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

Diabetes Metab Res Rev. 2014 Nov;30(8):736-41. doi: 10.1002/dmrr.2546.

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.

Publication types

  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute-Phase Proteins / urine*
  • Adult
  • Aged
  • Biomarkers / urine
  • Cross-Sectional Studies
  • Diabetes Mellitus, Type 2 / complications*
  • Diabetic Nephropathies / diagnosis*
  • Diabetic Nephropathies / physiopathology
  • Diabetic Nephropathies / urine
  • Early Diagnosis
  • Fatty Acid-Binding Proteins / urine*
  • Female
  • Glomerular Filtration Rate
  • Hepatitis A Virus Cellular Receptor 1
  • Hospitals, Public
  • Hospitals, University
  • Humans
  • Kidney Tubules / physiopathology*
  • Lipocalin-2
  • Lipocalins / urine*
  • Male
  • Membrane Glycoproteins / urine*
  • Middle Aged
  • Proto-Oncogene Proteins / urine*
  • Receptors, Virus
  • Republic of Korea
  • Up-Regulation*

Substances

  • Acute-Phase Proteins
  • Biomarkers
  • FABP1 protein, human
  • Fatty Acid-Binding Proteins
  • HAVCR1 protein, human
  • Hepatitis A Virus Cellular Receptor 1
  • LCN2 protein, human
  • Lipocalin-2
  • Lipocalins
  • Membrane Glycoproteins
  • Proto-Oncogene Proteins
  • Receptors, Virus