Effects of dietary polyunsaturated fatty acid supplementation on urinary eicosanoids in canine chronic renal failure

Abstract

Changes in renal eicosanoids may be an index of disease progression or response to therapy in chronic renal failure (CRF). This study measured urinary thromboxane B2 (TXB2) and prostaglandin E2 (PGE2) concentrations in control and CRF dogs fed protein/phosphorus restricted diets and supplemented with safflower (SFO) and menhaden fish (MFO) oils. Control dogs (n= 1 7) and CRF dogs (n=32) were assigned to one of three diets (WC, LPC, LPD) for basal diet acclimation. A crossover design was then implemented for oil supplementation, which included a 3 week washout period. Dietary compliance was determined by analysis of serum phospholipid fatty acid composition. Free-catch urine samples were collected for TXB2 and PGE2 determinations by ELISA, with PGE2 being first extracted on C 1 8silica columns. Values were normalized by urinary creatinine (UrCr) concentrations. A PGE2:TXB2 ratio was calculated as an index of renal vasodilation. Glomerular filtration rate (GFR) was determined at each sample period. Increased levels of PGE2 were found for control dogs compared to CRF dogs at study entry (P=0.00003) and after basal diet acclimation (P=0.003). Among all dogs, a decrease in PGE2 was found with MFO (P=0.03). Similarly, a decrease in PGE2 was found in MPC/MFO control dogs (P=0.05). In LPD/SFO CRF dogs, PGE2 was increased (P=0.02). Thromboxane B2 was unchanged for dogs. Individual responses showed a tendency for PGE2 to decrease with UTO and increase with SFO. There was an increase in GFR in CRF dogs after SFO. Decreased PGE2:TXB2 ratios were found for CRF dogs as compared to control dogs pre-basal diet period (P=0.0003) and after diet acclimation (P=0.006) for all diets combined. Differences after diet acclimation for the individual diets were not significant. No significant differences of ratios were found by paired t-test for oil supplements. It is concluded that decreased PGE2:TXB2 ratios may be an index of increased vasoconstriction in CRF canines. Safflower oil supplementation may increase renal vasodilation by increasing urinary PGE2, while TXB2 remains unchanged. Whether this effect is sufficient to overcome overall vasoconstrictive influences in failing kidneys remains to be established. If so, SFO may alter the progression of CRF as predicted by the hyperfiltration theory.