Early urinary CCL2 is associated with the later development of interstitial fibrosis and tubular atrophy in renal allografts

Transplantation
J HoPeter Nickerson

Abstract

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. The urinary proteins evaluated were CCL2, CXCL9, CXCL10, and alpha1-microglobulin (alpha1M) using ELISA and immunonephelometry. We first evaluated urines obtained at 1 to 3 months and found that alpha1M 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....Continue Reading

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