Abstract: Chronic kidney disease-mineral bone disorder is a common clinical picture encountered in patients with end-stage renal disease and is the result of additive pathophysiological processes. Renal transplantation remains the treatment of choice for these patients, especially as advances in this field have allowed for enhanced allograft survival. However, with increasing success of renal transplantation has come a greater appreciation of some of its subsequent complications, such as posttransplantation bone disease. Recently, persistent hyperparathyroidism and osteopenia-osteoporosis have been given specific attention. Traditionally, persistent hyperparathyroidism has been treated with parathyroidectomy, although the role that calcimimetics may play in the future is promising. Newer aspects to medical management of osteopenia-osteoporosis, such as the efficacy of bisphosphonate therapy and early steroid withdrawal, are becoming apparent and some of the newer drugs for the treatment of osteoporosis are yet to be investigated in this subgroup of patients.
Abstract: Sevelamer (Renagel), an orally administered metal-free cationic hydrogel polymer/resin that binds dietary phosphate in the gastrointestinal (GI) tract, is approved for use in the US, Europe and several other countries for the treatment of hyperphosphataemia in adult patients with end-stage renal disease (ESRD) on haemodialysis or peritoneal dialysis.Clinical evidence shows that sevelamer was at least as effective as calcium acetate and calcium carbonate at controlling serum phosphorus, calcium-phosphorus product (Ca x P) and intact parathyroid hormone (iPTH) levels, but generally reduced serum calcium levels to a greater extent and was associated with a lower risk of hypercalcaemic episodes than calcium-based phosphate binders. Sevelamer appeared to slow the progression of cardiovascular calcification in patients with ESRD and also had a beneficial effect on serum low-density lipoprotein-cholesterol (LDL-C) levels. In patients receiving chronic haemodialysis, there was no between-group difference in all-cause mortality between sevelamer and calcium-based phosphate binder therapy in the primary efficacy analysis in the large (n >2100), 3-year DCOR trial; in the smaller (n = 109) nonblind RIND trial in patients new to dialysis, data suggest there is an overall survival benefit with sevelamer versus calcium-based phosphate binder treatment. The relative survival benefits and cost effectiveness of these phosphate binder therapies remains to be fully determined. Sevelamer treatment was generally as well tolerated as calcium acetate or calcium carbonate treatment. Overall, sevelamer is a valuable option for the management of hyperphosphataemia in patients with ESRD on haemodialysis.
Abstract: The mortality rates which we have seen now over several decades of routine provision of renal replacement therapy are truly remarkable - even if, with time, we have become familiar, if not comfortable, with them. The remarkable nature of this mortality issue is its severity, and persistence, despite numerous efforts to combat it with 'active interventions'. These have included, in no particular order, correction of anaemia, better provision of dialysis adequacy, use of more permeable dialysis membranes, better control of dyslipidaemia, better control of mineral and bone metabolic parameters, correction of hyperhomocysteinaemia, and use of ACE inhibitors. One can now in 2008 be forgiven for some pessimism, nihilism (sometimes known as 'renalism') about the prospects for useful prolongation of life on dialysis except of course by transplantation. In this article (a fuller version of which appears also in Nephrology Dialysis and Transplantation, I discuss the reasons for the failure of the trials to date, the likely obstacles to future trials succeeding, and some suggestions for alternative strategies to try to grapple with this immense burden of vascular and all-cause morbidity and mortality.
Abstract: OBJECTIVE: The overall objective of this study was to estimate the costs and outcomes associated with treatment with sevelamer for hyperphosphataemia compared with calcium-based binders. METHODS: Using published data on mortality and hospitalisation rates, a Markov model was developed to predict health outcomes and associated costs for the treatment of hyperphosphataemia using either sevelamer or calcium binders in chronic kidney disease patients who had recently started haemodialysis. Patient outcomes were modelled for 5 years, and incremental cost-effective ratios (ICERs) were calculated for sevelamer relative to calcium carbonate and calcium acetate binders. The perspective adopted was that of the UK National Health Service. RESULTS: The total 5-year discounted treatment cost for patients treated with sevelamer is pound 24,216, while for the calcium carbonate group total cost was pound 17,695. This is an incremental cost of pound 6521 per sevelamer-treated patient over 5 years. Patients receiving sevelamer can be expected to experience 2.70 quality-adjusted life years (QALYs) compared to 2.46 for those treated with calcium carbonate (i.e. an incremental gain of 0.24 QALYs). This results in an incremental cost per QALY of pound 27,120 and an incremental cost per life year gained of pound 15,508. Results were similar with calcium acetate. CONCLUSION: Together with the unique morbidity and mortality benefits, this study suggests that treatment with sevelamer confers clinical benefits with a modest investment of additional economic resources.
Abstract: We report a case of post-transplantation lymphoproliferative disorder presenting as a symptomatic lymphocele 12 years after cadaveric renal transplantation for IgA nephropathy. The presentation, imaging, and management are discussed. We review current literature concerning PTLD, post-transplantation lymphoceles, and state-of-the-art imaging techniques.
Abstract: Calciphylaxis-calcific uremic arteriolopathy, is a serious disorder of arteriolar calcification of the arteriole media and is associated with endovascular fibrosis and thrombosis in subcutaneous adipose tissue. It frequently results in severe ischemia, intense pain, and tissue necrosis with nonhealing skin ulcerations. It usually occurs in chronic kidney disease and especially in patients requiring renal replacement therapy. It is associated with a very high mortality rate, and the number of reports and reviews seemed to have increased over the past 5 years. Advances in therapy and salvaging patients from this high mortality risk have recently been reported with the use of sodium thiosulfate. The new application for this old drug used to treat cyanide poisoning and recently preventing neurotoxic effects resulting in hearing loss in those patients with head and neck cancer receiving cisplatin and carboplatin therapy are discussed. Recently, multiple case reports have demonstrated that sodium thiosulfate therapy has resulted in rapid pain relief, healing of skin ulcerations, and prevention of high mortality risk. This emerging treatment and its success are relatively unknown to many physicians. The purpose of this report is to share with others the emerging role of sodium thiosulfate and its new application as a treatment option to be used in combination with other treatment modalities for calciphylaxis-calcific uremic arteriolopathy. Indeed, as with any new treatment this emerging therapy should be studied in greater detail, but this old drug seems to have a new life in the hands of treating physicians.
