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The Impact of Repeated Subclinical Acute Rejection on the Progression of Chronic Allograft Nephropathy

Seiichirou Shishido^*, Hiroshi Asanuma^*, Hideo Nakai, Yoshiaki Mori^*, Hiroyuki Satoh^*, Isamu Kamimaki, Hiroshi Hataya, Masahiro Ikeda, Masataka Honda and Akira Hasegawa^¶

*Department of Pediatric Urology and Kidney Transplantation, Tokyo Metropolitan Kiyose Children’s Hospital, Tokyo Japan; Department of Urology, Dokkyo University School of Medicine, Saitama, Japan; Division of Pediatrics, Clinical Research Department, National Saitama Hospital, Saitama, Japan; Department of Nephrology, Tokyo Metropolitan Kiyose Children’s Hospital, Tokyo Japan; and ^¶Department of Nephrology, Toho University, School of Medicine.

Correspondence to Dr. Seiichirou Shishido, Department of Pediatric Urology and Kidney Transplantation, Tokyo Metropolitan Kiyose Children’s Hospital, 1-3-1 Umezono, Kiyose-shi, Tokyo 204-8567, Japan. Phone: 81-424-91-0011; Fax: 81-424-91-0044;

ABSTRACT. Chronic allograft nephropathy (CAN) is due to both immunologic and non-immunologic factors and results in the development of nonspecific pathologic features that may even be present in long-term well-functioning renal allografts. To investigate the natural history of CAN and potential risk factors associated with progression of these histologic lesions, this study evaluated the of histologic alterations of 124 sequential protocol biopsies performed at 2, 3, and 5 yr after transplantation in 46 patients who exhibited histologic evidence of CAN in the 1-yr biopsy. The occurrence of late acute rejection (AR) greater than 4 mo posttransplant was significantly associated with the development of histologic CAN. In contrast, early clinical AR occurring within 3 mo had no impact on the subsequent development of CAN at 1 yr. Subclinical AR was evident in association with CAN in 50%, 32%, 19%, and 16% of cases with CAN at 1, 2, 3, and 5 yr, respectively. These acute lesions correlated significantly with histologic progression defined as an increased CADI score of the follow-up biopsies. Furthermore, a group of patients who exhibited repeated subclinical AR in the sequential follow-up biopsies had a lower creatinine clearance at 5 yr after transplantation and worse long-term graft survival. In contrast, the absence of evidence of acute inflammation in association with CAN at any time point was associated with minimal deterioration in renal function or progression of renal lesions during the observation period. These results suggest that the persistence of chronic active inflammation may be responsible for the histologic progression of CAN. E-mail: shishido@chp-kiyose-tokyo.jp

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Copyright © 2009 by the American Society of Nephrology. Online ISSN: 1533-3450 Print ISSN: 1046-6673