Increase in proteinuria >200 mg/g after late rejection is associated with poor graft survival

Background. There is no information on the effects of proteinuria on outcomes following rejection. Methods. We addressed this question in a retrospective study of 925 kidney transplant recipients between January 2003 and December 2007. Selection criteria were based on (i) biopsy proven diagnosis of a first episode of acute rejection, and (ii) available data on urine protein to creatinine (UPC) ratios at baseline (lowest serum creatinine before biopsy), time of biopsy and 1 month after biopsy. We examined the effects of a change in UPC (UPC = UPC 1 month after biopsy-baseline UPC) on outcomes. Results. We identified 82 patients with both acute rejection and available data on proteinuria. Mean time ( SE) to acute rejection was 19 +/- 2.3 months, and patients were followed up for 38.7 +/- 2.6 months after transplant. Median Delta UPC was 200 mg/g (95% confidence interval 0.00 to 0.300). Forty-two patients had a Delta UPC >= 200 (high proteinuria group). Baseline characteristics were similar between high and low proteinuria groups except for more induction therapy with interleukin-2 receptor blockade in the former (71 vs. 47%, P = 0.04). Patient with Delta UPC >= 200 had higher rates of graft loss (26 vs. 15%, P = 0.01) or combined graft loss or death (38 vs. 20%, P = 0.002 by log rank). In univariate and multivariate Cox regression analyses, Delta UPC >= 200 mg/g, sirolimus therapy 1 month after rejection and re-transplant status were significant factors associated with death-censored graft loss (hazard ratio (HR) 4.4, 14.9 and 6.2, P <= 0.008) or combined graft loss or patient death (HR 3.8, 6.5 and 3.9, P <= 0.03). Conclusions. An increase in proteinuria >= 200 mg/g after late acute rejection is associated with poor graft and patient outcomes. Clinical trials are needed to determine whether post-rejection anti-proteinuric strategies improve outcomes.