Kidney Week

Abstract: TH-PO354

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

Session Information

• Fluid, Electrolyte, and Acid-Base Disorders: Basic
  November 03, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
  Abstract Time: 10:00 AM - 12:00 PM

Category: Fluid‚ Electrolyte‚ and Acid-Base Disorders

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

Authors

• Wei, Kuangyu, Erasmus MC, Rotterdam, Zuid-Holland, Netherlands

Kuangyu Wei,

• Gritter, Martin, Erasmus MC, Rotterdam, Zuid-Holland, Netherlands

Martin Gritter,

• van Willigenburg, Hester, Erasmus MC, Rotterdam, Zuid-Holland, Netherlands

Hester van Willigenburg,

• Rotmans, Joris I., Leids Universitair Medisch Centrum, Leiden, Zuid-Holland, Netherlands

Joris I. Rotmans,

• Hoorn, Ewout J., Erasmus MC, Rotterdam, Zuid-Holland, Netherlands

Ewout J. Hoorn,

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 5/6^th nephrectomy (5/6^th 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 5/6^th 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 5/6^th Nx compared to sham rats. In 5/6^th 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 5/6^th Nx and in sham rats. This corresponded to an unchanged per-nephron kaliuresis in 5/6^th 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 5/6^th Nx compared to sham rats. After correction for eGFR, 5/6^th 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