Delayed omega-3 fatty acid supplements in renal transplantation. A double-blind, placebo-controlled study.

An earlier reported trial suggests that omega-3 fatty acids in fish oil supplements at 6 g/day with administration commencing at the time of engraftment may reduce acute CsA renal dysfunction. When started at the time of renal transplant, there are improvements in renal hemodynamics and blood pressure, and a decrease in rejection episodes. To examine the effect of later introduction of omega-3 fatty acids, 133 cadaver renal transplant recipients received CsA, prednisone, and AZA for 16 weeks (period 1). If patients were stable without rejection or infection activity, they were randomized to 9 g of eicosapentanoic acid (EPA), 18 g of EPA, 9 g of corn oil, or 18 g of corn oil in 1-g capsules as supplements. Glomerular filtration rate, renal blood flow, number of rejection episodes, blood pressure, and episodes of CsA nephrotoxicity were followed for 26 weeks in a double-blind manner (period 2). Ninety patients were evaluable and completed the protocol. There were 50 corn oil placebo patients, 22 low dose EPA patients, and 18 high dose EPA patients. In period 1, there were 27 rejection episodes in 21 patients without differences among subsequent treatment groups. In period 2, there were 13 rejection episodes in 4 patients. No patient with an EPA level in plasma statistically higher than placebo had a rejection episode. All allografts functioned for the entire 6 months with none lost to rejection. All 5 episodes of acute CsA nephrotoxicity occurred in placebo-treated patients without differences in whole blood CsA among toxic patients, other placebo patients, and EPA-treated recipients. At the end of the study, there were no differences in glomerular filtration rate, renal blood flow, or creatinine clearance among groups. Diastolic blood pressure fell by 9 mmHg during period 2 in high dose fish oil recipients and by 10 mmHg in low dose fish oil recipients (P < 0.05), while it rose by 2 mmHg in placebo patients. No serious adverse effects of EPA supplements were noted, although compliance based on plasma EPA was erratic. Based on our experience and that in the literature, administration of omega-3 fatty acids for purposes of kidney protection would seem to be most useful when started early after surgery. Late administration in our study was associated with minor clinical benefits.

Augmentation of proliferation and in vitro production of cytotoxic cells by 2-ME in the rat.

Low concentrations (10(-5) to 10(-8) M) of 2-mercaptoethanol (2-ME) greatly enhance the proliferation of allogeneic cells in the rat mixed lymphocyte culture (MLC). Studies were undertaken to determine the mode of action of 2-ME. MLC proliferation can occur in the absence of serum proteins (fetal calf serum, FCS) only if 2-ME is present; however, a synergistic effect is present with FCS plus 2-ME, with a 3-fold increase in 3HTdR incorporation with FCS concentrations as low as 0.1%. Kinetic studies show no shift in the peak of proliferation (92 hr) when comparing cultures with and without 2-ME; however, 2-ME-supplemented cultures have significant 3HTdR uptake at 24 hr, and the peak amount of uptake at 92 hr is two to four times higher. Delayed addition of 2-ME until 92 and 166 hr produces a further increase in 3HTdR uptake, indicating that the entire effect is not expressed at the time of allogeneic recognition. L-ascorbic acid, another reducing agent which lacks sulfhydryl groups, elicits a much lower effect on DNA synthesis than does 2-ME. The cytotoxicity of cells harvested from MLC supplemented with 2-ME is increased without loss of target specificity, whereas the same concentration of 2-ME has no direct effect upon the cytotoxicity assay except at higher concentrations where 2-ME suppresses cytotoxicity.