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Abstract: TH-PO026

Urinary Biomarkers and Kidney Injury in the VA NEPHRON-D Trial

Session Information

Category: Acute Kidney Injury

  • 102 AKI: Clinical‚ Outcomes‚ and Trials


  • Kiernan, Elizabeth, Johns Hopkins Medicine, Baltimore, Maryland, United States
  • Hu, David G., Johns Hopkins Medicine, Baltimore, Maryland, United States
  • Thiessen Philbrook, Heather, Johns Hopkins Medicine, Baltimore, Maryland, United States
  • Ix, Joachim H., University of California San Diego, La Jolla, California, United States
  • Coca, Steven G., Icahn School of Medicine at Mount Sinai, New York, New York, United States
  • Shlipak, Michael, University of California San Francisco School of Medicine, San Francisco, California, United States
  • Moledina, Dennis G., Yale School of Medicine, New Haven, Connecticut, United States
  • Bonventre, Joseph V., Brigham and Women's Hospital, Boston, Massachusetts, United States
  • Fried, Linda F., UPMC, Pittsburgh, Pennsylvania, United States
  • Parikh, Chirag R., Johns Hopkins Medicine, Baltimore, Maryland, United States

Clinical trials evaluating interventions that modify systemic or intraglomerular pressure lead to elevations in serum creatinine, which may or may not reflect true kidney injury. Urine biomarkers could help phenotype injury patterns in these trial participants.


A subset of participants in the VA NEPHRON-D trial had urinary biomarkers including Albumin: Creatinine ratio (ACR), YKL-40, KIM-1, MCP-1 and EGF measured at baseline and at 12-months. Urinary biomarkers were compared between treatment groups (combination vs monotherapy) and by Acute Kidney Injury (AKI) status. Biomarker results from NEPHRON-D were included in a meta-analysis with other large CKD trials (ACCORD and SPRINT) to assess global trends.


In 703 participants, with 2.2 years of follow-up, the incidence of AKI was higher (20.7%) in the combination therapy group as compared to the monotherapy group (12.7%) (RR 1.64 (1.2, 2.3)). Urine biomarkers at 12 months were either the same [MCP-1 -3% (-13%, 9%), KIM-1 -10% (-20%, 1%)] or lower [Albuminuria, -24% (-37%, -8%), YKL-40 -44% (-58%, -25%), EGF -7% (-12, -1%)] in the combination arm compared to monotherapy arm. Meta-analysis demonstrated reduction in albuminuria across 3 trials (pooled estimate -29% 95% CI (-36%, -22%)). No trial showed higher biomarkers in the intervention arm which induced rise in serum creatinine.


Treatment with combination ACE-i/ARB therapy was associated with a favorable decrease in urinary biomarkers, suggesting improved tubular health, despite higher risk of serum creatinine defined-AKI. This supports use of kidney injury biomarkers in phenotyping of renal injury.

eGFR and Urinary Biomarkers Associated with Interventions in 3 Large Clinical Trials


  • NIDDK Support