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Background Hemodialysis patients are at high risk of Covid-19, though vaccination has significant efficacy in preventing and reducing the severity of infection. Little information is available on disease severity and vaccine efficacy since the dissemination of the Omicron variant. Methods In a multi-center study, during a period of the epidemic driven by the Omicron variant, all hemodialysis patients positive for SARS-CoV-2 were identified. Outcomes were analyzed according to predictor variables including vaccination status. Risk of infection was analyzed using a Cox proportional hazards model. Results SARS-CoV-2 infection was identified in 1126 patients including 200 (18%) unvaccinated, 56 (5%) post first dose, 433 (38%) post second dose, and 437 (39%) at least 7 days beyond their third dose. The majority of patients had a mild course but 160 (14%) were hospitalized and 28 (2%) died. In regression models adjusted for age and comorbidity, two-dose vaccination was associated with a 39% (95%CI: 2%–62%) reduction in admissions, but third doses provided additional protection, with a 51% (95%CI: 25%–69%) further reduction in admissions. Among 1265 patients at risk at the start of the observation period, SARS-CoV-2 infection was observed in 211 (17%). Two-dose vaccination was associated with a 41% (95%CI: 3%–64%) reduction in the incidence of infection, with no clear additional effect provided by third doses. Conclusions These data demonstrate lower incidence of SARS-CoV-2 infection after vaccination in dialysis patients during an Omicron dominant period of the epidemic. Among those developing infection, severe illness was less common with prior vaccination, particularly after third vaccine doses.

BACKGROUND: Patients on dialysis with frequent comorbidities, advanced age, and frailty, who visit treatment facilities frequently, are perhaps more prone to SARS-CoV-2 infection and related death—the risk factors and dynamics of which are unknown. The aim of this study was to investigate the hospital outcomes in patients on dialysis infected with SARS-CoV-2. METHODS: Data on 224 patients on hemodialysis between February 29, 2020 and May 15, 2020 with confirmed SARS-CoV-2 were analyzed for outcomes and potential risk factors for death, using a competing risk-regression model assessed by subdistribution hazards ratio (SHR). RESULTS: Crude data analyses suggest an overall case-fatality ratio of 23% (95% CI, 17% to 28%) overall, but that varies across age groups from 11% (95% CI, 0.9% to 9.2%) in patients ≤50 years old and 32% (95% CI, 17% to 48%) in patients >80 years; with 60% of deaths occurring in the first 15 days and 80% within 21 days, indicating a rapid deterioration toward death after admission. Almost 90% of surviving patients were discharged within 28 days. Death was more likely than hospital discharge in patients who were more frail (WHO performance status, 3–4; SHR, 2.16 [95% CI, 1.25 to 3.74]; P=0.006), had ischemic heart disease (SHR, 2.28 [95% CI, 1.32 to 3.94]; P=0.003), cerebrovascular disease (SHR, 2.11 [95% CI, 1.20 to 3.72]; P=0.01), smoking history (SHR, 2.69 [95% CI, 1.33 to 5.45]; P=0.006), patients who were hospitalized (SHR, 10.26 [95% CI, 3.10 to 33.94]; P

BackgroundExit-site infection (ESI) and tunnel infection (TI) of the peritoneal dialysis (PD) catheter are significant causes of catheter or even method loss as well as patient morbidity. Among the methods that have been in use thus far, the removal and replacement of the catheter often needs to be followed by switching temporarily to hemodialysis, whereas catheter splicing or unroofing of the tunnel tract and shaving/removal of the superficial catheter cuff have not gained universal acceptance thus far.MethodsWe treat chronic ESI with exit-site relocation under local anesthetic with removal of the external cuff. For the purposes of this study, we conducted a retrospective cohort analysis of all exit-site relocations performed using that technique over a 5-year period.ResultsTwenty-seven patients (16 male, mean age 58 years, range 23 – 81 years) with chronic ESI underwent exit-site relocation under local anesthetic as a day-case procedure. Follow-up was 47.5 ± 22.4 months (range 10.8 – 79.4 months). No dialysate leaks occurred following the procedure. Peritoneal dialysis was resumed immediately. The procedure resulted in long-term resolution of the infection in 20 of the 27 patients (74%). In 7 patients (26%), the catheter had to be removed eventually, either because of ESI recurrence (5 patients) or TI (2 patients), which in 2 cases was subsequently complicated by PD peritonitis, and the patients were switched to hemodialysis.ConclusionThe technique described herein is a safe, straightforward, and effective method for the treatment of chronic ESI while the patient remains on PD and avoids switching to hemodialysis.

