Dialysis – Transplantation
Kidney International (2003) 64, 1883–1892; doi:10.1046/j.1523-1755.2003.00275.x
Aristolochic acid nephropathy and the peritoneum: Functional, structural, and molecular studies
Gaëlle Gillerot, Eric Goffin, Pierre Moulin, Volker M Arlt, David H Phillips, Jean-Pierre Cosyns and Olivier Devuyst
Division of Nephrology and Department of Pathology, Université Catholique de Louvain Medical School, Brussels, Belgium; Section of Molecular Carcinogenesis, Institute of Cancer Research, Sutton, United Kingdom
Correspondence: Olivier Devuyst, M.D., Ph.D., Division of Nephrology, Université Catholique de Louvain Medical School, 10 Avenue Hippocrate, B-1200 Brussels, Belgium. E-mail: devuyst@nefr.ucl.ac.be
Received 10 April 2003; Revised 8 June 2003; Accepted 26 June 2003.
Abstract
Aristolochic acid nephropathy and the peritoneum: Functional, structural, and molecular studies.
Background
Aristolochic acid nephropathy (AAN) is a rapidly progressive interstitial nephropathy linked to the exposure to aristolochic acid (AA) and characterized by extensive fibrosis and urothelial atypia. Although the fibrotic process has been documented in extrarenal tissues, the involvement of the peritoneum, as well as the efficacy of peritoneal dialysis in AAN patients, remain uncertain.
Methods
The structure of the peritoneal membrane and the expression of basic fibroblast growth factor (bFGF), collagen type III, endothelial nitric oxide synthase (eNOS), and aquaporin-1 (AQP1) were investigated in peritoneal biopsies from an index AAN patient, four other AAN patients, four regular peritoneal dialysis patients, and two controls. Similar methods were used to investigate a rabbit model of AAN after intraperitoneal exposure to high-dose AA. AA-DNA adducts were screened by 32P-postlabeling analysis.
Results
The AAN patients had renal failure, renal fibrosis, and urothelial atypia. The peritoneum of AAN patients had a normal structure, lacked cellular atypia, and, in comparison with regular peritoneal dialysis patients and controls, did not show abnormal regulation of fibrotic and endothelial markers. Furthermore, specific AA-DNA adducts were not identified in the peritoneum of AAN patients. In contrast, AA-DNA adducts were detected in peritoneal and kidney tissues of all exposed rabbits, and one of them developed a malignant mesothelioma.
Conclusion
These data demonstrate the lack of fibrotic and vascular alterations and the absence of cellular atypia in the peritoneum from AAN patients. Thus, peritoneal dialysis should not be discouraged in these patients. Nevertheless, studies in a rabbit model of high-dose AA exposure may suggest a potential risk of peritoneal malignancy.
Keywords:
aquaporin-1, aristolochic acid, DNA adducts, aristolochic acid, collagen, endothelial nitric oxide synthase, fibrosis, mesothelioma, peritoneal dialysis, peritoneal membrane
