Nonalbuminuric proteinuria as a biomarker for tubular damage in early development of nephropathy with type 2 diabetic patients

Abstract

Aim: The aim of this study was to evaluate the association between urinary nonalbumin protein (NAP) and urinary tubular markers in early diabetic nephropathy.

Methods: Urinary NAP was measured in 118 patients with type 2 diabetes with estimated glomerular filtration rates (eGFR) ≥60 mL/min/1.73 m². Urine levels of tubular markers [kidney injury molecule (KIM)-1, neutrophil gelatinase-assoicated lipocalin (NGAL) and liver-type fatty acid-binding protein (L-FABP)] were measured by using an Enzyme-linked immunosorbent assay (ELISA). Patients were divided into three groups according to urinary NAP values.

Results: The urine levels of KIM-1, NGAL and L-FABP were significantly higher in the third tertile group than in the first tertile group (all p < 0.001). There was a significant positive correlation between NAP and each tubular marker (KIM-1, NGAL and L-FABP) in univariate analysis (all p < 0.001). Urinary NAP was positively correlated with all urinary tubular markers after adjustment for age, duration of diabetes, systolic blood pressure, eGFR, low-density lipoprotein cholesterol, HbA1c and albumin-to-creatinine ratio (KIM-1 r = 0.170, p < 0.001; NGAL r = 0.142, p < 0.015 and L-FABP r = 0.262, p < 0.001). In normoalbuminuric patients (n = 58), urinary NAP was also significantly correlated with NGAL and L-FABP in multivariate regression analyses (r = 0.302, p = 0.030 and r = 0.430, p = 0.001).

Conclusions: These findings suggest that urinary NAP reflects tubular damage in the early-stage type 2 diabetic nephropathy (eGFR ≥ 60 mL/min/1.73 m²). We suggest that urinary NAP could be used as a biomarker for tubular damage in clinical practice.

Keywords: diabetic nephropathy; kidney tubule; nonalbuminuric proteinuria; type 2 diabetes mellitus.