Introduction During the coronavirus disease 2019 (COVID-19) pandemic in 2020, high rates of acute kidney injury (AKI) in critically unwell patients are being reported, leading to an increased demand for renal replacement therapy (RRT). Providing RRT for this large number of patients is proving challenging, and so alternatives to continuous renal replacement therapies (CRRT) in the intensive care unit (ICU) are needed. Peritoneal dialysis (PD) can be initiated immediately after percutaneous insertion of the catheter, but there are concerns about impact on ventilation and RRT efficacy. We sought to describe our recent experience with percutaneous catheter insertion and peritoneal dialysis in patients in the ICU with COVID-19 infection. Method Patients were selected according to local protocol, and catheters were inserted percutaneously by experienced operators using a Seldinger technique. Sequential Organ Failure Assessment (SOFA) score and ventilation requirements were recorded at the time of insertion and 24 hours later. Procedural complications, proportion of RRT provided by PD, renal recovery, and RRT parameters (serum potassium and maximum base excess) during PD were assessed. Results Percutaneous PD catheters were successfully inserted in 37 of 44 patients (84.1%) after a median of 13.5 days (interquartile range [IQR] = 10.0, 20.3 days) in the ICU. No adverse events were reported; SOFA scores and ventilation requirements were comparable before and after insertion; and adequate RRT parameters were achieved. The median proportion of RRT provided by PD following catheter insertion was 94.6% (IQR = 75.0, 100%). Conclusion Peritoneal dialysis provides a safe and effective alternative to CRRT in selected patients with AKI and COVID-19 infection requiring ventilation on intensive care., Graphical abstract

Movement of solutes across the peritoneum allows for the use of peritoneal dialysis to treat kidney failure. However, there is a large inter-individual variability in the peritoneal solute transfer rate (PSTR). Here, we tested the hypothesis that common genetic variants are associated with variability in PSTR. Of the 3561 participants from 69 centers in six countries, 2850 with complete data were included in a genome-wide association study. PSTR was defined as the four-hour dialysate/plasma creatinine ratio from the first peritoneal equilibration test after starting PD. Heritability of PSTR was estimated using genomic-restricted maximum-likelihood analysis, and the association of PSTR with a genome-wide polygenic risk score was also tested. The mean four-hour dialysate/plasma creatinine ratio in participants was 0.70. In 2212 participants of European ancestry, no signal reached genome-wide significance but 23 single nucleotide variants at four loci demonstrated suggestive associations with PSTR. Meta-analysis of ancestry-stratified regressions in 2850 participants revealed five single-nucleotide variants at four loci with suggestive correlations with PSTR. Association across ancestry strata was consistent for rs28644184 at the KDM2B locus. The estimated heritability of PSTR was 19%, and a permuted model polygenic risk score was significantly associated with PSTR. Thus, this genome-wide association study of patients receiving peritoneal dialysis bolsters evidence for a genetic contribution to inter-individual variability in PSTR.

Assessment in African populations suggest adjustment for ethnicity in estimated glomerular filtration rate (eGFR) equations derived from African Americans lead to overestimation of GFR and failure to determine severity in chronic kidney disease (CKD). However, studies in African Europeans are limited. We aimed to assess accuracy of eGFR equations, with and without ethnicity adjustment compared with measured GFR in people of Black ethnicity in the United Kingdom. Performance of MDRD, CKD-EPI (with and without ethnicity adjustment), Full Age Spectrum (FAS), revised Lund Malmö (LM Revised), and European Kidney Function Consortium (EKFC) eGFR equations were assessed compared to 51Cr-EDTA GFR studies extracted from hospital databases. Participants with albumin 51Cr-EDTA studies were included (Mean age-53.7yrs; 43.6% female; 14.1% Black ethnicity). Compared to White participants, eGFR-MDRD and eGFR-CKD-EPI equations in Black participants significantly overestimated GFR (bias 20.3 and 19.7 ml/min/1.73m2 respectively, p2 for eGFR-MDRD and eGFR-CKD-EPI respectively, p2 respectively). 30%-accuracy was superior for GFR≥60ml/min/1.73m2 compared to 2 using eGFR-CKD-EPI equation for both White and Black participants (p

