New insights into the mechanisms of salt and acid handling by te kidney
(2009)
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- Authors
- Supervisors
- Devuyst, Olivier
- Abstract
- The distal nephron plays an important role in the fine regulation of electrolytes and acid-base balance. Our studies focused on the molecular mechanisms involved in these processes. We revealed the crucial role of parvalbumin (PV) on distal tubule NaCl reabsorption. PV is a Ca2+-binding protein, exclusively expressed in the early distal convoluted tubule. We showed a functional relationship between PV and the apical thiazide-sensitive Na+-Cl− cotransporter (NCC), which mediates the major NaCl reabsorption pathway in the DCT. PV deficient mice exhibit discrete salt-losing, high aldosterone levels, kaliuresis and increased bone resistance, resembling at some points Gitelman s syndrome phenotype. Accordingly, PV knockout mice manifest decreased expression of NCC, paralleled by the absence of diuretic response to hydrochlorothiazide. Furthermore, in vitro studies performed on DCT cells showed that PV may regulate NCC expression by modulating the Ca2+-dependent signalling pathway. The collecting duct is committed to the fine-tuning of urinary acidification and ammonium excretion. The transport of ammonium in this nephron segment is believed to occur by non-ionic NH3 diffusion. We have shown that this longstanding assumption should be revised since this process is largely dependent of Rhcg, a protein related to the Rhesus antigens of red blood cells. Rhcg deficient mice have abnormal urinary acidification due to impaired ammonium excretion on acid loading -a feature of distal renal tubular acidosis. Male Rhcg knockout mice are also charcaterized by a reduction in reproductive capability associated with altered epididymal function. Our studies thus reveal the emerging role for Rhcg in ammonium handling and acid-base homeostasis both in the kidney and the male reproductive tract. In conclusion, our overall studies provide new insights in to the mechanisms of distal NaCl and acid-base transport and in the pathophysiology of inherited tubular disorders.
- Affiliations
UCLouvain MD/MINT/NEFR - Unité de néphrologie
Citations
Belge, H. (2009). New insights into the mechanisms of salt and acid handling by te kidney. https://hdl.handle.net/2078.5/111971