Biocompatible dialysis fluids for peritoneal dialysis

What is the issue?

Peritoneal dialysis is a form of dialysis therapy for people with kidney failure delivered at home. Patients are required to use peritoneal dialysis solutions to perform the dialysis by putting solution in their abdomen. Peritoneal dialysis uses the lining of the abdomen called the “peritoneal membrane” as a filter, across which toxins and fluids are removed from the body. The longevity of peritoneal dialysis can be limited by peritoneal membrane injury, which is partly as a result of biologically 'unfriendly' peritoneal dialysis solutions, which are acidic and consist of high levels of glucose and toxic glucose breakdown products. To overcome these hurdles, biocompatible peritoneal dialysis solutions (i.e. with a neutral pH and low levels of glucose breakdown products or with a glucose-alternative like icodextrin) have been manufactured with the aim of providing patient benefit.

What did we do?

We conducted a review of the literature to examine the benefits and harms from the use of biocompatible peritoneal dialysis solutions.

What did we find?

We identified 42 studies (3262 participants) examining the effects of these solutions on patient outcomes. When compared to conventional peritoneal dialysis solutions, we found that neutral pH, low glucose breakdown product peritoneal dialysis solutions resulted in better preservation of a patient's own kidney function including urine output. Patients who received non-glucose based (icodextrin) peritoneal dialysis solutions achieved greater fluid removal with their dialysis and were 70% less likely to experience uncontrolled episodes of fluid overload. No significant harms were identified with any of the biocompatible peritoneal dialysis solutions. Many of the studies were limited by small size, short follow-up duration, suboptimal methodological quality, and inconsistent reporting of outcomes. Consequently, the effects of biocompatible peritoneal dialysis solutions on the length of time that a patient is able to either remain on peritoneal dialysis or stay alive are uncertain.

Conclusions
Compared with peritoneal dialysis patients treated with conventional peritoneal dialysis solutions, those treated with biocompatible solutions experience important benefits including better preservation of their own kidney function and urine volume with neutral pH, low glucose breakdown product peritoneal dialysis solutions and more effective prevention of fluid overload due to increased dialysis-related fluid removal with icodextrin. Whether these benefits help patients to stay on peritoneal dialysis longer or live longer are uncertain and require further study.

Authors' conclusions: 

This updated review strengthens evidence that neutral pH, low GDP PD solution improves RRF and urine volume preservation with high certainty. These effects may be related to increased peritoneal solute transport and reduced peritoneal ultrafiltration, although the evidence for these outcomes is of low certainty due to significant heterogeneity and suboptimal methodological quality. Icodextrin prescription increased peritoneal ultrafiltration and mitigated uncontrolled fluid overload with moderate certainty. The effects of either neutral pH, low GDP solution or icodextrin on peritonitis, technique survival and patient survival remain uncertain and require further high quality, adequately powered RCTs.

Read the full abstract...
Background: 

Biocompatible peritoneal dialysis (PD) solutions, including neutral pH, low glucose degradation product (GDP) solutions and icodextrin, have previously been shown to favourably influence some patient-level outcomes, albeit based on generally sub-optimal quality studies. Several additional randomised controlled trials (RCT) evaluating biocompatible solutions in PD patients have been published recently. This is an update of a review first published in 2014.

Objectives: 

This review aimed to look at the benefits and harms of biocompatible PD solutions in comparison to standard PD solutions in patients receiving PD.

Search strategy: 

The Cochrane Kidney and Transplant Specialised Register was searched up to 12 February 2018 through contact with the Information Specialist using search terms relevant to this review. Studies in the Specialised Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register Search Portal and ClinicalTrials.gov.

Selection criteria: 

All RCTs and quasi-RCTs in adults and children comparing the effects of biocompatible PD solutions (neutral pH, lactate-buffered, low GDP; neutral pH, bicarbonate(± lactate)-buffered, low GDP; glucose polymer (icodextrin)) in PD were included. Studies of amino acid-based solutions were excluded.

Data collection and analysis: 

Two authors extracted data on study quality and outcomes. Summary effect estimates were obtained using a random-effects model, and results were expressed as risk ratios and 95% confidence intervals (CI) for categorical variables, and mean differences (MD) or standardised mean differences (SMD) and 95% CI for continuous variables.

Main results: 

This review update included 42 eligible studies (3262 participants), including six new studies (543 participants). Overall, 29 studies (1971 participants) compared neutral pH, low GDP PD solution with conventional PD solution, and 13 studies (1291 participants) compared icodextrin with conventional PD solution. Risk of bias was assessed as high for sequence generation in three studies, allocation concealment in three studies, attrition bias in 21 studies, and selective outcome reporting bias in 16 studies.

Neutral pH, low GDP versus conventional glucose PD solution

Use of neutral pH, low GDP PD solutions improved residual renal function (RRF) preservation (15 studies, 835 participants: SMD 0.19, 95% CI 0.05 to 0.33; high certainty evidence). This approximated to a mean difference in glomerular filtration rate of 0.54 mL/min/1.73 m2 (95% CI 0.14 to 0.93). Better preservation of RRF was evident at all follow-up durations with progressively greater preservation observed with increasing follow up duration. Neutral pH, low GDP PD solution use also improved residual urine volume preservation (11 studies, 791 participants: MD 114.37 mL/day, 95% CI 47.09 to 181.65; high certainty evidence). In low certainty evidence, neutral pH, low GDP solutions may make little or no difference to 4-hour peritoneal ultrafiltration (9 studies, 414 participants: SMD -0.42, 95% CI -0.74 to -0.10) which approximated to a mean difference in peritoneal ultrafiltration of 69.72 mL (16.60 to 122.00 mL) lower, and may increase dialysate:plasma creatinine ratio (10 studies, 746 participants: MD 0.01, 95% CI 0.00 to 0.03), technique failure or death compared with conventional PD solutions. It is uncertain whether neutral pH, low GDP PD solution use led to any differences in peritonitis occurrence, hospitalisation, adverse events (6 studies, 519 participants) or inflow pain (1 study, 58 participants: RR 0.51, 95% CI 0.24 to 1.08).

Glucose polymer (icodextrin) versus conventional glucose PD solution

In moderate certainty evidence, icodextrin probably reduced episodes of uncontrolled fluid overload (2 studies, 100 participants: RR 0.30, 95% CI 0.15 to 0.59) and augmented peritoneal ultrafiltration (4 studies, 102 participants: MD 448.54 mL/d, 95% CI 289.28 to 607.80) without compromising RRF (4 studies, 114 participants: SMD 0.12, 95% CI -0.26 to 0.49; low certainty evidence) which approximated to a mean creatinine clearance of 0.30 mL/min/1.73m2 higher (0.65 lower to 1.23 higher) or urine output (3 studies, 69 participants: MD -88.88 mL/d, 95% CI -356.88 to 179.12; low certainty evidence). It is uncertain whether icodextrin use led to any differences in adverse events (5 studies, 816 participants) technique failure or death.