Physiology of renal sodium transport

A wealth of studies performed with a spectrum of methods spanning simple clearance studies to the molecular identification of ion transporters has increased our understanding of how approximately 1.7 kg of NaCl and 180 L of H2O are absorbed by renal tubules in man and how the urinary excretion is fine-tuned to meet homeostatic requirements. This review will summarize our current understanding. In the proximal nephron, approximately 60 to 70% of the filtered Na+ and H2O is absorbed together with approximately 90% of the filtered HCO3-. The exact quantities are determined by many regulatory factors, such as glomerulotubular balance, angiotensin II, endothelin, sympathetic innervation, parathyroid hormone, dopamine, acid base status and others. The essential components of absorption are luminal membrane Na+/H+ exchange and the basolateral (Na+ + K+)-ATPase. In the thick ascending limb of the loop of Henle, 20 to 30% of the filtered NaCl is absorbed via Na(+)2Cl(-)K(+) cotransport driven by the basolateral (Na+ + K+)-ATPase. No H2O is absorbed at this nephron site. The transport rate is determined by the Na+ load and by several hormones and neurotransmitters, including prostaglandins, parathyroid hormone, glucagon, calcitonin, arginine vasopressin (AVP), and adrenaline. In the distal tubule, some 5 to 10% of the filtered load is absorbed via Na+Cl- cotransport in the luminal membrane driven by the basolateral (Na+ + K+)-ATPase. The rate of transport is again determined by the delivered load and by several hormones and neurotransmitters. One of the tasks of the collecting duct is to control the absorption of approximately 10 to 15% of the filtered H2O, regulated by AVP, and just a few percent of the filtered Na+, controlled by aldosterone and natriuretic hormone. The water absorption proceeds through the luminal membrane via aquaporin 2 and through the basolateral membrane via aquaporin 3 channels and is driven by the osmotic gradient built up by the counter current concentrating system. The Na+ absorption occurs via Na+ channels present in the luminal membrane driven by the basolateral (Na+ + K+)-ATPase. With no pharmacological interference, urinary excretion of Na+ can vary between less than 0.1% and no more than 3% of the filtered load, and that of H2O can vary between 0.3 and 15%.