Is hepatitis C more aggressive in renal transplant patients than in patients with end-stage renal disease?

BACKGROUND: The eventual impact of immunosuppression on the natural history of hepatitis C virus (HCV) infection in patients with end-stage renal disease (ESRD) is still unknown because of the lack of comparative data for HCV-infected patients with ESRD and renal transplant patients. The aim of this study was to compare the biochemical and histological characteristics of chronic HCV infection in renal transplants patients and ESRD patients undergoing hemodialysis. METHODS: Thirty-eight renal transplant patients and 38 ESRD patients undergoing hemodialysis who were chronically infected with HCV and were matched for gender, age at infection, and estimated time of infection were included in the study. The groups were compared regarding laboratory and histological variables. RESULTS: Renal transplant patients showed similar alanine aminotransferase and higher gamma-glutamyltransferase levels (P = 0.05) when compared with ESRD patients. Comparative analysis of histological variables revealed a higher proportion of cases with septal fibrosis (P = 0.04) and confluent necrosis (P = 0.01) among transplant-recipient patients. No difference between groups was observed regarding the intensity of portal and periportal inflammatory infiltrates. Steatosis was more prevalent among transplant-recipient patients (P < 0.001). There was no difference between groups regarding the prevalence of lymphoid aggregates or bile duct injury. CONCLUSION: Renal transplant patients had a larger proportion of cases with septal fibrosis and confluent necrosis than did ESRD patients, suggesting that renal transplantation might modify the natural history of hepatitis C in ESRD patients, leading to a more aggressive liver disease.     

Does renal failure cause an atherosclerotic milieu in patients with end-stage renal disease?

PURPOSE: Atherosclerotic vascular disease is the main cause of morbidity and mortality in patients with end-stage renal disease, but the independent contribution of renal failure rather than associated risk factors is unclear. We sought to examine the relative contribution of these factors to the severity of atherosclerosis by measuring intima-medial thickness and brachial artery reactivity in uremic patients and controls. SUBJECTS AND METHODS: Cardiovascular risk factors, including lipid and homocysteine levels, were evaluated in 213 patients (69 on hemodialysis, 60 on peritoneal dialysis, and 82 nonuremic controls). High-resolution B-mode ultrasonography with automated off-line analysis was used to measure the intima-medial thickness in the common carotid artery and to measure the lumen diameter of the brachial artery at rest, during reactive hyperemia, and after sublingual nitroglycerine. The correlations of risk factors with intima-medial thickness and brachial reactivity were examined using a general linear regression model. RESULTS: Patients with renal failure had a greater mean (+/- SEM) maximum intima-medial thickness than controls (0.83 +/- 0.02 mm versus 0.70 +/- 0.02 mm, P < 0.05), but the brachial artery response to reactive hyperemia was not significantly different between the renal failure patients and the control group (4.7% +/- 6.1% versus 6.1% +/- 8.6% dilatation, P > 0.05). The uremic state was an independent predictor of intima-medial thickness (r2 = 0.16, P < 0.001) but not of brachial artery reactivity (P = 0.99). CONCLUSION: The atherosclerotic burden in patients with renal failure, as indicated by an increased intima-medial thickness, may reflect effects of uremia that are independent of cardiovascular risk factors.     

Who does not need a statin: too late in end-stage renal disease or heart failure?

Current guidelines from large randomised trials recommend that all patients with diabetes type 2 or coronary artery disease after myocardial infarction should be treated with statin drugs. However, the recent 4D and CORONA trials show no improvement in mortality in elderly patients with ischaemic heart failure and patients with diabetes and end-stage renal disease receiving haemodialysis with the onset of statin treatment. The survival benefit from statin treatment appears to stem primarily from the prevention of progression of coronary artery disease. In clinical conditions where coronary artery disease does not significantly contribute to the cause of death statins seem to be less effective. In patients at risk for organ damage, statin treatment, therefore, has to be started early in the course of the disease. The effect of statin withdrawal in ischaemic heart failure or in patients with advanced renal disease is not known. On the basis of the available evidence, current statin treatment should not be stopped in these patients.     

Cardiac calcification in adult hemodialysis patients. A link between end-stage renal disease and cardiovascular disease?