Abstract: CASE REPORT: Septic arthritis due to Klebsiella species is a rare but serious infection that may destroy a joint and cause serious immobility. This is a report of two immunocompromised adult patients presenting with acute septic arthritis due to extended spectrum beta lactamase producing Klebsiella pneumoniae. The infection was treated successfully with a course of meropenem and amikacin in combination with early arthroscopic washout of the joint. Little information has been published on the management of this infection. We are therefore presenting a systematic literature review summarizing risk factors, clinical presentation, laboratory diagnosis, treatment regimens and outcome of this condition. DISCUSSION: On the basis of our study, we recommend an early diagnostic arthrocentesis of the joint for Gram stain microscopy, culture and antibiotic sensitivity testing to guide the appropriate use of antibiotics. In cases of hospital acquired infections where drug resistant Gram negative bacteria are suspected or prevalent, broad-spectrum antibiotics such as meropenem plus or minus amikacin may be given as the empirical treatment until the sensitivities are confirmed. In addition, adequate surgical joint lavage should be considered as the mainstay of treatment.
Abstract: Both chronic kidney disease (CKD) and type II diabetes mellitus (DM) are increasing in frequency among Western populations and both are potent risk factors for the development of anaemia. The presence of CKD and diabetes together represent the most important aetiopathogenic combination for the development of anaemia. New evidence has highlighted some of the underlying mechanisms which make diabetic patients more susceptible to dyserythropoiesis, particularly once they have developed concomitant CKD. In addition, recent publications from large-scale epidemiological studies have highlighted the impact of anaemia on diabetic patients. The purpose of this review was to focus on the pathophysiology and impact of anaemia in DM.
Abstract: For a long time, the inhibition of the renin-angiotensin-aldosterone (RAA) axis has been considered a must in almost all patients with progressive chronic kidney disease (CKD), with the aim of reducing the rate of progression to end-stage renal disease (ESRD). However, recent data from a meta-analysis, including the ALLHAT study, and a study in Canadian diabetic patients questioned the usefulness of angiotensin converting enzyme (ACE) inhibition in delaying the onset of dialysis. Publication of these data led to an intensive recent debate among reputed nephrologists, with numerous pros and cons regarding the pharmacological influence of CKD progression. The authors of the present review critically discuss the arguments and counterarguments of this challenging debate. Finally, a cautious view for the practicing nephrologist is expressed, highlighting the difference between study patients and real-life patients, and the possible overlooked aspects of recent renal protection studies (the importance of central blood pressure, of ambulatory blood pressure monitoring and possible, the impact of angiotensin converting inhibitors on stroke), are presented.
Abstract: We recently identified an erythrocyte nucleotide accumulating in end-stage renal disease as 4-pyridone-3-carboxamide ribonucleotide triphosphate (4PYTP), a nucleotide never described previously. Plasma tryptophan concentration has been previously reported to be reduced in patients in chronic renal failure that is in turn associated with elevated precursors of tryptophan metabolism, including L -kynurenine and quinolinic acid, both of which have been implicated in the neurotoxic manifestations of chronic renal failure. Here we compare mean erythrocyte 4PYTP, and plasma tryptophan concentrations, in controls and four patient groups with renal impairment (10 per group) and confirmed a reduction in plasma tryptophan in patients on dialysis that corrected with renal transplantation. We found: An inverse correlation between plasma tryptophan and red cell 4PYTP concentrations (R(2)=0.44, P<0.001) when all patients were grouped together. Restoration of both tryptophan and 4PYTP concentrations to control values was only achieved following renal transplantation. 4PYTP was absent from erythrocytes in Molybdenum cofactor (MoCF) deficiency implicating aldehyde oxidase/dehydrogenase, a Molybdenum requiring enzyme. High 4PYTP erythrocyte concentrations in adenine or hypoxanthine-phosphoribosyltransferase deficient patients in severe uremia (113 microM and 103 microM), confirmed the lack of involvement of either enzyme in 4PYTP formation. We propose that 4PYTP is formed by a novel route involving the oxidation of the intermediates of NAD turnover from quinolinic acid by aldehyde oxidase.
Abstract: Renal dysfunction is uncommon in patients with leukemic infiltration of the kidney due to Chronic Lymphocytic Leukanemia (CLL). Granulomatous interstitial nephritis (GIN) is also rare, but a characteristic hallmark of certain diseases such as sarcoidosis and tuberculosis. GIN has been associated with medications, infections, inflammation, Wegener's granulomatosis, and jejuno-ileal bypass. GIN combined with leukemic infiltration by CLL is very uncommon. We present a 72-year-old male with Binet stage A CLL who developed progressive renal failure over a period of four years requiring maintenance dialysis. During the course of his illness, he underwent renal biopsies at different time intervals, revealing varying degrees of involvement by GIN together with leukemic infiltration.
Abstract: Biopharmaceuticals have revolutionized the treatment and management of many diseases. The advent of recombinant erythropoietins has greatly benefited patients with anemia related to chronic kidney disease and cancer, virtually eliminating the need for blood transfusions. Currently, the patents for many biopharmaceutical molecules have expired or are approaching expiration and a number of biosimilars manufacturers are aiming to claim part of the market share. Unlike the situation for synthetic "small molecule" drugs, identical copies of far more complex biopharmaceuticals cannot be produced. A biopharmaceutical can be 100 to 1000 times larger than a synthetic chemical drug, with extremely complex three-dimensional structure and biological functions which are often not completely understood. Due to their nature and complexity, these fascinating therapeutic molecules are products of highly controlled biological processes. This review takes a look at how biosimilars are fundamentally different from their originator products by examining the biopharmaceutical production process and how it can influence the structure and function of the final drug product.
Abstract: Two organ recipients developed serologic evidence of syphilis infection after renal transplantation from a common deceased donor with a history of treated syphilis. Testing of donor serum for syphilis, which occurred after transplantation, gave results interpreted as consistent with past infection. However, subsequent serologic results in the recipients suggested transmission of infection at transplantation due to active infection of the donor. This may be explained by recent donor re-infection in view of the current syphilis epidemic in the United Kingdom. An initial error in the treatment of recipients further served to highlight unfamiliarity in managing this resurgent infection in the context of organ transplantation.
Abstract: Improvements in patient care and longevity on dialysis programmes together with the increased numbers of patients referred for renal replacement therapy will inevitably result in enlarging numbers of subjects with functioning renal transplants. While this translates to a boon for the patients in terms of survival and quality of life, a very real problem has begun to emerge, that of post-transplantation anaemia (PTA). The prevalence of this condition has been estimated by several studies as varying somewhere between one third and two thirds of all patients, with the same attendant problems as anaemia in the context of chronic kidney disease. PTA is multifactorial in origin and involves interplay between a number of risk factors, not least of all the immunosuppressive protocol. It is the purpose of this article to briefly review the contribution from transplant immunosuppression to PTA and to assess its likely effects on and treatment options for patients.
