BACKGROUND AND OBJECTIVES: Gitelman syndrome (GS) is a salt-wasting tubulopathy that results from the inactivation of the human thiazide-sensitive sodium chloride cotransporter located in the distal convoluted tubule. Tubular adaptation to renal sodium loss has been described and localized in the distal tubule in experimental models of GS but not in humans with GS. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: The tubular adaptation to renal sodium loss is described. Osmole-free water clearance and endogenous lithium clearance with furosemide infusion are used to compare 7 patients with genetically confirmed GS and 13 control participants. RESULTS: Neither endogenous lithium clearance nor osmole-free water clearance disclosed enhanced proximal fluid reabsorption in patients with GS. These patients displayed significantly lower osmole-free water clearance factored by inulin clearance (7.1 ± 1.9 versus 10.1 ± 2.2; P<0.01) and significantly lower fractional sodium reabsorption in the diluting nephron (73.2% ± 7.1% versus 86.1% ± 4.7%; P<0.005), consistent with the inactivation of the thiazide-sensitive sodium chloride cotransporter. The furosemide-induced reduction rate of fractional sodium reabsorption in the diluting segment was higher in patients with GS (75.6% ± 6.1% versus 69.9% ± 3.2%; P<0.039), suggesting that sodium reabsorption would be enhanced in the cortical part of the thick ascending limb of the loop of Henle in patients with GS. CONCLUSIONS: These findings suggest that tubular adaptation to renal sodium loss in GS would be devoted to the cortical part of the thick ascending limb of the loop of Henle in humans.
BACKGROUND AND OBJECTIVES:Gitelman syndrome (GS) is a salt-wasting tubulopathy that results from the inactivation of the human thiazide-sensitive sodium chloride cotransporter located in the distal convoluted tubule. Tubular adaptation to renal sodium loss has been described and localized in the distal tubule in experimental models of GS but not in humans with GS. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: The tubular adaptation to renal sodium loss is described. Osmole-free water clearance and endogenous lithium clearance with furosemide infusion are used to compare 7 patients with genetically confirmed GS and 13 control participants. RESULTS: Neither endogenous lithium clearance nor osmole-free water clearance disclosed enhanced proximal fluid reabsorption in patients with GS. These patients displayed significantly lower osmole-free water clearance factored by inulin clearance (7.1 ± 1.9 versus 10.1 ± 2.2; P<0.01) and significantly lower fractional sodium reabsorption in the diluting nephron (73.2% ± 7.1% versus 86.1% ± 4.7%; P<0.005), consistent with the inactivation of the thiazide-sensitive sodium chloride cotransporter. The furosemide-induced reduction rate of fractional sodium reabsorption in the diluting segment was higher in patients with GS (75.6% ± 6.1% versus 69.9% ± 3.2%; P<0.039), suggesting that sodium reabsorption would be enhanced in the cortical part of the thick ascending limb of the loop of Henle in patients with GS. CONCLUSIONS: These findings suggest that tubular adaptation to renal sodium loss in GS would be devoted to the cortical part of the thick ascending limb of the loop of Henle in humans.
Authors: D B Simon; R S Bindra; T A Mansfield; C Nelson-Williams; E Mendonca; R Stone; S Schurman; A Nayir; H Alpay; A Bakkaloglu; J Rodriguez-Soriano; J M Morales; S A Sanjad; C M Taylor; D Pilz; A Brem; H Trachtman; W Griswold; G A Richard; E John; R P Lifton Journal: Nat Genet Date: 1997-10 Impact factor: 38.330
Authors: D B Simon; F E Karet; J Rodriguez-Soriano; J H Hamdan; A DiPietro; H Trachtman; S A Sanjad; R P Lifton Journal: Nat Genet Date: 1996-10 Impact factor: 38.330
Authors: H H Lemmink; N V Knoers; L Károlyi; H van Dijk; P Niaudet; C Antignac; L M Guay-Woodford; P R Goodyer; J C Carel; A Hermes; H W Seyberth; L A Monnens; L P van den Heuvel Journal: Kidney Int Date: 1998-09 Impact factor: 10.612
Authors: Veena S Rao; Noah Planavsky; Jennifer S Hanberg; Tariq Ahmad; Meredith A Brisco-Bacik; Francis P Wilson; Daniel Jacoby; Michael Chen; W H Wilson Tang; David Z I Cherney; David H Ellison; Jeffrey M Testani Journal: J Am Soc Nephrol Date: 2017-07-24 Impact factor: 10.121