OBJECTIVES: We sought to determine clinical and laboratory correlates of calcification of the coronary arteries (CAs), aorta and mitral and aortic valves in adult subjects with end-stage renal disease (ESRD) receiving hemodialysis. BACKGROUND: Vascular calcification is known to be a risk factor for ischemic heart disease in non-uremic individuals. Patients with ESRD experience accelerated vascular calcification, due at least in part to dysregulation of mineral metabolism. Clinical correlates of the extent of calcification in ESRD have not been identified. Moreover, the clinical relevance of calcification as measured by electron-beam tomography (EBT) has not been determined in the ESRD population. METHODS: We conducted a cross-sectional analysis of 205 maintenance hemodialysis patients who received baseline EBT for evaluation of vascular and valvular calcification. We compared subjects with and without clinical evidence of atherosclerotic vascular disease and determined correlates of the extent of vascular and valvular calcification using multivariable linear regression and proportional odds logistic regression analyses. RESULTS: The median coronary artery calcium score was 595 (interquartile range, 76 to 1,600), values consistent with a high risk of obstructive coronary artery disease in the general population. The CA calcium scores were directly related to the prevalence of myocardial infarction (p < 0.0001) and angina (p < 0.0001), and the aortic calcium scores were directly related to the prevalence of claudication (p = 0.001) and aortic aneurysm (p = 0.02). The extent of coronary calcification was more pronounced with older age, male gender, white race, diabetes, longer dialysis vintage and higher serum concentrations of calcium and phosphorus. Total cholesterol (and high-density lipoprotein and low-density lipoprotein subfractions), triglycerides, hemoglobin and albumin were not significantly related to the extent of CA calcification. Only dialysis vintage was significantly associated with the prevalence of valvular calcification. CONCLUSIONS: Coronary artery calcification is common, severe and significantly associated with ischemic cardiovascular disease in adult ESRD patients. The dysregulation of mineral metabolism in ESRD may influence vascular calcification risk.     

Trace elements in end-stage renal disease – unfamiliar territory to be revealed

Although associated with unfavorable outcomes in the general population, abnormal blood levels of various trace elements have not been consistently studied in the end-stage renal disease population (with the notable exception of aluminum). This is surprising, as the uremic patient treated by chronic dialysis loses one major route of trace element excretion and is exposed systematically to a foreign environment (the dialysis fluid) possibly contaminated with significant amounts of potential deleterious trace elements. Moreover, some biological important trace elements may be lost through the dialysis membrane. Most studies to date demonstrated significantly altered blood levels of trace elements in ESRD patients compared to healthy controls. However, the biological impact of these abnormalities in renal disease is largely unknown and should be clarified by future studies. A further step would be the design of well-controlled randomized interventional studies, examining the potential therapeutic benefit of supplementing one or more trace elements in ESRD patients, a population characterized by an impressive mortality due to cardiovascular, infectious and neoplasic disease.     

Cholesterol in end-stage renal disease: the good, the bad or the ugly?

The incidence of cardiovascular disease is markedly increased in patients with end-stage renal disease (ESRD). High serum cholesterol is widely recognised as a cardiovascular risk factor in the general population. However, in patients with ESRD high concentrations of cholesterol are associated with a better survival. This reverse epidemiology is, amongst others, caused by confounding due to malnutrition and chronic inflammation. In this population, treatment with statins to lower the serum cholesterol remains a matter of debate. In ESRD, LDL cholesterol is modified by increased oxidative stress. These altered LDL particles play a pivotal role in the development of atherosclerosis. Treatment with the antioxidant vitamin E has not equivocally been shown to be beneficial in this population. This review tries to put data from literature on dyslipidaemia and oxidative stress in ESRD in perspective.     

Long-term blood pressure monitoring and echocardiographic findings in patients with end-stage renal disease: reverse epidemiology explained?

BACKGROUND: In patients with end-stage renal disease (ESRD) hypertension is common and often leads to left ventricular (LV) hypertrophy and diastolic dysfunction, but hypotension at the onset of dialysis is associated with increased mortality. We studied blood pressure data over longer periods of time in patients on haemodialysis and related them to echocardiographic outcome, in order to elucidate these contradictory findings. METHODS: In 50 haemodialysis patients mean arterial pressure (MAP) and pulse pressure (PP) were calculated in the first three months of haemodialysis, the complete period from the start of haemodialysis until echocardiography and the last three months of haemodialysis before echocardiography. Hypertension load, pulse pressure and interdialytic weight gain were quantified and related to echocardiography. RESULTS: LV mass index was associated with MAP in all three periods, and also with the hypertension load, PP and PP load. In patients with LV dilatation, MAP and PP averaged over the complete period of dialysis were 5 to 7 mmHg higher than in patients without LV dilatation. Blood pressure parameters were the same in patients with or without LV diastolic dysfunction or systolic dysfunction. Systolic dysfunction was more frequent in patients undergoing long-term haemodialysis treatment. Interdialytic weight gain was not associated with any of the echocardiographic variables. CONCLUSION: When long-term blood pressure values are considered, hypertension is associated with parameters of early cardiac damage such as increased LV mass index and not with parameters of advanced heart failure such as systolic dysfunction. This supports the hypothesis that the presence of advanced heart failure reciprocally influences blood pressure in a negative way, thereby explaining the 'reverse epidemiology' of blood pressure and mortality in ESRD.     

