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.

Trial registration: ClinicalTrials.gov NCT02017990.

Keywords: mortality; survival; transplantation; ω3 fatty acids.

Copyright © 2015 by the American Society of Nephrology.

Figures

Figure 1.

Flowchart of the inclusion of study participants.

Figure 2.

Kaplan–Meier survival curve in recipients of renal transplants. Shown are the proportions of surviving patients grouped according to age (age <60 and ≥60 years old) and marine n-3 polyunsaturated fatty acid (PUFA) levels (the sum of eicosapentaenoic, docosapentaenoic, and docosahexaenoic acid levels in weight percentage [wt%] of total plasma phospholipid fatty acids <7.95 wt% [low] and ≥7.95 wt% [high]).

Figure 3.

Estimated survival probability curve in recipients of renal transplants in multivariable–adjusted Cox proportional hazard regression model 2. Shown are the survival probabilities of patients belonging to quartiles 1–4 according to marine n-3 polyunsaturated fatty acid (PUFA) levels (the sum of eicosapentaenoic, docosapentaenoic, and docosahexaenoic acid levels in weight percentage [wt%] of total plasma phospholipid fatty acids) after adjustment for the following variables: recipient age, sex, n-6 PUFA levels, eGFR using the Modification of Diet in Renal Disease formula, time in dialysis before transplantation, preemptive transplantation, body mass index, number of antihypertensive drugs, diabetes mellitus, coronary artery, cerebrovascular and peripheral vascular diseases, and albumin and total plasma cholesterol concentrations. Quartile 1, marine n-3 PUFA ≤6.20 wt%; quartile 2, marine n-3 PUFA =6.21–7.94 wt%; quartile 3, n-3 PUFA =7.95–10.02 wt%; quartile 4, marine n-3 PUFA ≥10.03 wt%.