Effect of dietary fish oil on renal function and rejection in cyclosporine-treated recipients of renal transplants. Dietary fish oil in renal transplant recipients treated with cyclosporin-A: no beneficial effects shown. Delayed omega-3 fatty acid supplements in renal transplantation. A double-blind, placebo-controlled study. Prophylaxis of hemodialysis graft thrombosis with fish oil: double-blind, randomized, prospective trial. The effects of dietary supplementation with fish oil on renal function and the course of early postoperative rejection episodes in cyclosporine-treated renal transplant recipients. Fish oil supplementation in patients with heterozygous familial hypercholesterolemia. Renal effects of dietary supplementation with fish oil in cyclosporine-treated liver transplant recipients. Effect of dietary supplementation with n-3 fatty acids on coronary artery bypass graft patency. Dietary supplementation with fish oil modifies renal reserve filtration capacity in postoperative, cyclosporin A-treated renal transplant recipients. Therapy of post-renal transplantation hyperlipidaemia: comparative study with simvastatin and fish oil. Fish oil supplementation in patients with stable claudication.
Dietary fish oil exerts effects on renal hemodynamics and the immune response that may benefit renal-transplant recipients treated with cyclosporine. To evaluate this possibility, we studied the effect of fish oil on renal function, blood pressure, and the incidence of acute rejection episodes in cyclosporine-treated recipients of renal transplants.
                In a randomized, double-blind trial, 33 recipients of first cadaveric kidney transplants who were treated with cyclosporine and prednisolone ingested 6 g of fish oil daily during the first postoperative year (the fish-oil group), whereas another 33 renal-graft recipients treated with cyclosporine and prednisolone ingested 6 g of coconut oil daily for three months after which time it was stopped (the control group).
                One year after transplantation, the fish-oil group had higher median values than the controls for glomerular filtration rate (53 vs. 40 ml per minute per 1.73 m2, P = 0.038) and effective renal plasma flow (214 vs. 178 ml per minute per 1.73 m2, P = 0.023) and lower mean arterial pressure (103 vs. 118 mm Hg, P = 0.0011). The cyclosporine doses in the two groups were similar. The cumulative number of rejection episodes was 20 in the controls, as compared with 8 in the fish-oil group (P = 0.029). One-year graft survival also tended to be better in the fish-oil group, (97 vs. 84 percent, P = 0.097).
                The daily administration of 6 g of fish oil during the first postoperative year has a beneficial effect on renal hemodynamics and blood pressure in renal-transplant recipients treated with cyclosporine. Although the fish-oil group had significantly fewer rejection episodes than the control group, graft survival at one year was not significantly better in the fish-oil group. This study aimed to determine whether dietary supplementation with fish oil has a beneficial effect on graft function and the incidence of rejection in renal allograft recipients treated with cyclosporin A (CsA). Renal function, blood pressure, the incidence of acute rejection episodes, graft survival, and renal histology and immunochemistry were investigated. In a randomized, placebo-controlled, double-blind trial, groups of 25 recipients of primary cadaveric renal allografts who had been treated with CsA took fish oil (30% C20:5 omega-3 and 20% C22:6 omega-3) or coconut oil (63% C8:0 and 36% C10:0) at 6 g/day for 3 months. There were no differences between the two patient groups with regard to HLA matching, panel-reactive antibody titers, or the demographic characteristics of donors or recipients. The GFR and effective RPF were determined at 1, 3, and 12 months after transplantation by simultaneous measurement of (125I-)iothalamate and (131I-)hippuran clearances. At 1 yr after transplantation, patients treated with fish oil showed better renal function than did the control patients, but this difference was not statistically significant. Blood pressure and antihypertensive drug use were similar in both groups. The number of rejection episodes was also similar, and renal histopathological and immunohistochemical studies showed no significant differences between the fish-oil group and the control patients. It is concluded that fish oil, at a dose of 6 g/day, has no beneficial effect after renal transplantation within the time scale of the 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. Diets enriched with fish oil may favorably affect the vascular perturbations underlying synthetic graft thrombosis. Therefore, these studies were designed to test the hypothesis that diets enriched with fish oil would decrease the incidence of