High glucose decreases collagenase expression and increases TIMP expression in cultured human peritoneal mesothelial cells.
BACKGROUND Peritoneal sclerosis is a histopathologic finding that is probably causative of long-term system failure in peritoneal dialysis (PD). It may be due to uremic toxicity and the influence of peritoneal dialysate components. We intended to clarify to which degree peritoneal fibrosis and vascular changes were associated with the modalities of PD and the peritoneal transport characteristics. METHODS Peritoneal biopsies of 41 patients suffering from end-stage renal disease were examined. Sixteen patients were at the initiation of dialysis treatment, and 25 patients were studied during chronic PD treatment [9 patients on continuous ambulatory PD (CAPD) and 16 patients on automatic PD (APD)]. Twenty nonuremic patients undergoing abdominal surgery served as the controls. Samples were taken from the parietal peritoneum under standardized conditions and were examined by light microscopy using different staining techniques, semiquantitative grading, and computer-based histomorphometry. RESULTS A marked loss of mesothelial cells during PD treatment was only observed in cases with two or more preceding episodes of peritonitis, but an increase of the submesothelial fibrous tissue was a common finding and was related to the cumulative glucose load on PD. Patients on PD also had a significantly increased density of small vessels and capillaries in the submesothelial peritoneal layer (12.8 +/- 6.9 per field vs. 6.6 +/- 2.9 in normal controls, P < 0.01). The wall/lumen index of the vessels was increased indicating vascular sclerosis. The degree of vascularization correlated with the amount of fibrous tissue. Patients characterized as high transporters according to the peritoneal equilibration test (PET) had an increased submesothelial fibrous layer. Patients on APD tended to have an increased membrane diameter submesothelial stroma and vascularization (P = NS), although they were treated for a shorter period of time than the CAPD group. Some of the morphologic changes described could already be observed in uremic patients before the onset of dialysis. CONCLUSION Further research focusing on the clinical and biochemical backgrounds leading to peritoneal membrane changes is of major importance for developing strategies to improve long-term survival on PD.