Glomerular monocytes predict worse outcomes after acute renal allograft rejection independent of C4d status

Background. Both peritubular capillary (PTC) C4d deposition and macrophage/monocyte (MO) infiltration in acute rejection (AR) have separately been shown to be associated with reduced graft survival and recently were demonstrated to be closely correlated in AR. Whether MO infiltration is an independent predictor of graft outcome is uncertain. Methods. All patients with biopsy-proven AR (over a 3-year period) were included (N= 96). All biopsies (N= 121) were graded according to the Banff 97 criteria and immunohistochemically stained for C4d and MO (CD68). The primary outcome was glomerular filtration rate (GFR) < 30 mL/min 1-year posttransplant as estimated by the Modified Diet in Renal Disease (MDRD) Formula. Secondary outcomes at 2 and 4 years' posttransplant were also explored. A variety of clinical and biopsy variables were statistically analyzed to establish univariate predictors of graft outcome. Stepwise multivariate logistic regression modeling was applied to determine independent predictors of outcomes. Results. There was a close correlation between PTC C4d and glomerular MO infiltration (P < 0.001). Univariate predictors of primary outcome (GFR < 30 mL/min 1-year posttransplant) included mean glomerular MO count >= 1.0 MO/glomerulus (P= 0.014), female sex (P= 0.02), higher peak (P= 0.005), and pretransplant (P= 0.003) panel-reactive antibody levels, cadaveric donor (P= 0.006), transplant glomerulitis (P= 0.004), and longer cold ischemic time (CIT) (P= 0.002). Mean MO/glomerulus >= 1.0 [OR 10.3 (1.23, 87.1)], female sex [OR 5.27(1.31, 21.1)], and CIT [OR 1.14 (1.06, 1.25)] were identified as independent predictors of adverse graft outcome. Furthermore, mean MO/glomerulus >= 1.0 independently predicted poor renal function at 2 years [OR 3.89 (1.19, 12.70)] and 4 years [OR 4.03 (1.22, 13.28)] posttransplant. Conclusion. The results demonstrate that glomerular MO infiltration is an independent predictor of worse outcomes posttransplant following acute renal allograft rejection.