Cardiovascular Medicine, Urology and Nephrology

Glucose metabolism links kidney injury to mortality

Dr. David Legouis

Université de Genève
Hôpitaux Universitaires de Genève

PD Dr. Dr. Pietro E. Cippà

Ente Ospedaliero Cantonale, Lugano

The rapid decline of kidney function occurring in patients with acute kidney injury, abbreviated to AKI, is associated with high mortality and with an increased risk to transition to chronic kidney disease. Not only is our understanding of the mechanisms associated with AKI incomplete to date, the current options for therapy are also very limited. 

The kidney contributes to up to 40 % of glucose production through gluconeogenesis under fasting and stress conditions. The research team led by David Legouis and Pietro Cippà intended to establish whether glucose production in the kidneys is affected by AKI and how this influences the overall metabolism. To this end, they combined multiple experimental approaches at the cellular and molecular levels.  

Based on animal models, the researchers demonstrated that the renal glucose synthesis was altered during AKI. This change in renal metabolism was associated with systemic abnormalities characterized by low glucose and high lactate levels. Altered glucose metabolism associated with AKI was strongly related to patient mortality in the intensive care unit.  These results were confirmed in patients undergoing cardiac surgery and developing AKI as well as in kidney transplant recipients.  

Following this, the researchers also investigated the effects of thiamine (vitamin B1), which plays an important role in carbohydrate metabolism. They demonstrated in experiments that thiamine was needed for the renal production of glucose and, in a retrospective cohort study that thiamine supplementation was associated with metabolic improvement and with reduced mortality.  

This study demonstrated an association between renal glucose production, acute kidney injury and high mortality. Taken against the background of the therapeutic options for patients with this disease being highly unsatisfactory to date, these results obtained by the two scientists are important for further research in this field. 

Altered proximal tubular cell glucose metabolism during acute kidney injury is associated with mortality. David Legouis, Sven-Erick Ricksten, Anna Faivre, Thomas Verissimo, Karim Gariani, Charles Verney, Pierre Galichon, Lena Berchtold, Eric Feraille, Marylise Fernandez, Sandrine Placier, Kari Koppitch, Alexandre Hertig, Pierre-Yves Martin, Maarten Naesens, Jérôme Pugin, Andrew P McMahon, Pietro E Cippà, Sophie de Seigneux. 
Nat Metab. 2020 Aug; 2(8):732-743. doi: 10.1038/s42255-020-0238-1.