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

Abstract

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. Study Design: Systematic review of randomized controlled trials (RCTs), enriched with unpublished data from investigator-initiated and industry-sponsored studies. Setting & Study Populations: Individuals with kidney failure receiving regular PD treatment enrolled in clinical trials of dialysate composition. Selection Criteria for Studies: 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. Data Extraction: 2 independent reviewers selected studies and extracted data using a prespecified extraction instrument. Analytic Approach: 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. Results: 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 A 1c 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. Limitations: Trial quality was variable. The followup 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. Conclusions: 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 costeffectiveness associated with icodextrin is needed. T he prevalence of kidney replacement therapy is expected to increase steeply. 1 Approximately 15% of dialysis patients globally use peritoneal dialysis (PD), and this proportion is increasing. 2 PD is probably associated with the same survival as hemodialysis (HD) 3-6 but pre...

A Novel Formulation of Glucose-Sparing Peritoneal Dialysis Solutions with l-Carnitine Improves Biocompatibility on Human Mesothelial Cells

“…Icodextrin is a glucose polymer derived from starch which allows a slow but sustained peritoneal UF and is indicated for use during a single long dwell per day [14]. A recent systematic review and meta-analysis showed that the use of icodextrin-containing PD solution, compared to a glucose-only PD regimen, improves peritoneal UF and reduces episodes of fluid overload [15]. However, this acidic PD solution has been associated with increased local and systemic inflammation [16,17].…”

The osmo-metabolic approach: a novel and tantalizing glucose-sparing strategy in peritoneal dialysis

“…There are several studies suggesting that long-term utilization of icodextrin solution may extend patient and technique survival in PD [32][33][34]. A very recent systematic review and meta-analysis examined the efficacy and safety of icodextrin versus glucose-only PD regimens [35]. Data analyzed were from 19 randomized controlled trials, enriched with unpublished data from investigator-initiated and industry-sponsored studies.…”

Proteomic Research in Peritoneal Dialysis

“…Icodextrin is of particular value in high transporter PD patients, and it improves patient UF without increased risk of adverse effects. A recent systematic review and meta-analysis from 11 randomized controlled trials, enriched with unpublished data from industry-sponsored and investigator-initiated studies, has shown that compared to a glucose-only PD regimen, use of icodextrin-containing PD solution has clear fluid benefits, such as improvement of peritoneal UF and fewer episodes of fluid overload [ 51 ]. In 16 pediatric patients on APD, Bruschi et al [ 52 ] examined the proteomic profile (2DE and MS) of PDE after a 14-h daytime dwell, performed on two consecutive days with a 7.5% weight/volume icodextrin solution and a 3.86% weight/volume glucose solution.…”