thrombosis in newly constructed polytetrafluorethylene grafts. A double-blind, randomized trial was conducted. Twenty-four patients were randomized to receive 4000 mg of fish oil or 4000 mg of control oil. Both preparations were enriched with antioxidants and deodorized with peppermint. Patients began therapy within 2 wk after graft placement and were monitored for 12 mo or until thrombosis developed. With a permuted-block randomization schedule, 12 patients received fish oil and 12 patients received control oil. The primary patency rates at 365 d were 14.9% for the control group and 75.6% for the fish oil-treated group. Survival analysis revealed a significant difference between fish oil-treated and untreated patients (P < 0.03, Mantel-Cox test), with a power of 90%. Moreover, analysis of covariables, including age of > or =50 yr, gender, race, body weight, diabetes mellitus, bleeding times, and lipid profiles, indicated that this effect occurred principally as a result of fish oil administration. Importantly, fish oil treatment also decreased venous outflow resistance and systemic BP, compared with control values. Fish oils possess unique biologic properties that favorably affect the incidence of polytetrafluorethylene graft thrombosis, and they thus represent a potential treatment strategy for the prevention of access thrombosis. In a randomized prospective coconut oil (daily 6g[63% C8:0 and 36% C10:0] [EPA-] [n = 48])-controlled trial, we investigated the effect of a one-month dietary supplementation with daily 6 g fish oil (30% C20:5 omega-3 and 20% C22:6 omega-3 as their methyl esthers [EPA+] [n = 40]) on the incidence and course of early postoperative rejection in 88 first cadaveric, cyclosporine-treated renal transplant recipients. At one month there were no differences in renal function and incidence of rejection episodes. When analyzed separately for rejection (re+) or nonrejection (re-), the rejecting and fish oil-treated patients showed a significant better recovery of renal function after a histologically confirmed rejection episode, creatinine clearance being 43 ml/min/1.73m2 in the EPA+re+group versus 27 ml/min/1.73 m2 in the EPA-re+group (P less than 0.05), and serum creatinine being 183 and 283 mumol/l (P less than 0.05), respectively. The prerejection renal function and the decline of renal function during the rejection episode did not differ significantly between the EPA+re+ and the EPA-re+ groups. The nonrejecting fish oil-treated patients showed no better renal function than the nonrejecting coconut oil-treated patients. However, cyclosporine trough levels were significantly higher in the fish oil-treated group (EPA+re- 251 versus EPA-re- 200 ng/ml [P less than 0.05]). From these results we conclude that dietary supplements with fish oil favorably influence renal function in the recovery phase following a rejection episode in cyclosporine-treated renal transplant recipients. We further conclude that one month after grafting there is no difference in the incidence of rejection episodes between the fish- and coconut oil-treated patients. The same holds true for renal function in the absence of rejection, and for the decline in renal function during a rejection episode. Familial hypercholesterolemia is associated with premature coronary heart disease. In patients with familial hypercholesterolemia, monotherapy with hydroxymethylglutaril coenzyme. A reductase inhibitors rarely achieves the goal of desirable low-density lipoprotein levels. Epidemiological studies suggest that populations with a high dietary intake of marine n3 fatty acids are protected against coronary heart disease. Hepatic synthesis and secretion of very low density lipoproteins are reduced during fish oil supplementation while other effects on lipid and lipoprotein metabolism are controversial. Fourteen patients affected by familial heterozygous hypercholesterolemia on chronic treatment with simvastatin were enrolled in a double blind, placebo controlled, randomized crossover trial that evaluated the effect of fish oil ethyl ester (Esapent, 5.1 g/day) on lipid and lipoprotein serum concentrations. Total cholesterol, low density lipoprotein cholesterol, high density lipoprotein cholesterol, triglycerides, apoprotein B, apoprotein AI, lipoprotein (a) did not show any significant variation during the four week treatment period with fish oil ethyl ester. The present data suggest that the possible favourable influence of fish oil on the progression of atherosclerosis in these high-risk patients might involve mechanisms which are different from lipid metabolism. Nephrotoxicity is the main untoward effect of cyclosporine (CsA) treatment. Experimental and clinical data suggest that dietary supplementation with fish oil may lessen cyclosporine nephrotoxicity, possibly by lowering renal thromboxane (Tx) production. We have