Taurine Deficiency Is a Hallmark of Injured Kidney Allografts.

Autor:	Rinaldi A; Division of Nephrology, Department of Medicine, Ente Ospedaliero Cantonale, Lugano, Switzerland.; Laboratories for Translational Research, Ente Ospedaliero Cantonale, Bellinzona, Switzerland.; Division of Nephrology, Department of Medicine, Ente Ospedaliero Cantonale, Lugano, Switzerland., Cippà PE; Division of Nephrology, Department of Medicine, Ente Ospedaliero Cantonale, Lugano, Switzerland.; Laboratories for Translational Research, Ente Ospedaliero Cantonale, Bellinzona, Switzerland.; Division of Nephrology, Department of Medicine, Ente Ospedaliero Cantonale, Lugano, Switzerland., Nemazanyy I; Platform for Metabolic Analyses, Structure Fédérative de Recherche Necker, Institut National de la Santé et de la Recherche Médicale (INSERM) US24/CNRS UMS3633, Paris, France., Anglicheau D; INSERM U1151, Université Paris Cité, Paris, France.; Service de Néphrologie et Transplantation, Assistance Publique Hôpitaux de Paris, Hôpital Necker, Paris, France., Pallet N; Service de Biochimie, Assistance Publique Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Paris, France.; Université de Paris, INSERM UMRS1138, Centre de Recherche des Cordeliers, Paris, France.; Service de Néphrologie, Assistance Publique Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Paris, France.
Jazyk:	angličtina
Zdroj:	Transplantation [Transplantation] 2024 Sep 01; Vol. 108 (9), pp. e218-e228. Date of Electronic Publication: 2024 Mar 19.
DOI:	10.1097/TP.0000000000004987
Abstrakt:	Background: Taurine is one of the most abundant amino acids in humans. Low taurine levels are associated with cellular senescence, mitochondrial dysfunction, DNA damage, and inflammation in mouse, all of which can be reversed by supplementation. It is unknown whether taurine metabolism is associated with kidney allograft function and survival. Methods: We performed urine metabolomic profiling of kidney transplant recipients in the early and late phases after transplantation combined with transcriptomic analysis of human kidney allografts. Single-nucleus RNA sequencing data sets of mouse kidneys after ischemia-reperfusion injury were analyzed. We analyzed the association of urinary taurine levels and taurine metabolism genes with kidney function, histology, and graft survival. Results: Urine taurine concentrations were significantly lower in kidney transplant recipients who experienced delayed graft function. In a mouse model of ischemia-reperfusion injury, the taurine biosynthesis gene, CSAD , but not the taurine transporter SLC6A6 , was repressed. In the late stage of transplantation, low level of taurine in urine was associated with impaired kidney function and chronic structural changes. Urine taurine level in the lowest tertile was predictive of graft loss. Expression of the taurine transporter SLC6A6 in the upper median, but not CSAD , was associated with chronic kidney injury and was predictive of graft loss. Conclusions: Low urine taurine level is a marker of injury in the kidney allograft, is associated with poor kidney function, is associated with chronic histological changes, and is predictive of graft survival. The differential expression of CSAD and SLC6A6 , depending on the time after transplantation and marks of injury, highlights different mechanisms affecting taurine metabolism. Competing Interests: The authors declare no conflicts of interest. (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)
Databáze:	MEDLINE
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