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

Acute Kidney Injury / metabolism Adult Aged Animals Critical Illness Female Gluconeogenesis Glucose / metabolism Humans Kidney Tubules, Proximal / metabolism Lactic Acid / metabolism Male Mice Mice, Inbred C57BL Middle Aged Primary Cell Culture Propensity Score Renal Circulation Retrospective Studies Thiamine / therapeutic use Vitamin B Complex / therapeutic use Young Adult

Journal

Nature metabolism
ISSN: 2522-5812
Titre abrégé: Nat Metab
Pays: Germany
ID NLM: 101736592

Informations de publication

Date de publication:
08 2020
Historique:
received: 17 09 2019
accepted: 11 06 2020
pubmed: 23 7 2020
medline: 1 1 2021
entrez: 23 7 2020
Statut: ppublish

Résumé

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.

Identifiants

DOI: 10.1038/s42255-020-0238-1 PMID: 32694833
pubmed: 32694833
doi: 10.1038/s42255-020-0238-1
pii: 10.1038/s42255-020-0238-1
doi:

Substances chimiques

Vitamin B Complex 12001-76-2
Lactic Acid 33X04XA5AT
Glucose IY9XDZ35W2
Thiamine X66NSO3N35

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

732-743

Commentaires et corrections

Type : ErratumIn

Références

Hoste, E. A. J. et al. Epidemiology of acute kidney injury in critically ill patients: the multinational AKI-EPI study. Intensive Care Med. 41, 1411–1423 (2015).
pubmed: 26162677 doi: 10.1007/s00134-015-3934-7
Legouis, D. et al. Rapid occurrence of chronic kidney disease in patients experiencing reversible acute kidney injury after cardiac surgery. Anesthesiology 126, 39–46 (2017).
pubmed: 27755064 doi: 10.1097/ALN.0000000000001400
Gaudry, S. et al. Initiation strategies for renal replacement therapy in the intensive care unit. N. Engl. J. Med. 375, 122–133 (2016).
pubmed: 27181456 doi: 10.1056/NEJMoa1603017
Barbar, S. D. et al. Timing of renal replacement therapy in patients with acute kidney injury and sepsis. N. Engl. J. Med. 379, 1431–1442 (2018).
pubmed: 30304656 doi: 10.1056/NEJMoa1803213
Li, P. et al. High-dose versus low-dose haemofiltration for the treatment of critically ill patients with acute kidney injury: an updated systematic review and meta-analysis. BMJ Open 7, e014171 (2017).
pubmed: 29061597 pmcid: 5665234 doi: 10.1136/bmjopen-2016-014171
Billings, F. T. et al. High-dose perioperative atorvastatin and acute kidney injury following cardiac surgery: a randomized clinical trial. JAMA 315, 877–888 (2016).
pmcid: 4843765 doi: 10.1001/jama.2016.0548 pubmed: 4843765
Meybohm, P. et al. A multicenter trial of remote ischemic preconditioning for heart surgery. N. Engl. J. Med. 373, 1397–1407 (2015).
pubmed: 26436208 doi: 10.1056/NEJMoa1413579
Gerich, J. E., Meyer, C., Woerle, H. J. & Stumvoll, M. Renal gluconeogenesis: its importance in human glucose homeostasis. Diabetes Care 24, 382–391 (2001).
pubmed: 11213896 doi: 10.2337/diacare.24.2.382
Epstein, F. H. Oxygen and renal metabolism. Kidney Int. 51, 381–385 (1997).
pubmed: 9027710 doi: 10.1038/ki.1997.50
Meyer, C., Dostou, J. M. & Gerich, J. E. Role of the human kidney in glucose counterregulation. Diabetes 48, 943–948 (1999).
pubmed: 10331396 doi: 10.2337/diabetes.48.5.943
Yudkin, J. & Cohen, R. D. The contribution of the kidney to the removal of a lactic acid load under normal and acidotic conditions in the conscious rat. Clin. Sci. Mol. Med. 48, 121–131 (1975).
Sa, H. et al. Severe hyperlactatemia, lactate clearance and mortality in unselected critically ill patients. Intensive Care Med. 42, 202–210 (2016).
Cippà, P. E. et al. Transcriptional trajectories of human kidney injury progression. JCI Insight 3, e123151 (2018).
Cippà, P. E. et al. A late B lymphocyte action in dysfunctional tissue repair following kidney injury and transplantation. Nat. Commun. 10, 1157 (2019).
