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Abstract: SA-PO1048

High K Intake Modulates Thiazide Sensitive Na-Cl Cotransporter Mediated Na and K Transport: Effects of Gender and Angiotensin II Type 1a (AT1a) Receptor

Session Information

  • Na+, K+, Cl-
    November 04, 2017 | Location: Hall H, Morial Convention Center
    Abstract Time: 10:00 AM - 10:00 AM

Category: Fluid, Electrolytes, and Acid-Base

  • 703 Na+, K+, Cl- Basic


  • Li, Jing, Yale University, New Haven, Connecticut, United States
  • Xu, Shuhua, Yale University, New Haven, Connecticut, United States
  • Wang, Claire J, Yale University, New Haven, Connecticut, United States
  • Hu, Haiyan, Yale University, New Haven, Connecticut, United States
  • Weinstein, Alan Mark, Weill Medical College of Cornell, New York, New York, United States
  • Palmer, Lawrence G., Weill Medical College of Cornell, New York, New York, United States
  • Wang, Tong, Yale University, New Haven, Connecticut, United States

The thiazide-sensitive Na-Cl cotransporter (NCC) plays a key role in controlling NaCl absorption in the distal tubule, and also modulates salt and fluid delivery to downstream portions of the nephron, thus regulating K secretion. Previously we reported that higher NCC expression correlates with activity in female WT, and that gender-specific differences were absent in AT1a receptor knockout (KO) mice. We have now studied the gender difference in response to high K intake in WT and AT1a receptor KO animals.


Renal clearance experiments were performed on male WT and KO mice treated with normal and high K (5% KCl, 7 days) diets. Urine volume (UV), glomerular filtration rate (GFR), absolute (ENa, EK) and fractional (FENa, FEK) Na and K excretion were measured and compared at peak changes after a bolus iv injection of hydrochlorothiazide (HCTZ; 30mg/kg). Total NCC (tNCC) and Na/H-exchanger isoform 3 (NHE3) expressions in the kidney were examined by Western blotting.


In WT mice, HK reduced tNCC abundance by 70% in females and by 60% in males. In KO mice HK produced more reduction of tNCC in male (60%) than female (33%). Functional measurements showed that in WT, K loading diminished HCTZ-dependent FENa by 53% in females and 42% in males. FENa was not reduced by high-K diet in KO mice. High-K intake significantly increased HCTZ-induced kaliuresis (EK) by 129% in WT male, but reduced EK in WT female (68%), KO male (51%) and KO female (55%). NHE3 expression was significantly reduced with high-K diet in all groups. There was no hyperkalemia in any group.


These results suggest that i) NCC activity decreases in response to a high-K diet, in part through decreased protein expression; ii) these responses depend on gender as well as on the presence of the AT1a receptor; iii) Proximal tubule function is also regulated by chronic high-K intake.


  • NIDDK Support