N-3 FATTY-ACIDS REDUCE PROTEINURIA IN PATIENTS WITH CHRONIC GLOMERULAR-DISEASE

Dietary supplementation with n-3 polyunsaturated fatty acids (n-3 PUFA) has been shown to reduce proteinuria in experimental models of renal diseases, but their potential role in the treatment of human renal disease is unknown. We administered n-3 PUFA in the form of triglycerides [with eicosapentenoic (EPA) + docosahexaenoic (DHA) = 3 g/day into 4 patients] and of ethyl esters (EPA + DHA = 7.7 g/day) into 10 patients (one patient twice) with chronic glomerular disease (membranous glomerulonephritis and focal glomerular sclerosis), all diagnosed histologically. Serum albumin was > 2.4 g/dl and serum creatinine < 2.5 mg/dl in all patients. Treatment was given for periods of six weeks, followed by a prolonged follow-up for 27 weeks in 10 cases. Dietary supplementation with n-3 PUFA caused the expected reduction in platelet generation of thromboxane B2 (Mean +/- SEM, froM 490 +/- 70 ng/ml at baseline, to 342 +/- 147 ng/ml at 6 weeks, P < 0.05) of serum triglycerides (from 236 +/- 60 to 170 +/- 43, P < 0.01), and a prolongation of the bleeding time (from 5.8 +/- 0.4 min to 7.7 +/- 0.4 min, P < 0.01) in patients treated with ethyl esters. A modest but significant reduction in serum total cholesterol was noticed (from 275 +/- 27 to 252 +/- 24 mg/dl). Urinary thromboxane B2 excretion (as a reflection of renal TXA2 production) and urinary 6-keto-PGF1alpha excretion (as a reflection Of renal PGI2 production), assayed by extraction, chromatographic separation and RIA with antibodies cross-reacting with metabolites of the n-3 series, were both similarly reduced by the ethyl ester treatment (for TXB2: 7.8 +/- 1.7 ng/hr at week 0; 4.2 +/- 0.6 ng/hr at week 6, P = 0.06; for 6-keto-PGF1alpha: 24.4 +/- 5.1 ng/hr at week 0; 16.4 +/- 2.9 ng/hr at week 6, P = 0.09). Serum albumin, creatinine and creatinine clearance did not change significantly throughout the study. The high dose regimen, however, caused a significant reduction in proteinuria (from 3.7 +/- 1.0 g/24 hr at week 0 to 2.6 +/- 0.7 g/24 hr at week 6, P < 0.05). This was sustained at weeks 10 and 16 and returned to baseline values at week 27. A modest reduction in blood pressure was also noticed, but it did not correlate with the change in proteinuria. Thus, n-3 PUFA may have a therapeutic role in reducing proteinuria in patients with chronic glomerular disease. The relationship of modifications in renal eicosanoids with this effect is uncertain.