Elevated urinary fatty acid-binding protein 4 level predicts future renal dysfunction and poor prognosis in Japanese patients with diabetes: a longitudinal cohort study

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Background: Fatty acid-binding protein 4 (FABP4) is an adipokine secreted from adipocytes and macrophages and is also expressed in injured, but not normal, glomerular endothelial cells. Elevated levels of urinary FABP4 (U-FABP4) have been reported to be associated with glomerular damage and increased proteinuria. Methods: The associations of levels of U-FABP4 at baseline with future events including renal dysfunction defined by a 30% decline in estimated glomerular filtration rate (eGFR) and all-cause death were investigated in 660 patients with diabetes (type 1/2, 57/603). Results: During a follow-up period (median: 62 months), 90 patients (13.6%) developed renal dysfunction, and 66 patients (10.0%) died (median follow-up period 65 months). Kaplan-Meier survival curves showed that there were significant differences in cumulative incidences for a 30% decline in eGFR and all-cause death in patients divided by the tertiles of U-FABP4 level. Furthermore, multivariable Cox proportional hazard models with a restricted cubic spline showed that hazard ratios for a 30% decline in eGFR and all-cause death increased with a higher level of logarithmically transformed (log) U-FABP4 after adjustment for age, sex, type of diabetes, body mass index, current smoking habit, duration of diabetes, comorbidities of hypertension and dyslipidemia, eGFR, and the categorical classification of urinary albumin-creatinine ratio. The addition of log U-FABP4 to traditional risk factors significantly increased the discriminatory capacities for renal dysfunction in net reclassification improvement and integrated discrimination improvement and for all-cause death in NRI. Conclusion: U-FABP4 is a predictive biomarker for future renal dysfunction and poor prognosis in patients with diabetes.

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