NephrologyNow The Ultimate Guide to Kidney Disease Research

This is an RCT conducted in London on the effect of new biocompatible peritoneal dialysis solution vs usual PD solutions. The study funding is not indicated. The investigators have received educational and travel grants from both Baxter and Fresenius.
The objective of the study was identified as changes in residual renal function over 1 year defined by the 24 hour urine volume and normalized creatinine clearance. The rational for choosing this as the primary endpoint is not explained in sufficient detail to understand how the biocompatible solutions impact on renal function. Entry criteria were incident PD patients in their units not on the Baxter UV flash system. Randomization method is not described. The recruitment period is from Jan 2004 to Dec 2005 but time from recruitment to allocation of treatment is not given. The study is unblinded however the outcome measures are objective. Residual renal function defined as urine volume over 24 hours and the mean of urea and normalized creatinine clearance over 24 hours assessed by 24 hour urine at 3 and 12 months from starting PD were the outcome measures. A pre-study sample size calculation was reported estimating 80% power to show a difference in residual renal function between the two groups using Student’s t-test with an alpha of 0.05. A separate analysis for non-inferiority was planned for preservation of residual renal function of 1 ml/min and urine volume of 300ml per day.
The treatment and control groups were comparable in table 1, although Hb levels trended higher in the control group with standard solutions. Of 118 randomized 93 are reported (21% loss) and the reasons for loss described. No side effects were noted.

Statistical procedures were described with Student’s t for the main outcome measures and Kaplan-Meier PD survival curves for secondary endpoints including peritonitis and PD technique survival. The main results were presented with means and the SEM rather than confidence intervals.

No differences were found between the two solutions for residual renal function, technique survival, peritonitis rates or on additional end points including CRP and D/Pcreat and 4 hour UF rates during a PET.

The non-inferiority tests were significant for non-inferiority.

This study demonstrates the difficulty of demonstrating superiority in a small RCT where loss to follow up, wide confidence intervals, small numbers, and end points that lack true validation (and also that likely differ between dialysis units lowering generalizability) reduce the chances of finding a difference if one truly exists. We must be cautious in our interpretations because all of these factors make it more likely to find significant non-inferiority in this kind of study.

The conclusions of the manuscript are valid and I agree with them: No clinically significant advantage was found with the biocompatible solutions over standard PD solutions and additional studies (larger and more rigorous) are needed to determine if advantages are seen with longer term use. Hopefully industry will step up to the plate.

Finally, in relatively healthy subjects I don’t think that the detrimental effect of standard solutions on mesothelial cells and the immune system of the peritoneum found in the basic science lab will manifest rapidly enough to show up within a year, particularly on residual renal function. My guess is that the potential benefit of biocompatible solutions would be demonstrated quickest on the recovery of a sick mesothelium such as patients with peritonitis where more rapid healing and recovery with a return to normal cell counts faster may be a better test of their potential benefit to our PD patients. Otherwise, this kind of study requires many more patients followed over longer time.