Background Exercise capacity, which is predictive of all-cause mortality and cardiovascular disease risk, is reduced significantly in patients with non–dialysis-dependent chronic kidney disease. This pilot study examined the effect of moderate-intensity exercise training on kidney function and indexes of cardiovascular risk in patients with progressive chronic kidney disease stages 3 to 4. Study Design Single-blind, randomized, controlled, parallel trial. Setting & Participants 20 patients (aged 18-80 years; 17 men) randomly assigned to rehabilitation (n=10) or usual care (n=10). Participants were included if they were 18 years or older and had evidence of rate of decline in creatinine-based estimated glomerular filtration rate (eGFR cr )≥2.9mL/min/1.73m 2 per year for 12 months preintervention. Patients were excluded if they had unstable medical conditions or had recently started regular exercise. Intervention The rehabilitation group received resistance and aerobic training (3 days per week) for a 12-month period. The usual care group received standard care. Outcomes Kidney function assessed by comparing mean rate of change in eGFR cr (mL/min/1.73m 2 per year) from a 12-month preintervention period against the 12-month intervention period. Pulse wave velocity (PWV), peak oxygen uptake (Vo 2peak ), and waist circumference assessed at 0, 6, and 12 months. Measurements eGFR assessed using creatinine, cystatin C (eGFR cys ), and a combination of both values (eGFR cr-cys ). Results 18 participants (rehabilitation, 8; usual care, 10) completed the study. A significant mean difference in rate of change in eGFR cr (+7.8±3.0 [95% CI, 1.1-13.5] mL/min/1.73m 2 per year; P =0.02) was observed between the rehabilitation and usual care groups, with the rehabilitation group demonstrating a slower decline. No significant between-group mean differences existed in absolute eGFR cr , eGFR cr-cys , or eGFR cys at 12 months of study intervention. Significant between-group mean differences existed in PWV (−2.30 [95% CI, −3.02 to −1.59] m/s), waist circumference (−7.1±12.8 [95% CI, −12.4 to −3.2] cm), and Vo 2peak (5.7 [95% CI, 1.34-10.10] mL/kg/min). Change in eGFR cr was correlated inversely with PWV ( r =−0.5; P =0.04) at 12 months. Limitations Small sample size, inconsistency between primary and secondary measures of kidney function. Conclusions The effect of a 1-year exercise intervention on progression of kidney disease is inconclusive. A larger study with longer follow-up may be necessary.

Background: Observational studies from the United States have identified black race as conferring a survival advantage on dialysis. This study represents the first large single-center study from a UK dialysis unit examining the outcome of ethnic minorities on renal replacement therapy (RRT). Methods: A retrospective analysis of all patients of white or black race initiating RRT at King’s College Hospital Renal Unit, London, between 1996 and 2008 was performed. A total of 1,340 patients were studied, of which 952 (71%) were of white race, and 388 (29%) were of black race. Kaplan-Meier survival curves, the log rank test and Cox’s proportional hazard models were used to compare survival between groups. Results: The results revealed black ethnicity to be associated with a significant survival benefit on dialysis. This was the case even after adjustment for age, gender, diabetes, transplantation, and deprivation. In those patients not transplanted, black race conferred a hazard ratio (HR) of 0.51 (95% CI 0.41 – 0.63) over 5 years. Conclusions: This study provides evidence for a lower mortality rate amongst black patients on dialysis in comparison with their white counterparts in the UK. The reasons behind this remain poorly understood but a lower incidence of cardiovascular disease in black patients and more kidney-limited disease may be important.

