Urinary biomarkers of tubular injury to predict renal progression and end stage renal disease in type 2 diabetes mellitus with advanced nephropathy: A prospective cohort study

J Diabetes Complications. 2019 Sep;33(9):675-681. doi: 10.1016/j.jdiacomp.2019.05.013. Epub 2019 May 25.

Abstract

Background: Novel potential tubular biomarkers in diabetic nephropathy could improve risk stratification and prediction. The study aimed to evaluate the association of tubular damage markers with rapid renal progression and incidence of end stage renal disease (ESRD) in type 2 diabetes (T2DM).

Methods: A prospective cohort study, involving a total of 257 patients with T2DM, was included. The baseline values of urine albumin, cystatin-C, angiotensinogen, kidney injury molecule-1 (KIM-1) and neutrophil-gelatinase associated lipocalin (NGAL) were measured. The composite outcomes included a rapid glomerular filtration rate (GFR) decline or incident of ESRD at 3-year follow-up.

Main findings: The composite outcomes were noted in 26.1%. Using univariate followed by multivariate COX proportional hazard regression analysis, the patients with highest quartiles of urine cystatin-C (HR 2.96, 95% CI, 1.38-6.35), urine angiotensinogen (HR 2.93, 95% CI, 1.40- 6.13) urine KIM-1 (HR 2.77, 95% CI, 1.27-6.05) and urine NGAL (HR 2.53, 95% CI, 1.11-5.76) were significantly associated with rapid renal progression when compared with the patients with the lowest quartiles of all tubular biomarkers.

Conclusions: Patients with T2DM with high levels of baseline urine tubular biomarkers (cystatin-C, angiotensinogen, KIM-1 and NGAL) had a greater incidence of ESRD and rapid GFR decline.

Keywords: Diabetic nephropathy; Urine KIM-1; Urine NGAL; Urine angiotensinogen; Urine biomarker; Urine cystatin-C.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Albuminuria / physiopathology
  • Angiotensinogen / urine
  • Biomarkers / urine*
  • Cohort Studies
  • Cystatin C / urine
  • Diabetes Mellitus, Type 2 / complications*
  • Diabetes Mellitus, Type 2 / urine
  • Diabetic Nephropathies / physiopathology
  • Diabetic Nephropathies / urine*
  • Disease Progression*
  • Female
  • Glomerular Filtration Rate
  • Hepatitis A Virus Cellular Receptor 1 / analysis
  • Humans
  • Kidney Failure, Chronic / urine*
  • Kidney Tubules / physiopathology*
  • Lipocalin-2 / urine
  • Male
  • Middle Aged
  • Prospective Studies
  • Sensitivity and Specificity

Substances

  • Biomarkers
  • CST3 protein, human
  • Cystatin C
  • HAVCR1 protein, human
  • Hepatitis A Virus Cellular Receptor 1
  • LCN2 protein, human
  • Lipocalin-2
  • Angiotensinogen