Kidney Week

Abstract: FR-PO051

The Association of Fenofibrate with Kidney Tubular Injury in a Subgroup of Participants in the ACCORD Trial

Session Information

• AKI: Clinical, Outcomes, Trials - I
  October 26, 2018 | Location: Exhibit Hall, San Diego Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Acute Kidney Injury

• 102 AKI: Clinical, Outcomes, and Trials

Authors

• Debnath, Neha, Icahn School of Medicine at Mount Sinai, New York, New York, United States

Neha Debnath,

• Chauhan, Kinsuk, Icahn School of Medicine at Mount Sinai, New York, New York, United States

Kinsuk Chauhan,

• Nadkarni, Girish N., Icahn School of Medicine at Mount Sinai, New York, New York, United States

Girish N. Nadkarni,

• Garg, Amit X., London Health Sciences Centre, London, Ontario, Canada

Amit X. Garg,

• Parikh, Chirag R., Yale University and VAMC, New Haven, Connecticut, United States

Chirag R. Parikh,

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

Steven G. Coca,

Background

In ACCORD, 48% of those randomized to fenofibrate demonstrated a ≥20% increase in the concentration of serum creatinine within 4 months, a finding consistent with other trials. The effect of fibrates on markers of kidney tubular injury is unknown.

Methods

We obtained stored urine samples from a subgroup of 571 ACCORD participants randomized to either placebo (n= 329) or fenofibrate (n=242) where all patients also received statins. Our outcome was 2-year changes in the concentration of two urine biomarkers of injury: kidney injury molecule-1 (KIM-1), interleukin-18 (IL-18), and 2 urine biomarkers of repair: YKL-40 and monocyte chemoattractant protein (MCP-1), along with the changes in eGFR and urine albumin to creatinine ratios (UACR) measured from random samples. We adjusted for clinical variables and randomization arm and compared the changes in the markers via analysis of covariance (ANCOVA).

Results

Baseline clinical characteristics and measures of eGFR (88 ml/min/1.73m²), UACR (12 mcg/mg), and all 4 biomarkers were similar in the 2 groups. At 24 months, eGFR was 14.2 ml/min/1.73m² lower with fenofibrate vs. placebo and serum creatinine was 0.18 mg/dl higher. In contrast, UACR and all 4 urine biomarkers of kidney injury or repair were similar or decreased from baseline in fenofibrate vs. placebo (Figure). In a stratified analysis, even participants with the highest quintile 24-month decrements in eGFR with fenofibrate (-30.4 to -73.5 ml/min/1.73 m²) still had lower or unchanged UACR and urine biomarkers.

Conclusion

These findings indicate the increase in the concentration serum creatinine with fibrates is not due to intrinsic damage to kidney tubule cells.

24-month change in eGFR, Serum Creatinine, UACR and Urinary Kidney Injury and Repair Biomarkers in ACCORD Participants Randomized to Fibrates vs. Placebo

Funding

• NIDDK Support