Background and objectives In patients with end-stage renal disease (ESRD), the rate of deaths preceded by dialysis withdrawal is high. However, rates vary across studies and national renal registries. This study aimed to (i) determine how dialysis withdrawal mortality is defined in the literature and (ii) whether mortality rates preceded by dialysis withdrawal change over time. Methods MEDLINE (1946 to March 2012) and EMBASE (1980 to March 2012) databases were searched. We included epidemiological studies that reported data permitting calculation of crude (unadjusted) mortality rates preceded by dialysis withdrawal. Definitions of dialysis withdrawal were also extracted. Crude mortality rates and 95% confidence intervals were calculated using OpenEpi software. Non-English language studies were excluded. Results Twenty-three eligible studies were identified; these included 14 527 885 dialysis patients at risk from six countries. Crude mortality rates preceded by dialysis withdrawal ranged from 3 to 50.2 per 1000 person-years. Seven different definitions of dialysis withdrawal were identified, with no assessment of validity. Crude mortality rates preceded by withdrawal have increased over time across the study period 1966 (3 per 1000 person-years) to 2010 (48.6 per 1000 person-years), although these rates are difficult to interpret because of differences in classification. In the USA crude mortality rates preceded by dialysis withdrawal are higher in the older population and have increased over time in the age group 65+ years. In this age group, the crude mortality rate preceded by dialysis withdrawal was 89.4 per 1000 person-years (2008-10) compared with 26.1 per 1000 person-years in the age group 50-64 years (2008-10). Conclusion Mortality rates preceded by dialysis withdrawal over time should be interpreted with caution because of differences in classification. Types of dialysis withdrawal need more careful elucidation, and we propose a unified classification of dialysis withdrawal based on trajectories and causal criteria.

A combined liver and kidney transplantation (CLKT) is advocated for selected individuals with chronic kidney disease undergoing liver transplantation (LT). The aim was to develop a risk score to identify the patients whose estimated glomerular filtration rate (eGFR) would decline during the year post-LT to aid future patient selection for CLKT.A training dataset of LT recipients was identified retrospectively from a prospectively compiled database (2000-2007). The eGFR was calculated at 1 year and those with an eGFR less than 30 mL/min were identified. Variables determined at the LT assessment were analyzed by logistic regression, discriminant function, and area under the receiver operating characteristic curve (AUC) analysis to develop the score. The score was validated in a prospective patient cohort.Three hundred sixty-eight LT recipients were followed up for 1 year (training dataset). The mean eGFR declined by 11.2+/-23.5 mL/min during that time (P0.001). A pre-LT risk score to predict an eGFR less than 30 mL/min at 1-year post-LT was generated: -1.8+(1.5 if a history of hypertension)+(0.65 x proteinuria in g/24 hr)+(0.013 x serum creatinine in micromol/L)+(0.001 x duration of acute kidney injury or eGFR60 mL/min in days). Reversible renal impairment should first be excluded. Progression was likely with a score more than 2.16. Sensitivity, specificity, and AUC were 99.2%, 100%, and 0.99, respectively. All, but one patient, in the validation cohort (n=149) were correctly classified.This information will complement previously published criteria for CLKT patient selection.

Background. Renal impairment post-liver transplant (LT) is often attributed to calcineurin inhibitors (CNIs). A renal biopsy can be a useful tool but may be complicated in LT recipients. We aimed to determine the clinical scenarios that prompted a decision to perform a renal biopsy in this patient population, to assess histological findings and evaluate patient management and survival and renal outcome. Methods. Information on clinical variables and renal histology was extracted from single-centre prospectively compiled databases from 1996 onwards. Results. Over 2100 adults received an LT in the time period studied, and 54 of these (35 males and 19 females) were referred for renal review. Of these, 43% underwent a renal biopsy. They had a higher creatinine (P = 0.02), a greater deterioration in creatinine over the year prior to review and were more likely to be nephrotic (both P < 0.01). Histological findings included hypertensive changes (44%), CNI nephrotoxicity (48%), IgA nephropathy (9%), membranoproliferative glomerulonephritis (17%), acute tubular necrosis (4%), crescentic glomerulonephritis (4%) and diabetic nephropathy (9%). Major bleeding complications occurred in 17%. Treatment changed in the majority but, it was not significantly different in the two groups. Although initial renal function was worse in the biopsied group, final patient and renal survival did not differ between the two groups. Conclusion. A renal biopsy is a valuable tool in those with renal insufficiency and/or proteinuria and haematuria but the benefits must be weighed against the relatively high complication rate in LT recipients.