Chen, Z. et al. Hepatocyte TRAF3 promotes insulin resistance and type 2 diabetes in mice with obesity. Mol. Metab. 4, 951–960 (2015).
pubmed: 26909311 pmcid: 4731737 doi: 10.1016/j.molmet.2015.09.013
Tigas, S. K., Sunehag, A. L. & Haymond, M. W. Impact of duration of infusion and choice of isotope label on isotope recycling in glucose homeostasis. Diabetes 51, 3170–3175 (2002).
pubmed: 12401707 doi: 10.2337/diabetes.51.11.3170
Wu, H., Kirita, Y., Donnelly, E. L. & Humphreys, B. D. Advantages of single-nucleus over single-cell RNA sequencing of adult kidney: rare cell types and novel cell states revealed in fibrosis. J. Am. Soc. Nephrol. 30, 23–32 (2019).
pubmed: 30510133 doi: 10.1681/ASN.2018090912
Liu, J. et al. Molecular characterization of the transition from acute to chronic kidney injury following ischemia/reperfusion. JCI Insight 2, e94716 (2017).
Ayyaz, A. et al. Single-cell transcriptomes of the regenerating intestine reveal a revival stem cell. Nature 569, 121–125 (2019).
pubmed: 31019301 doi: 10.1038/s41586-019-1154-y
Lee, J. W., Chou, C.-L. & Knepper, M. A. Deep sequencing in microdissected renal tubules identifies nephron segment-specific transcriptomes. J. Am. Soc. Nephrol. 26, 2669–2677 (2015).
pubmed: 25817355 pmcid: 4625681 doi: 10.1681/ASN.2014111067
Depeint, F., Bruce, W. R., Shangari, N., Mehta, R. & O’Brien, P. J. Mitochondrial function and toxicity: role of the B vitamin family on mitochondrial energy metabolism. Chem. Biol. Interact. 163, 94–112 (2006).
pubmed: 16765926 doi: 10.1016/j.cbi.2006.04.014 pmcid: 16765926
Paquet, R. J. & Mehlman, M. A. Thiamin deficiency. Effect of fatty acids on glucose synthesis in kidney cortex slices from thiamin-deficient rats. J. Biol. Chem. 247, 4905–4907 (1972).
pubmed: 5052223 doi: 10.1016/S0021-9258(19)44996-X pmcid: 5052223
Paquet, R. J., Mackerer, C. R. & Mehlman, M. A. Effects of thiamine deficiency and octanoate administration, in vivo, on gluconeogenesis in rat kidney slices and on amino acid profile in rat liver. Proc. Soc. Exp. Biol. Med. 140, 934–936 (1972).
pubmed: 5039394 doi: 10.3181/00379727-140-36583 pmcid: 5039394
Kang, H. M. et al. Defective fatty acid oxidation in renal tubular epithelial cells has a key role in kidney fibrosis development. Nat. Med. 21, 1–11 (2014).
Poyan Mehr, A. et al. De novo NAD+ biosynthetic impairment in acute kidney injury in humans. Nat. Med. 24, 1351–1359 (2018).
Tran, M. T. et al. PGC1α drives NAD biosynthesis linking oxidative metabolism to renal protection. Nature 531, 528–532 (2016).
pubmed: 26982719 pmcid: 4909121 doi: 10.1038/nature17184
Lemos, D. R. et al. Interleukin-1β Activates a MYC-dependent metabolic switch in kidney stromal cells necessary for progressive tubulointerstitial fibrosis. J. Am. Soc. Nephrol. 29, 1690–1705 (2018).
pubmed: 29739813 pmcid: 6054344 doi: 10.1681/ASN.2017121283
Zager, R. A., Johnson, A. C. M. & Becker, K. Renal cortical pyruvate depletion during AKI. J. Am. Soc. Nephrol. 25, 998–1012 (2014).
pubmed: 24385590 pmcid: 4005311 doi: 10.1681/ASN.2013070791
Hakimi, P. et al. Phosphoenolpyruvate carboxykinase and the critical role of cataplerosis in the control of hepatic metabolism. Nutr. Metab. 2, 33 (2005).
doi: 10.1186/1743-7075-2-33
Burgess, S. C. et al. Impaired tricarboxylic acid cycle activity in mouse livers lacking cytosolic phosphoenolpyruvate carboxykinase. J. Biol. Chem. 279, 48941–48949 (2004).
pubmed: 15347677 doi: 10.1074/jbc.M407120200
Levraut, J. et al. Low exogenous lactate clearance as an early predictor of mortality in normolactatemic critically ill septic patients. Crit. Care Med. 31, 705–710 (2003).
pubmed: 12626973 doi: 10.1097/01.CCM.0000045561.85810.45
Freire Jorge, P. et al. The association of early combined lactate and glucose levels with subsequent renal and liver dysfunction and hospital mortality in critically ill patients. Crit. Care 21, 218 (2017).
