A new peritoneal dialysis fluid for Japanese patients: a randomized non-inferiority clinical trial of safety and efficacy

Masaaki Nakayama,Teruhiko Maeba,Yoshindo Kawaguchi,Shigeko Hara,Noriaki Yorioka,Mark R Marshall,Masao Kim,Takashi Akiba,James A Sloand,Hidemune Naito

doi:10.1007/s10157-016-1346-9

Abstract

BackgroundWe report here two new peritoneal dialysis fluids (PDFs) for Japan [BLR 250, BLR 350 (Baxter Limited, Japan)]. The PDFs use two-chamber systems, and have bicarbonate and lactate buffer to a total of 35 mmol/L. In separate trials, the new PDFs were compared to two “standard” systems [PD-4, PD-2 (Baxter Limited, Japan)]. The trials aimed to demonstrate non-inferiority of peritoneal creatinine clearance (pCcr), peritoneal urea clearance (pCurea) and ultrafiltration volume (UF), and compare acid–base and electrolyte balance.MethodsWe performed randomized, multicenter, parallel group, controlled, open-label clinical trials in stable continuous ambulatory peritoneal dialysis (CAPD) patients. The primary endpoints were pCcr and UF. The secondary endpoints were serum bicarbonate and peritoneal urea clearance. The active phase was 8 weeks. These trials were performed as non-inferiority studies, with the lower limit of non-inferiority for pCcr and UF set at 3.2 L/week/1.73 m2 and 0.12 L/day, respectively.Results108 patients (28 centers) and 103 patients (29 centers) took part in the two trials. Groups were well balanced at baseline. The investigative PDFs were non-inferior to the “standard” ones in terms of primary endpoints, comparable in terms of pCurea, and superior in terms acid–base balance, especially correcting those with over-alkalinization at baseline.ConclusionsWe demonstrated fundamental functionality of two new PDFs and showed superior acid–base balance. Given the propensity of Japanese CAPD patients for alkalosis, it is important to avoid metabolic alkalosis which is associated with increased cardiovascular mortality risk and accelerated vascular calcification. The new PDFs are important progress of CAPD treatment for Japanese patients.

Highlights

There is global interest in expanded use of peritoneal dialysis (PD) to improve clinical outcomes and meet increasing resource constraints
Background We report here two new peritoneal dialysis fluids (PDFs) for Japan [BLR 250, BLR 350 (Baxter Limited, Japan)]
Given the propensity of Japanese continuous ambulatory peritoneal dialysis (CAPD) patients for alkalosis, it is important to avoid metabolic alkalosis which is associated with increased cardiovascular mortality risk and accelerated vascular calcification

Summary

Introduction

There is global interest in expanded use of peritoneal dialysis (PD) to improve clinical outcomes and meet increasing resource constraints. Vintage on PD therapy in Japan is longer than that in either the US or European countries This prolonged exposure to PD fluid has been of major clinical concern in those countries, due to the untoward cellular, local, and systemic effects from un-physiologic components within them. The biocompatibility of PD fluids (PDFs) can be increased through the use of a multi-compartment bag system that separates out the buffer from the glucose. The first system using these new PDFs (PhysionealÒ, Baxter Healthcare Inc, containing bicarbonate 25 mmol/L and lactate 15 mmol/L) was developed approximately 20 years ago and continues to be available in many parts of the world today. We report here two new peritoneal dialysis fluids (PDFs) for Japan [BLR 250, BLR 350 (Baxter Limited, Japan)]. The new PDFs were compared to two ‘‘standard’’ systems [PD-4, PD-2 (Baxter Limited, Japan)]. Medical University, Tokyo, Japan 6 Kaikou Clinic, Osaka, Japan 7 Osaka Dialysis Department, Kaiko-Kai Clinic, Osaka, Japan 8 Naito Medical Research Laboratory, Kobe, Hyogo, Japan 9 Hakubi-kai, Sano Ikawadani Hospital, Kobe, Hyogo, Japan

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Conclusion