Abstract: AIMS/HYPOTHESIS: We investigated the relationship between haemoglobin (Hb) and diabetes in patients with renal disease. SUBJECTS, MATERIALS AND METHODS: All adult patients with stable chronic kidney disease attending renal or diabetic outpatient clinics in a six-month period were identified. Patients' notes and electronic patient records were used to build a comprehensive biochemical and clinical database. Results were analysed for the predictors of Hb, the severity of anaemia in both groups and the relative impact of diabetes on haemoglobin and anaemia. RESULTS: The study group consisted of 468 patients, of whom 204 had diabetes and 264 did not. At every level of renal function haemoglobin levels were lower by an average of 10 g/l in subjects with diabetes than in those without. Likewise, anaemia was found to occur at an earlier stage of chronic kidney disease (and to be of greater severity) in diabetic patients. Independent predictors of haemoglobin included female sex, diabetes, renal function and serum albumin, with diabetes and renal function being the greatest predictors. Multiple logistic regression showed that patients with diabetes had an odds ratio of 4 for being anaemic. Had we used an estimated GFR of less than 60 ml/min to trigger investigation of anaemia, we would have detected 85% of anaemic patients. CONCLUSIONS/INTERPRETATION: Anaemia is frequently found in diabetic patients with renal disease, occurs earlier and is more severe than in similar but non-diabetic subjects. In contrast to previous publications, our findings suggest that anaemia is prevalent at the earliest stages of chronic kidney disease. We advocate an estimated GFR threshold of <60 ml/min to trigger investigation for anaemia in diabetic subjects.
Abstract: BACKGROUND: Chronic kidney disease (CKD) patients have a 3-30-fold increased risk of death compared with the general population. This mortality difference is even more pronounced in younger subjects. Two markers of aortic stiffness--aortic pulse wave velocity (PWV) and augmentation index (AIx)--have been prospectively related to all-cause and cardiovascular (CV) mortality in end-stage renal disease (ESRD) populations. The aims of our study were first, to confirm the important deleterious effect of arterial stiffness in uraemia and second, to assess the impact on survival of increased AIx in a relatively young non-diabetic dialysis population, with minimal CV disease. METHODS: Ninety-two patients (mean age 42.6 +/- 11.2 years) were included in the study and followed for a period of 61 +/- 25 months. None of the patients had diabetes mellitus, and only 3.3% had prior history of CV disease. AIx was determined by applantation tonometry using a SphygmoCor device (AtCor, PWV Inc., Westmead, Sydney, Australia). RESULTS: Mean AIx in our study population was 19.9 +/- 13.7%; other significant haemodynamic parameters were: systolic blood pressure (SBP) 129 +/- 24 mmHg, pulse pressure 35.3 +/- 17.5 mmHg with 27.2% of the study population receiving angiotensin-converting enzyme inhibitors (ACE-I). On univariate analysis, in our group AIx correlated with: body weight (P < 0.001), radial SBP (P < 0.001) and haemoglobin levels (P < 0.05). There was no correlation between AIx and any of the echocardiographic parameters. In the stepwise multiple regression analysis, the only independent predictors for AIx were weight (P < 0.001), SBP (P < 0.001) and haemoglobin (P < 0.05) with the model explaining 33% of the AIx variability (adjusted R(2) = 0.33). During the follow-up period, 15 deaths were recorded. In the Cox analysis (P = 0.014; chi square 20.7 for the model) the only independent predictors for all-cause mortality were age (P = 0.001), left ventricular mass index (P = 0.032) and ACE-I therapy (P = 0.039) while AIx did not reach statistical significance. There was no difference in patients' survival when divided by AIx tertiles, assessed by the log rank test (P = 0.78). CONCLUSION: Our results fail to support the notion that an increased effect of wave reflections on central arteries is a strong and independent predictor of mortality in all ESRD patients on haemodialysis. The effect of arterial wave reflections might be in fact dependent on patient age and concurrent comorbidity status.
Abstract: BACKGROUND: The commonest cause of renal transplant loss is death with a functioning graft, usually from an excess of cardiovascular disease (CVD). Anaemia is becoming increasingly recognized as a reversible risk factor for the development of CVD. The purpose of this study was to estimate the prevalence of post-transplantation anaemia (PTA) in a large population of stable adult and paediatric renal transplants in one centre and to correlate the estimated glomerular filtration rate (eGFR), iron indices and the use of immunosuppressants with the prevalence of anaemia. METHODS: Every adult and paediatric patient with a functioning renal transplant and more than 3 months post-engraftment at Guy's hospital, London, as of 31 December 2004 and who had a valid creatinine and haemoglobin, in the period 1 September-31 December 2004 inclusive, was identified. A large database of clinical and biochemical indices was built up on the basis of medical notes and electronic patient records. Results were analysed for the prevalence of anaemia and risk factors for its development. Anaemia was defined according to the WHO criteria. All patients on treatment with an erythropoiesis stimulating agent were classified as anaemic, irrespective of haemoglobin. RESULTS: A total of 878 adults and 73 children were identified. Mean haemoglobin in adults was 12.9 +/- 1.6 g/dl and 11.8 +/- 1.4 g/dl in the children. Mean eGFR was 49.3 +/- 20.1 ml/min in adults and 65.7 +/- 18.8 ml/min in the paediatric cohort. Haemoglobin correlated positively with the eGFR in both cohorts (R = 0.33 and 0.29 in adults and children, respectively (P < 0.0001 for both)). We identified anaemia in 45.3% of adults and 22% in children. Ferritin levels were lower in children than in adults (79 +/- 93 vs 204 +/- 353 mg/l), but were higher in both cohorts among the non-anaemic populations than in those with anaemia. 58% of adults taking mycophenolate mofetil (MMF) were anaemic compared with 22% of children. One child, and 68 adults, were on recombinant erythropoietin. Multiple regression analyses identified age, female gender, eGFR and serum ferritin levels as independent predictors of haemoglobin in adult subjects. CONCLUSIONS: The prevalence of PTA was high in both adult and paediatric cohorts while comparatively few patients were being treated with erythropoiesis stimulating agents. The strongest predictors of haemoglobin in this cohort of patients were age, female sex and graft function. Immunosuppression including MMF or sirolimus was associated with a higher prevalence of anaemia, but this was likely to be the result of poorer graft function in these subjects. Iron deficiency did not seem to be a causative factor for anaemia in this population.