studied the renal effects of a daily supplementation for 2 months of 12 g fish oil (18% C20:5 n-3 eicosapentaenoic acid [EPA] and 12% C22:6 n-3 docosahexanoic acid [DHA]) in a placebo-controlled (12 g corn oil), prospective, randomized, double-blind study of stable CsA-treated liver transplant recipients. Thirteen patients ingested corn oil capsules and 13 fish oil. Compliance with dietary regimen was confirmed by fatty acid chromatography that showed increased plasma concentrations of EPA (from 0.4 +/- 0.02% to 4.6 +/- 0.5%, P < .0001) and DHA (from 1.8 +/- 0.2% to 3.9 +/- 0.1%, P < .0001) in the fish oil group and increased plasma concentration of linoleic acid (C18:2 n-6) in the corn oil group (from 25 +/- 2% to 28.4 +/- 2%, P < .001). At the end of the 2 months of the study, in the fish oil group the effective renal plasma flow increased by 22% (P = .012), the glomerular filtration rate increased by 33% (P = .057), the renal blood flow increased by 17% (P = .024), and the calculated total renal vascular resistances decreased by 20% (P = .034). In contrast, none of these parameters changed in the corn oil group. The renal functional reserve determined during L-arginine infusion, plasma renin activity (PRA), and plasma aldosterone (PA) remained unchanged during the study in either group.(ABSTRACT TRUNCATED AT 250 WORDS) Epidemiologic and experimental data suggest that a high dietary intake of long-chain polyunsaturated n-3 fatty acids may reduce the risk of atherothrombotic disease. In a randomized, controlled study, 610 patients undergoing coronary artery bypass grafting were assigned either to a fish oil group, receiving 4 g/day of fish oil concentrate, or to a control group. All patients received antithrombotic treatment, either aspirin or warfarin. Their diet and serum phospholipid fatty acid profiles were monitored. The primary end point was 1-year graft patency, which was assessed by angiography in 95% of patients. Vein graft occlusion rates per distal anastomoses were 27% in the fish oil group and 33% in the control group (odds ratio 0.77, 95% confidence interval, 0.60 to 0.99, p = 0.034). In the fish oil group, 43% of the patients had > or = 1 occluded vein graft(s) compared with 51% in the control group (odds ratio 0.72, 95% confidence interval, 0.51 to 1.01, p = 0.05). Moreover, in the entire patient group, there was a significant trend to fewer patients with vein graft occlusions with increasing relative change in serum phospholipid n-3 fatty acids during the study period (p for linear trend = 0.0037). Thus, in patients undergoing coronary artery bypass grafting, dietary supplementation with n-3 fatty acids reduced the incidence of vein graft occlusion, and an inverse relation between relative change in serum phospholipid n-3 fatty acids and vein graft occlusions was observed. The effect of a daily supplementation of 6 g fish oil (30% C20:5 omega-3 = EPA and 20% C22:6 omega-3 = DHA) for 1 month on renal function variables was investigated in a placebo-controlled (6 g coconut oil), prospective, randomized, double-blind study in acute postoperative cyclosporin A (CyA)-treated renal transplant recipients. Seventeen patients ingested placebo capsules (EPA-) and 14 patients fish oil (EPA+). Renal function tests were performed using the simultaneous determination of 125I-iothalamate and 131I-hippuran clearances for glomerular filtration rate (GFR) and effective renal plasma flow (ERPF), respectively. Renal reserve filtration capacity was assessed by dopamine infusion, amino acid infusion, and a combination of both stimuli. After 1 month there were no significant differences in rejection episodes, CyA dose, or CyA levels. In contrast to our earlier observations, serum creatinine, creatinine clearance, GFR, and ERPF did not differ between the EPA- and EPA+ groups. Filtration fraction (FF) differed significantly, being 0.21 in the EPA- group versus 0.26 in the EPA+ group. To exclude the possible influence of a rejection episode, the nonrejecting patients were analyzed separately, creating the subgroups EPA + re - and EPA - re -. These two groups were comparable in age, donor age, and GFR. The EPA + re-group had a significantly lower ERPF (164 ml/min per 1.73 m2) than the EPA-re- group (262 ml/min per 1.73 m2). FF was significantly higher in the EPA+ re-group (0.26) than in the EPA-re-group (0.21).(ABSTRACT TRUNCATED AT 250 WORDS) Recipients of renal transplantation (RT) exhibit disturbances of serum lipids and apoproteins that may contribute to their cardiovascular morbidity and mortality. In our renal transplant department the hypercholesterolaemia prevalence at the first and fifth year of RT is 70.0% and 81.2%, respectively. Lipid-lowering therapy has been utilized in many Transplant Units. The aim of our study was to evaluate post-RT hyperlipidaemia control with simvastatin or fish oil.