Fischer, K. F., Lees, J. A. & Newman, J. H. Hypoglycemia in hospitalized patients. Causes and outcomes. N. Engl. J. Med. 315, 1245–1250 (1986).
pubmed: 3534567 doi: 10.1056/NEJM198611133152002
Haviv, Y. S., Sharkia, M. & Safadi, R. Hypoglycemia in patients with renal failure. Ren. Fail. 22, 219–223 (2000).
pubmed: 10803766 doi: 10.1081/JDI-100100866
Moskowitz, A. et al. Thiamine as a renal protective agent in septic shock. a secondary analysis of a randomized, double-blind, placebo-controlled trial. Ann. Am. Thorac. Soc. 14, 737–741 (2017).
pubmed: 28207287 pmcid: 5427738 doi: 10.1513/AnnalsATS.201608-656BC
Lan, R. et al. Mitochondrial pathology and glycolytic shift during proximal tubule atrophy after ischemic AKI. J. Am. Soc. Nephrol. 27, 3356–3367 (2016).
pubmed: 27000065 pmcid: 5084876 doi: 10.1681/ASN.2015020177
Katsyuba, E. et al. De novo NAD+ synthesis enhances mitochondrial function and improves health. Nature 563, 354–359 (2018).
pubmed: 30356218 pmcid: 6448761 doi: 10.1038/s41586-018-0645-6
Ricksten, S.-E., Bragadottir, G. & Redfors, B. Renal oxygenation in clinical acute kidney injury. Crit. Care 17, 221 (2013).
Singh, P., Ricksten, S.-E., Bragadottir, G., Redfors, B. & Nordquist, L. Renal oxygenation and haemodynamics in acute kidney injury and chronic kidney disease. Clin. Exp. Pharmacol. Physiol. 40, 138–147 (2013).
pubmed: 23360244 pmcid: 3710120 doi: 10.1111/1440-1681.12036
Redfors, B., Bragadottir, G., Sellgren, J., Swärd, K. & Ricksten, S.-E. Acute renal failure is NOT an “acute renal success”—a clinical study on the renal oxygen supply/demand relationship in acute kidney injury. Crit. Care Med. 38, 1695–1701 (2010).
pubmed: 20512036 doi: 10.1097/CCM.0b013e3181e61911 pmcid: 20512036
Kellum, J. A. & Lameire, N., KDIGO AKI Guideline Work Group. Diagnosis, evaluation, and management of acute kidney injury: a KDIGO summary (Part 1). Crit. Care 17, 204 (2013).
pubmed: 23394211 pmcid: 4057151 doi: 10.1186/cc11454
Chung, S. T., Chacko, S. K., Sunehag, A. L. & Haymond, M. W. Measurements of gluconeogenesis and glycogenolysis: a methodological review. Diabetes 64, 3996–4010 (2015).
pubmed: 26604176 pmcid: 4657587 doi: 10.2337/db15-0640
Allsop, J. R., Wolfe, R. R. & Burke, J. F. Tracer priming the bicarbonate pool. J. Appl. Physiol. 45, 137–139 (1978).
pubmed: 670025 doi: 10.1152/jappl.1978.45.1.137 pmcid: 670025
McCabe, B. J. & Previs, S. F. Using isotope tracers to study metabolism: application in mouse models. Metab. Eng. 6, 25–35 (2004).
pubmed: 14734253 doi: 10.1016/j.ymben.2003.09.003 pmcid: 14734253
Ekberg, K. et al. Contributions by kidney and liver to glucose production in the postabsorptive state and after 60 h of fasting. Diabetes 48, 292–298 (1999).
pubmed: 10334304 doi: 10.2337/diabetes.48.2.292 pmcid: 10334304
Kobayashi, A. et al. Six2 defines and regulates a multipotent self-renewing nephron progenitor population throughout mammalian kidney development. Cell Stem Cell 3, 169–181 (2008).
pubmed: 18682239 pmcid: 2561900 doi: 10.1016/j.stem.2008.05.020
Wu, Y., Tamayo, P. & Zhang, K. Visualizing and interpreting single-cell gene expression datasets with similarity weighted nonnegative embedding. Cell Syst. 7, 656–666 (2018).
pubmed: 30528274 pmcid: 6311449 doi: 10.1016/j.cels.2018.10.015
Schubert, M. et al. Perturbation-response genes reveal signaling footprints in cancer gene expression. Nat. Commun. 9, 20 (2018).
pubmed: 29295995 pmcid: 5750219 doi: 10.1038/s41467-017-02391-6
Legouis, David et al. Ex vivo analysis of renal proximal tubular cells. BMC Cell Biol. 16, 12 (2015).
pubmed: 25881040 pmcid: 4379601 doi: 10.1186/s12860-015-0058-4
Liu, J. et al. Cell-specific translational profiling in acute kidney injury. J. Clin. Invest. 124, 1242–1254 (2014).
pubmed: 24569379 pmcid: 3938273 doi: 10.1172/JCI72126

