Altered proximal tubular cell glucose metabolism during acute kidney injury is associated with mortality.

Nature Metabolism
David LegouisSophie de Seigneux

Abstract

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...Continue Reading

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Citations

Feb 3, 2021·Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association·Anthony Bonavia, Nicholas Stiles
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Oct 18, 2021·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·Lente J S LerinkJan H N Lindeman

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Methods Mentioned

BETA
biopsies
RNA-seq
electrophoresis
PCR
fluorescence-activated cell sorting
biopsy
Assay
protein assay

Software Mentioned

FindClusters
PROGENy
ImageJ
edgeR package
Envigo
FeaturePlot
R
SQL
TSNEPlot
RunPCA

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