Abstract: In renal transplantation the calcineurin inhibitors (CNIs) have played a crucial role in the reduction in acute rejection rates. Unfortunately this has not been matched by an improvement in long-term graft survival rate. The development of chronic allograft nephropathy (CAN) is the second most common cause of graft loss, after death from cardiovascular causes. CAN has a multifactorial aetiology that includes immunological and nonimmunological factors relating to both donor and recipient. The use of CNIs has been strongly implicated as a risk factor for the development of CAN. With the ongoing development of new immunosuppressant agents the possibility of avoiding the CNIs now exists. Many studies have been designed to investigate strategies to minimise or avoid CNI exposure and to prolong graft survival. To achieve CNI withdrawal whilst avoiding rejection, additional immunosuppressants need to be substituted into the drug regimen. Long-term side effects of the immunosuppressant used need to be taken into account when drug changes are being considered. In light of current evidence, CNI reduction with optimal use of mycophenolate mofetil appears to be the most effective strategy in managing the patient with CAN.
Abstract: There is increasing evidence that even mild renal dysfunction is a novel potent cardiovascular risk factor in the general elderly population. With more severe renal impairment, cardiovascular risk increases proportionately. This issue deserves attention, as chronic kidney disease (CKD) is predominantly a disease of the elderly, and the mean age of end-stage renal disease patients entering dialysis is growing constantly. In the dialysis population, when clinically significant cardiovascular disease (CVD) (particularly congestive heart failure) is present, survival is worse. Thus, every effort should be made to identify and treat cardiovascular risk factor in the early stages of CKD. However, elderly renal patients receive less proper cardiovascular therapy compared to non-renal subjects of the same age. This review deals briefly with the most significant data published in the last decade on CVD in elderly with CKD.
Abstract: BACKGROUND: Measures of aortic stiffness--aortic pulse wave velocity (PWV) and augmentation index (AIx)--have been shown to be powerful predictors of survival in adult haemodialysis (HD) patients. Very few data have been reported regarding arterial stiffness in paediatric renal populations. METHODS: PWV and aortic AIx were determined from contour analysis of arterial waveforms recorded by applanation tonometry using a SphygmoCor device in 14 children on HD (age = 14.1 years) and in 15 age, height matched children controls. RESULTS: Pre-HD AIx (29.7 +/- 15.4%) and PWV (6.6 +/- 1.0 m/s) were significantly higher compared with children controls (8.3 +/- 8.0% and 5.4 +/- 0.6 m/s, respectively, P < 0.0001). The only significant difference between normal and HD children was BP level: 103/61 vs 114/72 mmHg, P < 0.05. In children of HD patients, a multiple linear regression model including BP, age, height, weight, Ca and P levels as independent variables accounted for 57% of the variability in AIx. Dialysis had no impact on AIx (post-HD: 28.5 +/- 12.7%) or on PWV (post-HD: 6.7 +/- 0.8 m/s). CONCLUSIONS: We show, in this first-ever report of increased arterial stiffness in children on dialysis, that end-stage renal disease is associated with abnormalities in arterial wall elastic properties, comparable with adult levels, even in childhood. Most importantly, the absence of a discernible amelioration with dialysis implies that purely structural and not functional alterations lie behind the increased arterial stiffness.
Abstract: Renal disease is rare today in classic adult gout, and gout is rare in renal disease--especially in the young. Here we summarise studies in 158 patients from 31 kindreds diagnosed with familial juvenile hyperuricaemic nephropathy FJHN from a total of 230 kindred members studied in Great Britain. Some patients have been followed for up to 30 years, and allopurinol has ameliorated the progression of the renal disease in all 113 surviving members provided: They have been diagnosed and treated sufficiently early.Compliance with allopurinol treatment and diet has been as important as early recognition.Hypertension has been rigorously controlled.The use of oral contraceptives has been avoided, as has pregnancy in any female with a Glomelar Filtration Rate GFR <70 ml/min.The question arising is: Why is FJHN the most prevalent genetic purine disorder diagnosed in Britain? Is it a lack of awareness which needs to be improved Europe-wide?
Abstract: BACKGROUND: Few studies have addressed the description of serial changes in left ventricular mass (LVM) and relevant risk factors. All these studies were initiated before the implementation of EBPG or K/DOQI guidelines. The aims of our study were to prospectively describe trends in left ventricular (LV) structure and function, evaluate risk factors for progression of LVM derived from serial echocardiographic measurements starting January 2003, 6 months after full implementation of EBPG in our unit. METHODS: One hundred seventy-six patients were enrolled at baseline, between 1 January 2003 and 1 October 2004; 33 patients were excluded from analysis due to poor echocardiographic window, 14 patients died and 26 were transplanted or transferred during the follow-up period of minimum 12 months. One hundred and three patients were included in the final analysis (mean age 51 years, mean follow-up 24.1 +/- 14.4 months). Echocardiography was performed at inclusion and at the end of study. Biochemical, blood pressure (BP) and medication data were collected and the means of monthly values were used. RESULTS: At baseline, 86.4% of the patients had left ventricular hypertrophy (LVH) (56.3% concentric hypertrophy, 30.1% eccentric hypertrophy, 6.8% concentric remodeling and only 6.8% normal LV geometry), 25.6% had systolic dy-sfunction and 50.5% had abnormal LV volume index (LVVI). Similar data were recorded at follow-up (82.5%, 44.7%, 37.9%, 7.7%, 9.7%, and 19.5%, respectively). Baseline left ventricular mass index (LVMI) significantly correlated with hemoglobin (Hb) and total protein level. LVMI at follow-up correlated to Hb, SBP, PP, mean level of serum phosphate, calcium x phosphate product and cholesterol. Independent predictors for LVMI (multiple regressions) were anemia and mineral metabolism markers. In our population, 62.1% of the patients had a regression of LVMI, with a mean decrease in LVMI of 12 g/m 2 (1.7 +/- 11.7 g/m 2 /month) over more than 12 months of guideline implementation. Regressors had a significant improvement of anemia, serum phosphate level and calcium x phosphate product (p<0.05). CONCLUSION: Our study suggests that a holistic interventional approach, targeting various pathogenic mechanisms, as per guidelines, can elicit at least a partial regression in LV structural and functional abnormalities in hemodialysis patients.
