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Abstract: TH-PO354

Experimental CKD Increases Per-Nephron Sodium Reabsorption and Impairs Acute Kaliuresis

Session Information

Category: Fluid‚ Electrolyte‚ and Acid-Base Disorders

  • 1001 Fluid‚ Electrolyte‚ and Acid-Base Disorders: Basic

Authors

  • Wei, Kuangyu, Erasmus MC, Rotterdam, Zuid-Holland, Netherlands
  • Gritter, Martin, Erasmus MC, Rotterdam, Zuid-Holland, Netherlands
  • van Willigenburg, Hester, Erasmus MC, Rotterdam, Zuid-Holland, Netherlands
  • Rotmans, Joris I., Leids Universitair Medisch Centrum, Leiden, Zuid-Holland, Netherlands
  • Hoorn, Ewout J., Erasmus MC, Rotterdam, Zuid-Holland, Netherlands
Background

Chronic kidney disease (CKD) predisposes to salt-sensitive hypertension and hyperkalemia. This suggests alterations in tubular sodium (Na+) and potassium (K+) handling, but how CKD changes this is unclear.

Methods

CKD was induced by 5/6th nephrectomy (5/6th Nx) in rats. The estimated glomerular filtration rate (eGFR) was measured by a validated plasma creatinine- and urea-based equation. We compared Na+ and K+ transporter activity in CKD and sham-operated rats by assessing the response to furosemide, hydrochlorothiazide (HCTZ), or amiloride. Furthermore, the responses in plasma K+ and urine K+ excretion were studied after 16h fasting followed by 3h 0% K+, 2.5% potassium chloride (KCl), or 2.5% potassium citrate (KCit) diet.

Results

A trend towards a greater natriuretic response in 5/6th Nx than sham rats was observed after furosemide, while no differences were observed with HCTZ or amiloride (Table). After correction for eGFR, this corresponded to a 4.3, 2.7, and 4.2-fold increase in per-nephron Na+ reabsorption in the thick ascending limb, distal convoluted tubule, and collecting duct, respectively in 5/6th Nx compared to sham rats. In 5/6th Nx rats, the kaliuretic response to furosemide and HCTZ was lower than in sham rats, although this only reached significance for the latter. Amiloride produced a similar K+-sparing effect in 5/6th Nx and in sham rats. This corresponded to an unchanged per-nephron kaliuresis in 5/6th Nx despite greater distal Na+ delivery compared to sham rats. Both the 2.5% KCl and 2.5% KCit diet caused significantly less kaliuresis and higher plasma K+ in 5/6th Nx compared to sham rats. After correction for eGFR, 5/6th Nx increased the kaliuretic response to the 2.5% KCl and 2.5% KCit diets compared to sham rats (2.9 and 2.6-fold, respectively).

Conclusion

Experimental CKD increases per-nephron Na+ reabsorption in the thick ascending limb, distal convoluted tubule and collecting duct. The impaired thiazide-induced kaliuretic response points towards an impaired kaliuretic response to an increased distal Na+ delivery in CKD. These alterations in Na+ and K+ handling may explain the tendency towards salt-sensitive hypertension and hyperkalemia in CKD.

Table