Impact of incremental versus conventional initiation of haemodialysis on residual kidney function : study protocol for a multicentre feasibility randomised controlled trial

© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.INTRODUCTION: Preserving residual kidney function (RKF) may be beneficial to patients on haemodialysis (HD) and it has been proposed that commencing dialysis incrementally rather than three times a week may preserve RKF. In Incremental HD, target dose includes a contribution from RKF, which is added to HD dose, allowing individualisation of the HD prescription. We will conduct a feasibility randomised controlled trial (RCT) comparing incremental HD and conventional three times weekly treatments in incident HD patients. The study is designed also to provide pilot data to allow determination of effect size to power a definitive study. METHODS AND ANALYSIS: After screening to ensure native renal urea clearance >3 mL/min/1.73 m2, the study will randomise 54 patients within 3 months of HD initiation to conventional in-centre thrice weekly dialysis or incremental in-centre HD commencing 2 days a week. Subjects will be followed up for 12 months. The study will be carried out across four UK renal centres.The primary outcome is to evaluate the feasibility of conducting a definitive RCT and to estimate the difference in rate of decline of RKF between the two groups at 6 and 12 months time points. Secondary outcomes will include the impact of dialysis intensity on vascular access events, major adverse cardiac events and survival. Impact of dialysis intensity on patient-reported outcomes measures, cognition and frailty will be assessed using EQ-5D-5L, PHQ-9, Illness Intrusiveness Rating Score, Montreal Cognitive assessment and Clinical Frailty Score. Safety outcomes include hospitalisation, fluid overload episodes, hyperkalaemia events and vascular access events.This study will inform the design of a definitive study, adequately powered to determine whether RKF is better preserved after incremental HD initiation compared with conventional initiation. ETHICS AND DISSEMINATION: Ethics approval has been granted by Cambridge South Research Ethics Committee, United Kingdom(REC17/EE/0311). Results will be disseminated via peer-reviewed publication. TRIAL REGISTRATION NUMBER: NCT03418181.Peer reviewedFinal Published versio

Membranoproliferative glomerulonephritis.

Membranoproliferative glomerulonephritis is an uncommon kidney disorder characterized by mesangial cell proliferation and structural changes in glomerular capillary walls. It can be subdivided into idiopathic and secondary forms, which are differentially diagnosed by a review of clinical features, laboratory data, and renal histopathology. Three types-I, II, and III-have been defined by pathologic features. All three types are associated with hypocomplementemia, but they manifest somewhat different mechanisms of complement activation. Type II, also known as "dense deposit disease", is associated with the presence of C3-nephritic factor. Membranoproliferative glomerulonephritis primarily affects children and young adults, with patients presenting with nephrotic or nephritic syndrome or with asymptomatic renal disease. This type of glomerulonephritis often progresses slowly to end-stage renal disease, and it tends to recur after renal transplantation, especially type II. The efficacy of various forms of treatment remains controversial; however, long-term steroid treatment seems to be effective in children with nephrotic-range proteinuria. Improvement in renal outcomes largely relies on the evaluation of more selective agents in carefully controlled studies

A multicenter feasibility randomized controlled trial to assess the impact of incremental versus conventional initiation of hemodialysis on residual kidney function

© 2021 Published by Elsevier, Inc., on behalf of the International Society of Nephrology.Twice-weekly hemodialysis, as part of incremental initiation, has reported benefits including preservation of residual kidney function (RKF). To explore this, we initiated a randomized controlled feasibility trial examining 55 incident hemodialysis patients with urea clearance of 3 ml/min/1.73 m 2 or more across four centers in the United Kingdom randomized to standard or incremental schedules for 12 months. Incremental hemodialysis involved twice-weekly sessions, upwardly adjusting hemodialysis dose as RKF was lost, maintaining total (Dialysis+Renal) Std Kt/V above 2. Standard hemodialysis was thrice weekly for 3.5-4 hours, minimum Dialysis Std Kt/V of 2. Primary outcomes were feasibility parameters and effect size of group differences in rate of loss of RKF at six months. Health care cost impact and patient-reported outcomes were explored. Around one-third of patients met eligibility criteria. Half agreed to randomization; 26 received standard hemodialysis and 29 incremental. At 12 months, 21 incremental patients remained in the study vs 12 in the standard arm with no group differences in the urea clearance slope. Ninety-two percent of incremental and 75% of standard arm patients had a urea clearance of 2 ml/min/1.73 m 2 or more at six months. Serious adverse events were less frequent in incremental patients (Incidence Rate Ratio 0.47, confidence interval 0.27-0.81). Serum bicarbonate was significantly lower in incremental patients indicating supplementation may be required. There were three deaths in each arm. Blood pressure, extracellular fluid and patient-reported outcomes were similar. There was no signal of benefit of incremental hemodialysis in terms of protection of RKF or Quality of Life score. Median incremental hemodialysis costs were significantly lower compared to standard hemodialysis. Thus, incremental hemodialysis appears safe and cost-saving in incident patients with adequate RKF, justifying a definitive trial.Peer reviewe

Predicting outcome in patients with anti-GBM glomerulonephritis

Background and objectives Large studies on long-term kidney outcome in patients with anti-glomerular basement membrane (anti-GBM) GN are lacking. This study aimed to identify clinical and histopathologic parameters that predict kidney outcome in these patients. Design, setting, participants, &measurements This retrospective analysis included a total of 123 patients with anti-GBM GN between 1986 and 2015 from six centers worldwide. Their kidney biopsy samples were classified according to the histopathologic classification for ANCA-associated GN. Clinical data such as details of treatment were retrieved from clinical records. The primary outcome parameter was the occurrence of ESRD. Kidney survival was analyzed using the log-rank test and Cox regression analyses. Results The 5-year kidney survival rate was 34%, with an improved rate observed among patients diagnosed after 2007 (P=0.01). In patients with anti-GBM GN, histopathologic class and kidney survival were associated (P˂ 0.001). Only one of 15 patients with a focal class biopsy sample (≥50% normal glomeruli) developed ESRD. Patients with a sclerotic class biopsy sample (≥50% globally sclerotic glomeruli) and patients with 100% cellular crescents did not recover from dialysis dependency at presentation. Inmultivariable analysis, dialysis dependency at presentation (hazard ratio [HR], 3.17; 95% confidence interval [95% CI], 1.59 to 6.32), percentage of normal glomeruli (HR, 0.97; 95% CI, 0.95 to 0.99), and extent of interstitial infiltrate (HR, 2.02; 95% CI, 1.17 to 3.50) were predictors of ESRD during follow-up. Conclusions Dialysis dependency, low percentage of normal glomeruli, and large extent of interstitial infiltrate are associated with poor kidney outcome in anti-GBM GN. Kidney outcome has improved during recent years; the success rate doubled after 2007