Abstract: BACKGROUND: Clopidogrel, in addition to aspirin, has become a common treatment of acute coronary syndrome and for stent thrombosis prevention, when given before percutaneous transluminal coronary angioplasty. However, some patients turn out to have surgical coronary artery disease and are sent for coronary artery bypass grafting (CABG) where the irreversible effect of aspirin and clopidogrel on platelet function becomes a concern. This study was conducted to evaluate the role of preoperative use of clopidogrel in bleeding complications after CABG. MATERIAL AND METHODS: A total of 462 patients who underwent CABG between 2001 and 2003 were studied as a retrospective cohort. Comparison was made between patients who had taken clopidogrel within 7 days of surgery (n=162), and those who were not exposed to clopidogrel (n=300). Chest tube output and bleeding index (a modified TIMI criteria), were the primary outcomes measured. RESULTS: Our data showed that patients taking clopidogrel within 7 days of surgery have a higher bleeding index than those who were not exposed to the drug (p = 0.024). Similarly, chest tube output was significantly higher in those who were exposed to clopidogrel within 7 days compared to those not taking clopidogrel (p = 0.01). To further dissect this relationship, we divided our population into three categories. We found that patients taking clopidogrel within 3 days prior to CABG (immediate exposure) have a higher bleeding index and TIMI major bleeding than either patients taking the drug between 3 and 7 days (recent exposure) or patients not exposed to clopidogrel at all (p = 0.009 and 0.03 respectively for inter-groups comparison). The same was true for chest tube output (p = 0.05 and 0.01 respectively). CONCLUSION: Clopidogrel increased the risk of post-CABG bleeding if taken within three days prior to surgery but not if taken before that.
Abstract: The availability of biopharmaceuticals has been increasing over the past decade and as their patents expire, the emergence of biosimilar agents approaches. The primary issue of concern for the safety of these agents is the potential for immunogenicity. Both product- and host-related factors have documented impact on the immune response, but many factors are still unknown. Although in many cases the presence of antibodies may have little clinical consequence, the upsurge of pure red cell aplasia cases further increased concerns about potential clinical consequences of extensive use of biopharmaceuticals and biosimilars. Available laboratory measurement methods are insufficient to predict biological and clinical properties of biopharmaceuticals, or even to compare their bioequivalence. Comparison of results from different studies is complicated by the variability of assay measurements, presentation of data and lack of standardization.
Abstract: Anemia in the setting of chronic kidney disease is a well-recognized phenomenon that is associated with decreasing renal function and deficiency of or resistance to erythropoietin. However, anemia in the post-renal transplantation setting has received comparatively less attention in the literature. In this review, we aim critically to appraise the available literature regarding posttransplantation anemia, concentrating in particular on the prevalence of posttransplantation anemia, its etiopathogenesis, potential effects on morbidity and mortality, and the rationale for intervention and treatment. Despite deficiencies in the literature, we conclude that posttransplantation anemia is a common phenomenon that can occur either early or late posttransplantation, and its causation is usually multifactorial and includes contributions notably from poor or decreasing renal function, immunosuppression, and iron deficiency. Conversely, there is a shortage of well-conducted prospective studies looking at the morbidity attributable to posttransplantation anemia and a lack of trial evidence to determine whether intervention improves patient morbidity and outcome.
Abstract: Increased aortic stiffness-measured as aortic augmentation index (AIx), a global stiffness marker-has emerged as a powerful predictor of survival in hemodialysis (HD). A single HD session is known to produce considerable improvement in aortic stiffness. We set out, for the first time, to examine the relative contributions to the post-HD drastic improvement in aortic stiffness of ultrafiltration rate and volume, or blood pressure (BP) changes. Aortic AIx (difference between the first and the second systolic peak of the aortic pressure waveform divided by pulse wave height) was determined hourly and recorded by applanation tonometry using a SphygmoCor device in 20 chronic HD patients (9 males, age 55.1 years). The other parameters recorded were: weight pre- and post-HD, ultrafiltration volume (UFV), hemoglobin, albumin, creatinine, urea reduction rate (URR), calcium and PTH, and BP. The dialysis significantly decreased AIx from 24.2+/-11.27% to 15.57+/-12.58% (p<0.05). In a univariate analysis, the intradialytic decrease in AIx (AIx 0-4) did not correlate with UFV, URR or with any of the biochemical markers. Significant correlations for AIx 0-4 were age (p=0.018), systolic blood pressure (SBP) at the beginning of HD (p=0.049), the intradialytic decrease in the SBP (p=0.001), and in pulse pressure (PP) (p=0.009). Multivariate stepwise regression showed that the decrease in SBP, PP, and intradialytic percentage reduction in weight explained 64.9% of the total variation in AIx 0-4. The decrease in SBP was the most important factor influencing the AIx variation (b=1.54, p=0.007). The most significant reduction in AIx was from the beginning of HD to the third hour (p=0.039), and correlated with the reduction in SBP (p=0.006) and PP (p=0.025) between the same moments. A single HD session produces a drastic improvement in aortic stiffness. The effect is not explained by the UFV depletion but is highly correlated with the decrease in SBP and PP. Further work is now needed to explore a potential role for endothelin and nitric oxide metabolism.
Abstract: According to recent data, arterial stiffness is a major independent risk factor for cardiovascular morbidity and mortality in both the general and renal populations. Because of several factors (vascular calcifications among them), large arteries are stiffer in patients with chronic kidney disease compared with the nonrenal population, contributing to the enormous cardiovascular mortality in renal patients. This review briefly analyzes methods for determination of arterial stiffness, focusing on 2 parameters, pulse wave velocity and the augmentation index, particularly useful in assessing arterial compliance in renal patients. Effects of different methods of renal replacement therapy on arterial wall properties also are discussed. Finally, the most promising novel and/or potential therapies regarding reduction of arterial stiffness in renal patients are reviewed.
Abstract: BACKGROUND: Chronic allograft nephropathy (CAN) is the most common cause of long-term renal-allograft dysfunction and the second most common cause of transplant loss. There are concerns that prolonged patient exposure to calcineurin inhibitors (CNIs) exacerbates or promotes the process of CAN. METHODS: In our unit, we carried out an observational study over the period 2000 to 2003 using low-dose mycophenolate mofetil (MMF) to facilitate a phased reduction in the dose of CNI in a group of patients with CAN. Low doses of MMF were chosen to minimize adverse effects and to reduce levels of CNIs without the attendant risks of under-immunosuppression. RESULTS: A step-wise reduction in mean reciprocalised creatinine was evident over the run-in period (mean 1/creatinine before MMF=0.005739-0.000083*month; R=0.77) with a step-wise monthly improvement postintroduction of MMF and dose reduction of CNI (mean 1/creatinine after MMF=0.004609+0.000049*month; R=0.74) (P<0.0001). The mean Cockroft-Gault estimated creatinine clearances were 47.1+/-24.2, 37.2+/-16.3, and 41.6+/-21.1 mL/min at time [t]=-12, t=0 and t=+12 months, respectively. Low-dose MMF therapy was well tolerated (only 7/89 patients stopped MMF because of side-effects in the first 12 months), and acute rejection was noted in only one patient. At latest follow-up, only 17 transplant losses had occurred, of which 6 patients had died with a functioning graft. CONCLUSIONS: Low-dose MMF was well tolerated and resulted in prolonged graft survival.
