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Altered proximal tu...
Altered proximal tubular cell glucose metabolism during acute kidney injury is associated with mortality
- Article/chapterEnglish2020
Publisher, publication year, extent ...
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2020-07-20
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Springer Science and Business Media LLC,2020
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LIBRIS-ID:oai:gup.ub.gu.se/296477
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https://gup.ub.gu.se/publication/296477URI
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https://doi.org/10.1038/s42255-020-0238-1DOI
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Subject category:ref swepub-contenttype
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Subject category:art swepub-publicationtype
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Acute kidney injury (AKI) is strongly associated with mortality, independently of its cause. The kidney contributes to up to 40% of systemic glucose production by gluconeogenesis during fasting and under stress conditions. Whether kidney gluconeogenesis is impaired during AKI and how this might influence systemic metabolism remain unknown. Here we show that glucose production and lactate clearance are impaired during human and experimental AKI by using renal arteriovenous catheterization in patients, lactate tolerance testing in mice and glucose isotope labelling in rats. Single-cell transcriptomics reveal that gluconeogenesis is impaired in proximal tubule cells during AKI. In a retrospective cohort of critically ill patients, we demonstrate that altered glucose metabolism during AKI is a major determinant of systemic glucose and lactate levels and is strongly associated with mortality. Thiamine supplementation increases lactate clearance without modifying renal function in mice with AKI, enhances glucose production by renal tubular cells ex vivo and is associated with reduced mortality and improvement of the metabolic pattern in a retrospective cohort of critically ill patients with AKI. This study highlights an unappreciated systemic role of renal glucose and lactate metabolism under stress conditions, delineates general mechanisms of AKI-associated mortality and introduces a potential intervention targeting metabolism for a highly prevalent clinical condition with limited therapeutic options.
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Ricksten, Sven-Erik,1953Gothenburg University,Göteborgs universitet,Institutionen för kliniska vetenskaper, Avdelningen för anestesiologi och intensivvård,Institute of Clinical Sciences, Department of Anesthesiology and Intensive care(Swepub:gu)xricsv
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Faivre, A.
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Verissimo, T.
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Gariani, K.
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Verney, C.
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Galichon, P.
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Berchtold, L.
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Feraille, E.
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Fernandez, M.
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Placier, S.
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Koppitch, K.
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Hertig, A.
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Martin, P. Y.
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Naesens, M.
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Pugin, J.
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McMahon, A. P.
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Cipp, P. E.
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de Seigneux, S.
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Göteborgs universitetInstitutionen för kliniska vetenskaper, Avdelningen för anestesiologi och intensivvård
(creator_code:org_t)
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In:Nature Metabolism: Springer Science and Business Media LLC2:82522-5812
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Legouis, D.
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Ricksten, Sven-E ...
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Faivre, A.
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Verissimo, T.
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Gariani, K.
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Verney, C.
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Galichon, P.
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Berchtold, L.
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Feraille, E.
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Fernandez, M.
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Placier, S.
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Koppitch, K.
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Hertig, A.
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Martin, P. Y.
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Naesens, M.
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Pugin, J.
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McMahon, A. P.
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Cipp, P. E.
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de Seigneux, S.
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University of Gothenburg