Urinary Fibrinogen as a Predictor of Progression of CKD.

Abstract

Fibrinogen has been reported to be involved in kidney tubulointerstitial fibrosis and podocyte injury in mouse models. However, the relationship between urinary fibrinogen and kidney outcomes has not been clarified in patients with CKD. We evaluated 402 patients with CKD and kidney biopsies, including 101 with diabetic nephropathy, 94 with idiopathic membranous nephropathy, 55 with idiopathic FSGS, and 152 with IgA nephropathy. We quantified urinary fibrinogen by ELISA and tested associations with kidney histology and progression to ESRD. Median (interquartile range) urinary fibrinogen-to-creatinine ratio was 536 (191-1461) ng/mg for patients with CKD, significantly higher than 2 (2-3) ng/mg for healthy controls (P<0.001). Urinary fibrinogen was positively correlated with urine protein (r=0.64; P<0.001) and interstitial fibrosis and tubular atrophy (r=0.10; P=0.04), and it was negatively correlated with eGFR (r=-0.20; P<0.001). Over a median follow-up period of 35 months (interquartile range, 24-78 months), 68 of 402 patients (17%) developed ESRD. Higher urinary fibrinogen level was associated with increased risk of ESRD (hazard ratio, 2.12; 95% confidence interval, 1.31 to 3.26) per log10 higher urinary fibrinogen-to-creatinine ratio (P=0.003) adjusting for age, sex, BP, urine protein, disease type, eGFR, and interstitial fibrosis and tubular atrophy. For prediction of ESRD, the addition of urinary fibrinogen to eGFR, urine protein, and BP increased the area under the receiver operating curve from 0.73 to 0.76, and the Akaike information criterion improved from 333.6 to 327.0. Urinary fibrinogen correlated with interstitial fibrosis and tubular atrophy and was an independent risk factor for progression of CKD to ESRD.