Abstract: BACKGROUND: CyA A (CyA) may induce intrarenal vasoconstriction, endothelial dysfunction, and hypertension. There are only two contradictory reports describing the acute effect of CyA on renal resistances measured by color Doppler flowmetry. Therefore, we studied the acute influence of oral CyA on arterial haemodynamics by assessing simultaneous changes in blood pressure, applanation tonometry-derived pulse wave analysis and duplex ultrasound-derived intrarenal resistance indices. METHODS: Augmentation index (AIx) (difference between the first and second systolic peak on the aortic pressure waveform divided by the pulse pressure = AIx) was determined from contour analysis of arterial waveforms recorded by applanation tonometry using the AtCor device in 18 live-related renal transplants (11 females/7 males, age = 32.0 +/- 8.1 years, transplantation duration = 17.5 +/- 16.1 months, and mean serum creatinine = 133 +/- 70 micromol/L). All studies were performed just before (C0), and 2 hours after (C2) the oral administration of CyA. At the same C0 and C2 moments the resistive index (RI) = (peak systolic frequency shift - minimum diastolic frequency shift)/peak systolic frequency shift, and pulsatility index (PI) = (peak systolic frequency shift - minimum diastolic frequency shift)/mean frequency shift were calculated from Doppler recorded waveforms. RESULTS: Blood pressure and heart rate did not differ significantly at C0 and at C2 serum levels: 134.3/82.9 vs. 128.1/80.0 mm Hg and 72.0 vs. 71.0 beats/min, respectively, despite a marked increase in whole blood concentration (CyA(C0)= 90.8 +/- 45.9 vs. CyA(C2)= 547.4 +/- 251.3 ng/mL) (P= 0.05). Mean AIx fell significantly from 17.2 +/- 13.8 to 12.9 +/- 14.2 (P < 0.0001). There was no correlation between the extent (expressed as absolute or relative change) of the measured alteration in AIx and total administered CyA dose, or increment in blood level between C0 and C2. In support, the intake of CyA did not induce a significant increase in Doppler resistance (RI(C0)= 0.68 +/- 0.08 vs. RI(C2)= 0.70 +/- 0.09) and pulsatility indices (PI(C0)= 1.32 +/- 0.31 vs. PI(C2)= 1.33 +/- 0.28). Finally, three patients were studied twice (>1 week): one under two levels of creatinine, one with no antihypertensives, and a third receiving verapamil initially. All these maintained a significant decrease in AIx at C2 from C0 supporting the reproducibility of the phenomenon. CONCLUSION: We demonstrate that Neoral CyA acutely improves large arterial compliance function and does not induce an acute rise in intrarenal resistance in stable renal transplant subjects with normal renal function. We speculate that there may be an effect of vitamin E, the diluent vehicle in which CyA is carried (1000 IU/100 mg CyA), shown to improve endothelial function.
Abstract: Development of microalbuminuria increases the risk for cardiovascular disease (CVD) in type 2 diabetes. The nature of this relationship is unclear but may involve arterial stiffness, an independent risk marker for CVD mortality. Aortic pulse wave velocity (Ao-PWV) and albumin creatinine ratio (ACR) were measured in 134 consecutive patients with type 2 diabetes without overt renal impairment (serum creatinine <150 micromol/L). ACR ranged from 0.2 to 153 mg/mmol. Patients with raised ACR (>/=3 mg/mmol) had higher Ao-PWV, poorer diabetic control, and higher pulse pressure (PP) and systolic BP (SBP) (all P < 0.05) than those with normal ACR. The closest univariate associations of Ao-PWV were positively with age, duration of diabetes, SBP, PP, ACR, and insulin treatment and negatively with GFR and weight (all P < 0.01). In a multiple linear step-down regression analysis, the significant predictors of Ao-PWV were age, SBP or PP, duration of diabetes, gender, number of antihypertensive medications, and use of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, which together explained 55% of the variance of Ao-PWV. When ACR was offered in place of arterial pressure to a separate model, ACR emerged as a significant predictor of Ao-PWV. After age adjustment, patients with lower, below median GFR had higher Ao-PWV than those with GFR above the median (P = 0.043). In patients with type 2 diabetes without overt renal impairment, raised ACR is associated with higher Ao-PWV, a relationship most likely mediated by raised BP. The association of Ao-PWV with reduced GFR suggests that even modest renal dysfunction may affect the viscoelastic properties of large arteries.
Abstract: OBJECTIVE: To report the largest single series of renal transplant patients (adults and children) with urolithiasis, assess the risk factors associated with urolithiasis in renal transplant recipients, and report the outcome of the multimodal management by endourological and open procedures. PATIENTS AND METHODS: The records of all patients undergoing renal transplantation between 1977 and 2003 were reviewed. In all, 2085 patients had a renal transplant at our centre and 21 (17 adults and four children) developed urinary tract calculi. Their mode of presentation, investigations, treatments, complications and outcomes were recorded. Investigations included one or more of the following; ultrasonography (US), plain abdominal X-ray, intravenous urography, nephrostogram and computed tomography. Management of these calculi involved extracorporeal shock wave lithotripsy (ESWL), flexible ureteroscopy and in situ lithotripsy, percutaneous nephrolithotomy (PCNL), open pyelolithotomy and open cystolitholapaxy. RESULTS: Thirteen patients had renal calculi, seven had ureteric calculi and one had bladder calculi. The incidence of urolithiasis was 21/2085 (1.01%) in the series. Urolithiasis was incidentally discovered on routine US in six patients, six presented with oliguria or anuria, including one with acute renal failure, four with a painful graft, three with haematuria, one with sepsis secondary to obstruction and infection and in one, urolithiasis was found after failure to remove a stent. Ten patients (63%) had an identifiable metabolic cause for urolithiasis, two by obstruction, two stent-related, one secondary to infection and in six no cause was identifiable. Thirteen required more than one treatment method; 13 (69%) were treated by ESWL, eight of whom required multiple sessions; eight required ureteric stent insertion before a second procedure and four required a nephrostomy tube to relieve obstruction. Two patients had flexible ureteroscopy and stone extraction, three had a PCNL and one had open cystolithotomy. PCNL failed in one patient who subsequently had successful open pyelolithotomy. All patients were rendered stone-free when different treatments were combined. CONCLUSIONS: The incidence of urolithiasis in renal transplant patients is low. There is a high incidence of metabolic causes and therefore renal transplant patients with urolithiasis should undergo comprehensive metabolic screening. Management of these patients requires a multidisciplinary approach by renal physicians, transplant surgeons and urologists.
