Haptoglobin genotype and risk markers of cardiovascular disease in patients with chronic kidney disease

Sudden cardiac death and atherosclerosis have a major impact on cardiovascular mortality in chronic kidney disease (CKD). Inflammation with elevated high-sensitive C-reactive protein (hs-CRP) is involved in both sudden cardiac death and atherosclerosis, and decreased heart rate variability (HRV) is a predictor of both sudden cardiac death and atherosclerosis. Haptoglobin (Hp) is characterised by three genotypes (1-1, 2-1, and 2-2) with different antioxidant abilities. The aim was to examine whether HRV and hs-CRP were associated with Hp genotype in CKD patients. Fifty-six patients with CKD stage 2–5 were included. Hp genotype was determined by high-performance liquid chromatography. HRV was analysed from the 24 h Holter recordings. Hs-CRP was measured using an immunoturbidimetric assay. The results show that the HRV indices SDNN and SDANN were significantly lower in the Hp 2-2 patients (P=0.02 and 0.04, resp.). In an adjusted linear regression model, Hp 2-2 was associated with both SDNN (P=0.005) and SDANN (P=0.01). Hs-CRP was higher in the Hp 2-2 patients (P=0.002). In an adjusted linear regression model, the association between Hp 2-2 and hs-CRP remained significant (P=0.003). In conclusion, a negative association was observed between Hp 2-2 and HRV, and Hp 2-2 was positively associated with hs-CRP in CKD patients

Marine n-3 Polyunsaturated Fatty Acid Supplementation and Quality of Life After Kidney Transplant

Marine n-3 polyunsaturated fatty acids (PUFAs) may improve cardiovascular, renal, and mental health. No previous trial has investigated the effects of marine n-3 PUFA supplementation on quality of life (QoL) indices after renal transplant. Methods - In this trial, 132 renal transplant recipients were randomized to receive daily either 2.6 g of marine n-3 PUFAs or an equivalent dose of olive oil (controls) on top of standard care for 44 weeks. We used a Short Form 36 (SF-36) questionnaire at baseline (8 weeks post transplant) and at the end of the study (1 year after transplant) to assess QoL. Results were expressed as net change (Δ) in SF-36 individual and composite mental and physical scores during follow-up. Results - We found no improvement of Δ SF-36 individual or composite scores after marine n-3 PUFA supplementation compared with controls. In per-protocol analysis, patients who received marine n-3 PUFAs had a Δ emotional role function (mean, 17% [SD, 50%] vs mean, 3% [SD, 37%]; P = .11). In addition, plasma marine n-3 PUFA levels showed a weak but statistically significant correlation with Δ composite mental function score (r = .18; P =  .04). Conclusion - Marine n-3 PUFA supplementation did not improve QoL after renal transplant

Marine n-3 fatty acid consumption in a Norwegian renal transplant cohort: Comparison of a food frequency questionnaire with plasma phospholipid marine n-3 levels

Background High levels of plasma marine n-3 fatty acids (n-3FAs) are associated with improved patient and graft survival in renal transplant recipients (RTRs). The aim of this study was to evaluate the utility of a new food frequency questionnaire (FFQ) to estimate marine n-3FA consumption in future epidemiological research. Methods We developed an FFQ with a simple design of 10 questions to assess intake of marine sources of n-3FAs. RTRs included in the recent ORENTRA trial (n = 132) completed the study FFQ at the baseline visit eight weeks after engraftment and at the end of study visit one year post-transplant. We measured the reference biomarker plasma phospholipid (PL) marine n-3FA levels by gas chromatography at the same time points to evaluate association and degree of agreement between FFQ based marine n-3FA consumption estimates and the biomarker. Results The median plasma PL marine n-3FA level was 6.0 weight percentage (wt)% (interquartile range [IQR] 4.7 to 7.3) at baseline and 6.3 wt% (IQR 4.8 to 7.4) at end of study. Median FFQ based marine n-3FA consumption estimates were 22.8 g/month (IQR 13.0 to 34.0) at baseline and 20.3 g/month (IQR 14.5 to 32.3) at end of study. FFQ based marine n-3FA consumption estimates showed a moderate correlation with plasma PL marine n-3FA levels at baseline (Spearman’s correlation coefficient rs = 0.43, p<0.001) and a stronger correlation at end of study (rs = 0.62, p<0.001). Bland Altman plots showed a reasonable degree of agreement between the two methods at both time points. Conclusions Marine n-3FA consumption estimates based on the FFQ showed a moderate correlation with the reference biomarker plasma PL marine n-3FA levels. The FFQ might be useful in epidemiological studies where resources are limited

Marine n-3 Polyunsaturated Fatty Acids and Cellular Senescence Markers in Incident Kidney Transplant Recipients: The Omega-3 Fatty Acids in Renal Transplantation (ORENTRA) Randomized Clinical Trial

Rationale & Objective Deterioration of kidney graft function is associated with accelerated cellular senescence. Marine n-3 polyunsaturated fatty acids (PUFAs) have favorable properties that may counteract cellular senescence development and damage caused by the senescence-associated secretory phenotype (SASP) secretome. Our objective was to investigate the potential effects of marine n-3 PUFA supplementation on the SASP secretome in kidney transplant recipients. Study Design Exploratory substudy of the Omega-3 Fatty Acids in Renal Transplantation trial. Setting & Participants Adult kidney transplant recipients with a functional kidney graft (defined as having an estimated glomerular filtration rate of >30 mL/min/1.73 m2) 8 weeks after engraftment were included in this study conducted in Norway. Analytical Approach The intervention consisted of 2.6 g of a marine n-3 PUFA or olive oil (placebo) daily for 44 weeks. The outcome was a predefined panel of SASP components in the plasma and urine. Results A total of 132 patients were enrolled in the Omega-3 Fatty Acids in Renal Transplantation trial, and 66 patients were allocated to receive either the study drug or placebo. The intervention with the marine n-3 PUFA was associated with reduced plasma levels of granulocyte colony-stimulating factor, interleukin 1α, macrophage inflammatory protein 1α, matrix metalloproteinase (MMP)-1, and MMP-13 compared with the intervention in the control group. Limitations Post hoc analysis. Conclusions The results suggest that marine n-3 PUFA supplementation has mitigating effects on the plasma SASP components granulocyte colony-stimulating factor, interleukin 1α, macrophage inflammatory protein 1α, MMP-1, and MMP-13 in kidney transplant recipients. Future studies with kidney transplant recipients in maintenance phase, combined with an evaluation of cellular senescence markers in kidney transplant biopsies, are needed to further elucidate the potential antisenescent effect of marine n-3 PUFAs. This trial is registered as NCT01744067