Death from head injuries has been a feature of conflicts throughout the world for centuries. The burden of mortality has been variously affected by the evolution in weaponry from war-hammers to explosive ordnance, the influence of armour on survivability and the changing likelihood of infection as a complicating factor. Surgery evolved from haphazard trephination to valiant, yet disjointed, neurosurgery by a variety of great historical surgeons until the Crimean War of 1853-1856. However, it was events initiated by the Great War of 1914-1918 that not only marked the development of modern neurosurgical techniques, but our approach to military surgery as a whole. Here the author describes how 100 years of conflict and the input and intertwining relationships between the 20th century's great neurosurgeons established neurosurgery in the United Kingdom and beyond.

Background: Hemodialysis is a palliative treatment for patients with established renal failure (ERF), and volume overload is a common problem for hemodialysis patients with low urinary output. Volume overload is thought to be mostly attributable to interdialytic fluid intake by the patient and is associated with an increased symptom burden and the development of serious medical complications. Repeated episodes of volume overload may adversely affect staff–patient relationships and the perception of care in this patient population. The aim of this case series study was to evaluate the effect and experience of a psychological intervention on interdialytic weight gain in a small group of patients.Methods: Five patients were treated. The intervention involved using techniques derived from both cognitive behavior therapy and motivational interviewing. The main outcome measures were interdialytic weight gain and patient perception of the intervention.Results: Three of the five patients reduced both mean interdialytic weight gain and the frequency with which they gained in excess of 3% of their dry weight during the intervention phase. The intervention was found to be acceptable to patients.Significance of results: The intervention was effective in helping three of the five patients to reduce both the frequency and the severity of volume overload, and two of these patients maintained this for at least 6 months post intervention. The intervention used actively engaged the patients and appeared to be experienced positively. The methods used to mobilize patient resources and optimize staff–patient relationships as vehicles of change are discussed. Both may have implications for treatment concordance and the perception of care delivered.

Background. Renal disease in sarcoidosis may occur due to granulomatous interstitial nephritis. However, granulomatous interstitial nephritis in the absence of features of extrarenal sarcoid, or other causes, has been reported very rarely. In this report we describe seven such patients. Methods. Since 1995, we have identified a number of patients with biopsy-proven granulomatous interstitial nephritis. Patients were excluded if they had (i) evidence of extrarenal sarcoid, (ii) infections that may have contributed to pathogenesis or (iii) an obvious drug-related aetiology. Results. Seven patients were identified, of whom five were male and two female, with a median age of 69. Median calculated creatinine clearance at presentation was 14 mlumin. Two had raised serum calcium at presentation and three had a raised serum angiotensin-converting enzyme. All patients were treated with steroids and five out of seven had an improvement in their renal function. Two patients progressed to end-stage renal failure despite treatment with steroids. Conclusions. Idiopathic granulomatous interstitial nephritis may represent a renal-limited form of sarcoid. It may be associated with hypercalcaemia and a raised serum angiotensin-converting enzyme and usually responds to treatment with corticosteroids.

1. Endothelin-1 infusion (5-40 pmol kg-1 min-1) in the normal anaesthetized rabbit, produced a dose-dependent increase in mean arterial blood pressure (MAP) and reduced renal blood flow (RBF) and glomerular filtration rate (GFR), when compared with an equivalent infusion of physiological saline. 2. Endothelin, 20 pmol kg-1 min-1, was also assessed in animals pretreated with either indomethacin (2 mg kg-1), methylene blue (1.6 mg kg-1 h-1) or NG-monomethyl L-arginine (L-NMMA, 10 mg kg-1 h-1). 3. The effect of endothelin on MAP and RBF was enhanced (P = 0.05 and < 0.01 respectively) by the cyclo-oxygenase inhibitor, indomethacin, without any significant change in the effect on GFR. 4. Methylene blue and L-NMMA, inhibitors of endothelium-derived relaxant factor (EDRF), enhanced the effect of endothelin on each of the parameters measured (P < 0.01). 5. Our results are consistent with endothelin having a predominant effect on pre-glomerular vascular resistance to reduce GFR. Endothelin appears to stimulate the release of vasodilator prostanoids and EDRF which oppose its effects. Thus endothelin may have an important role in the complex control of GFR in the rabbit.

