Combination of peritubular c4d and transplant glomerulopathy predicts late renal allograft failure

Abstract

The histologic associations and clinical implications of peritubular capillary C4d staining from long-term renal allografts are unknown. We identified 99 renal transplant patients who underwent an allograft biopsy for renal dysfunction at least 10 yr after transplantation, 25 of whom were C4d-positive and 74 of whom were C4d-negative. The average time of the index biopsy from transplantation was 14 yr in both groups. Compared with C4d-negative patients, C4d-positive patients were younger at transplantation (29 +/- 13 versus 38 +/- 12 yr; P < 0.05) and were more likely to have received an allograft from a living donor (65 versus 35%; P < 0.001). C4d-positive patients had more inflammation, were more likely to have transplant glomerulopathy, and had worse graft outcome. The combined presence of C4d positivity, transplant glomerulopathy, and serum creatinine of >2.3 mg/dl at biopsy were very strong predictors of rapid graft loss. C4d alone did not independently predict graft loss. Retrospective staining of historical samples from C4d-positive patients demonstrated C4d deposition in the majority of cases. In summary, these data show that in long-term renal allografts, peritubular capillary staining for C4d occurs in approximately 25% of biopsies, can persist for many years after transplantation, and strongly predicts graft loss when combined with transplant glomerulopathy.

Figure 1.

Kaplan Meier curves showing graft outcome after biopsy. (A) C4d and graft failure. (B) TG and graft failure. (C) C4d interacts with glomerulopathy to be the strongest predictor of graft outcome.

Figure 2.

Interactions with C4d predict graft failure and Kaplan Meier survival curve in predictive model. Cox proportional hazard model was used to identify significant independent variables between groups. A scoring system was developed by approximating ratios of the RR values of the significant variables from the Cox proportional hazard model. Serum creatinine >2.3 mg/dl was assigned 1 point, TG 1 point, and TG and C4d positivity 2 points, reflective of RR values 5.3, 3.7, and 9.3, respectively.