Omega 3 Fatty Acids Attenuate the Acute Kidney Injury to CKD Transition and Renal Fibrosis: Identification of Antifibrotic Metabolites.

KEY POINTS

Omega-3 polyunsaturated fatty acids prevent AKI to CKD transition and renal fibrosis. Eicosapentaenoic acid metabolites 18-hydroxyeicosapentaenoic acid, 17,18-epoxyeicosatetraenoic acid, and 17,18-dihydroxyeicosatetraenoic acid have antifibrotic effects.

BACKGROUND

AKI is an established risk factor for developing CKD. Recently, the renoprotective effect of omega-3 polyunsaturated fatty acids (3PUFAs) has attracted attention. The aims of this study were to evaluate the effect of 3PUFAs on the transition of AKI to CKD and to identify fatty acid active metabolites in renal tissue.

METHODS

Two mice models of the AKI to CKD transition (7-week, male) and unilateral ureteral obstruction–induced renal fibrosis (11-week, male) were fed linseed oil, rich in 3PUFAs (Lin group), or with soybean oil, low in 3PUFAs (Soy group). Renal fatty acids and metabolites composition in mice were measured by liquid chromatography-mass spectrometry. Rat renal fibroblast cells were used for study.

RESULTS

At day 14 after 35 minutes of bilateral renal ischemia reperfusion, significant increase in survival was observed in the Lin group compared with the Soy group. Using the 30-minute bilateral renal ischemia–reperfusion model (AKI to CKD model), the Lin group showed attenuated renal tissue damage and fibrosis. In addition, the antifibrotic effect of the Lin group was also observed in the unilateral ureteral obstruction renal fibrosis model. In the two mice models, levels of eicosapentaenoic acid (EPA) and its metabolites were significantly elevated in renal tissue of mice fed with Lin. Cultured NRK-49F incubated with EPA and its metabolites 18-hydroxyeicosapentaenoic acid, 17,18-epoxyeicosatetraenoic acid, and 17,18-dihydroxyeicosatetraenoic acid displayed suppressed TGF-1–stimulated -smooth muscle actin protein expression. These effects were suppressed in the presence of an inhibitor of a cytochrome P450 involved in EPA metabolism. This observation suggests that the EPA metabolites have antifibrotic effects.

CONCLUSIONS

3PUFAs prevent the AKI to CKD transition and renal fibrosis. Moreover, the EPA metabolites 18-hydroxyeicosapentaenoic acid, 17,18-epoxyeicosatetraenoic acid, and 17,18-dihydroxyeicosatetraenoic acid were found to have antifibrotic effects.