From 56 to 48 hours is a step too far The European Working Time Directive was produced by the Council of the European Union in 1993 and incorporated into British law in 1998 as the Working Time Regulations.1 Various aspects of the directive have had a major effect on the practice of medicine in the United Kingdom, most importantly the reduction in the maximum working week to 56 hours in 2007, a planned further reduction to 48 hours in 2009, and the need for a minimum of 11 hours’ rest in any 24 hour period. Although not clearly stated in the directive, the aims of the council presumably were to protect workers from being coerced by employers to work excessive hours; to improve the quality of life of workers by permitting sufficient free time for family and leisure; and to reduce risk caused by tired workers. Although many industries are affected by the change in the law, medicine poses particular problems because of the need to train junior medical staff and to provide a 24 hour service that can respond to variable demand while ensuring continuity of, often complicated, patient care. Furthermore, unlike many other professions, junior and now senior doctors are paid per hour, which exposes the length of the working day and week to legislation. If the directive was meant to improve clinical care and the quality of life and training for junior medical staff, its effect has been the opposite. The changes to working hours have had a major negative effect on the working life, free time, and education of …

Background: The Rosenheim report, published in 1972, was aimed at decreasing the transmission of hepatitis B virus (HBV) in the renal unit. A review in 1996, revealed the non-compliance of some centres with the guidance to vaccinate individuals against HBV. Objectives: To describe two events of acute hepatitis B virus (HBV) infection within 9 weeks in individuals attending the renal unit and the steps taken to prevent further transmission. Study design: Serological and molecular testing was carried out on the two individuals with acute HBV and other HBV carriers in the unit. Epidemiological information was collected along with information on HBV vaccination and HBsAg screening. Results: There were 15 known HBV carriers in the unit. HBV genotype E was transmitted from a carrier to patient 1 when they were in the same ward. Transmission to patient 2 occurred when he followed patient 1 on the theatre list. Breaks in infection control were identified and steps were taken to prevent further transmission events. Conclusions: Breaks in infection control procedures were rectified. No further transmission of HBV was identified. This highlights the need for vigilance regarding infection control practices in the renal unit setting.

BACKGROUND: Evaluating the effects of decreasing low-density lipoprotein (LDL) cholesterol levels requires large randomized trials. In preparation for such a trial, we assessed the biochemical efficacy, safety, and tolerability of adding ezetimibe, 10 mg/d, to simvastatin, 20 mg/d, as initial therapy for such patients. METHODS: Two hundred three patients (152 predialysis patients with creatinine levels > or = 1.7 mg/dL [> or = 150 micromol/L], 18 patients on peritoneal dialysis therapy, and 33 patients on hemodialysis therapy) were randomly assigned to the administration of simvastatin, 20 mg/d, plus ezetimibe, 10 mg/d; or simvastatin, 20 mg, plus placebo ezetimibe daily. RESULTS: After 6 months, allocation to simvastatin monotherapy was associated with a 31-mg/dL (0.8-mmol/L) decrease in nonfasting LDL cholesterol levels compared with baseline. Allocation to simvastatin plus ezetimibe produced an additional 18-mg/dL (0.47-mmol/L) decrease in LDL cholesterol level, representing an incremental 21% reduction over that achieved with simvastatin monotherapy (P < 0.0001). There were no statistically significant effects of the addition of ezetimibe to simvastatin on triglyceride or high-density lipoprotein cholesterol levels. Ezetimibe was not associated with an excess risk of abnormal liver function test results or of elevated creatine kinase levels and did not impair absorption of fat-soluble vitamins. There were no serious adverse events caused by study treatment. CONCLUSION: This 6-month study shows that the addition of ezetimibe to simvastatin, 20 mg/d, as initial therapy for patients with chronic kidney disease was well tolerated and produced an additional 21% decrease in LDL cholesterol levels. The clinical efficacy and safety of combination therapy in this population are now being assessed in a large randomized trial.

