Urinary Biomarkers of Tubular Health and Risk for Kidney Function Decline or Mortality in Diabetes

Am J Nephrol. 2022;53(11-12):775-785. doi: 10.1159/000528918. Epub 2023 Jan 11.

Abstract

Introduction: Diabetes is a leading cause of end-stage kidney disease (ESKD). Biomarkers of tubular health may prognosticate chronic kidney disease (CKD) progression beyond estimated glomerular filtration rate (eGFR) and urine albumin-to-creatinine ratio (UACR).

Methods: We examined associations of five urinary biomarkers of tubular injury and repair (NGAL, KIM-1, IL-18, MCP-1, YKL-40) with kidney function decline (first occurrence of a decrease in eGFR ≥30 mL/min/1.73 m2 if randomization eGFR ≥60 or ≥50% if randomization eGFR <60; ESKD) and all-cause mortality among 1,135 VA NEPHRON-D trial participants with baseline UACR ≥300 mg/g and available urine samples. Covariates included age, sex, race, BMI, systolic BP, HbA1c, treatment arm, eGFR, and UACR. In a subset of participants with 12-month samples (n = 712), we evaluated associations of KIM-1, MCP-1, and YKL-40 change (from baseline to 12 months) with eGFR decline (from 12 months onward).

Results: At baseline, mean age was 65 years, mean eGFR was 56 mL/min/1.73 m2, and median UACR was 840 mg/g. Over a median of 2.2 years, 13% experienced kidney function decline and 9% died. In fully adjusted models, the highest versus lowest quartiles of MCP-1 and YKL-40 were associated with 2.18- and 1.76-fold higher risks of kidney function decline, respectively. One-year changes in KIM-1, MCP-1, and YKL-40 were not associated with subsequent eGFR decline. Higher baseline levels of NGAL, IL-18, MCP-1, and YKL-40 levels (per 2-fold higher) were independently associated with 10-40% higher risk of mortality.

Conclusion: Among Veterans with diabetes and CKD, urinary biomarkers of tubular health were associated with kidney function decline and mortality.

Keywords: Diabetic kidney disease; IL-18; KIM-1; MCP-1; Mortality; NGAL; YKL-40.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Aged
  • Biomarkers / urine
  • Chitinase-3-Like Protein 1
  • Diabetes Mellitus*
  • Glomerular Filtration Rate
  • Humans
  • Interleukin-18
  • Kidney
  • Kidney Failure, Chronic* / complications
  • Lipocalin-2 / urine
  • Renal Insufficiency, Chronic* / complications

Substances

  • Interleukin-18
  • Chitinase-3-Like Protein 1
  • Lipocalin-2
  • Biomarkers