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Arteriosclerosis in Histological Evaluations Using Zero-Time Biopsy Is a Risk Factor for Tacrolimus-Induced Nephrotoxicity

T. Yagisawa, K. Omoto, T. Shimizu, T. Nozaki, H. Ishida, K. Honda, J. Koike, K. Tanabe

Urology, Tokyo Women's Medical University, Tokyo, Japan
Pathology, Tokyo Women's Medical University, Tokyo, Japan
Pathology, Kawasaki Municipal Tama Hospital, Kawasaki, Japan

Meeting: 2013 American Transplant Congress

Abstract number: B1087

Introduction: Zero-time renal allograft biopsies provide important information as the initial state of allograft histological findings. To the best of our knowledge, no studies have been reported on the association between arteriosclerosis (AS) in zero-time biopsy and the incidence of tacrolimus-induced (TAC) nephrotoxicity. In this study, we investigated these associations and set out to determine the influence of TAC nephrotoxicity on allograft survival rate.

Materials and Methods: Subjects were 512 patients who underwent living-related kidney transplantation at our institution between January 2001 and December 2010, of whom 348 patients received tacrolimus and had no pre-existence of anti-donor HLA antibodies. All patients underwent zero-time and protocol biopsies. Episode biopsies were performed in patients with clinical problems. The biopsy specimens were evaluated according to the Banff 07 classification, and TAC nephrotoxicity was evaluated by aah (alternate quantitative scoring for hyaline arteriolar thickening). The target trough level of tacrolimus was 8 to 10, 6 to 8, and 4 to 6 ng/ml in the postoperative state, 1 to 6 months, and more than 6 months later, respectively.

Results: Of the 348 zero-time biopsies, 203 (58.3%) specimens had AS findings. The number of patients with TAC nephropathy was 68 (19.5%) patients. Of these 68, 29 (42.6%), 28 (41.2%) and 11 (16.2%) patients showed aah 1, 2 and 3, respectively. Of the 203 cases with AS in zero-time biopsy, 50 (24.6%) cases showed TAC nephrotoxicity. The incidence of TAC nephrotoxicity in allografts with AS was significantly higher than that in allografts without AS (24.6 vs. 12.4%; p = 0.004). Multivariate analysis revealed that the existence of AS in zero-time biopsies affected the incidence of TAC nephrotoxicity (HR: 2.1, 95% CI: 1.15-3.84). On the other hand, the AS grading in zero-time biopsy was not associated with the grade of the aah score (p = 0.49). There were no patients with allograft loss due to TAC nephrotoxicity.

Conclusions: Existence of AS in pre-transplant allografts is a risk factor for TAC nephrotoxicity. Therefore, histological evaluations using zero-time biopsies are useful in predicting TAC nephrotoxicity after kidney transplantation.

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To cite this abstract in AMA style:

Yagisawa T, Omoto K, Shimizu T, Nozaki T, Ishida H, Honda K, Koike J, Tanabe K. Arteriosclerosis in Histological Evaluations Using Zero-Time Biopsy Is a Risk Factor for Tacrolimus-Induced Nephrotoxicity [abstract]. Am J Transplant. 2013; 13 (suppl 5). https://atcmeetingabstracts.com/abstract/arteriosclerosis-in-histological-evaluations-using-zero-time-biopsy-is-a-risk-factor-for-tacrolimus-induced-nephrotoxicity/. Accessed May 17, 2025.

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