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Decreased Renal Gluconeogenesis Is a Hallmark of Chronic Kidney Disease

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Decreased Renal Gluconeogenesis Is a Hallmark of Chronic Kidney Disease. / Verissimo, Thomas; Faivre, Anna; Rinaldi, Anna; Lindenmeyer, Maja; Delitsikou, Vasiliki; Veyrat-Durebex, Christelle; Heckenmeyer, Carolyn; Fernandez, Marylise; Berchtold, Lena; Dalga, Delal; Cohen, Clemens; Naesens, Maarten; Ricksten, Sven-Erik; Martin, Pierre-Yves; Pugin, Jérôme; Merlier, Franck; Haupt, Karsten; Rutkowski, Joseph M; Moll, Solange; Cippà, Pietro E; Legouis, David; de Seigneux, Sophie.

In: J AM SOC NEPHROL, Vol. 33, No. 4, 04.2022, p. 810-827.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Verissimo, T, Faivre, A, Rinaldi, A, Lindenmeyer, M, Delitsikou, V, Veyrat-Durebex, C, Heckenmeyer, C, Fernandez, M, Berchtold, L, Dalga, D, Cohen, C, Naesens, M, Ricksten, S-E, Martin, P-Y, Pugin, J, Merlier, F, Haupt, K, Rutkowski, JM, Moll, S, Cippà, PE, Legouis, D & de Seigneux, S 2022, 'Decreased Renal Gluconeogenesis Is a Hallmark of Chronic Kidney Disease', J AM SOC NEPHROL, vol. 33, no. 4, pp. 810-827. https://doi.org/10.1681/ASN.2021050680

APA

Verissimo, T., Faivre, A., Rinaldi, A., Lindenmeyer, M., Delitsikou, V., Veyrat-Durebex, C., Heckenmeyer, C., Fernandez, M., Berchtold, L., Dalga, D., Cohen, C., Naesens, M., Ricksten, S-E., Martin, P-Y., Pugin, J., Merlier, F., Haupt, K., Rutkowski, J. M., Moll, S., ... de Seigneux, S. (2022). Decreased Renal Gluconeogenesis Is a Hallmark of Chronic Kidney Disease. J AM SOC NEPHROL, 33(4), 810-827. https://doi.org/10.1681/ASN.2021050680

Vancouver

Verissimo T, Faivre A, Rinaldi A, Lindenmeyer M, Delitsikou V, Veyrat-Durebex C et al. Decreased Renal Gluconeogenesis Is a Hallmark of Chronic Kidney Disease. J AM SOC NEPHROL. 2022 Apr;33(4):810-827. https://doi.org/10.1681/ASN.2021050680

Bibtex

@article{0f8457535c4c479ab30a105279ea6f8e,
title = "Decreased Renal Gluconeogenesis Is a Hallmark of Chronic Kidney Disease",
abstract = "INTRODUCTION: CKD is associated with alterations of tubular function. Renal gluconeogenesis is responsible for 40% of systemic gluconeogenesis during fasting, but how and why CKD affects this process and the repercussions of such regulation are unknown.METHODS: We used data on the renal gluconeogenic pathway from more than 200 renal biopsies performed on CKD patients and from 43 kidney allograft patients, and studied three mouse models, of proteinuric CKD (POD-ATTAC), of ischemic CKD, and of unilateral urinary tract obstruction. We analyzed a cohort of patients who benefitted from renal catheterization and a retrospective cohort of patients hospitalized in the intensive care unit.RESULTS: Renal biopsies of CKD and kidney allograft patients revealed a stage-dependent decrease in the renal gluconeogenic pathway. Two animal models of CKD and one model of kidney fibrosis confirm gluconeogenic downregulation in injured proximal tubule cells. This shift resulted in an alteration of renal glucose production and lactate clearance during an exogenous lactate load. The isolated perfused kidney technique in animal models and renal venous catheterization in CKD patients confirmed decreased renal glucose production and lactate clearance. In CKD patients hospitalized in the intensive care unit, systemic alterations of glucose and lactate levels were more prevalent and associated with increased mortality and a worse renal prognosis at follow-up. Decreased expression of the gluconeogenesis pathway and its regulators predicted faster histologic progression of kidney disease in kidney allograft biopsies.CONCLUSION: Renal gluconeogenic function is impaired in CKD. Altered renal gluconeogenesis leads to systemic metabolic changes with a decrease in glucose and increase in lactate level, and is associated with a worse renal prognosis.",
keywords = "Animals, Gluconeogenesis/physiology, Humans, Kidney/metabolism, Kidney Tubules, Proximal/metabolism, Mice, Renal Insufficiency, Chronic/metabolism, Retrospective Studies",
author = "Thomas Verissimo and Anna Faivre and Anna Rinaldi and Maja Lindenmeyer and Vasiliki Delitsikou and Christelle Veyrat-Durebex and Carolyn Heckenmeyer and Marylise Fernandez and Lena Berchtold and Delal Dalga and Clemens Cohen and Maarten Naesens and Sven-Erik Ricksten and Pierre-Yves Martin and J{\'e}r{\^o}me Pugin and Franck Merlier and Karsten Haupt and Rutkowski, {Joseph M} and Solange Moll and Cipp{\`a}, {Pietro E} and David Legouis and {de Seigneux}, Sophie",
note = "Copyright {\textcopyright} 2022 by the American Society of Nephrology.",
year = "2022",
month = apr,
doi = "10.1681/ASN.2021050680",
language = "English",
volume = "33",
pages = "810--827",
journal = "J AM SOC NEPHROL",
issn = "1046-6673",
publisher = "American Society of Nephrology",
number = "4",

