Resolution of low-grade proteinuria is associated with improved outcomes after renal transplantation-a retrospective longitudinal study.

Low-grade proteinuria and systolic hypertension (SHT) are risk factors for allograft failure. Both are dynamic variables and their relationship is not independent. We have simultaneously analyzed the effects of proteinuria and SHT on graft outcomes in 805 adult Kidney Transplant Recipients and impact of their changes over time. Proteinuria and systolic blood pressure (SBP) were recorded for years 1 and 3 posttransplantation. Subjects with proteinuria >1 g/day were excluded. Patients were divided into groups based on proteinuria (Absent(A) <150 mg/day or low-grade(P)150 mg-1 g/day) and blood pressure (Normotensive-SBP <140 mmHg or hypertensive-SBP ≥ 140 mmHg). Graft survival was assessed in all four groups over 10 years by multivariate analysis. At the three annual time points (Year 1, 2 and 3) hypertensive patients with proteinuria had the worst graft survival. Patients with persistent proteinuria between years 1-2 and 2-3 had the poorest graft survival with an improvement if proteinuria regressed (P-A), especially in the Hypertensive group. The impact of proteinuria was highest in persistently hypertensive patients between years 1-3. Thus both proteinuria and SHT were associated with poor graft survival and the combination of the two led to the worst outcomes. Importantly, SHT was associated with significantly worse outcomes in patients with proteinuria. Patient cohort with SHT and low-grade proteinuria represent a selective group that might benefit from intervention.

Impact of cold ischemia on renal transplant outcomes following donation after cardiac death.

Donation after cardiac death (DCD) provides grafts in renal transplantation but is associated with increased early graft dysfunction. Cold ischemia time (CIT) is a factor that is thought to affect outcomes in renal transplantation. We sought to assess the impact of the length of CIT among our DCD cohort of renal transplants performed between April 2002 and December 2009. Since the median CIT was 15.5 hours, we formed two groups CIT < 15.5 (n = 100) and CIT > 15.5 hr (n = 98). We demonstrated an increased incidence of DGF among the extended CIT group, but the long outcomes and the mean graft function were otherwise comparable. In conclusion, CIT affects early graft function; every effort should be made to minimize it in renal transplantation using DCD kidneys.

Soluble CD30 as a prognostic factor for outcome following renal transplantation.

AIMS: To determine whether measurement of soluble CD30 (sCD30) levels predicts for early rejection in a cohort of first deceased kidney transplant recipients. METHODS: Pre-transplant serum samples were analysed for sCD30 levels using a commercial ELISA kit (Biotest). A 100 U/ml cut-off for "high sCD30" was applied. Clinical outcome parameters were biopsy-proven rejection episodes, creatinine levels and glomerular filtration rate. RESULTS: In the cohort of patients who experienced at least one episode of rejection in the first 6 months post-transplant, levels of pre-transplant sCD30 were significantly higher than in those who did not experience rejection. Despite this association, the occurrence of a high sCD30 level did not predict for rejection on an individual basis. CONCLUSIONS: The prognostic value of pre-transplant sCD30 testing is diminished by the large number of patients with high sCD30 levels who do not develop rejection. Although this limits the utility of the test in informing clinical management of individual patients, a high pre-transplant sCD30 level should still be considered a risk factor for poorer outcome.

Ureteric complications of renal transplantation: the impact of the double J stent and the anterior extravesical ureteroneocystostomy.

The urological complications of renal transplantation are well documented. In 1990, our experience of 507 consecutive renal transplants using the Leadbetter-Politano technique, which was unsplinted in the vast majority of patients, had a ureteric complication rate of 7.7%. Here, we report the long-term incidence and management of our ureteric complications in 1186 consecutive renal transplants done over the following 11 years using an extravesical onlay stented ureteroneocystostomy. We report a considerable reduction in the urological complications of renal transplantation to 3.8%. Furthermore, we were able to use percutaneous radiological techniques to salvage the majority (84.7%) of ureteric complications. Recourse to surgery was required rarely but enabled salvage of all treatment failures.

Compliance of renal transplant recipients with advice about sun protection measures: completing the audit cycle.

Renal transplant recipients are at increased risk for development of nonmelanoma skin carcinoma, owing to a number of causes, including ultraviolet exposure. It has been shown that, despite education, there is poor compliance by these patients with the advice given for protecting their skin from the sun. This repeat study was conducted to determine whether there had been an improvement in compliance over the last 6 years. Two hundred twenty-seven patients were invited to complete the questionnaire used in the previous study. This questionnaire was designed to establish whether patients understood the need for extra care, whether they recalled any education about protective measures, and what actual measures were taken. There was a significant increase in the proportion of patients taking appropriate precautions. Hence there has been a significant improvement in the compliance of renal transplant recipients in Yorkshire with skin protection measures since this was originally audited in 1998.