Is endovascular revascularisation worthwhile in diabetic patients with critical limb ischemia who also have end-stage renal disease?

To present the outcomes of endovascular treatment of diabetics patients with critical limb ischemia who have end-stage renal disease. Limb-salvage was achieved in 58.6% of the limbs during a mean follow-up period of 12.4 months. No major amputations were required on patients with rest pain or with grade 1 lesions.     

Outcomes in ANCA-associated vasculitis patients with end-stage kidney disease on renal replacement therapy—A meta-analysis

BackgroundEnd-stage kidney disease (ESKD) is associated with poor prognosis in patients with anti-neutrophilic cytoplasmic antibody (ANCA)-associated vasculitis (AAV). This study summarizes the existing evidence regarding outcomes in AAV patients with ESKD on renal replacement therapy.MethodsSearches of the MEDLINE and Embase databases were performed from inception until December 2021. Any study reporting outcomes after ESKD in patients with AAV on haemodialysis or peritoneal dialysis was included. The mortality rate per 100 person-years (100 py) calculated with a random-effects meta-analysis model was the primary outcome. Rates of infections and relapses were secondary outcomes.Results2470 citations were found; 22 studies of 952 adult patients with over 3600 person-years of follow-up were included. The pooled mortality rate was 10.90 per 100 py (95% CI: 7.11 - 14.68, I² = 90.8%). The pooled 1-year survival was 80.9% (95% CI: 75.6 – 86.1%, I² = 86.1%) while the pooled 5-year survival was 61.0% (95% CI: 46.0 – 76.0%, I² = 0.0%). The pooled severe infection rate was 66.57 per 100 py (95% CI: 13.64 – 119.50, I² = 99.6%). The pooled relapse rate was 6.22 per 100 py (95% CI: 4.64 - 7.80, I² = 46.6%). Only 1 paediatric study met the inclusion criteria and reported a mortality rate of 11.7 ± 1.9 deaths per 100 py (95% CI: 0.23 – 23.20) amongst 9 patients.ConclusionsPatients with AAV and ESKD have a lower risk of relapse, but higher infection and mortality rates. More prospective research exploring the role of immunosuppression after ESKD is needed.     

Statin therapy in renal disease: Harmful or protective?

Chronic kidney disease (CKD) creates one of the highest-risk atherosclerotic states that can occur in human beings. The use of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) has gained widespread acceptance in the general population for the purposes of lowering low-density lipoprotein cholesterol (LDL-C) and reducing the future risks of myocardial infarction, stroke, and cardiac death. In patients with CKD, these benefits are believed to be enjoyed to the same or greater degrees. Reductions in LDL-C with statins may be associated with a reduced progression of CKD. Importantly, recent studies suggest statins are associated with a reduction in rates of acute renal failure after cardiopulmonary bypass surgery and exposure to iodinated contrast. In patients with end-stage renal disease (ESRD), recent data suggest that the annual rate of coronary artery calcification can be attenuated or reduced with LDL-C reduction. However, two large trials demonstrating LDL-C reduction with statins and with these drugs have failed to demonstrate a reduction in cardiovascular events in ESRD. Thus, the potential benefits of statins and LDL-C reduction in CKD have to be considered in light of evidence suggesting a reduced benefit if any, in patients with ESRD. In addition, studies suggest that there are higher adverse drug effects with statins in CKD.     

Statin therapy in renal disease: Harmful or protective?

