Elevated Urinary CCL2: Cr at 6 Months Is Associated With Renal Allograft Interstitial Fibrosis and Inflammation at 24 Months

Background. We have demonstrated that 6-month urinary CCL2: Cr is a predictor of interstitial fibrosis and tubular atrophy (IFTA) on 24-month biopsy and death-censored graft loss. However, IFTA is no longer considered prognostically significant, whereas patients with graft loss frequently have interstitial fibrosis and inflammation (IF+i= ci>0+i>0). As early CCL2: Cr predicts late graft loss, the goal of this study was to determine if 6-month urinary CCL2: Cr was a predictor of IF+i at 24 months. Methods. Urinary CCL2 at 6 months was measured with ELISA and correlated with IF+i on 24-month surveillance biopsies from a prospective, multicenter adult renal transplant cohort (n=111). Results. Six-month urinary CCL2: Cr was significantly higher in IF+i and transplant glomerulopathy patients compared with normal histology at 24 months. By multivariate analysis, 6-month urinary CCL2: Cr was independently correlated with IF+i at 24 months (OR 2.78, 95% CI 1.38-6.12, AUC 0.695, P=0.003). Six-month urinary CCL2: Cr was also an independent correlate of 6-month IF+i (OR 1.99, 95% CI 1.03-4.18, AUC 0.63, P=0.04). Six-month urinary CCL2: Cr distinguished noninflamed renal tissue (normal, fibrosis) from IF+i with a sensitivity/specificity of 0.71/0.62 at a cutoff of 15 ng CCL2/mmol Cr (AUC 0.695, P=0.003, n=91). Conclusions. Urinary CCL2: Cr may be useful for the noninvasive identification of patients with or at risk for IF+i. These patients may benefit from avoidance of drug minimization/withdrawal protocols and more intensive post-transplant surveillance. Furthermore, urinary CCL2: Cr may also identify individuals who may benefit from novel interventional trials targeting IF+i.