Influence of recipient and donor IL-1alpha, IL-4, and TNFalpha genotypes on the incidence of acute renal allograft rejection.

AIMS: To determine whether polymorphisms of the genes encoding donor or recipient interleukin 1alpha (IL-1alpha), tumour necrosis factor alpha (TNFalpha), or IL-4 have any impact on the incidence of acute rejection after renal transplantation. METHODS: All donors and recipients were genotyped for three polymorphisms in the three cytokine genes: IL1A -889, TNFA -308, and IL4 -590. RESULTS: Statistical analysis of the data obtained revealed no association between the cytokine gene polymorphisms tested and the incidence of post-transplant acute rejection. After stratification for human leucocyte antigen (HLA) matching, it was found that kidneys from donors positive for the TNFA-A allele had a significantly increased incidence of acute rejection in HLA-DR mismatched transplants. CONCLUSIONS: This finding argues for prospective TNFA genotyping of renal donors, with avoidance of allocation of kidneys from donors positive for the TNFA-A allele to HLA-DR mismatched recipients.

Specialist follow up of patients before end stage renal failure and its relationship to survival on dialysis.

The high mortality rate of patients with end stage renal failure (ESRF) treated by dialysis is determined principally by irreversible factors such as age and comorbidity. In this single centre retrospective study of all 1260 ESRF patients who started dialysis between 1980 and 1999 it has been demonstrated that a short duration of specialist predialysis follow up is associated with a worse long term outcome on dialysis. Kaplan-Meier survival curves were plotted according to duration of predialysis follow up (group A, < or = 90 days; group B > 90 days), censoring for first transplant, and compared using a log rank test. Differences between groups were examined using an unpaired t test. Cox regression analysis was performed to examine the influence of selected variables on survival. Group A had the worst mortality (survival proportions of 87%, 74%, and 31% in A and 94%, 87%, and 55% in B at four months, one year, and five years respectively, p < 0.001). The increased risk of death was seen principally during the first few months of dialysis. ESRF associated with systemic disease was more prevalent in A. There were small but significant differences in predialysis clinical data, including age and serum albumin (p < 0.001). Fewer patients in A were suitable for transplant listing (p < 0.01). In the regression analysis, age, diabetes, predialysis serum albumin, suitability for transplant work-up and listing ("transplantability"), and the interval between referral and dialysis were significant predictors of survival. In summary, this study strengthens the previously reported association between late referral of ESRF patients and subsequent poor survival on dialysis. This important message is relevant to all potential referring physicians.

A randomized study of oral vs intravenous iron supplementation in patients with progressive renal insufficiency treated with erythropoietin.

BACKGROUND: Correction of anaemia as a result of renal failure improves cardiovascular function and also provides significant cognitive and emotional benefits. The most appropriate route for iron supplementation has not been determined for patients with chronic renal failure who are not yet on dialysis. METHODS: Forty-five anaemic patients with progressive renal insufficiency (PRI) were prospectively randomized to receive oral (ferrous sulphate 200 mg tds) or intravenous (300 mg iron sucrose monthly) iron treatment. Erythropoietin (rHuEpo) was simultaneously commenced and the dose adjusted according to a pre-established protocol. RESULTS: There were no significant differences in baseline patient characteristics between the two groups. The average follow-up was 5.2 months. Three patients suffered possible allergic reactions to iron sucrose. Haemoglobin response and changes in red cell hypochromasia were similar in the two groups, but serum ferritin was significantly higher in the intravenous group. The starting dose of rHuEpo could be temporarily discontinued in 43% of patients on oral iron and 33% of patients receiving iron sucrose (NS). rHuEpo was increased after 3 months in 9% of patients on oral iron and 19% of patients receiving iron sucrose (NS). Final doses of rHuEpo were 33.5 (0-66) and 41.6 (0-124) U/kg/week respectively in the oral and intravenous groups (NS). Although gastro-intestinal symptoms were more commonly reported in patients taking oral iron, these were mild according to scores on visual analogue scales. Dietary protein and energy intake were not significantly different in the two groups at 0, 3 and 6 months. CONCLUSIONS: In pre-dialysis patients, the efficacy of monthly 300 mg iron sucrose given intravenously is not superior with regard to haemoglobin response and rHuEpo dose as compared with a daily oral dose of 600 mg of ferrous sulphate or equivalent. Where intravenous iron is preferred, lower doses may help to reduce the incidence of allergic or "free iron" reactions, especially in patients with low body mass.

Ondansetron therapy for uremic pruritus in hemodialysis patients.

