Efficacy of tapioca derivative-based peritoneal dialysis solution compared with glucose-based and corn derivative-based solutions

Abstract

To investigate the safety and effectiveness of the new product tapioca derivative-based peritoneal dialysis fluid (PDF) compared to corn derivative-based PDF and standard glucose-based PDF, in-vitro and in-vivo toxicity as well as ex-vivo fluid shift were studied. The in-vivo cytotoxicity using LDH assay, cell proliferation, and cell death were assessed in different cell cultures, including primary human mesothelial peritoneal cells (HMPCs), fibroblast cell line, and peripheral mononuclear cells. After the cells exposure to various PDFs, the apoptotic and necrotic fibroblast and PBMC were labeled with Annexin V/propidium lodide and counted by FACS Calibur Flow Cytometer, Viability and proliferation of fibroblast and PBMC were assessed by MTT assay. Bal/C mice were subjected to daily injection with 1) intra-peritoneal (IP) route of 20% tapioca-based PDF 2) intravenously (IV) route of 15% TPDF at dosage of 5 and 10 mL/kg 3) IP and IV routes of 0.9% normal saline served as controls. After 14-day injections, mice were sacrificed for gross pathology and histology examinations. The ex-vivo effectiveness study was experimented by filling various PDFs into 10 kDa cut-off cellophane bags placed in water & plasma containers. Mass changes of the bags were measured and calculated. The HPLC was also performed to detect the starch derivatives inside and outside the bag. The mathematic formulation and computer-simulation were proposed to imitate the fluid flux across the membrane. 7.5% tapioca-based pull larger amount of fluid but slower rate of flux compared to the glucose-based PDF; however, it dragged slightly higher amount but equivocal rate compared to the corn-based PDF. Besides colloid osmotic pressure, the diffusion of small molecule also affected the fluid shift. A mathematical model also confirmed this phenomenon. HMPC were more venerable to injure with PDF compared to fibroblast and mononuclear cells. Treatments with tapioca-and corned-based PDFs yielded better cell preservation in terms of morphology, proliferation, and cell death, although the higher dosage of tapioca-based PDF (15%) were used, compared to glucose-based PDF. No significant clinical parameters, weight reduction, and animal lost were detected. Moreover, the gross pathology and histology yielded no significant abnormalities compared to control group. In conclusion, tapioca-based and corned-based PDF have similar fluid recruitment and cellular preservation effects but are superior to conventional glucose PDF in terms of safety and efficacy. Usage of tapioca-based solution seems to be possible in the clinical practice as a polyglucose PDF.