Clinical Significance of an Early Protocol Biopsy in Living-Donor Renal Transplantation: Ten-Year Experience at a Single Center

Abstract

We report here our 10-year experience of a biopsy performed at day 14 after transplantation in 304 patients with stable graft function. The factors that may have influenced subclinical rejection were analyzed according to histology. The incidence of subclinical rejection was 13.2%. Addition of mycophenolate mofetile (MMF) as a primary immunosuppressant significantly decreased the incidence of subclinical rejection compared with patients without such treatment (odds ratio, 0.23; p < 0.05). On the other hand, HLA-DR antigen mismatch (odds ratio, 2.39) and unrelated donor (odds ratio, 2.10) were also significantly associated with decreased subclinical rejection (p < 0.05). The incidence of acute rejection in patients with normal findings was lower than in those with borderline changes or subclinical rejection (0.23 ± 0.05 vs. 0.48 ± 0.07 and 0.60 ± 0.11, respectively; p < 0.05). The graft survival rates in patients with subclinical rejection were lower than in patients with normal or borderline changes at 1 (88.4% vs. 97.9% and 99.1%; p < 0.05), 5 (77.8% vs. 96.2% and 95.9%; p < 0.05) and 10 (62.3% vs. 96.2% and 93.7%; p < 0.05) years. Thus, a protocol biopsy performed on day 14 after transplantation is useful for predicting graft survival. Triple therapy including MMF, related donor and HLA-DR antigen match are important factors for reducing subclinical rejection in living-donor renal transplantation.

Protocol Transplant Biopsies

“…In the Winnipeg studies, the prevalence of subclinical rejection in protocol biopsies that were performed at 1, 2, and 3 mo was 0, 25, and 20%; 32, 32, and 30%; and 30, 37, and 63% in zero, one, and two HLA-DR mismatched patients, respectively (25). A correlation between HLA mismatches and the prevalence of subclinical rejection has been reported also by others (10,14). Moreover, our group found that subclinical rejection is more prevalent in patients who are presensitized to class I or class II HLA antigens as detected by flow cytometry (26).…”

“…Our current definition of subclinical rejection requires that the serum creatinine be increased by Ͻ10% 2 wk before the protocol biopsy and that the histologic Banff score is "ai2at2" (type IA acute rejection) or greater. Numerous groups since have confirmed the occurrence of subclinical rejection as defined above, in both adults (7)(8)(9)(10)(11)(12)(13)(14) and children (15,16). Some investigators include "borderline" rejection (Banff score Ͻai2at2) in the subclinical rejection category (7,9 -11,14).…”

“…In some studies, the use of cyclosporine microemulsion (21,22) and MMF (14,21,22) reduced the prevalence of subclinical rejection. However, this was not observed in all studies (20).…”

Protocol Transplant Biopsies

“…In addition, in a 10-yr study of 304 patients with stable graft function, those with borderline changes or SCR in protocol biopsy specimens at 14 d posttransplantation were found to have a higher incidence of acute rejection than those with normal biopsies (0.48 and 0.60 versus 0.23, respectively; P Ͻ 0.05) (10). Moreover, the graft survival rates in patients with SCR in day 14 biopsies in this study were lower than those with normal or borderline changes at 1 yr (88.4 versus 97.9 and 99.1%; P Ͻ 0.05), 5 yr (77.8 versus 96.2 and 95.9%; P Ͻ 0.05), and 10 yr (62.3 versus 96.2 and 93.7%; P Ͻ 0.05).…”

Renal Allograft Fibrosis: Biology and Therapeutic Targets

“…Thus, early inflammation detected in protocol biopsies predicts progression of renal fibrosis and shorter renal allograft survival (248)(249)(250).…”