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 alpha1-microglobulin (alpha1M) using ELISA and immunonephelometry.


RESULTS
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. In comparison, alpha1M, CXCL9, and CXCL10 were not associated with late graft outcomes.


CONCLUSIONS
This study demonstrates that early urinary CCL2 is an independent predictor for the subsequent development of IFTA at 24 months.
Ho
Julie
J
Section of Nephrology, University of Manitoba, Winnipeg MB. jho@hsc.mb.ca
Rush
David N
DN
Gibson
Ian W
IW
Karpinski
Martin
M
Storsley
Leroy
L
Bestland
Jennifer
J
Stefura
William
W
HayGlass
Kent T
KT
Nickerson
Peter W
PW
D000328:Adult; D000704:Analysis of Variance; D001284:Atrophy; D015415:Biomarkers / Q000652:urine; D018932:Chemokine CCL2 / Q000652:urine*; D054357:Chemokine CXCL10 / Q000652:urine; D054370:Chemokine CXCL9 / Q000652:urine; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007674:Kidney Diseases / Q000145:classification / Q000601:surgery; D016030:Kidney Transplantation / Q000473:pathology*; D007684:Kidney Tubules / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009395:Nephritis, Interstitial / Q000473:pathology*; D012307:Risk Factors
D015415:Biomarkers; D018932:Chemokine CCL2; D054357:Chemokine CXCL10; D054370:Chemokine CXCL9