Kidney Week

Abstract: FR-OR114

Urinary Biomarkers of Injury and Repair and Risk for Kidney Function Decline or Mortality: Results from VA NEPHRON-D

Session Information

• Translating Discovery to Patients with Diabetic Kidney Disease
  November 08, 2019 | Location: 207, Walter E. Washington Convention Center
  Abstract Time: 05:06 PM - 05:18 PM

Category: Diabetic Kidney Disease

• 602 Diabetic Kidney Disease: Clinical

Authors

• Chen, Teresa K., Johns Hopkins University School of Medicine, Baltimore, Maryland, United States

Teresa K. Chen, MD

• Coca, Steven G., Icahn School of Medicine at Mount Sinai, New York, New York, United States

Steven G. Coca,

• Thiessen Philbrook, Heather, Johns Hopkins University, Newton, Massachusetts, United States

Heather Thiessen Philbrook,

• L Heerspink, Hiddo Jan, University Medical Center Groningen, Groningen, Netherlands

Hiddo Jan L Heerspink,

• Obeid, Wassim, John Hopkins University, Baltimore, Maryland, United States

Wassim Obeid,

• Ix, Joachim H., UCSD, San Diego, California, United States

Joachim H. Ix,

• Parikh, Chirag R., Johns Hopkins University, Newton, Massachusetts, United States

Chirag R. Parikh,

Group or Team Name

• CKD Biomarkers Consortium (BioCon)

Background

Diabetes is the leading cause of ESRD worldwide. Biomarkers of kidney injury and repair may prognosticate diabetic kidney disease beyond that of eGFR and albuminuria.

Methods

Baseline urinary biomarkers of tubular injury and repair (neutrophil gelatinase-associated lipocalin [NGAL], kidney injury molecule-1 [KIM-1], interleukin-18 [IL-18], monocyte chemoattractant protein-1 [MCP-1], chitinase-3-like protein-1 [YKL-40]) were measured by multiplex immunoassays. Using Cox proportional hazards models, we studied the associations of each biomarker with kidney function decline (first occurrence of absolute decrease in eGFR≥30 ml/min/1.73 m² if randomization eGFR≥60, relative decrease ≥50% if randomization eGFR<60, or ESRD) and all-cause mortality. Covariates included age, sex, race, BMI, blood pressure, HgbA1c, treatment arm, eGFR, and UACR.

Results

We included 1136 VA NEPHRON-D participants with available baseline urine samples. Mean age was 65 years, 99% were male, mean eGFR was 56 ml/min/1.73 m², and median UACR was 840 mg/g. Over a median follow-up of 2.2 years (IQR 1.3, 3.1), 148 (13%) experienced kidney function decline and 103 (9%) died. In unadjusted models, the hazard risk of kidney function decline was ~20-30% higher per two-fold greater baseline level of urine NGAL, IL-18, MCP-1, and YKL-40. These associations attenuated and were no longer significant after adjusting for baseline eGFR and UACR. Higher levels of urine NGAL, MCP-1, and YKL-40 were independently associated with higher risk of death (Table).

Conclusion

Among diabetic individuals with CKD, baseline values of urinary biomarkers of tubular injury and repair were associated with risk of death but not kidney function decline.

Funding

• NIDDK Support