Auteurs

David Legouis (D)

Laboratory of Nephrology, Department of Medicine and Cell Physiology, University Hospital and University of Geneva, Geneva, Switzerland. david.legouis@unige.ch.
Division of Intensive Care, University Hospital of Geneva, Geneva, Switzerland. david.legouis@unige.ch.
ORCID: 0000-0002-2924-9737

Sven-Erick Ricksten (SE)

Department of Anaesthesiology, Intensive Care Medicine, Sahlgrenska Academy, University of Gothenburg, Sahlgrenska University Hospital, Gothenburg, Sweden.

Anna Faivre (A)

Laboratory of Nephrology, Department of Medicine and Cell Physiology, University Hospital and University of Geneva, Geneva, Switzerland.

Thomas Verissimo (T)

Laboratory of Nephrology, Department of Medicine and Cell Physiology, University Hospital and University of Geneva, Geneva, Switzerland.

Karim Gariani (K)

Division of Endocrinology, Diabetes, Hypertension and Nutrition, Department of Internal Medicine Specialties, University Hospital of Geneva, Geneva, Switzerland.

Charles Verney (C)

French National Institute of Health and Medical Research UMR_S1155, Rare and Common Kidney Diseases, Matrix Remodeling and Repair; AP-HP, Tenon Hospital, Renal Intensive Care Unit, Sorbonne Université, Paris, France.
ORCID: 0000-0001-8922-6038

Pierre Galichon (P)

French National Institute of Health and Medical Research UMR_S1155, Rare and Common Kidney Diseases, Matrix Remodeling and Repair; AP-HP, Tenon Hospital, Renal Intensive Care Unit, Sorbonne Université, Paris, France.
ORCID: 0000-0002-2771-1596

Lena Berchtold (L)

Laboratory of Nephrology, Department of Medicine and Cell Physiology, University Hospital and University of Geneva, Geneva, Switzerland.
Service of Nephrology, University Hospitals of Leuven, Leuven, Belgium.

Eric Feraille (E)

Department of Cell Biology and Metabolism, University of Geneva, Geneva, Switzerland.

Marylise Fernandez (M)

Laboratory of Nephrology, Department of Medicine and Cell Physiology, University Hospital and University of Geneva, Geneva, Switzerland.

Sandrine Placier (S)

French National Institute of Health and Medical Research UMR_S1155, Rare and Common Kidney Diseases, Matrix Remodeling and Repair; AP-HP, Tenon Hospital, Renal Intensive Care Unit, Sorbonne Université, Paris, France.

