Impact of Increased Duration of Trimethoprim-Sulfamethoxazole Prophylaxis for Pneumocystis Pneumonia After Renal Transplant.

BACKGROUND Trimethoprim-sulfamethoxazole (TMP-SMX) is recommended as prophylaxis against Pneumocystis pneumonia (PCP) in renal transplant recipients. The optimal duration of prophylaxis is unknown. Longer duration of prophylaxis may increase the risk of adverse effects. The aim of this retrospective observational cohort study was to assess the impact of increasing duration of TMP-SMX prophylaxis from 3 to 6 months after transplant on drug-resistant urinary tract infection (UTI), hyperkalemia, peripheral blood cytopenias, and incidence of PCP. MATERIAL AND METHODS Patients transplanted over a 4.5-year period before and after a change in protocol from 3- to 6-months TMP-SMX prophylaxis in our unit were grouped according to planned duration of prophylaxis, and results were analyzed on an intention-to-treat basis. Baseline characteristics, laboratory values, and all urine microbiology results in the 6 months after transplant were analyzed. RESULTS The overall UTI incidence rate was higher in the 3-month (3-m) treatment group than the 6-month (6-m) treatment group (0.52 vs. 0.33 UTI per 100 patient days; rate ratio 1.56 [95% CI 1.27-1.95]). However, this was not attributable to TMP-SMX: the incidences were significantly different in months 0-3 but not months 4-6. Twenty-eight multi-resistant UTIs occurred in the 3-m group, but there were none in the 6-m group (p=0.004). There were no significant differences in renal function, serum potassium, or cytopenias during the first 6 months. There were 15 cases of PCP in the 3-m group, 3 cases in the 6-m group, and no cases during prophylaxis. CONCLUSIONS Extending the duration of TMP-SMX prophylaxis was not associated with change in frequency of UTIs or multi-drug-resistant UTIs, nor was it associated with increased adverse events. TMP-SMX is an effective PCP prophylaxis, and these data support recommendations to extend the duration of prophylaxis after transplant.

Diagnosing nephrogenic systemic fibrosis in the post-FDA restriction era.

The emergence of an association between gadolinium-based contrast agents (GBCA) and the rare condition nephrogenic systemic fibrosis (NSF) led to a warning in 2006 from the Food and Drug Administration (FDA) restricting the use of the GBCAs to patients with an estimated glomerular filtration rate of >30 mL/min/1.73m(2) . We discuss our experience with a post-FDA restriction presentation of NSF and subsequent patient death in which the prolonged lead-time of ∼5.5 years led to challenges in ensuring a secure diagnosis of NSF and establishing risk exposures. Accurate contemporary records of contrast administration and clinical factors alongside clinical and pathological expertise ensured that we were able to confidently diagnose NSF, despite the length of lead time and confounding factors.

Double bag or Y-set versus standard transfer systems for continuous ambulatory peritoneal dialysis in end-stage kidney disease.

BACKGROUND: Peritonitis is the most frequent serious complication of continuous ambulatory peritoneal dialysis (CAPD). It has a major influence on the number of patients switching from CAPD to haemodialysis and has probably restricted the wider acceptance and uptake of CAPD as an alternative mode of dialysis.This is an update of a review first published in 2000. OBJECTIVES: This systematic review sought to determine if modifications of the transfer set (Y-set or double bag systems) used in CAPD exchanges are associated with a reduction in peritonitis and an improvement in other relevant outcomes. SEARCH METHODS: We searched the Cochrane Renal Group's Specialised Register through contact with the Trials Search Co-ordinator. Studies contained in the Specialised Register are identified through search strategies specifically designed for CENTRAL, MEDLINE and EMBASE. Date of last search: 22 October 2013. SELECTION CRITERIA: Randomised controlled trials (RCTs) or quasi-RCTs comparing double bag, Y-set and standard peritoneal dialysis (PD) exchange systems in patients with end-stage kidney disease. DATA COLLECTION AND ANALYSIS: Data were abstracted by a single investigator onto a standard form and analysed by Review Manager. Analysis was by a random effects model and results were expressed as risk ratio (RR) or mean difference (MD) with 95% confidence intervals (CI). MAIN RESULTS: Twelve eligible trials with a total of 991 randomised patients were identified. Despite the large total number of patients, few trials covered the same interventions, small numbers of patients were enrolled in each trial and the methodological quality was suboptimal. Y-set and twin-bag systems were superior to conventional spike systems (7 trials, 485 patients, RR 0.64, 95% CI 0.53 to 0.77) in preventing peritonitis in PD. AUTHORS' CONCLUSIONS: Disconnect systems should be the preferred exchange systems in CAPD.

