The Association between Marine n-3 Polyunsaturated Fatty Acid Levels and Survival after Renal Transplantation

Abstract

Background and objectives Several studies have reported beneficial cardiovascular effects of marine n-3 polyunsaturated fatty acids. To date, no large studies have investigated the potential benefits of marine n-3 polyunsaturated fatty acids in recipients of renal transplants.Design, setting, participants, & measurements In this observational cohort study of 1990 Norwegian recipients of renal transplants transplanted between 1999 and 2011, associations between marine n-3 polyunsaturated fatty acid levels and mortality were investigated by stratified analysis and multivariable Cox proportional hazard regression analysis adjusting for traditional and transplant-specific mortality risk factors. Marine n-3 polyunsaturated fatty acid levels in plasma phospholipids were measured by gas chromatography in a stable phase 10 weeks after transplantation.Results There were 406 deaths (20.4%) during a median follow-up period of 6.8 years. Mortality rates were lower in patients with high marine n-3 polyunsaturated fatty acid levels ($7.95 weight percentage) compared with low levels (,7.95 weight percentage) for all age categories (pooled mortality rate ratio estimate, 0.69; 95% confidence interval, 0.57 to 0.85). When divided into quartiles according to marine n-3 polyunsaturated fatty acid levels, patients in the upper quartile compared with the lower quartile had a 56% lower risk of death (adjusted hazard ratio, 0.44; 95% confidence interval, 0.26 to 0.75) using multivariable Cox proportional hazard regression analysis. There was a lower hazard ratio for death from cardiovascular disease with high levels of marine n-3 polyunsaturated fatty acid and a lower hazard ratio for death from infectious disease with high levels of the marine n-3 polyunsaturated fatty acid eicosapentaenoic acid, whereas there was no association between total or individual marine n-3 polyunsaturated fatty acid levels and cancer mortality.Conclusions Higher plasma phospholipid marine n-3 polyunsaturated fatty acid levels were independently associated with better patient survival.

Effects of marine n-3 fatty acid supplementation in renal transplantation: A randomized controlled trial

“…5,[12][13][14][15] A recent randomized clinical trial (RCT) in myocardial infarction survivors reported less development of myocardial fibrosis in patients who received high-dose marine n-3 FA supplements. 17,18 In that observational cohort, plasma marine n-3 FA levels were inversely associated with plasma creatinine, inflammatory biomarkers and triglycerides, acute rejections beyond the early posttransplant phase, and development of interstitial fibrosis (IF) during the first year after transplantation. 17,18 In that observational cohort, plasma marine n-3 FA levels were inversely associated with plasma creatinine, inflammatory biomarkers and triglycerides, acute rejections beyond the early posttransplant phase, and development of interstitial fibrosis (IF) during the first year after transplantation.…”

“…17,18 In that observational cohort, plasma marine n-3 FA levels were inversely associated with plasma creatinine, inflammatory biomarkers and triglycerides, acute rejections beyond the early posttransplant phase, and development of interstitial fibrosis (IF) during the first year after transplantation. [17][18][19][20][21] The present study is the largest RCT investigating the effects of marine n-3 FA supplementation in renal transplantation performed to date, and the first to include data on renal graft histopathological indices and endothelial function. The main objective of this trial was to evaluate whether daily supplementation of 2.6 g marine n-3 FAs for 44 weeks, compared with controls, would improve renal function beyond standard care in renal transplant recipients.…”

“…16 We have previously shown that higher plasma phospholipid marine n-3 FA levels were associated with better patient and graft survival in a large cohort (n = 1990) of Norwegian renal transplant recipients. [17][18][19][20][21] The present study is the largest RCT investigating the effects of marine n-3 FA supplementation in renal transplantation performed to date, and the first to include data on renal graft histopathological indices and endothelial function. [17][18][19][20][21] The present study is the largest RCT investigating the effects of marine n-3 FA supplementation in renal transplantation performed to date, and the first to include data on renal graft histopathological indices and endothelial function.…”

“…34 Patients in the present trial had high baseline plasma marine n-3 FA levels, typical of patients on a Nordic diet rich in fish and seafood and about 5 times higher than levels reported from American cohorts. 17,36,37 Patients with low baseline levels (<6.0 wt%) had a steeper increase in plasma marine n-3 FA level after supplementation and a statistically significant improvement of mGFR during follow-up compared with controls. These findings suggest that patients with low background marine n-3 FA consumption might be more likely to benefit more from marine n-3 FA supplementation.…”

“…Gastrointestinal discomfort was experienced by nearly a third of the patients and is common in renal transplant recipients receiving mycophenolate and tacrolimus. 17,18 Thus, larger studies with longer duration are needed to investigate whether marine n-3 FAs preserve renal function and improve patient and graft survival. Previous RCTs focusing on marine n-3 FA supplementation in renal transplant recipients report very limited data on adverse events.…”