Kari Koppitch (K)

Department of Stem Cell Biology and Regenerative Medicine, Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research, University of Southern California, Los Angeles, CA, USA.

Alexandre Hertig (A)

French National Institute of Health and Medical Research UMR_S1155, Rare and Common Kidney Diseases, Matrix Remodeling and Repair; AP-HP, Tenon Hospital, Renal Intensive Care Unit, Sorbonne Université, Paris, France.
ORCID: 0000-0002-2903-3303

Pierre-Yves Martin (PY)

Laboratory of Nephrology, Department of Medicine and Cell Physiology, University Hospital and University of Geneva, Geneva, Switzerland.
Service of Nephrology, Department of Internal Medicine Specialties, University Hospital of Geneva, Geneva, Switzerland.

Maarten Naesens (M)

Service of Nephrology, University Hospitals of Leuven, Leuven, Belgium.

Jérôme Pugin (J)

Division of Intensive Care, University Hospital of Geneva, Geneva, Switzerland.

Andrew P McMahon (AP)

Department of Stem Cell Biology and Regenerative Medicine, Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research, University of Southern California, Los Angeles, CA, USA.

Pietro E Cippà (PE)

Department of Stem Cell Biology and Regenerative Medicine, Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research, University of Southern California, Los Angeles, CA, USA.
Division of Nephrology, Ente Ospedaliero Cantonale, Lugano, Switzerland.

Sophie de Seigneux (S)

Laboratory of Nephrology, Department of Medicine and Cell Physiology, University Hospital and University of Geneva, Geneva, Switzerland.
Service of Nephrology, Department of Internal Medicine Specialties, University Hospital of Geneva, Geneva, Switzerland.

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Classifications MeSH

questionsmedicales.fr › Maladies urogénitales › Maladies urologiques › Maladies du rein › Insuffisance rénale › Atteinte rénale aigüe › Altered proximal tubular cell glucose...
questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Altered proximal tubular cell glucose...
questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Sujet âgé › Altered proximal tubular cell glucose...
questionsmedicales.fr › Eucaryotes › Animaux › Altered proximal tubular cell glucose...
questionsmedicales.fr › États, signes et symptômes pathologiques › Processus pathologiques › Caractéristiques de la maladie › Maladie grave › Altered proximal tubular cell glucose...
questionsmedicales.fr › Métabolisme › Métabolisme glucidique › Néoglucogenèse › Altered proximal tubular cell glucose...
questionsmedicales.fr › Glucides › Sucres › Oses › Hexose › Glucose › Altered proximal tubular cell glucose...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Altered proximal tubular cell glucose...
questionsmedicales.fr › Appareil urogénital › Voies urinaires › Rein › Néphrons › Tubules rénaux › Tubules contournés proximaux › Altered proximal tubular cell glucose...
questionsmedicales.fr › Composés chimiques organiques › Acides carboxyliques › Hydroxyacides › Lactates › Acide lactique › Altered proximal tubular cell glucose...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Altered proximal tubular cell glucose...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Lignées consanguines de souris › Souris de lignée C57BL › Altered proximal tubular cell glucose...
questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Adulte d'âge moyen › Altered proximal tubular cell glucose...
questionsmedicales.fr › Techniques d'investigation › Techniques in vitro › Techniques de culture › Techniques de culture cellulaire › Culture de cellules primaires › Altered proximal tubular cell glucose...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Statistiques comme sujet › Probabilité › Score de propension › Altered proximal tubular cell glucose...
questionsmedicales.fr › Phénomènes physiologiques respiratoires et circulatoires › Phénomènes physiologiques cardiovasculaires › Circulation sanguine › Circulation rénale › Altered proximal tubular cell glucose...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Caractéristiques des études épidémiologiques › Études épidémiologiques › Études de cohortes › Études rétrospectives › Altered proximal tubular cell glucose...
questionsmedicales.fr › Composés hétérocycliques › Composés hétéromonocycliques › Pyrimidines › Thiamine › Altered proximal tubular cell glucose...
questionsmedicales.fr › Actions chimiques et utilisations › Actions pharmacologiques › Effets physiologiques des médicaments › Complexe vitaminique B › Altered proximal tubular cell glucose...
questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Jeune adulte › Altered proximal tubular cell glucose...