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.