Substituting Citrate for Lactate in Peritoneal Dialysis Fluid Improves Ultrafiltration in Rats

Abstract

Background Exposure to peritoneal dialysis (PD) fluid induces an inflammatory response in the peritoneal cavity. Blockers of complement and coagulation have improved ultrafiltration in animal models of PD. Citrate is a clinically established anticoagulant that also blocks complement activation. Objective The aim of the present study was to evaluate the effects on ultrafiltration of a gradual substitution of citrate for lactate in an experimental model of PD. Methods Fractions (0, 5, 10, and 15 mmol/L) of the 40 mmol/L lactate buffer of filter-sterilized 2.5% glucose PD fluid were replaced by citrate. The modified fluids were compared in a rat model of single PD fluid exposure through an indwelling catheter. The initial kinetics of citrate and ionized calcium were evaluated in separate, single, short time dwell experiments. Results Replacing 10 and 15 mmol/L of the lactate buffer by sodium citrate significantly increased osmotic ultrafiltration (by 24.7% ± 7.7% at 10 mmol/L), net ultrafiltration, and glucose retention at 4 hours of dwell time in the rat model. Osmotic ultrafiltration was significantly correlated to citrate concentration and glucose concentration. Citrate was rapidly eliminated from the peritoneal cavity, concentrations falling to less than half in 1 hour and concentrations of calcium ions concomitantly normalized. Conclusions Substituting citrate for lactate induced a dose-dependent increase in ultrafiltration. Mechanisms probably involve the relation between diffusion and ultrafiltration, leading to increased glucose retention. The increase in ultrafiltration was quantitatively important at a citrate concentration (10 mmol/L) that is compatible with clinical applications of citrate.

Catheter Patency and Peritoneal Morphology and Function in a Rat Model of Citrate-Buffered Peritoneal Dialysis

“…Intraperitoneal volume was determined from the dilution of radiolabeled albumin used as volume marker (3,9-11). Thus, 10 kBq 125 I-labeled human serum albumin (GE Healthcare, Kjeller, Norway) was added to the PD fluid in combination with 1 mg unlabeled BSA to block surface adsorption of the tracer.…”

“…After collecting the 2-hour sample, 10 mL PD fluid without volume marker was injected through the catheter and a final sample was obtained. The dilution of tracer, induced by this injection, was used to calculate the final intraperitoneal fluid volume (3,12). Osmotic UF, net UF, and fluid reabsorption were calculated by combining data from tracer dilution during the dwell with the measured final intraperitoneal fluid volume and the known total activity of tracer infused.…”

“…The study in humans was preceded by a study in rats that showed slightly different results. There was also improvement in net UF but, in the animal model, this was accounted for mainly by improved osmotic (transcapillary) UF (3).…”

“…Single dwells of citrate-supplemented (2) or citrate-substituted (3) PD fluids seem to be safe in rats and humans. Citrate is a well-established anticoagulant in clinical use.…”

Ultrafiltration and the Buffer: One More Interaction to Consider?

“…In this issue of Peritoneal Dialysis International , Cavallini and colleagues report yet another interaction between glucose (the osmotic agent employed) and a new buffer system that partially substitutes lactate with citrate (12). This is an acute rat study that reports an increase in net UF of about 25% during a 4-hour dwell when 10 mmol/L lactate is substituted with citrate.…”