Abstract: BACKGROUND: Increased aortic stiffness markers - aortic pulse wave velocity (PWV) and augmentation index (AIx) - are powerful predictors of survival in ESRD patients - well-recognized for the high prevalence of coronary artery disease (CAD) and unusually high PWV and AIx. Recently, decreased aortic compliance has been shown to be predictive of primary coronary events in hypertensive patients with normal renal function. We aimed to explore relationships between arterial stiffness and CAD in cohorts of patients with chronic kidney disease (CKD). METHODS AND RESULTS: 46 patients with chronic kidney disease (33 males, aged 55.7+/- 13.2 years, 20 on dialysis, 18 post renal transplantation, and 8 with glomerular filtration rate (GFR) between 10 and 25 ml/min) underwent coronary angiography for the assessment of CAD. PWV and aortic AIx were determined from pulse waveform analysis of arterial waveforms recorded by applanation tonometry using a SphygmoCortm device. The atherosclerosis burden score was calculated by adding the percentage luminal reduction of the most severe lesion in each artery. Patients with normal angiograms had significantly less arterial stiffness (as reflected by both a lower PWV=8.42+/-1.53 m/s and a lower AIx=17.9+/-5.55 %) compared with the 35 subjects with evidence of obstructive coronary disease at angiography (PWV=9.21+/-1.15 m/s and AIx=23.4+/-5.4 %, P<0.05 for both). Moreover, as more coronary vessels were affected, PWV and AIx increased proportionally. Based on receiver operating characteristics (ROC) curve analysis mean PWV levels showed an optimal cut-off point at 8.35 m/s (sensitivity=0.77; specificity=0.60), while mean AIx levels showed an optimal cut-off point at 17% (sensitivity=0.87; specificity=0.70). There was a statistically significant linear relationship between the atherosclerosis burden and both measures of arterial stiffness: PWV (r=0.31, p=0.007) and AIx (r=0.46, p=0.003). Independent predictors for the arterial stiffness parameters in this CKD population (multiple stepwise regression analysis) were age (r=0.69 for PWV and r=0.62 for AIx), and mean arterial pressure (MAP) (for AIx, p<0.0001). CONCLUSION: This study provides the first direct evidence in a cross-sectional investigation that PWV and AIx are related to the extent of coronary obstruction in CKD patients.
Abstract: BACKGROUND: Abnormalities of diurnal blood pressure (BP) rhythm ("nondipping") are well-described in dialysis patients, and have prognostic importance. It is controversial whether successful renal transplantation (RTx) improves diurnal BP rhythm. To date, no study has attempted to define and model the evolution of diurnal BP rhythm profiles from dialysis to engraftment, focusing on the immediate (4-6 weeks) and medium-term (>1 year) postengraftment periods. METHODS: To test if kidney transplantation normalizes the BP profile, ambulatory blood pressure monitoring (ABPM) was performed in 20 living related transplants (age, 30.3+/-5.1 years; 11 males, on dialysis for 25.6 months) 1 month preRTx and repeated 1 month and >1 year (ABPM3) after successful RTx. Dipping was defined as a sleep-to-awake ratio>0.92 (for systolic BP) and >0.90 (for diastolic BP). RESULTS: PreRTx only 15% patients were dippers. At 1 month postRTx (creatinine clearance, 65.8 ml/min), all patients were complete nondippers. However, after >1 year postRTx (creatinine clearance, 70.4 ml/min), 40% were now dippers. Most importantly, overall, 30% of the patients improved significantly their circadian rhythm (35.3% of the initial preRTx nondippers). Despite successful renal transplantation, 55% patients maintained unchanged their nondipping profile throughout all three ABPM recordings. The only determinants of "long-term" postRTx circadian rhythm are the contemporary level of the renal function and the baseline, dialysis dipping profile: SBP3 sleep-to-awake ratio is related with serum creatinine3 (r=0.58, P=0.001), creatinine clearance (r=-0.41, P=0.036) and SBP1 sleep-to-awake ratio (r=0.48, P=0.034); similarly DBP3 sleep-to-awake ratio is related with serum creatinine3 (r=0.63, P=0.001), creatinine clearance (r=-0.471, P=0.036) and SBP1 sleep-to-awake ratio (r=0.53, P=0.016). In all, 57% of the variance in dipping status can be attributed and explained by the contribution of renal function and initial circadian variability. CONCLUSIONS: Half of the nondipper dialysis patients maintain a permanently abnormal circadian rhythm, despite successful RTx. In the short term, RTx is associated with a highly abnormal diurnal profile, exclusively related to ciclosporin dose and levels. However, in the longer term, renal transplantation leads to a significant improvement of the circadian blood pressure profile, influenced by the renal function level and by the pretransplantation dipping profile.
Abstract: Given the potency of modern immunosuppressive agents, kidney transplantation across alloantingen barriers is a routine phenomenon with excellent 1-year graft survival in most centers. However, the improvement in 1-year graft survival has not been matched by improvements in long-term graft function and chronic allograft nephropathy (CAN) remains the second commonest cause of graft attrition over time. Calcineurin inhibitors, namely cyclosporine A (CyA) and tacrolimus, have been implicated as causal agents in the development of the fibrotic processes that are the hallmarks of CAN. Many studies have, therefore, concentrated on the improvement of long term graft function through the modulation of immunosuppressive therapy. It is the purpose of this review to describe and appraise the available evidence for the prevention and management of CAN through modulation of immunosuppressive agents.
