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Abstract: PO2494

Decreased Renal Gluconeogenesis Is a Hallmark of CKD

Session Information

Category: CKD (Non-Dialysis)

  • 2103 CKD (Non-Dialysis): Mechanisms

Authors

  • Verissimo, Thomas, Universite de Geneve Departement de Physiologie Cellulaire et Metabolisme, Geneve, GE, Switzerland
  • Faivre, Anna, Universite de Geneve Departement de Physiologie Cellulaire et Metabolisme, Geneve, GE, Switzerland
  • Rinaldi, Anna, Repubblica e Cantone Ticino Ente Ospedaliero Cantonale, Bellinzona, Ticino, Switzerland
  • Lindenmeyer, Maja, University Medical Center Hamburg-Eppendorf - III. Medical Department - Germany, Hamburg, Germany
  • Heckenmeyer, Carolyn, Universite de Geneve Departement de Physiologie Cellulaire et Metabolisme, Geneve, GE, Switzerland
  • Fernandez, Marylise, Universite de Geneve Departement de Physiologie Cellulaire et Metabolisme, Geneve, GE, Switzerland
  • Cippa, Pietro E., Repubblica e Cantone Ticino Ente Ospedaliero Cantonale, Bellinzona, Ticino, Switzerland
  • Legouis, David, Universite de Geneve Departement de Physiologie Cellulaire et Metabolisme, Geneve, GE, Switzerland
  • De Seigneux, Sophie M., Hopitaux Universitaires Geneve, Geneve, Genève, Switzerland
Background

Chronic kidney disease (CKD) is associated with alterations of tubular function. Renal gluconeogenesis is responsible for 40% of systemic gluconeogenesis during fasting, but how and why this process is affected by CKD and the repercussions of such regulations are unknown.

Methods

We used data from more than 200 renal biopsies performed in CKD patients and from 43 kidney allograft patients. We studied three complementary mice models of chronic kidney disease in vivo and ex vivo. We analyzed a cohort of patients having benefitted from renal catheterization and a retrospective cohort of patients hospitalized in the intensive care unit (ICU).

Results

Renal biopsies of CKD and kidney allograft patients revealed a stage-dependent decrease in the renal gluconeogenic pathway. Three different animal models of CKD confirm a proximal tubular cell-specific gluconeogenic down-regulation. This resulted in an alteration of renal glucose production and lactate clearance during an exogenous lactate load. Decreased renal glucose production and lactate clearance were confirmed by the isolated perfused kidney technique in animal models, and by renal venous catheterization in CKD patients. In CKD patients hospitalized in the ICU, systemic alterations of glucose and lactate levels were more prevalent and associated with increased mortality and worse renal prognosis at follow-up. Decreased expression of the gluconeogenesis pathway and its regulators predicted faster histological progression of renal disease in kidney allograft biopsies.

Conclusion

Renal gluconeogenic function is impaired during CKD. Altered renal gluconeogenesis leads to systemic metabolic changes with a decrease in glucose and increase in lactate level, and associates with a worse renal prognosis.

Funding

  • Private Foundation Support