Calcium reabsorption in the distal convoluted and connecting tubule of the nephron.
Renal calcium and uric acid handling and kidney stones
Kidney stones constitute an important health issue, in terms of (i) pain (renal colic), felt by about 10% of the population at least once during lifetime; (ii) complications, with significant number of hospitalizations and surgery related to kidney stones; (iii) long-term morbidity that may arise from severe complications (infection, end stage renal disease and dialysis,...) in a few patients; and (iv) as an overall financial burden for the health system. Moreover, kidney stone can be seen as an early marker of cardiovascular diseases and of the metabolic syndrome.
Despite the large and increasing kidney stone epidemic, only a paucity of effort is dedicated to kidney stone research and to the development of new therapeutical approaches. We established a translational research program devoted to unravel how kidneys are handling calcium and uric acid, two of the main constituents of kidney stones.
Kidneys are key organs in keeping calcium and uric acid in balance. In order to achieve this goal, tight regulation of several transport mechanisms is mandatory. Recently, several transporters for calcium or for uric acid have been described in the kidney, but their precise role in calcium, respectively uric acid homeostasis and in kidney stone formation remain elusive. We are studying the specific role of a calcium transporter (the sodium/calcium exchanger, NCX1) in renal calcium handling and of a newly discovered uric acid transporter (SLC2A9) in renal uric acid handling. Mouse models in which these transporters are specifically inactivated in the kidney have been established and are studied.
An in-depth characterization of the role of these transporters in vivo may help identifying new therapeutical targets.