Early Subclinical Rejection as a Risk Factor for Late Chronic Humoral Rejection

Background. Subclinical rejection and interstitial fibrosis and tubular atrophy (IF/TA) in protocol biopsies are associated with outcome. We study the relationship between histologic lesions in early protocol biopsies and histologic diagnoses in late biopsies for cause. Materials and Methods. Renal transplants with a protocol biopsy performed within the first 6 months posttransplant between 1988 and 2006 were reviewed. Biopsies were evaluated according to Banff criteria, and C4d staining was available in biopsies for cause. Results. Of the 517 renal transplants with a protocol biopsy, 109 had a subsequent biopsy for cause which showed the following histological diagnoses: chronic humoral rejection (CHR) (n = 44), IF/TA (n = 42), recurrence of the primary disease (n = 11), de novo glomerulonephritis (n = 7), T-cell-mediated rejection (n = 4), and polyoma virus nephropathy (n = 1). The proportion of retransplants (15.9% vs. 2.3%, P = 0.058) and the prevalence of subclinical rejection were higher in patients with CHR than in patients with IF/TA (52.3% vs. 28.6%, P = 0.0253). Demographic donor and recipient characteristics and clinical data at the time of protocol biopsy were not different between groups. Logistic regression analysis showed that subclinical rejection (relative risk, 2.52; 95% confidence interval, 1.1-6.3; P = 0.047) but not retransplantation (relative risk, 6.7; 95% confidence interval, 0.8 - 58.8; P = 0.085) was associated with CHR. Conclusion. Subclinical rejection in early protocol biopsies is associated with late appearance of CHR.