Effect of Dietary Fish Oil on Renal Function and Rejection in Cyclosporine-Treated Recipients of Renal Transplants

Heide, Jaap J. Homan van der; Bilo, Henk J. G.; Donker, J.M. Ab; Wilmink, J. M.; Tegzess, Adam

doi:10.1056/nejm199309093291105

Cited by 185 publications

(68 citation statements)

References 24 publications

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“…Another strategy reported is dietary supplementation with fish oil. van der Heide et al (68) observed that recipients of a primary cadaveric kidney transplant who were treated with CsA and who ingested fish oil daily during the first postoperative year had higher glomerular filtration rate and renal plasma flow than those not ingesting fish oil. However, a more recent randomized, double-blind, placebo-controlled in transplant patients taking CsA showed no beneficial effect of fish oil on glomerular filtration rate and renal plasma flow, as well as on renal histopathology.…”

Section: Invited Reviewmentioning

confidence: 99%

New insights into the pathophysiology of cyclosporine nephrotoxicity: a role of aldosterone

Bobadilla¹,

Gamba²

2007

American Journal of Physiology-Renal Physiology

117

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Cyclosporine A (CsA), a calcineurin inhibitor, has improved allograft survival in solid organ transplantation and has been increasingly applied in the management of autoimmune diseases. While marked progress has been made in patient and allograft survival rates, clinical use of CsA is often limited by its nephrotoxic effect, which can be presented as two distinct and well-characterized forms: acute and chronic nephrotoxicity. The acute form is characterized by renal vasoconstriction, induced by an imbalance of vasoactive substances release, which leads to renal dysfunction. This form is reversible. The chronic toxicity, in contrast, is characterized by the vasoconstriction plus the development of structural damage that includes arteriolopathy and tubulointerstitial fibrosis that are often not reversible. The exact mechanisms of these deleterious effects are not fully understood, but major advances have occurred over the last few years. Here we review the current literature regarding the pathogenesis and strategies that have been used to ameliorate renal injury in chronic CsA nephrotoxicity. Recent observations suggest that aldosterone plays a central role in the pathogenesis of CsA nephrotoxicity and that spironolactone could be a useful agent to prevent it. These studies and the use of mineralocorticoid receptor blockade are discussed.

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Section: Invited Reviewmentioning

confidence: 99%

New insights into the pathophysiology of cyclosporine nephrotoxicity: a role of aldosterone

Bobadilla¹,

Gamba²

2007

American Journal of Physiology-Renal Physiology

117

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“…Therefore, these agents (particularly the n-3 series) have found clinical applications in the treatment of various inflammatory diseases such as rheumatoid arthritis and Crohn's disease relapses (33,35,36) and as immunosuppressive agents (32). Despite the broad clinical use of PUFAs, the mechanism of PUFA-induced T cell inhibition had not been elucidated.…”

Section: -Bromopalmitate Inhibits Fyn Fatty Acylation and Signaling mentioning

confidence: 99%

“…Polyunsaturated fatty acids (PUFAs), particularly the n-3 series, are used clinically as immunosuppressive agents (32) and in the treatment of various inflammatory diseases (33)(34)(35)(36). Recently, it was reported that PUFAs inhibit T cell signal transduction by displacing Fyn and Lck from the DRMs (37).…”

mentioning

confidence: 99%

Inhibition of Protein Palmitoylation, Raft Localization, and T Cell Signaling by 2-Bromopalmitate and Polyunsaturated Fatty Acids

Webb¹,

Hermida-Matsumoto

Resh

2000

Journal of Biological Chemistry

428

366

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The ability of the Src family kinases Fyn and Lck to participate in signaling through the T cell receptor is critically dependent on their dual fatty acylation with myristate and palmitate. Here we identify a palmitate analog, 2-bromopalmitate, that effectively blocks Fyn fatty acylation in general and palmitoylation in particular. Treatment of COS-1 cells with 2-bromopalmitate blocked myristoylation and palmitoylation of Fyn and inhibited membrane binding and localization of Fyn to detergent-resistant membranes (DRMs). In Jurkat T cells, 2-bromopalmitate blocked localization of the endogenous palmitoylated proteins Fyn, Lck, and LAT to DRMs. This resulted in impaired signaling through the T cell receptor as evidenced by reductions in tyrosine phosphorylation, calcium release, and activation of mitogen-activated protein kinase. We also examined the ability of long chain polyunsaturated fatty acids (PUFAs) to inhibit protein fatty acylation. PUFAs have been reported to inhibit T cell signaling by excluding Src family kinases from DRMs. Here we show that the PUFAs arachidonic acid and eicosapentaenoic acid inhibit Fyn palmitoylation and consequently block Fyn localization to DRMs. We propose that inhibition of protein palmitoylation represents a novel mechanism by which PUFAs exert their immunosuppressive effects.

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“…Other studies did not report such an effect for fish oil in either rat or rabbit models of cardiac transplantation (55,56). On the other hand, the benefits of fish oil in the prevention of chronic rejection were reported in kidney transplant recipients (21). Regardless, the lower number of rejection The distribution of rejection grades are not significantly (P ϭ 0.241) different among groups according to the 2 -test analysis.…”

Section: Discussionmentioning

confidence: 92%

A comparison of the effects of fish oil and flaxseed oil on cardiac allograft chronic rejection in rats

Othman

Suh²,

Fischer³

et al. 2008

American Journal of Physiology-Heart and Circulatory Physiology

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Effect of Dietary Fish Oil on Renal Function and Rejection in Cyclosporine-Treated Recipients of Renal Transplants

Cited by 185 publications

References 24 publications

New insights into the pathophysiology of cyclosporine nephrotoxicity: a role of aldosterone

New insights into the pathophysiology of cyclosporine nephrotoxicity: a role of aldosterone

Inhibition of Protein Palmitoylation, Raft Localization, and T Cell Signaling by 2-Bromopalmitate and Polyunsaturated Fatty Acids

A comparison of the effects of fish oil and flaxseed oil on cardiac allograft chronic rejection in rats

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