In the United States, blacks are more frequently diagnosed than whites with end-stage renal failure (ESRF) from primary hypertension or diabetic nephropathy. We performed a validation retrospective case-note study of all blacks with ESRF who started renal replacement therapy (RRT) at three teaching hospitals in London, England, during 1991 to 1995 to investigate and validate the causes of primary renal disease using standard criteria. We identified 144 black patients with a mean age of 52.0 ± 16.0 (SD) years; 59% were men and 32% had renal histological data. One hundred forty-four whites who were matched for age, sex, and onset of RRT (42% with renal histological data) underwent a similar validation exercise. Before the validation, the principal working diagnosis in the black patients had been diabetic nephropathy in 35% (89%, type 2; 11%, type 1); primary hypertension, 19%; glomerulonephritis (GN), 18%; and uncertain cause, 15%. After validation analysis, this changed to diabetes, 38% (16% biopsy proven); uncertain, 24%; GN, 20%; and primary hypertension, only 10% (28% biopsy proven). Among the uncertain cases (n = 34), 19 patients had hypertension, but this could not be established as the primary disease; 94% of all blacks had hypertension, accelerated in 21%. Among whites, only 3.5% had primary hypertension, and this proportion was not changed by the validation study. Type 2 diabetes is the most common single cause of ESRF in black patients in London, and although hypertension is more common and more severe in blacks, the proportion of renal failure attributed to primary hypertension is overestimated, and the diagnosis is often made using inadequate criteria.

Background. Renal allograft outcome, during an 8 year period (1985-1992), has been assessed in 56 renal transplants performed in 55 patients who had endstage renal failure as a consequence of urological abnormalities. The abnormalities were: primary vesicoureteric reflux (WR) or renal dysplasia (26 patients); posterior urethral valves (PUV) (15); neuropathic bladders (6); vesico-ureteric tuberculosis (5); bladder exstrophy (3); and prune belly syndrome (1). Six patients had augmented bladders, and eight transplants were performed in seven patients with urinary diversions.Results. Overall, 1 and 5 year actuarial graft survival was 89 and 66%, with mean creatinine of 154 mu mol/l +/- 11 (SE) and 145 +/- 9 respectively. Patients with abnormal bladders or conduits (n=28) had worse graft function than those with normal bladders (n= 28) although graft survival was not significantly different in the two groups at 1 and 5 years: 93 and 75% with normal bladders vs 86 and 57% with abnormal systems. Symptomatic urinary tract infections were common in the first 3 months after transplantation (63%); fever and systemic symptoms occurred in 39% with normal bladders and 59% with abnormal bladders. Urinary tract infection directly contributed to graft loss in six patients with abnormal bladders, but had no consequences in those with normal bladders.Conclusions. Abnormal bladders must be assessed urodynamically before transplantation, and after transplantation adequacy of urinary drainage must be re-assessed frequently. Prophylactic antibiotics are now given for the first 6 months and urinary tract infections must be treated promptly. With these measures, good results, similar to those of patients without urological problems, can be obtained.

This study examined whether renal parenchymal imaging using Tc-99m DMSA scintigraphy with tomography is a sensitive measure of renal scarring in renal transplant recipients with an abnormal lower urinary tract and whether such scars correlate with impairment of renal function. Three groups of patients were compared: group 1, patients with an abnormal lower urinary tract and deteriorating renal function (n = 9); group 2, abnormal lower urinary tract and stable renal function (n = 5); and group 3, normal lower urinary tract and deteriorating renal function (n = 8). Eight of the nine patients in group 1 had multiple scars visible on Tc-99m DMSA scans and this correlated with histology when a renal biopsy was performed; the only patient without scars had a transplant glomerulopathy. The presence of scars was associated with either raised intravesical pressures or recurrent urinary tract infections (UTIs). Only one patient in each of groups 2 and 3 had visible scars and both these patients had a history of recurrent UTIs. Patients in group 3 with deteriorating renal function due to chronic rejection documented by biopsy did not have cortical scars visible with Tc-99m DMSA tomography.Tc-99m DMSA scanning with tomography is a useful investigation in the management of renal transplant patients with declining renal function; multiple scars may indicate abnormal lower urinary tract function and are not seen in chronic rejection.