Chronic kidney disease (CKD) creates one of the highest-risk atherosclerotic states that can occur in human beings. The use of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) has gained widespread acceptance in the general population for the purposes of lowering low-density lipoprotein cholesterol (LDL-C) and reducing the future risks of myocardial infarction, stroke, and cardiac death. In patients with CKD, these benefits are believed to be enjoyed to the same or greater degrees. Reductions in LDL-C with statins may be associated with a reduced progression of CKD. Importantly, recent studies suggest statins are associated with a reduction in rates of acute renal failure after cardiopulmonary bypass surgery and exposure to iodinated contrast. In patients with end-stage renal disease (ESRD), recent data suggest that the annual rate of coronary artery calcification can be attenuated or reduced with LDL-C reduction. However, two large trials demonstrating LDL-C reduction with statins and with these drugs have failed to demonstrate a reduction in cardiovascular events in ESRD. Thus, the potential benefits of statins and LDL-C reduction in CKD have to be considered in light of evidence suggesting a reduced benefit, if any, in patients with ESRD. In addition, studies suggest that there are higher adverse drug effects with statins in CKD.     

C-reactive protein in end-stage renal disease: are there reasons to measure it?

Cardiovascular disease (CVD) remains the major cause of morbidity and mortality in end-stage renal disease (ESRD) patients. As traditional risk factors cannot alone explain the unacceptable high prevalence and incidence of CVD in this population, inflammation (a common phenomenon in ESRD), and other non-traditional risk factors are likely to contribute. Among several inflammatory biomarkers used to assess inflammation, high-sensitivity C-reactive protein (hs-CRP) has attracted the most interest. Indeed, in the general population the consistency of prognostic data for hs-CRP and the practicality of its use have led to suggestions that CRP should be used as a clinical criterion for global cardiovascular risk prediction. As CRP is so strongly associated with vascular disease, it has been suggested that this protein is not only a marker, but also a mediator, of atherogenesis. Indeed, recent in vitro data from studies on endothelial cells, monocytes-macrophages and smooth muscle cells support a direct role for CRP in atherogenesis. In ESRD, hs-CRP has been proven to be a strong predictor of both cardiovascular and all-cause mortality, and associated with oxidative stress, vascular calcification and endothelial dysfunction. As recent studies suggest that interleukin-6 may be a somewhat better outcome predictor than hs-CRP, comparative studies are needed to evaluate which inflammation biomarker is the most cost-effective predictor of outcome in the ESRD patient population.     

Is it necessary to treat Helicobacter pylori infection in patients with end-stage renal failure and in renal transplant recipients?

Uraemic patients frequently complain of gastrointestinal ailments. There are a lot of factors responsible for the occurrence of these symptoms. It is considered--among other things--that high level of urea in gastric juice and hypergastrinaemia contribute to the damage of stomach and duodenum mucosa. Does H. pylori infection also produce pathological changes within upper gastrointestinal tract in these patients? The aim of the study was to determine the prevalence of H. pylori infection and macroscopic and microscopic estimation of oesophagus, stomach and duodenum mucosa in haemodialysis patients and renal transplant recipients. A total of 39 patients were taken under investigation: 27 among them were treated with haemodialyses and 12 were after kidney transplantation. In all patients upper gastrointestinal endoscopies were performed with collection of biopsy specimens for histological analysis and a urease test. Serological examinations were carried out in order to detect anti-CagA H. pylori antibody. In summary, we found that prevalence of H. pylori infection in uremic patients on chronic haemodialysis and renal transplant recipients was significantly lower than that in patients with normal renal function. This may be a consequence of medication and/or protection by a high urea concentration. Elevated blood urea seems to correlate with a high prevalence of gastroduodenal mucosal lesions.     

The prevalence of colorectal neoplasia in patients with end-stage renal disease: a case–control study

BACKGROUND AND PURPOSE: The scarcity of organs for transplantation has led to aggressive pretransplant evaluations. Many younger kidney transplant patients with end-stage renal disease, who would be ordinarily at average risk for colorectal cancer, undergo screening colonoscopy as part of this evaluation. The purpose of this study was to determine the prevalence of colorectal neoplasia in patients with end-stage renal disease who are potential transplant candidates. MATERIALS AND METHODS: We performed a retrospective chart review analysis on 57 kidney transplant candidates who underwent pretransplant screening colonoscopy between August 1999 and December 2004. The control group was comprised of 60 age- and gender-matched subjects without end-stage renal disease who underwent routine screening colonoscopy. RESULTS: The prevalence of polyps in end-stage renal disease patients was 37 vs 22% in the control group (p = 0.07, not significant). None of the risk factors studied were found to predict the presence of polyps in the study group. CONCLUSION: These results suggest that screening guidelines for colorectal cancer for the general population should be adequate for potential kidney transplant recipients.