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

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.

Initiating haemodialysis twice-weekly as part of an incremental programme may protect residual kidney function.

BACKGROUND: Initiating twice-weekly haemodialysis (2×HD) in patients who retain significant residual kidney function (RKF) may have benefits. We aimed to determine differences between patients initiated on twice- and thrice-weekly regimes, with respect to loss of kidney function, survival and other safety parameters. METHODS: We conducted a single-centre retrospective study of patients initiating dialysis with a residual urea clearance (KRU) of ≥3 mL/min, over a 20-year period. Patients who had 2×HD for ≥3 months during the 12 months following initiation of 2×HD were identified for comparison with those dialysed thrice-weekly (3×HD). RESULTS: The 2×HD group consisted of 154 patients, and the 3×HD group 411 patients. The 2×HD patients were younger (59 ± 15 versus 62 ± 15 years: P = 0.014) and weighed less (70 ± 16 versus 80 ± 18 kg: P < 0.001). More were females (34% versus 27%: P = 0.004). Fewer had diabetes (25% versus 34%: P = 0.04) and peripheral vascular disease (PVD) (13% versus 23%: P = 0.008). Baseline KRU was similar in both groups (5.3 ± 2.4 for 2 × HD versus 5.1 ± 2.8 mL/min for 3 × HD: P = 0.507). In a mixed effects model correcting for between-group differences in comorbidities and demographics, 3×HD was associated with increased rate of loss of KRU and separation of KRU. In separate mixed effects models, group (2×HD versus 3×HD) was not associated with differences in serum potassium or phosphate, and the groups did not differ with respect to total standard Kt/V. Survival, adjusted for age, gender, weight, baseline KRU and comorbidity (prevalence of diabetes, cardiac disease, PVD and malignancy) was greater in the 2×HD group (hazard ratio 0.755: P = 0.044). In sub-analyses, the survival benefit was confined to women, and those of less than median bodyweight. CONCLUSION: 2×HD initiation as part of an incremental programme with regular monthly monitoring of KRU was safe and associated with a reduced rate of loss of RKF early after dialysis initiation and improved survival. Randomized controlled trials of this approach are indicated.

Measuring Residual Renal Function in Hemodialysis Patients without Urine Collection.

Many patients on hemodialysis retain significant residual renal function (RRF) but currently measurement of RRF in routine clinical practice can only be achieved using inter-dialytic urine collections to measure urea and creatinine clearances. Urine collections are difficult and inconvenient for patients and staff, and therefore RRF is not universally measured. Methods to assess RRF without reliance on urine collections are needed since RRF provides useful clinical and prognostic information and also permits the application of incremental hemodialysis techniques. Significant efforts have been made to explore the use of serum based biomarkers such as cystatin C, ß-trace protein and ß2 -microglobulin to estimate RRF. This article reviews blood-based biomarkers and novel methods using exogenous filtration markers which show potential in estimating RRF in hemodialysis patients without the need for urine collection.