}

RIS

TY - JOUR

T1 - Decreased Renal Gluconeogenesis Is a Hallmark of Chronic Kidney Disease

AU - Verissimo, Thomas

AU - Faivre, Anna

AU - Rinaldi, Anna

AU - Lindenmeyer, Maja

AU - Delitsikou, Vasiliki

AU - Veyrat-Durebex, Christelle

AU - Heckenmeyer, Carolyn

AU - Fernandez, Marylise

AU - Berchtold, Lena

AU - Dalga, Delal

AU - Cohen, Clemens

AU - Naesens, Maarten

AU - Ricksten, Sven-Erik

AU - Martin, Pierre-Yves

AU - Pugin, Jérôme

AU - Merlier, Franck

AU - Haupt, Karsten

AU - Rutkowski, Joseph M

AU - Moll, Solange

AU - Cippà, Pietro E

AU - Legouis, David

AU - de Seigneux, Sophie

N1 - Copyright © 2022 by the American Society of Nephrology.

PY - 2022/4

Y1 - 2022/4

N2 - INTRODUCTION: CKD is associated with alterations of tubular function. Renal gluconeogenesis is responsible for 40% of systemic gluconeogenesis during fasting, but how and why CKD affects this process and the repercussions of such regulation are unknown.METHODS: We used data on the renal gluconeogenic pathway from more than 200 renal biopsies performed on CKD patients and from 43 kidney allograft patients, and studied three mouse models, of proteinuric CKD (POD-ATTAC), of ischemic CKD, and of unilateral urinary tract obstruction. We analyzed a cohort of patients who benefitted from renal catheterization and a retrospective cohort of patients hospitalized in the intensive care unit.RESULTS: Renal biopsies of CKD and kidney allograft patients revealed a stage-dependent decrease in the renal gluconeogenic pathway. Two animal models of CKD and one model of kidney fibrosis confirm gluconeogenic downregulation in injured proximal tubule cells. This shift resulted in an alteration of renal glucose production and lactate clearance during an exogenous lactate load. The isolated perfused kidney technique in animal models and renal venous catheterization in CKD patients confirmed decreased renal glucose production and lactate clearance. In CKD patients hospitalized in the intensive care unit, systemic alterations of glucose and lactate levels were more prevalent and associated with increased mortality and a worse renal prognosis at follow-up. Decreased expression of the gluconeogenesis pathway and its regulators predicted faster histologic progression of kidney disease in kidney allograft biopsies.CONCLUSION: Renal gluconeogenic function is impaired in CKD. Altered renal gluconeogenesis leads to systemic metabolic changes with a decrease in glucose and increase in lactate level, and is associated with a worse renal prognosis.

AB - INTRODUCTION: CKD is associated with alterations of tubular function. Renal gluconeogenesis is responsible for 40% of systemic gluconeogenesis during fasting, but how and why CKD affects this process and the repercussions of such regulation are unknown.METHODS: We used data on the renal gluconeogenic pathway from more than 200 renal biopsies performed on CKD patients and from 43 kidney allograft patients, and studied three mouse models, of proteinuric CKD (POD-ATTAC), of ischemic CKD, and of unilateral urinary tract obstruction. We analyzed a cohort of patients who benefitted from renal catheterization and a retrospective cohort of patients hospitalized in the intensive care unit.RESULTS: Renal biopsies of CKD and kidney allograft patients revealed a stage-dependent decrease in the renal gluconeogenic pathway. Two animal models of CKD and one model of kidney fibrosis confirm gluconeogenic downregulation in injured proximal tubule cells. This shift resulted in an alteration of renal glucose production and lactate clearance during an exogenous lactate load. The isolated perfused kidney technique in animal models and renal venous catheterization in CKD patients confirmed decreased renal glucose production and lactate clearance. In CKD patients hospitalized in the intensive care unit, systemic alterations of glucose and lactate levels were more prevalent and associated with increased mortality and a worse renal prognosis at follow-up. Decreased expression of the gluconeogenesis pathway and its regulators predicted faster histologic progression of kidney disease in kidney allograft biopsies.CONCLUSION: Renal gluconeogenic function is impaired in CKD. Altered renal gluconeogenesis leads to systemic metabolic changes with a decrease in glucose and increase in lactate level, and is associated with a worse renal prognosis.

KW - Animals

KW - Gluconeogenesis/physiology

KW - Humans

KW - Kidney/metabolism

KW - Kidney Tubules, Proximal/metabolism

KW - Mice

KW - Renal Insufficiency, Chronic/metabolism

KW - Retrospective Studies

U2 - 10.1681/ASN.2021050680

DO - 10.1681/ASN.2021050680

M3 - SCORING: Journal article

C2 - 35273087

VL - 33

SP - 810

EP - 827

JO - J AM SOC NEPHROL

JF - J AM SOC NEPHROL

SN - 1046-6673

IS - 4

ER -