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, Jahrgang 33, Nr. 4, 04.2022, S. 810-827.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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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 -