Early Urinary CCL2 is Associated With the Later Development of Interstitial Fibrosis and Tubular Atrophy in Renal Allografts

Background. Chronic renal allograft injury resulting in progressive interstitial fibrosis and tubular atrophy (IFTA) is a leading cause of graft loss. The goal of this study was to identify early urinary predictors for the subsequent development of IFTA in a prospective cohort of patients (n=111) who underwent serial protocol biopsies at 0, 6, and 24 months. Methods. The urinary proteins evaluated were CCL2, CXCL9, CXCL10, and alpha 1-microglobulin (alpha 1M) using ELISA and immunonephelometry. Results. We first evaluated urines obtained at 1 to 3 months and found that alpha 1M and CXCL10 were associated with IFTA at 6 months but not at 24 months. Next, we evaluated urines at 6 months and found that CCL2 was associated with both IFTA and graft dysfunction at 24 months. On univariate analysis, 6-month urinary CCL2 was a risk factor for developing 24-month IFTA, defined as ci+ct score more than 0 (odds ratio 1.045, 95% confidence interval: 1.005-1.084, P=0.028). Furthermore, CCL2 remained an independent predictor of IFTA on multivariate analysis (odds ratio 1.049, 95% confidence interval: 1.006-1.094, P=0.024) when adjusted for donor age, delayed graft function, deceased donation, and angiotensin-converting enzyme inhibitor/angiotensin receptor blocker exposure. In comparison, alpha 1M, CXCL9, and CXCL10 were not associated with late graft outcomes. Conclusion. This study demonstrates that early urinary CCL2 is an independent predictor for the subsequent development of IFTA at 24 months.