Abstract: BACKGROUND: Accurate diagnosis of hypertension is essential in chronic kidney disease patients, as it is linked to increased left ventricular mass, stroke, cardiovascular mortality and morbidity, and progression to end-stage renal disease. Elevated blood pressure (BP) detected by ambulatory BP monitoring (ABPM) has been shown to be predictive of worse outcome in chronic kidney disease patients. Another predictor of worse outcome is diurnal BP variation, measured also by ABPM. In this study, the authors examined the relationship (concordance or discordance) between blood pressure measured by ABPM compared with daytime office BP, and also explored the predictors of diurnal variation in renal transplant recipients. METHODS: All the patients who underwent renal transplantation and follow-up at the authors' institution from January 1998 to January 2003 were involved in this study (n=177) in addition to another randomly selected 64 patients that underwent transplantation before 1998. All patients had their ABPM performed according to previously described protocols at least 2 weeks after discharge from the hospital, dialysis-independent and with a functioning renal allograft. RESULTS: The authors found a positive correlation between systolic BP (SBP) diurnal variation and age (r =0.263, P <0.0001), glomerular filtration rate (GFR) (r =-0.229, P <0.0001), cyclosporine trough (r =0.171, P =0.047), and ABPM-to-transplant interval (r =-0.133, P =0.039). After fitting a regression model, the authors found that only GFR (P <0.0001) and age (P =0.001) were independent predictors of SBP diurnal variation (r =0.357). Concordance rate between casual BP and ABPM was 80%, and by using casual BP, only 15% of hypertensive renal transplant patients would be erroneously diagnosed as normotensive. CONCLUSIONS: The authors found that SBP diurnal variation is predicted independently by age and GFR, although it does correlate with cyclosporine trough and ABPM-to-transplant interval. In addition, the authors showed that ABPM is a more sensitive method for diagnosing hypertension than is sole reliance on office BP in renal transplant recipients.
Abstract: A patient with isolated severe epistaxis and non-specific history or examination findings was shown to have anaemia, raised erythrocyte sedimentation rate (ESR), renal impairment and raised total protein with hypercoagulable blood. Waldenstrom's macroglobulinaemia was diagnosed after serum electrophoresis and bone marrow studies. Urgent plasma exchange and chemotherapy were undertaken to good effect. This case was a diagnostic dilemma, as the presentation of this common complaint did not initially suggest the rare underlying cause.
Abstract: BACKGROUND: Cardiovascular disease (CVD) is more common in patients with renal failure, even after renal transplantation. We wished to examine the relationship between markers of inflammation and CVD in stable renal transplant patients. METHODS: Ninety stable renal transplant outpatients with no recent illnesses or rejection were invited for study. Blood was drawn for a variety of inflammatory markers including total plasma sialic acid (SA) levels. RESULTS: Patients with CVD were significantly older than patients without (54 +/- 12 vs. 42 +/- 14 yr, p < 0.01) and had significantly lower total cholesterol (4.5 +/- 1.6 vs. 5.1 +/- 1.0 mmol/L, p < 0.01). Time from transplantation, present creatinine and blood pressure, smoking history were similar in both groups. Patients with CVD had significantly higher levels of SA (89.2 +/- 22.3 vs. 77.4 +/- 13.9 mg/dL, p = 0.01); fibrinogen [4.6 (2.2-6.7) vs. 3.6(1.9-5.7) g/L; p = 0.05); and C-reactive protein (CRP) [2.2 (1.5-8.0) vs 1.5 (0.7-3.0) microg/dL] than those without CVD. A logistic multiple linear regression analysis of the data with CVD as the dependent variable, and all the other parameters as independent variables, showed significant associations (F = 16.9; p < 0.001) with diastolic blood pressure (beta = 5.6; p = 0.02) and CRP (beta = 4.4; p = 0.04). CONCLUSIONS: This study suggests that inflammation is associated with a higher prevalence of cardiovascular disease in patients with renal allografts. The measurement of sialic acid as a risk factor may be superior to that of CRP in this group as its concentration is independent of renal function.
Abstract: Cardiovascular disease (CVD) is one of the major causes of mortality in patients with renal diseases, with increased odds ratio of mortality with risk factors as diverse as cholesterol, vascular stiffness, chronic inflammation and hyperhomocysteinemia. Several factors have been incriminated to explain the increase in coronary vascular calcification (CVC) in this particular population. Increased duration of dialysis, dyslipidemia, altered calcium-phosphorus metabolism, and chronic inflammation have all been associated with increased CVC. We present here four case reports illustrating the differences in the pathophysiology, therapy and prognosis of calcific coronary heart disease seen in uremic patients.
Abstract: BACKGROUND: Patients with end-stage renal disease (ESRD) are at increased risk of cardiovascular mortality and morbidity. Many complications arise in ESRD patients as a result of the twin arterial pathologies of atherosclerosis and arteriosclerosis. Part of this latter process is calcification of the arterial media, which is thought significantly to increase vascular stiffness. The aim of our study was to explore the relationship between measures of arterial stiffness-pulse wave velocity (PWV)-and the extent of calcification in the coronary arteries (CAC). METHODS: Over a period of 2 years 82 patients from our renal unit were invited to participate in our study. Sixty-two patients agreed to undergo electron beam computerized tomography (EBCT), and in 55 (38 males and 17 females), PWV measurements were made. EBCT and PWV measurements were done according to previously described protocols. RESULTS: The mean age of the 55 patients was 56.4 years. The mean duration of dialysis was 65.4 months, and the mean CAC score was 2551. The mean PWV was 9.13 m/s. PWV strongly correlated with total CAC even after correction for age, dialysis duration, and time averaged C-reactive protein (CRP) (P= 0.0001). CAC scores were significantly different when compared according to PWV tertiles (P= 0.0001). CONCLUSION: We have demonstrated that PWV is strongly related to the degree of EBCT-derived coronary artery calcium score in chronic kidney disease patients.
Abstract: BACKGROUND: Increased aortic stiffness markers--aortic pulse wave velocity (PWV) and augmentation index (AIx)--have emerged as powerful predictors of survival in haemodialysis (HD). Various and often contradictory abnormalities of endothelium-dependent (ED) and endothelium-independent (EID) vasomotor function, have been described in dialysis subjects, pre- and post-dialysis, using methods that are difficult to export to the clinical setting or to large prospective trials assessing their relevance. Therefore, we determined the influence of a HD session on PWV and the ED and EID vascular reactivity, employing pulse wave analysis (PWA) of the aortic waveforms, combined with provocative pharmacological stimuli known to reduce wave reflection. METHODS: PWV and aortic AIx (difference between the first and second systolic peak on the aortic pressure waveform divided by the pulse wave height) were determined from PWA of arterial waveforms recorded by applanation tonometry using a SphygmoCor device in 41 HD (20 males, age 41.8 years) and in 20 controls with essential hypertension (10 males, age 43.6 years). ED and EID vascular reactivity were assessed by changes in AIx following inhaled salbutamol and sublingual nitroglycerin (GTN), respectively, pre- and post-dialys
