Renal water transport in health and disease

Abstract

Saving body water by optimal reabsorption of water filtered by the kidney leading to excretion of urine with concentrations of solutes largely above that of plasma allowed vertebrate species to leave the aquatic environment to live on solid ground. Filtered water is reabsorbed for 70% and 20% by proximal tubules and thin descending limbs of Henle, respectively. These two nephron segments express the water channel aquaporin-1 located along both apical and basolateral membranes. In the proximal tubule, the paracellular pathway accounts for at least 30% of water reabsorption, and the tight-junction core protein claudin-2 plays a key role in this permeability. The ascending limb of Henle and the distal convoluted tubule are impermeant to water and are responsible for urine dilution. The water balance is adjusted along the collecting system, i.e. connecting tubule and the collecting duct, under the control of arginine-vasopressin (AVP). AVP is synthesized by the hypothalamus and released in response to an increase in extracellular osmolality or stimulation of baroreceptors by decreased blood pressure. In response to AVP, aquaporin-2 water channels stored in subapical intracellular vesicles are translocated to the apical plasma membrane and raise the water permeability of the collecting system. The basolateral step of water reabsorption is mediated by aquaporin-3 and -4, which are constitutively expressed. Drugs targeting water transport include classical diuretics, which primarily inhibit sodium transport; the new class of SGLT2 inhibitors, which promotes osmotic diuresis and the non-peptidic antagonists of the V2 receptor, which are pure aquaretic drugs. Disturbed water balance includes diabetes insipidus and hyponatremias. Diabetes insipidus is characterized by polyuria and polydipsia. It is either related to a deficit in AVP secretion called central diabetes insipidus that can be treated by AVP analogs or to a peripheral defect in AVP response called nephrogenic diabetes insipidus. Diabetes insipidus can be either of genetic origin or acquired. Hyponatremia is a common disorder most often related to free water excess relying on overstimulated or inappropriate AVP secretion. The assessment of blood volume is key for the diagnosis and treatment of hyponatremia, which can be classified as hypo-, eu-, or hypervolemic.

Excess dietary sodium partially restores salt and water homeostasis caused by loss of the endoplasmic reticulum molecular chaperone, GRP170, in the mouse nephron

“…The GRP170 NT-/- animals also excreted less sodium and potassium than controls (Figures 2C, E). Because the most efficient means of preserving intravascular volume is to retain sodium and water, GRP170 NT-/- mice on a HS diet are also expected to produce a relatively more concentrated urine than those on a standard diet, provided functional ion channels and transporters are present at the epithelial cell apical membrane (17). The fixed and relatively low urine osmolality of GR170 deficient animals (Fig.…”

“…2D) indicates, therefore, that a HS diet does not reverse the severe urine concentrating defect. This may be a consequence of damaged PT cells, impaired sodium reabsorption in the loop of Henle and distal collecting duct, and/or diminished water transport in the collecting duct (17).…”

“…These energy-intensive processes likely explain the abundance of mitochondria in the PT epithelium—second only to the density in the myocardium—and the importance of the PT in AKI pathogenesis (13, 14) . Downstream of the PT, the distal convoluted tubule (DCT) and collecting duct, which are under the control of aldosterone and antidiuretic hormone, are vital for fine-tuning sodium, potassium, and water reabsorption largely via the epithelial sodium channel (ENaC), the renal outer medullary potassium channel (ROMK), aquaporin 2 (AQP2), and aquaporin 4 (AQP4) (15–17) .…”

The kidneys matter

“…The role of the kidney in the control of electrolyte and water homeostasis is highlighted in a second section. Hummler et al examine glucocorticoid signaling in kidney and adrenal gland [ 16 ], while Feraille and Hoorn analyze the current state of understanding how renal handling of water controls water balance [ 6 ]. McDonough and Fenton review mechanisms of extrarenal and renal sensing of potassium and its transport in the kidney [ 9 ] followed by a discussion by Pearce, Nesterov, and Korbmacher on the function of the distal segments of the nephron in sodium transport [ 10 ].…”

Genetic effects of double muscle and slick hair mutations on selection criteria and genomic study for water efficiency in senepol cattle

“…Concomitantly, the networks of biological processes were enriched for water transport, fluid transport, water homeostasis, and renal water transport. In general, water balance results from water intake and excretion via the urinary system, mainly dependent on the processes of reabsorption and filtration related to water transport (67). The network was also enriched for biological processes linked to DNA transcription, which is connected to the transcription mechanism, and response to cAMP, resulting in a change in the metabolism state or activity, such as gene expression (68).…”