[29] Kidney transport


A major role of the kidney is to maintain whole-body homeostasis. The kidney filters about 180 liters of water and 25 moles of sodium every day. About 90% of this ultrafiltrate is then reabsorbed by the kidney tubule. Chronic kidney failure (CRF), a condition in which kidney function is progressively lost, represents a major challenge to public health. Genetic or acquired dysregulation of the general (Renin-angiotensin-aldosterone system, sympathetic nervous system,...) or local (tubulo-glomerular feedback, coordination between tubular transport pathways,...) mechanisms that modulate tubular sodium reabsorption that may lead to severe diseases such as hypertension and renal failure.


Our research focuses on two distinct topics. We are studying the physiological mechanisms of control of sodium-chloride and water transport par renal tubule epithelial cells with a special focus on collecting duct principal cells that account for the fine tuning of sodium reabsorption process. We contributed to the demonstration that both sodium and water reabsorption are tightly controlled by aldosterone and vasopressin as well as by non-hormonal stimuli such as tubular flux, intracellular sodium concentration and extracellular tonicity. Thanks to the support of the FNS we are currently trying to elucidate the mechanism of coordination between apical and basolateral transport of ions and water. We are also studying the mechanism of coupling between transcellular and paracellular ion transport pathways. Finally, we are investigating the role of the primary cilium, a recently rediscovered organelle, on regulation of ion and water transport by renal tubule epithelial cells.


Our second research axis consists in studying the role of sodium transport-dependent renal tubular cell metabolic activity on progression of chronic renal disease. Indeed, progression of chronic renal failure is better correlated with tubular than glomerular injury. The progression of chronic kidney diseases is mostly dependent on chronic inflammation and fibrosis or renal interstitium. Our project supported by the NCCR Kidney.ch is aimed at highlighting the relationship between metabolic work of renal tubular cells in response to variations of aldosterone levels and dietary sodium intake, the activity of major cellular metabolic sensors such as HIF, AMPK and mTOR and mechanisms leading to cell death.