title: NaCl transport deficiencies--hemodynamics to the rescue.
abstract: Hereditary defects in the renal handling of filtered NaCl and water have important implications for understanding the physiological mechanisms that enable the kidney to optimize the match between glomerular filtration rate and tubular reabsorption. Null mutations in the water channel aquaporin 1 (AQP1) or the Na/H exchanger NHE3, two major fluid transporters in the proximal tubule, are states in which a reduction in proximal fluid absorption is accompanied by proportionate decrements in glomerular filtration rate. Compensation of the transport defect by a reduction in filtered load is so efficient that clinically symptomatic Na losses are not observed in either AQPI or NHE3 deficiency. On the other hand, severe syndromes of salt wasting are caused by transport deficiencies in the thick ascending limb or the collecting duct, indicating that the severity of Na dysregulation is unrelated to the basal absorption of NaCl in a given nephron segment. Loss of function of the Na,K,2Cl-cotransporter (NKCC2) or of the epithelial Na channel (ENaC) reduces Na absorption in thick ascending limbs or collecting ducts. In these states, the increased delivery of Na to downstream segments is not monitored by a sensor linked to the site of filtrate formation. In the absence of adaptations in the filtered load, intrarenal compensation of a circumscribed NaCl malabsorption by adjustment of NaCl transport in other nephron segments is remarkably insufficient, particularly in the immature kidney of the newborn.
authors.affiliation: National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA. jurgens@intra.niddk.nih.gov
authors.forename: J
authors.initials: J
authors.lastname: Schnermann
mesh_terms: D000042:Absorption; D000818:Animals; D001692:Biological Transport / Q000502:physiology; D005919:Glomerular Filtration Rate; D006439:Hemodynamics; D006801:Humans; D007668:Kidney / Q000378:metabolism*; D012964:Sodium / Q000378:metabolism; D012965:Sodium Chloride / Q000378:metabolism*
chemical_list: D012965:Sodium Chloride; D012964:Sodium