How safe is renal replacement therapy? A national study of mortality and adverse events contributing to the death of renal replacement therapy recipients.

BACKGROUND: Patients receiving treatment with renal replacement therapy (RRT) have high mortality, and ensuring patient safety in this population is difficult. We aimed to estimate the incidence and nature of medical adverse events contributing to the death of patients being treated with RRT. METHODS: This population registry-based retrospective case review study included all patients being treated with RRT for established renal failure in Scotland and who died between 1 January 2008 and 30 June 2011. Deaths were reviewed by consultant nephrologists using a structured questionnaire to identify factors contributing to death occurring in both the inpatient and outpatient setting. Reviewers were able to use any information source deemed relevant, including paper and electronic clinical records, mortality and morbidity meetings and procurator fiscal (Scottish coroner) investigations. Deaths occurring in 2008 and 2009 where avoidable factors were identified that may have or did lead to death of a patient were subject to further review and root cause analysis, in order to identify recurrent themes. RESULTS: Of 1551 deaths in the study period, 1357 were reviewed (87.5%). Cumulative RRT exposure in the cohort was 2.78 million person-days. RRT complications were the primary cause of death in 28 (2.1%). Health-care-associated infection had contributed to 9.6% of all deaths. In 3.5% of deaths, factors were identified which may have or did contribute to death. These were both organizational and human error related and were largely due to five main causes: management of hyperkalaemia, prescribing, out of hours care, infection and haemodialysis vascular access. CONCLUSIONS: Adverse events contributing to death in RRT recipients mainly relate to the everyday management of common medical problems and not the technical aspects of RRT. Efforts to avoid harm in this population should address these ubiquitous causes of harm.

Early focal segmental glomerulosclerosis as a cause of renal allograft primary nonfunction.

Background. Primary focal segmental glomerulosclerosis (FSGS) is one of the commonest causes of glomerular disease and if left untreated will often progress to established renal failure. In many cases the best treatment option is renal transplantation; however primary FSGS may rapidly recur in renal allografts and may contribute to delayed graft function. We present a case of primary nonfunction in a renal allograft due to biopsy-proven FSGS. Case Report. A 32-year-old man presented with serum albumin of 22 g/L, proteinuria quantified at 12 g/L, and marked peripheral oedema. Renal biopsy demonstrated tip-variant FSGS. Despite treatment, the patient developed progressive renal dysfunction and was commenced on haemodialysis. Cadaveric renal transplantation was undertaken; however this was complicated by primary nonfunction. Renal biopsies failed to demonstrate evidence of acute rejection but did demonstrate clear evidence of FSGS. The patient was treated to no avail. Discussion. Primary renal allograft nonfunction following transplantation is often due to acute kidney injury or acute rejection. Recurrent FSGS is recognised as a phenomenon that drives allograft dysfunction but is not traditionally associated with primary nonfunction. This case highlights FSGS as a potentially aggressive process that, once active in the allograft, may prove refractory to targeted treatment. Preemptive therapies in patients deemed to be at high risk of recurrent disease may be appropriate and should be considered.

Five-year outcomes after a change from a cyclosporin-based to a 'low-dose' tacrolimus-based primary immunosuppression regimen for incident kidney transplants--the Glasgow experience.

In January 2007, our centre changed from a cyclosporin (CyA)/azathioprine (Aza)/ prednisolone (Pred) primary immunosuppression regimen (with basiliximab induction and mycophenolate mofetil [MMF] for those at immunologically high risk) to a tacrolimus (Tac) (low dose)/MMF/Pred regimen with basiliximab induction, following presentation of Symphony trial results. This analysis assesses the impact of this change on 5-year outcomes. Three hundred consecutive renal-only transplants were identified: 140 from the 2005-06 era and 160 from the 2007-08 era. The proportions of living donor (37.5 vs. 22.9%; p = 0.04) and donors after circulatory death (11.9 vs. 5.0%; p = 0.03) were higher in the 2007-08 cohort. Five-year actuarial patient survival was higher in the 2007-08 cohort (96.8 vs. 87.1%; p = 0.003), with a trend toward higher 5-year transplant survival (84.7 vs. 76.3%; p = 0.08). Estimated glomerular filtration rate (eGFR) was higher than in the 2005-06 era at 1 (53.5 vs. 44.5 ml/min/1.73m2; p = 0.0006) and 3 years (50.9 vs. 43.4 ml/min/1.73m2; p = 0.02), with a trend toward higher eGFR at 5 years (41.8 vs. 49.6 ml/min/1.73m2; p = 0.09). Differences were consistent when living donor and deceased donor transplants were analysed separately. In a "real world" population, a change from a CyA-based to a Tac (low-dose)/MMF/Pred primary immunosuppression regimen has been associated with better 5-year outcomes.

