Polymorphisms in <scp>CYP</scp>‐mediated arachidonic acid routes affect the outcome of renal transplantation

Gervasini, Guillermo; García-Cerrada, Montserrat; Vergara, Esther; García-Pino, Guadalupe; Alvarado, Raúl; Fernández-Cavada, Maria Jesús; Barroso, Sérgio; Doblaré, Emilio; Cubero, Juan José

doi:10.1111/eci.12507

Cited by 16 publications

(18 citation statements)

References 40 publications

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“…Interestingly, in two other studies, the CYP2C8*3 variant in the Spanish recipients (not in donors) showed only a borderline association with DGF. These findings indicate that the relationship between this variant and the risk of DGF may be inconsistent in Spanish patients.…”

Section: Discussionmentioning

confidence: 82%

Influence of ABCC2, CYP2C8, and CYP2J2 Polymorphisms on Tacrolimus and Mycophenolate Sodium–Based Treatment in Brazilian Kidney Transplant Recipients

et al. 2017

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Section: Discussionmentioning

confidence: 82%

Influence of ABCC2, CYP2C8, and CYP2J2 Polymorphisms on Tacrolimus and Mycophenolate Sodium–Based Treatment in Brazilian Kidney Transplant Recipients

et al. 2017

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“…More recently, inactivating variants in CYP4F2 and CYP4A11 were associated with delayed graft function and post-transplant diabetes mellitus. 167,168 Similarly, variants in CYP2C8, CYP2J2, and sEH that reduce levels of EETs are associated with allograft dysfunction. [168][169][170] These results suggest that both 20-HETE and EETs may have a protective role in renal transplant.…”

Section: Transplantmentioning

confidence: 99%

Effect of Cytochrome P450 Metabolites of Arachidonic Acid in Nephrology

Fan

Roman

2017

JASN

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Thirty-five years ago, a third pathway for the metabolism of arachidonic acid by cytochrome P450 enzymes emerged. Subsequent work revealed that 20-hydroxyeicosatetraenoic and epoxyeicosatrienoic acids formed by these pathways have essential roles in the regulation of renal tubular and vascular function. Sequence variants in the genes that produce 20-hydroxyeicosatetraenoic acid are associated with hypertension in humans, whereas the evidence supporting a role for variants in the genes that alter levels of epoxyeicosatrienoic acids is less convincing. Studies in animal models suggest that changes in the production of cytochrome P450 eicosanoids alter BP. However, the mechanisms involved remain controversial, especially for 20-hydroxyeicosatetraenoic acid, which has both vasoconstrictive and natriuretic actions. Epoxyeicosatrienoic acids are vasodilators with anti-inflammatory properties that oppose the development of hypertension and CKD; 20-hydroxyeicosatetraenoic acid levels are elevated after renal ischemia and may protect against injury. Levels of this eicosanoid are also elevated in polycystic kidney disease and may contribute to cyst formation. Our review summarizes the emerging evidence that cytochrome P450 eicosanoids have a role in the pathogenesis of hypertension, polycystic kidney disease, AKI, and CKD.

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“…Toll-like receptor 4 signaling has long been investigated as a mediator for renal fibrosis after transplantation and over the course of various nephropathies (36)(37)(38)(39)(40)(41). In contrast to that, derivatives of arachidonic acids and their mimics were shown to exhibit anti-fibrotic effects and polymorphisms in their CYP-dependent metabolism to influence susceptibility to renal injury (42)(43)(44).…”

Section: Discussionmentioning

confidence: 99%

The proteome of small urinary extracellular vesicles after kidney transplantation as an indicator of renal cellular biology and a source for markers predicting outcome

Braun

Rinschen

Buchner

et al. 2019

Preprint

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One Sentence Summary: This study represents the first atlas of the proteomic changes in small urinary extracellular vesicles throughout living donor kidney transplantation identifying PCK2 abundance as a biomarker for renal function 12 months after transplantation *corresponding authors Abstract:Kidney transplantation is the preferred renal replacement therapy available. Yet, the biological processes during and after kidney transplantation and how they translate into the overall functional graft outcome are insufficiently understood. Recent developments in the field of extracellular vesicle research allow the deeper exploitation of this non-invasive source. We separated small urinary extracellular vesicles (suEVs) throughout the course of living donor kidney transplantation. SuEVs were collected longitudinally from both the donor and the recipient in 22 living donor kidney transplantations. Unbiased proteomic analysis revealed specific temporal patterns of suEV proteins indicative of the cellular processes involved in the allograft's response after transplantation with proteins playing a role in complement activation being among the most dynamically regulated components. Using a leave-one-out cross validation model, we identified potential prognostic markers of kidney function at 1 year after transplantation. One of the proteins identified -phosphoenol pyruvate carboxykinase (PCK2) -could be confirmed in an independent validation cohort of another 22 donor-recipient pairs using targeted mass spectrometry. This study sheds the light on early molecular processes during the course of kidney transplantation and shows the future potential of suEVs as a source of biomarkers in this setting. The data set is provided as a unique resource directly accessible through an online tool that allows dynamic interrogation of this first comprising suEV proteome atlas after kidney transplantation.

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Polymorphisms in CYP‐mediated arachidonic acid routes affect the outcome of renal transplantation

Abstract: Taken together, these results indicate that variability in the CYP450 genes involved in the synthesis of eicosanoids from AA may have a significant impact on graft function and survival in renal transplantation.

Cited by 16 publications

References 40 publications

Influence of ABCC2, CYP2C8, and CYP2J2 Polymorphisms on Tacrolimus and Mycophenolate Sodium–Based Treatment in Brazilian Kidney Transplant Recipients

Influence of ABCC2, CYP2C8, and CYP2J2 Polymorphisms on Tacrolimus and Mycophenolate Sodium–Based Treatment in Brazilian Kidney Transplant Recipients

Effect of Cytochrome P450 Metabolites of Arachidonic Acid in Nephrology

The proteome of small urinary extracellular vesicles after kidney transplantation as an indicator of renal cellular biology and a source for markers predicting outcome

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