal function assessed through the creatinine clearance, creatinine blood levels, protein and sodium urine excretion. Significant reduction in SBP (p < 0.001) and DBP (p < 0.001), compared to the baseline values, was reached in both treatments. Creatinine blood levels (p < 0.05) and creatinine clearance (p < 0.01) significantly increased in the manidipine group. Protenuria did not significantly change in the manidipine group but increased in the nifedipine group (p < 0.05). The number of patients with severe adverse reactions differed significantly (p < 0.01) between the groups with the highest frequency for nifedipine (14.5%) compared to manidipine (8.5%). The withdrawal rate was not significantly different between the groups. Manidipine is equally safe and effective as nifedipine and it may have more activity on renal function and less severe side effects compared to nifedipine.
Abstract: Nephrotic syndrome in patients with Gaucher disease is rare; most of the few reported cases have had a well-defined glomerulopathy often with Gaucher cells in the glomeruli. We report the case of a 54-year-old woman with Gaucher disease, who had splenectomy at age 25, preeclampsia with renal biopsy disclosing only endotheliosis at age 32, and improvement of proteinuria and reappearance of heavy proteinuria (7.2 g/24 h) at age 41. Renal biopsy disclosed Gaucher cells in glomeruli and interstitium. The patient did not receive therapy specifically for glomerular disease. Enzyme replacement, begun 4 years later and maintained until now, was associated with amelioration of systemic symptoms and virtual disappearance of proteinuria with a follow-up of 10 years. This case apparently is the first instance of nephrotic syndrome consequent to Gaucher disease itself and successful treatment with specific enzyme replacement.
Abstract: Maintenance dialysis induces a clinical state of immunodeficiency. The pathway of circulating T cells from haemodialyzed patients is changed and characterized by an increase of Th1 cells. The unbalanced T helper differentiation derives from an altered regulation of interleukin-12 (IL-12), which represents an important inducer of Th1. IL-18 is a pro-inflammatory cytokine expressed by a variety of cell types that is structurally related to the Th1 family and shares biological properties with IL-12 as the promotion of Th1 responses. To explain the involvement of IL-18 in the typical disorders of dialysis, we analyzed IL-18 serum levels in a group of haemodialyzed patients. We enrolled 16 patients on chronic haemodialysis (HD) treatment for end-stage renal failure and 16 healthy volunteers as the control group. IL-18 levels were assessed by immunoenzymatic methods (detection limit was <12.5 pg/ml). HD patients strongly showed higher IL-18 serum levels compared to healthy donors (508.47 +/- 314.39 vs. 193.44 +/- 56.33 pg/ml, p < 0.005). Moreover, IL-18 levels in HD directly correlated to dialytic age (Rho = 0.544, p = 0.0419) and indirectly to Kt/V (Rho = 0.703, p = 0.0086). Our data represent the first evidence of the relation between IL-18 serum levels and HD. In the light of our results, we think that the unbalanced T helper differentiation may depend, at least in part, on an abnormality in the IL-18 production.
Abstract: In 1938 Procaccini showed scientific interest in a new kind of ameba, and called it "nephrouroameba" from which the disease "nephrouroamebiasis" is derived. He wrote a paper titled "La Nefrouroamoebiasi" thus describing its history, the biopathogenetic evolutionary cycle of the protozoon, its therapeutic, epidemiological, anatomo-biological, diagnostic, cultural, biological and morphological features. Between 1934 and 1939, Procaccini had the opportunity to follow many patients belonging to a group of Italian soldiers serving in the Eastern Italian Army in Ethiopia. At that time he was responsible for the biopathological laboratory. After a short preclinical stage of fatigue, patients suffering from nephrouroamebiasis showed a nephrotic syndrome with gross hematuria. The symptoms ceased within a few days but residual microhematuria, albuminuria and urine casts persisted for many months. After microscopic observation, he reproduced some protozoons and classified them as a kind of ameba. Critical analysis of his report leads to the morphological identification of Trichomonas, thus excluding his classification as nephrouroamebas.
Abstract: The two words that mean sexual dysfunction, impotence and erectile dysfunction (ED), express two different concepts. Impotence is a general male sexual dysfunction that includes libidinal, orgasmic, and ejaculatory dysfunction. ED is the inability to achieve or maintain an erection sufficient to allow satisfactory sexual intercourse and is part of the general male sexual dysfunction termed impotence that includes libidinal, orgasmic, and ejaculatory dysfunction. Uremic men of different ages report a variety of sexual problems, including sexual hormonal pattern alterations, reduction in or loss of libido, infertility, and impotence, conditioning their well-being status. In evaluating and treating sexual dysfunction, a nephrologist must consider factors involved in its pathogenesis, such as hypothalamic-pituitary-gonadal axis alterations, psychological problems related to chronic disease, secondary hyperparathyroidism, anemia, autonomic neuropathy, derangements in arterial supply or venous outflow, and the normal structure of cavernous body smooth muscle cells. The introduction of sildenafil to treat impotent patients has completely changed the approach to evaluating these subjects because this drug is considered an effective well-tolerated treatment for men with ED. In the past, we proposed an algorithm that gave the opportunity to explore the previously mentioned factors using such instrumental interventions as the nocturnal penile tumescence test, penile echo color Doppler, nervous conduction velocity, and cavernous body biopsy, addressed to prescribe needed surgical or medical interventions. The complexity of the proposed algorithm requires many diagnostic procedures and much time and economic resources to localize the pathological lesions responsible for ED. Because of the new oral drug sildenafil, we propose a new algorithm to test the possibility of obtaining an erection and classify patients as responders or nonresponders to the sildenafil test.