                Forty-three RT patients (26 men and 17 women) with persistent hypercholesterolaemia and stable graft function which were resistant to a lipid-lowering diet (American Heart Association Step Two) were randomized into two groups and treated for 3 months with simvastatin (S) (10mg/day; n = 25) and fish oil (F) (6 g/day; n = 18). Total cholesterol (TC), LDL-cholesterol (LDL-C), HDL-cholesterol (HDL-C), lipoprotein a (Lp(a)), apolipoprotein A1 (Apo A1), and apolipoprotein B (Apo B) were monitored and at the study baseline they were similar between the two groups.
                No side effects were detected after 3 months of therapy. In group S, the concentrations of TC (271 +/- 46 mg% vs 228 +/- 49 mg%; P < 0.001), TG (180 +/- 78 vs 134 +/- 45; P < 0.01), LDL-C (177 +/- 40 vs 144 +/- 43; P < 0.01) and Apo B (96 +/- 18 vs 82 +/- 16; P < 0.001) were significantly reduced, and Apo A1 concentration had increased (135 +/- 24 vs 149 +/- 30; P < 0.01). In group F, the concentrations of TC (266 +/- 25 vs 240 +/- 31; P < 0.001), TG (203 +/- 105 vs 156 +/- 72; P = 0.02) and HDL-C (63 +/- 15 vs 53 +/- 12; P < 0.01) were significantly reduced.
                We concluded that low-dose simvastatin and fish oil are both effective and safe in correcting post-RT hyperlipidaemia. Further prospective studies with larger follow-up are needed to clarify whether this therapy has an impact on cardiovascular morbidity and mortality in RT patients. Increased blood viscosity occurs in patients with claudication. This increase in viscosity, which is mainly due to elevated fibrinogen levels and a decreased red cell deformability, adversely influences blood flow. In addition to a positive effect on blood pressure, blood lipids, and platelet responsiveness, fish oil may improve blood flow due to a favorable influence on hemorrheology. In a prospective, randomized, double-blind study, we evaluated the effect of six capsules of fish oil (1.8 g eicosapentaenoic acid and 1.2 g docosahexaenoic acid) versus six capsules of corn oil (3 g linoleic acid), administered for 4 months, on walking distances, pressure indices during rest and after exercise, blood pressure, red cell deformability, fibrinogen, and lipid levels in 32 patients with stable claudication. No significant changes in walking distances and pressure indices during rest and after exercise occurred, despite a significant increase in red cell deformability in the fish oil group. Fibrinogen levels did not change in either group. In the fish oil group, a favorable change in blood lipids was noted; high-density cholesterol increased and triglycerides decreased. Mean arterial blood pressure declined to a similar extent in both groups. Thus, short-term supplementation with fish oil does not lead to clinically significant improvement of symptoms in patients with stable claudication. This suggests that red cell deformability is of minor importance in the arterial blood flow in the legs of these patients.
There is insufficient evidence from currently available RCTs to recommend fish oil therapy to improve renal function, rejection rates, patient survival or graft survival. The improvements in HDL cholesterol and diastolic blood pressure were too modest to recommend routine use. To determine a benefit in clinical outcomes, future RCTs will need to be adequately powered with these outcomes in mind.