Pruritus is a distressing symptom affecting up to 90% of dialysis patients. Conventional treatment with antihistamines is often ineffective and may have unacceptable side effects. Serotonin (5-hydroxytryptamine type 3 [5-HT(3)]) is known to enhance pain perception and pruritic symptoms through receptors on sensory nerve endings. Antagonism of 5-HT(3) receptors may be of use in treating uremic pruritus. We randomly assigned 16 hemodialysis patients with persistent pruritus to treatment with the 5-HT(3)-receptor antagonist, ondansetron (8 mg), or placebo three times daily for 2 weeks each in a prospective, placebo-controlled, double-blind crossover study. Patients scored their intensity of pruritus daily on a 0-to-10 visual analogue scale (0 = no pruritus, 10 = maximal pruritus), and daily use of antihistamines as escape medication was recorded. The median daily pruritus score did not change significantly during active or placebo treatment (preondansetron, 5. 3; interquartile range [IQR], 3.4 to 6.3; during ondansetron, 3.9; IQR, 2.7 to 5.0; P = not significant; preplacebo, 3.7; IQR, 3.0 to 4. 6; during placebo, 3.6; IQR, 2.4 to 4.8; P = not significant). The median daily percentage of escape medication use decreased from 21% (IQR, 9 to 61) to 9% (IQR, 0 to 33) with ondansetron (P = not significant) and from 53% (IQR, 0 to 88) to 5% (IQR, 0 to 31) with placebo (P = not significant). There was no difference in predialysis biochemistry test results or dialysis efficacy during treatment phases. Ondansetron does not improve pruritus in hemodialysis patients. Use of antihistamines decreased with both ondansetron and placebo.

Percentage hypochromic red cells and the response to intravenous iron therapy in anaemic haemodialysis patients.

INTRODUCTION: Iron deficiency is commonly encountered in haemodialysis (HD) patients and may be overcome by i.v. iron therapy. We have examined the percentage hypochromic red cells (%HRC) for predicting response to i.v. iron in subjects with a low serum ferritin. METHODS: Prospective study of i.v. iron saccharate (trivalent iron 200 mg/week for 8 weeks) in anaemic (Hb < 10 g/dl) HD patients with serum ferritin < 100 microg/l despite oral iron therapy. Response to i.v. iron was assessed by comparing Hb at 0 and 8 weeks according to %HRC at baseline (0-3%, 4-9%, > or = 10%). Results are mean+/-1 SD. RESULTS: For all subjects (n=82), Hb and ferritin increased between 0 and 8 weeks (8.9+/-1.0 to 10.1+/-1.4, P<0.0001; 55+/-24 to 288+/-126, P<0.0001). Patients were stratified into three groups according to %HRC at baseline (0-3%, 4-9%, > or = 10%). Hb increased significantly in all three groups. The mean increase in Hb was greater (0-3%, 0.6+/-1.2; 4-9%, 1.2+/-1.0; > or = 10%, 1.6+/-1.4; P=0.02) and the proportion of patients showing a > or = 1 g/dl increase in Hb was greater (0-3%, 27%; 4-9%, 57%; > or = 10%, 67%; P=0.02) in those with the largest %HRC pre-treatment. CONCLUSION: Intravenous iron therapy is effective in improving Hb in anaemic HD patients with a low ferritin. However, the magnitude of this response and the proportion of patients responding is related to the percentage hypochromic red cells prior to treatment.

Hemodynamics and survival of patients with acute renal failure treated by continuous dialysis with two synthetic membranes.

Synthetic membranes are not identical and have specific interactions that may be harmful or beneficial. We have investigated the incidence of hypotension and the outcome of acute renal failure (ARF) in ventilated patients treated by continuous venovenous dialysis with 2 different synthetic membranes. In Study 1, the mean arterial pressure (MAP) and systemic vascular resistance (SVR) were monitored during the first 12 min of dialysis with polyacrylonitrile (PAN). In Study 2, the MAP and survival rates were compared in patients randomly assigned to either PAN or polysulfone. No subjects were receiving angiotensin converting enzyme inhibitors. In Study 1, the MAP decreased due to a reduction in the SVR during the first 6 min of dialysis but returned to the baseline value by 12 min in 22 patients during 27 dialysis treatments. In Study 2, the MAP was lower than the baseline value at 6 min during 233 dialysis treatments in 133 patients randomly assigned to PAN or polysulfone membranes (PAN group, 81.5 +/- 15 to 78.7 +/- 15.6 mm Hg, p = 0.001; and polysulfone group, 81.3 +/- 15.4 to 80.0 +/- 15.7 mm Hg, p = 0.06). Severe reductions in the MAP were seen during 13.2% of the PAN and 7.2% of the polysulfone treatments (chi 2, p = NS). The age, APACHE II score, MAP, inotrope requirement, and primary diagnosis did not differ according to membrane material in a total of 197 consecutive patients (PAN, n = 97; polysulfone, n = 100). Patients survival was 29% (PAN) and 27% (polysulfone). In multivariate analysis, APACHE II score, inotrope requirement, and liver failure were significant determinants of survival. In conclusion, PAN and polysulfone membranes were not different with respect to hypotensive reactions or survival in critically ill patients undergoing continuous venovenous hemodialysis.