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

Edgar R Miller 3rd, Stephen P Juraschek, Cheryl A Anderson, Eliseo Guallar, Karen Henoch-Ryugo, Jeanne Charleston, Sharon Turban, Michael R Bennett, Lawrence J Appel, Edgar R Miller 3rd, Stephen P Juraschek, Cheryl A Anderson, Eliseo Guallar, Karen Henoch-Ryugo, Jeanne Charleston, Sharon Turban, Michael R Bennett, Lawrence J Appel

Abstract

OBJECTIVE Long-chain n-3 polyunsaturated fatty acid (n-3 PUFA) supplements 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/m(2), median eGFR was 76.9 mL/min/1.73 m(2), 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.

Trial registration: ClinicalTrials.gov NCT01092390.

Figures

Figure 1
Figure 1
Participant flow during the trial.
Figure 2
Figure 2
Mean percent difference in 24-h urinary excretion of KIM-1, NGAL, LFABP, NAG, and albumin (ALB) comparing the n-3 PUFA to the control period. (A high-quality color representation of this figure is available in the online issue.)
Figure 3
Figure 3
Mean percent difference in 24-h urinary excretion of KIM-1, NGAL, LFABP, NAG, and albumin (ALB) comparing the n-3 PUFA to the control period, stratified by diuretic use (yes/no), statin use (yes/no), diabetes medication use (yes/no), and RAAS-inhibitor (ACE/ARB) use (yes/no). (A high-quality color representation of this figure is available in the online issue.)

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