The upswing in application of peritoneal dialysis as a chronic ambulatory technique has renewed interest in the transport properties of the peritoneal membrane. Previous work has centered on studies of peritoneal clearance using isotonic solutions and has given rise to the concept that the peritoneum functions like a pore containing semipermeable membrane that is far more open than cuprophane dialysis membrane but is of small surface area. Although various anatomical structures (e.g. capillary endothelium, basement membrane, interstitium, mesothelial membrane, and attendant stagnant fluid films) have been identified as potential barriers to transport, the relative importance of each element is at present both unknown and difficult to test. Our preliminary studies in the rabbit have shown that diffusional transport across the peritoneum shows no restriction to solute diffusion over a broad range of solute sizes, supporting the present concept of a very open membrane structure. Convective transport resulting from osmotically induced ultrafiltration, however, indicates a surprisingly tight membrane structure. This paradox of the same membrane performing simultaneously as an open diffusion barrier and a tight ultrafiltration barrier may be resolved by proposing a dual barrier model of peritoneal transport. Our model predicts that during convective transport it is the tight proximal membrane, i.e. capillary endothelium, that determines the solute reflection coefficient. During diffusional transport, however, the relatively thick, yet open interstitium is the major mass transfer resistance for solutes of all sizes. The capillary endothelium, generally considered to be the major diffusional mass transfer barrier, is shown to be relatively unimportant in governing diffusional transport across the peritoneum. Our goal for this work is to verify this dual barrier model in the rabbit. With details of the experimental design in hand these studies will be repeated in man to confirm or (deny) that the rabbit is a useful experimental model for human peritoneal dialysis. This more fundamental understanding of peritoneal transport will permit a more scientific approach to selecting alternative osmotic agents than glucose, to improve dosing schedules for periotoneally administered anticancer agents, and most importantly, to better understand and assess the impact on peritoneal transport of both time on dialysis and peritonitis.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK035862-03
Application #
3234131
Study Section
General Medicine B Study Section (GMB)
Project Start
1985-07-01
Project End
1988-09-30
Budget Start
1987-07-01
Budget End
1988-09-30
Support Year
3
Fiscal Year
1987
Total Cost
Indirect Cost
Name
University of California San Diego
Department
Type
Schools of Medicine
DUNS #
077758407
City
La Jolla
State
CA
Country
United States
Zip Code
92093
Leypoldt, J K; Henderson, L W (1992) The effect of convection on bidirectional peritoneal solute transport: predictions from a distributed model. Ann Biomed Eng 20:463-80
Bell, J L; Leypoldt, J K; Frigon, R P et al. (1990) Hydraulically-induced convective solute transport across the rabbit peritoneum. Kidney Int 38:19-27