title: 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.
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.
authors.affiliation: Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. ermiller@jhmi.edu
authors.forename: Edgar R
authors.initials: ER
authors.lastname: Miller
authors.forename: Stephen P
authors.initials: SP
authors.lastname: Juraschek
authors.forename: Cheryl A
authors.initials: CA
authors.lastname: Anderson
authors.forename: Eliseo
authors.initials: E
authors.lastname: Guallar
authors.forename: Karen
authors.initials: K
authors.lastname: Henoch-Ryugo
authors.forename: Jeanne
authors.initials: J
authors.lastname: Charleston
authors.forename: Sharon
authors.initials: S
authors.lastname: Turban
authors.forename: Michael R
authors.initials: MR
authors.lastname: Bennett
authors.forename: Lawrence J
authors.initials: LJ
authors.lastname: Appel
mesh_terms: D000368:Aged; D000419:Albuminuria / Q000652:urine; D015415:Biomarkers / Q000652:urine*; D018592:Cross-Over Studies; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000652:urine*; D015525:Fatty Acids, Omega-3 / Q000627:therapeutic use*; D005260:Female; D005919:Glomerular Filtration Rate / Q000502:physiology; D006801:Humans; D007668:Kidney / Q000187:drug effects* / Q000473:pathology*; D008297:Male; D008875:Middle Aged
chemical_list: D015415:Biomarkers; D015525:Fatty Acids, Omega-3