The Effects of n-3 Long-Chain Polyunsaturated Fatty Acid Supplementation on Biomarkers of Kidney Injury in Adults With Diabetes

Results of the GO-FISH trial

  1. Lawrence J. Appel, MD, MPH1,2,3
  1. 1Johns Hopkins University School of Medicine, Baltimore, Maryland
  2. 2Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland
  3. 3The Welch Center for Prevention, Epidemiology and Clinical Research, Johns Hopkins University, Baltimore, Maryland
  4. 4Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio
  1. Corresponding author: Edgar R. Miller, III, ermiller{at}jhmi.edu.

Abstract

OBJECTIVE Long-chain n-3 polyunsaturated fatty acids supplements (n-3 PUFA) may have renoprotective effects in patients with diabetes, but previous trials have been inconsistent. We performed a randomized controlled trial of n-3 PUFA supplementation on urine albumin excretion and markers of kidney injury in adults with type 2 diabetes.

RESEARCH DESIGN AND METHODS We conducted a randomized, placebo-controlled, two-period crossover trial to test the effects of 4 g/day of n-3 PUFA supplementation on markers of glomerular filtration and kidney injury in adults with adult-onset diabetes and greater than or equal to trace amounts of proteinuria. Each period lasted 6 weeks and was separated by a 2-week washout. The main outcome was urine albumin excretion and, secondarily, markers of kidney injury (kidney injury molecule-1, N-acetyl β-d-glucosaminidase [NAG], neutrophil gelatinase-associated lipocalin [NGAL], and liver fatty acid–binding protein [LFABP]), serum markers of kidney function (cystatin C, β2-microglobulin, and creatinine), and estimated glomerular filtration rate (eGFR).

RESULTS Of the 31 participants, 29 finished both periods. A total of 55% were male, and 61% were African American; mean age was 67 years. At baseline, mean BMI was 31.6 kg/m2, median eGFR was 76.9 mL/min/1.73 m2, and median 24-h urine albumin excretion was 161 mg/day. Compared with placebo, n-3 PUFA had nonsignificant effects on urine albumin excretion (−7.2%; 95% CI −20.6 to 8.5; P = 0.35) and significant effects on urine NGAL excretion (−16% [−29.1 to −0.5%]; P = 0.04). There was no effect on serum markers of kidney function or eGFR. In subgroup analyses, there were significant decreases in 24-h urinary excretion of albumin, NGAL, LFABP, and NAG among participants taking medications that block the renin–angiotensin–aldosterone system (RAAS).

CONCLUSIONS These results suggest a potential effect of n-3 PUFA supplementation on markers of kidney injury in patients with diabetes and early evidence of kidney disease. In the context of prior studies, these results provide a strong rationale for long-term trials of n-3 PUFA on chronic kidney disease progression.

  • Received September 23, 2012.
  • Accepted November 16, 2012.

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This Article

  1. Diabetes Care
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