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

Teresa K. Chen, Steven G. Coca, Heather R. Thiessen-Philbrook, Hiddo J.L. Heerspink, Wassim Obeid, Joachim H. Ix, Linda F. Fried, Joseph V. Bonventre, Joe M. El-Khoury, Michael G. Shlipak, Chirag R. Parikh

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)775-785
Number of pages11
JournalAmerican Journal of Nephrology
Volume53
Issue number11-12
DOIs
StatePublished - Mar 1 2023

Keywords

  • Diabetic kidney disease
  • IL-18
  • KIM-1
  • MCP-1
  • Mortality
  • NGAL
  • YKL-40

ASJC Scopus subject areas

  • Nephrology

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