Predictors of chronic allograft nephropathy from protocol biopsies using histological and immunohistochemical techniques

Abstract

Chronic allograft nephropathy is a predictor of poor allograft survival. Protocol and diagnostic biopsies were used to identify markers contributing to its pathogenesis. Diagnostic, 3- and 12-month protocol biopsies in renal transplant recipients were examined. Immunohistochemical staining with monoclonal antibodies for memory T cells (CD45RO), macrophages (CD68) and alpha smooth muscle actin was undertaken on protocol biopsies. Protocol biopsies revealed the incidence of chronic allograft nephropathy to be 10.7% (3/28) at 3 and 57.6% (19/33) at 12 months. There was a trend towards a higher serum creatinine in patients with chronic allograft nephropathy compared with those without (0.15 +/- 0.04 vs 0.12 +/- 0.04 mmol/L, P = 0.047). The strongest predictor of chronic allograft nephropathy at 12 months was the presence of arteriolar hyaline change (P = 0.035; odds ratio 1.22, 95% CI 0.036-0.887) whereas a higher CD45RO and CD68 count at 12 months was associated with chronic allograft nephropathy (74.7 +/- 56.9 cells/mm(2) and 22.4 +/- 23.5 cells/mm(2)) compared with patients without it (29.2 +/- 29.2 cells/mm(2) and 8.3 +/- 9.9 cells/mm(2), P = 0.006 and P = 0.03, respectively). The number of smooth muscle actin positive cells correlated significantly with chronic allograft nephropathy at 12 month (107.6 +/- 44 vs 73.9 +/- 20.8 cells/mm(2), P = 0.009). The high prevalence of chronic allograft nephropathy in renal transplant recipients is associated with renal dysfunction. Arteriolar hyalinosis was the most significant predictor at 12 months. There was a significantly higher macrophage and T cell infiltrate in stable grafts undergoing chronic allograft nephropathy at 12 months post transplant.