Patients with chronic renal failure undergoing renal transplantation have a high prevalence of cardiovascular disease. Invasive investigation may identify those at risk of cardiac death during or after renal transplantation, but which patients should undergo cardiac catheterization is currently not clear. In 95 patients awaiting renal transplantation we assessed the ability of echocardiography and exercise electrocardiography to identify patients at risk of cardiac death. Echocardiography identified impaired left ventricular (LV) systolic function in 20%, severe in 8%. Of the patients with severe LV dysfunction, 25% died before transplantation. Of those undergoing exercise electrocardiography, 44% did not achieve 85% of maximum predicted heart rate. No coronary artery disease requiring intervention was identified by exercise testing. These findings indicate that echocardiography, but not exercise electrocardiography, should be part of the assessment for renal transplantation.

1. The endothelium releases a number of vasoactive compounds, including the vasodilator prostaglandins, prostacyclin (PGI2) and prostaglandin E2 (PGE2) and endothelium-derived relaxing factor (EDRF), which play an important role in the regulation of vascular tone in the microcirculation. Nephrotoxicity is the major complication of cyclosporin (CS) therapy and is related to an increase in intrarenal vascular tone. Endothelial cell generation of PGI2 is inhibited by CS although this cannot fully explain the changes in vascular tone observed. We have investigated the possibility that EDRF-dependent vasodilatation is also affected by CS therapy in vivo. 2. CS nephrotoxicity was induced in rabbits with CS (15 mg kg-1 per day s.c. for 20 days (n = 6]; 6 rabbits were given CS vehicle (Veh) and 9 animals were studied without any treatment. Creatinine clearance fell significantly during treatment in the CS-treated rabbits (11.78 +/- 1.5 ml min-1, mean +/- s.e. mean, to 7.79 +/- 1.2 after 20 days treatment) but did not change in the vehicle-treated animals. 3. The responses to the endothelium-dependent (acetylcholine (ACh] and endothelium-independent (nitroprusside (NP) and PGI2) vasodilators were assessed in indomethacin-treated isolated perfused kidneys (IPKs) from untreated, CS- and Veh-treated animals. Vascular tone was induced with a constant infusion of noradrenaline 150 nM and the perfusion rate adjusted to produce a perfusion pressure of 90 mmHg. Perfusate flow rate (22.3 +/- 4.6 vs 20.4 +/- 3.1 ml min-1) and glomerular filtration rate (2.04 +/- 0.37 vs 1.88 +/- 0.16 nl min-1) did not differ between IPKs from CS- and Veh-treated animals. 4. The vasodilator response to ACh was reduced in the kidneys from CS-treated animals compared with those from untreated and Veh-treated animals (mean reduction 35.3 + 2.3% compared with Veh) as were the responses to both NP (42.8 + 3.6%) and PGI2 (27.7 + 7.4%). 5. This suggests that CS nephrotoxicity is not mediated via an effect on endothelium-dependent responses and that it is more likely that CS has a direct effect on vascular smooth muscle.

1. The effects of endothelin infusion on renal vascular resistance (RVR), glomerular filtration rate (GFR) and the interaction with locally generated endothelium-derived relaxant factor (EDRF) were studied in the rabbit isolated perfused kidney (IPK). For comparison the effects of infusions of angiotensin II (AII) and noradrenaline (NA) were also assessed. 2. Each kidney was perfused at a constant rate of 10 ml min-1 and alterations in RVR determined by measuring changes in perfusion pressure. GFR was determined by the clearance of [51Cr]-EDTA, using timed urine collections. 3. Endothelin (10(-11)-10(-9) M) produced a dose-related increase in RVR. Endothelin was approximately 30 times more potent in molar terms than AII and 500 times more than NA at inducing a 50 mmHg increase in perfusion pressure. 4. Endothelin appeared to be a weak inducer of EDRF release in the IPK as EDRF inhibitors methylene blue (10 microM) or haemoglobin (10 microM) only slightly augmented the increase in RVR at a given concentration of endothelin. In contrast the effect of NA on RVR was significantly increased by methylene blue (10 microM) whereas that induced by AII was not affected. 5. Endothelin infusion produced a significant, dose-dependent decrease in GFR of the IPK, contrasting with an increase in GFR during AII infusion and a minimal effect of NA on GFR. This supports evidence that AII is predominantly a constrictor of effernt glomerular arterioles and that NA constricts both afferent and efferent glomerular vessels. We suggest that the vasoconstrictive effect of endothelin in the kidney is predominantly preglomerular, which explains its effect on GFR.