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Impact of Uremia, Diabetes, and Peritoneal Dialysis Itself on the Pathogenesis of Peritoneal Sclerosis: A Quantitative Study of Peritoneal Membrane Morphology

Kazuho Honda^*, Chieko Hamada, Masaaki Nakayama, Masanobu Miyazaki, Ali M. Sherif^||, Takashi Harada^¶, Hiroshi Hirano^**; on behalf of the Peritoneal Biopsy Study Group of the Japanese Society for Peritoneal Dialysis

^* Department of Pathology, Tokyo Women's Medical University, Tokyo, Division of Nephrology, Department of Internal Medicine, Juntendo Medical University, Tokyo, Research Division of Dialysis and Chronic Kidney Disease, Tohoku University Graduate School of Medicine, Sendai, Department of Medicine, Nagasaki University School of Medicine, and Miyazaki Clinic, Nagasaki, ^|| Department of Kidney and Hypertension, Jikei University School of Medicine, Tokyo, ^¶ Department of Blood Purification, Nagasaki University Hospital of Medicine and Dentistry, Nagasaki, and ^** Department of Medicine, Okinawa Hokubu-Ishikai Hospital, Okinawa, Japan

Correspondence: Dr. Kazuho Honda, Department of Pathology, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162-8666, Japan. Phone: +81-3-3353-8111, ext. 22342; Fax: +81-3-5269-7473; E-mail: honda{at}research.twmu.ac.jp

Background and objectives: Peritoneal interstitial fibrosis and hyalinizing vasculopathy were induced by peritoneal dialysis and other associated conditions (e.g., uremia). A quantitative method for peritoneal biopsy evaluation is required to investigate possible causative factors and severity of the peritoneal dialysis–related peritoneal alterations.

Design, setting, participants, & measurements: Peritoneal biopsy specimens from 173 uremic (before peritoneal dialysis) and 80 peritoneal dialysis patients with or without impaired ultrafiltration capacity were evaluated by average peritoneal thickness of submesothelial compact zone measured at five randomly selected points of peritoneum and by lumen/vessel diameter ratio at postcapillary venule.

Results: The average peritoneal thickness was increased in uremic patients and progressively thickened as the duration of peritoneal dialysis prolonged. The lumen/vessel diameter ratio was lower in uremia than normal and progressively decreased as the duration of peritoneal dialysis prolonged. In pre–peritoneal dialysis peritoneum, patients with diabetes showed significant decrease in lumen/vessel diameter ratio compared with patients without diabetes. The average peritoneal thickness was significantly higher in patients with impaired ultrafiltration capacity than in patients with maintained ultrafiltration capacity; however, no significant difference was observed in the postcapillary venule thickness and lumen/vessel diameter ratio between the two groups.

Conclusions: The average peritoneal thickness and lumen/vessel diameter ratio were useful morphologic parameters to quantify the severity of the peritoneal alterations in uremic and peritoneal dialysis patients. Uremia and diabetes had an impact on the pathogenesis of peritoneal sclerosis in pre–peritoneal dialysis peritoneum. Peritoneal dialysis treatment itself had a much stronger impact on the progression of peritoneal sclerosis.