The Standard Peritoneal Permeability Analysis in the Rabbit: A Longitudinal Model for Peritoneal Dialysis

Abstract

Objective The development of an experimental peritoneal dialysis (PD) model in rabbits to investigate peritoneal transport characteristics during a longitudinal follow-up and to assess normal values of these peritoneal transport parameters. Design Peritoneal transport parameters were determined in conscious, unrestrained rabbits by standard peritoneal permeability analysis adjusted for rabbits (SPAR). In this test a 1-hour dwell with 3.86% glucose dialysate is used. Dextran 70 (1 g/L) was added to the dialysate to allow calculation of fluid kinetics. Dialysate samples were taken before, 10, and 40 minutes after instillation and at the end of the dwell. Blood was drawn at the end of the dwell. Experimental Animals Eighteen female New Zealand White rabbits (2565 g) were included for catheter implantation. SPARs were performed in 15 animals; the other 3 were excluded due to complications. Main Outcome The mass transfer area coefficients (MTACs) of the low molecular weight solutes urea (MTACurea) and creatinine (MTACcr) were calculated. The clearances of albumin (Clalb) and IgG (ClIgG), glucose absorption, and fluid transport were computed. Coefficients of intraindividual variation (Vc) were calculated for these parameters. Results The main complications were catheter obstruction and/or dislocation. Five rabbits underwent uncomplicated PD during a 4-week period. Fifteen SPARs in 15 stable rabbits were performed and analyzed to obtain normal values. Means and standard deviations of the transport parameters were as follows: MTACurea 2.24 ± 0.57 mL/min, MTACcr 1.61 ± 0.30 mL/min, Clalb 52.9 ± 17.2 μL/min, ClIgG 44.5 ± 22.9 μL/min. The transcapillary ultrafiltration rate was 0.66 ± 0.13 mL/min and the lymphatic absorption rate 0.47 ± 0.26 mL/min. The parameters of solute transport were upscaled to those in humans using two different methods. MTACs of low molecular weight solutes in rabbits and patients were of the same order of magnitude, but the clearance of albumin was approximately four times higher in rabbits than in patients, and that of IgG eight times. In all rabbits sieving of sodium was observed. The dialysate/plasma (D/P) of sodium decreased to a minimum at 40 min ( p < 0.003 vs the initial value), followed by a rise to 60 min. The minimal value was 0.884 ± 0.002. The coefficients of variation calculated on 7 rabbits that underwent two or more SPARs were similar to those assessed from the patient data. This indicates stability of the model and reproducibility of the SPAR. Conclusion The conscious rabbit model for PD can be used for repeated studies on peritoneal transport.

Ultrafiltration Characteristics of Glucose Polymers with Low Polydispersity

“…The results from this study demonstrate that differences in UF characteristics between solutions containing two experimental glucose polymers with low polydispersity can be revealed using a rabbit model of PD. Rabbit models have been used for decades to evaluate PD solutions and peritoneal transport (15)(16)(17)(18)(19), but no such evaluations of dialysis solutions containing glucose polymers as osmotic agents have been published, except for our previous work in abstract form (10). There are two advantages to using a rabbit model, compared with a rat model, to evaluate dialysis solutions containing glucose polymers as osmotic agents: • The kinetics of UF in rat models of PD using icodextrin as the osmotic agent have been reported to differ significantly from those in human PD (13,(20)(21)(22).…”

Experimental systems to study the origin of the myofibroblast in peritoneal fibrosis

“…The use of immunofluorescence labeling of epithelial and myofibroblast markers to identify cells undergoing EMT has been criticized. This provides only a static picture of the cellular response to injury, and we have shown that this picture looks very different depending on the point of time in the injury response [33] , [45] . Furthermore, there are criticisms of immunofluorescence studies including the nonspecificity of antibodies used and image-processing artifacts.…”

“…In a standard acute model of PD, fluid is infused by intraperitoneal injection or a temporary catheter into the peritoneal cavity in mice, rats, rabbit, and sheep [43] , [44] . This model has been important in understanding properties of solute transport across the peritoneal membrane, changes in the interstitial matrix, and changes in attachment and morphology of mesothelial cells during injury [ [45] , [46] , [47] ]. The chronic infusion model of PD uses a peritoneal catheter implanted into rodents which then receive a daily or twice daily infusion of dialysis fluid for a span of 4–20 weeks [48] .…”

Animal Models in Peritoneal Dialysis Research: A Need for Consensus

“…High serum amylase levels are not unique to rats, occurring also in other rodents, such as mice and guinea pigs (51). Mouse (52)(53)(54) and rabbit models (55)(56)(57) have also been used in PD research. Although rabbit models allow PD to be performed for long periods of time and mimic certain aspects of the human situation (The ratio of peritoneal surface area and exchange volume in rabbits and human is similar.…”