Icodextrin Versus Glucose Solutions for the Once-Daily Long Dwell in Peritoneal Dialysis: An Enriched Systematic Review and Meta-analysis of Randomized Controlled Trials

Rationale & Objective</br> The efficacy and safety of icodextrin versus glucose-only peritoneal dialysis (PD) regimens is unclear. The aim of this study was to compare once-daily long-dwell icodextrin versus glucose among patients with kidney failure undergoing PD.</br> Study Design</br> Systematic review of randomized controlled trials (RCTs), enriched with unpublished data from investigator-initiated and industry-sponsored studies.</br> Setting & Study Populations</br> Individuals with kidney failure receiving regular PD treatment enrolled in clinical trials of dialysate composition.</br> Selection Criteria for Studies</br> Medline, Embase, CENTRAL, Ichushi Web, 10 Chinese databases, clinical trials registries, conference proceedings, and citation lists from inception to November 2018. Further data were obtained from principal investigators and industry clinical study reports.</br> Data Extraction</br> 2 independent reviewers selected studies and extracted data using a prespecified extraction instrument.</br> Analytic Approach</br> Qualitative synthesis of demographics, measurement scales, and outcomes. Quantitative synthesis with Mantel-Haenszel risk ratios (RRs), Peto odds ratios (ORs), or (standardized) mean differences (MDs). Risk of bias of included studies at the outcome level was assessed using the Cochrane risk-of-bias tool for RCTs.</br> Results</br> 19 RCTs that enrolled 1,693 participants were meta-analyzed. Ultrafiltration was improved with icodextrin (medium-term MD, 208.92 [95% CI, 99.69-318.14] mL/24 h; high certainty of evidence), reflected also by fewer episodes of fluid overload (RR, 0.43 [95% CI, 0.24-0.78]; high certainty). Icodextrin-containing PD probably decreased mortality risk compared to glucose-only PD (Peto OR, 0.49 [95% CI, 0.24-1.00]; moderate certainty). Despite evidence of lower peritoneal glucose absorption with icodextrin-containing PD (medium-term MD, −40.84 [95% CI, −48.09 to −33.59] g/long dwell; high certainty), this did not directly translate to changes in fasting plasma glucose (−0.50 [95% CI, −1.19 to 0.18] mmol/L; low certainty) and hemoglobin A1c levels (−0.14% [95% CI, −0.34% to 0.05%]; high certainty). Safety outcomes and residual kidney function were similar in both groups; health-related quality-of-life and pain scores were inconclusive.</br> Limitations</br> Trial quality was variable. The follow-up period was heterogeneous, with a paucity of assessments over the long term. Mortality results are based on just 32 events and were not corroborated using time-to-event analysis of individual patient data.</br> Conclusions</br> Icodextrin for once-daily long-dwell PD has clinical benefit for some patients, including those not meeting ultrafiltration targets and at risk for fluid overload. Future research into patient-centered outcomes and cost-effectiveness associated with icodextrin is needed.