Research scientists and clinicians involved : Régine Chambrey
Chronic kidney disease (CKD) has an incidence that has reached epidemic proportions and continues to increase world-wide, in line with the increasing prevalence of metabolic diseases like diabetes, obesity, and hypertension.
Figure 1 : Study of 365 patients (Service d’explorations fonctionnelles rénales, CHU Réunion). % of patients with diabetes increases dramatically as renal function decreases, suggesting that chronic kidney disease precipitates the onset of diabetes.
The loss of kidney function characterizing CKD is progressive and kidney damage is irreversible potentially leading to complete destruction of the organ. Current therapeutic options for end stage CKD include dialysis, which is associated with increased morbidity and mortality, and renal transplantation, which is limited by the supply of compatible organs. Therefore, elucidating the molecular basis of kidney disease development should help to establish new therapies in order to improve the survival and quality of life of patients.
Metabolic acidosis is an inescapable complication of advanced chronic renal disease and has been identified as a factor accelerating the progression of chronic renal failure. Conversely, alkali therapy slows the progression of the disease.
CKD is also frequently associated with abnormal glucose homeostasis. An increasing number of epidemiological studies show that the % of diabetic patients increases dramatically as CKD progresses, suggesting that CKD precipitates the onset of diabetes. Interestingly, acidosis also contributes to the insulin resistance that precedes the onset of type 2 diabetes.
Our goal is to investigate the contribution of acidosis to the progression of CKD and associated disorders of glucose homeostasis.
Related major publications of the team :
– Karen I. Lopez-Cayuqueo et al. A Mouse Model of pseudohypoaldosteronism type II Reveals a Novel Mechanism of Renal Tubular Acidosis. Kidney Int. 2018; 94:514-523.
– Sinning A et al. Double knockout of the Na+-Driven Cl–/HCO3 exchanger and NaCl cotransporter induces hypokalemia and volume depletion. J Am Soc Nephrol. 2016 ; 28(1):130-139.
– Gueutin V et al. Pivotal role of β-intercalated cells in maintaining body fluid and electrolyte balance. J Clin Invest. 2013 ; 123(10):4219-31.
– Chambrey R et al. Renal intercalated cells are rather energized by a proton than a sodium pump. Proc Natl Acad Sci U S A. 2013;110(19):7928-33.