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

Joe Chan, Ivar A Eide, Tone M Tannæs, Bård Waldum-Grevbo, Trond Jenssen, My Svensson, Joe Chan, Ivar A Eide, Tone M Tannæs, Bård Waldum-Grevbo, Trond Jenssen, My Svensson

Abstract

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.

Keywords: Assay validation; cellular senescence; fatty acid; interleukin; intervention; kidney transplantation; macrophage inflammatory protein; matrix metalloproteinase; monocyte chemoattractant protein; multiplex; omega-3; senescence-associated secretory phenotype; transforming growth factor; tumor necrosis factor.

© 2021 The Authors.

Figures

Figure 1
Figure 1
Study flowchart presenting patient screening, randomization, reasons for withdrawal from the trial, and the number of plasma and urine samples available from each group at baseline and at the end of the study. Abbreviations: ITT, intention to treat; PP, per protocol; PUFA, polyunsaturated fatty acid.

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Source: PubMed

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