Automated vs continuous ambulatory peritoneal dialysis: a systematic review of randomized controlled trials.

BACKGROUND: A systematic review of randomized controlled trials (RCTs) comparing continuous ambulatory peritoneal dialysis (CAPD) with all forms of automated peritoneal dialysis (APD) was performed to assess their comparative clinical effectiveness. METHODS: The Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE and CINAHL, were searched for relevant RCTs. Analysis was by a random effects model and results expressed as relative risk (RR) and weighted mean difference (WMD) with 95% confidence intervals (CI). RESULTS: Three trials (139 patients) were identified. APD when compared to CAPD was found to have significantly lower peritonitis rates (two trials, 107 patients, rate ratio 0.54, 95% CI 0.35-0.83) and hospitalization rates (one trial, 82 patients, rate ratio 0.60, 95% CI 0.39-0.93) but not exit-site infection rates (two trials, 107 patients, rate ratio 1.00, 95% CI 0.56-1.76). However no differences were detected between APD and CAPD in respect to risk of mortality (RR 1.49, 95% CI 0.51-4.37), peritonitis (RR 0.75, 95% CI 0.50-1.11), switching from the original peritoneal dialysis (PD) modality to a different dialysis modality including an alternative form of PD (RR 0.50, 95% CI 0.25-1.02), PD catheter removal (RR 0.64, 95% CI 0.27-1.48) and hospital admissions (RR 0.96, 95% CI 0.43-2.17). Patients on APD were found to have significantly more time for work, family and social activities. CONCLUSIONS: APD appears to be more beneficial than CAPD, in terms of reducing peritonitis rates and with respect to certain social issues that impact on patients' quality of life. Further, adequately powered trials are required to confirm the benefits for APD found in this review and detect differences with respect to other clinically important outcomes that may have been missed by the trials included in this review due to their small size and short follow-up periods.

Comparison of hemodialysis, hemofiltration, and acetate-free biofiltration for ESRD: systematic review.

BACKGROUND: We performed a systematic review of randomized controlled trials (RCTs) comparing hemodialysis (HD), hemofiltration (HF), hemodiafiltration (HDF), and acetate-free biofiltration (AFB) in the treatment of patients with end-stage renal disease to assess their clinical effectiveness. METHODS: The Cochrane CENTRAL Registry, MEDLINE, EMBASE, CINAHL, the American College of Physicians Database, Database of Abstracts of Reviews of Effectiveness, and reference lists were searched for randomized trials of HF, HDF, and AFB compared with HD; HDF compared with AFB; and HF compared with HDF. Two reviewers extracted data for all-cause mortality; hypotension, headache, nausea, vomiting, and any other adverse symptoms; quality of life (QoL); hospitalization; dialysis adequacy; and end-of-treatment beta 2 -microglobulin levels. Analysis was by means of a random-effects model, and results are expressed as relative risk (RR) and weighted mean difference (WMD) with 95% confidence intervals (CIs). RESULTS: Eighteen eligible trials (588 patients) were identified. HDF was associated with significantly greater mortality risk than HD (4 trials, 326 patients; RR, 3.52; 95% CI, 1.37 to 9.47). Risk for mortality was not different among the other comparisons. Risks for hypotension episodes and dialysis-related symptoms were not significantly different with HD, HF, HDF, and AFB (18 trials, 583 patients). QoL, assessed by using an unvalidated scoring tool, appeared to be significantly improved in patients on HDF therapy than those on HD therapy (1 trial, 67 patients; WMD, 0.6; 95% CI, 0.3 to 0.9), but this was not evident when validated QoL assessment tools were used. Use of AFB compared with HDF was not associated with a significant difference in risk for hospitalization (1 trial, 11 patients; WMD, -0.45; 95% CI, -1.42 to 0.52). HDF in comparison to HD did not reduce the risk for carpal tunnel syndrome (1 trial, 67 patients; RR, 2.04; 95% CI, 0.59 to 7.00). Kt/V was significantly different with HDF compared with HD (3 trials, 124 patients; WMD, 0.14; 95% CI, 0.05 to 0.22). No other substantial data for these interventions and their impact on major patient-centered outcomes were available. CONCLUSION: The trials assessed were not powered adequately and had suboptimal method quality. It is not possible on the basis of effectiveness to prefer one extracorporeal renal replacement therapy modality to the other for end-stage kidney disease because significant differences in clinically important outcomes have not been shown by available published RCTs.