Increased urinary CCL2: Cr ratio at 6 months is associated with late renal allograft loss.

Background: Early noninvasive markers that identify patients at risk of renal allograft loss may stratify patients for more intensive monitoring or therapy. CCL2 is a CCR2 receptor chemokine that is a chemoattractant protein for monocytes/macrophages, T cells, and natural killer cells. We have previously demonstrated in a multicenter cohort that urinary CCL2 at 6 months is an independent predictor for the development of IFTA at 24 months. The goal of this study was to determine if early urinary CCL2 is a predictor of graft loss in an independent patient cohort.

Methods: A prospective, observational cohort study was conducted in the Transplant Manitoba Adult Kidney Program (n=231 patients) from 1997 to 2008. Six-month urinary CCL2 was measured by ELISA, corrected for urinary creatinine, and correlated with long-term graft outcomes.

Results: Urine CCL2: Cr at 6 months was significantly associated with death-censored graft loss (HR, 2.42; 95% CI, 1.54-3.82, P<0.0001). On multivariate analysis, urinary CCL2: Cr at 6 months remained an independent predictor of death-censored graft loss (HR, 2.20; 95% CI, 1.18-4.10, P=0.01) after adjustment for pretransplant/de novo donor-specific antibody and delayed graft function. An early posttransplant (≤6 months) multivariate model of CCL2, recipient age, and delayed graft function yielded an AUC 0.87 for prediction of death-censored graft loss. A cutoff value of urinary CCL2: Cr 34.8 ng/mmol yielded a strong positive predictive value of 0.96.

Conclusions: This study confirms in an independent prospective cohort that early urinary CCL2 at 6 months is a noninvasive, independent predictor for late renal allograft loss.