Abstract: Autonomic nervous system dysfunction is a common feature in uremia and may have a number of clinical sequelae. Simple cardiovascular reflex screening can be performed in patients during conservative treatment, on periodic dialysis therapy, or after kidney transplantation to diagnose and follow up autonomic function impairment. Other approaches, such as heart-rate variability studies in the frequency domain by power spectral analysis, can provide a more accurate investigation of the disease.
Abstract: Hypertension is a major risk for cardiovascular complications in dialysis patients. The pathogenesis of hypertension is multifactorial and is not completely understood. Hypervolemia has always been considered a major pathogenetic factor. In addition, a disturbed hormone profile with an activated renin angiotensin system, increased catecholamine, vasopressin and endothelin, and perhaps decreased nitrous oxide activity seem to play a role in the high incidence of hypertension in dialysis patients. The influence of autonomic dysfunction on blood pressure control in hemodialysis patients is not clear. The frequent use of erythropoietin during the last decade may have contributed to the increased incidence of hypertension in the dialysis population. Data from the First Report on Dialysis and Transplant in Sicily showed that hypertension is the cause of end-stage renal disease in 8% of dialysis patients and that the incidence of hypertension, as a cause of end-stage renal disease, increased with age.
Abstract: BACKGROUND: There is good evidence that power spectral analysis (PSA) of heart rate variability may provide an insight into the understanding of autonomic disorders. METHODS: We investigated 30 chronic uremic patients who were on periodic bicarbonate hemodialysis by a battery of six cardiovascular autonomic tests (beat-to-beat variations during quiet breathing and deep breathing, heart rate responses to the Valsalva maneuver and standing, blood pressure responses to standing and sustained handgrip) and PSA of heart rate variations. RESULTS: Eleven patients (37%) had an abnormal response to only one parasympathetic test. Twelve patients (40%) had a definite parasympathetic damage, as indicated by at least two abnormal heart rate tests, whereas four (13%) had combined parasympathetic and sympathetic damage. Multivariate analysis of the cardiovascular tests revealed that 19 patients (63%) had moderate-to-severe autonomic neuropathy (AN), and 11 patients exhibited normal autonomic function. Among the symptoms suggestive of autonomic dysfunction, only impotence in males was significantly associated with test-proven AN. The PSA of the heart rate variability demonstrated a good discrimination of low-frequency (LF) and high-frequency (HF) bands (LF, 0.03 to 0.15 Hz; HF, 0.15 to 0.33 Hz) among controls, uremic patients without test-proven AN, and uremic patients with test-proven AN. A significant reduction of the LF value on supine uremic patients without AN suggests that an early sympathetic involvement exists that traditional autonomic tests were unable to detect. CONCLUSIONS: Our study indicates that the current opinion of a major parasympathetic damage in chronic uremic patients on hemodialysis has to be modified in favor of a more widespread autonomic dysfunction involving both the sympathetic and parasympathetic pathways.
Abstract: The subcutaneous reservoir is a new vascular access for patients on regular hemodialysis (HD). A double chamber in Titanium- Pirolytic Carbon with siliconic boreable superior caps is inserted in to a subcutaneous subclavian side, and always in subcutis connected to two siliconic catheters located in the right jugular resulting in the right atrium. The puncture of each chamber is performed with a special hemodialysis-cannula telescopically assembled on a "dilatation tube", in which a stylet is inserted. In correct sequence, the cutaneous planes and the caps are bored, dilated, and finally the HD cannula after sliding over the previous structures is positioned in the inner chamber, closing the HD circuit. In our study two patients were implanted, with a survival of 24 months, good compliance, no cardiovascular impairments and lack of catheteral pathology.
Abstract: Increased anticardiolipin antibodies (aCL) serum levels have been recently described in haemodialysis patients and in renal transplant recipients, with a prevalence ranging from 4.8 to 46.4%. The causes and the clinical significance of aCL positivity in these patients are uncertain. We measured IgG- and IgM-aCL serum levels in 61 haemodialysis patients, in 14 renal transplant recipients and in 38 healthy controls. Increased levels of IgG-aCL were found in 4 haemodialysis patients (6.55%), in 2 transplant patients (14%) and in 2 of the healthy controls (5.26%). IgM-aCL serum levels were normal in all the patients. After one year of follow-up, no vascular events have been observed in aCL positive patients. It is probable that the presence of aCL in the serum of patients with end-stage renal disease is only an epiphenomenon and does not play a pathogenetic role.
Abstract: DESIGN OF STUDY: Two groups of patients undergoing long-term dialysis were studied in order to evaluate the importance of ethylene oxide (EtO) in causing allergic reactions during dialysis. The first group of 50 subjects had never shown any hypersensitivity reactions related to dialysis, whereas the second group of 20 subjects had previously complained of reactions. All the patients underwent a prick test with a standard kit of aeroallergens in order to assess the presence of atopy (in doubtful cases a RAST test was carried out with the same aeroallergens). A blood sample for the investigation of EtO specific IgE antibodies was taken from all the patients; the immunoenzymatic method was used. RESULTS: Sensitivity to EtO is significantly higher in the group of patients with previous allergic reactions during dialysis (55 vs 6% in the control group).
