Endogenous endothelins mediate increased acidification in remnant kidneys

Area of Science:

• Nephrology
• Renal Physiology
• Endocrinology

Background:

• Dietary acid intake increases renal acidification, mediated by endothelins (ET).
• Reduced renal mass, as seen in nephrectomized (Nx) animals, leads to increased urinary ET-1 excretion.
• This study investigated the role of ET in renal acidification in remnant kidneys.

Purpose of the Study:

• To test the hypothesis that endothelins mediate increased renal acidification in remnant kidneys.
• To determine the effect of ET receptor antagonism on acid-base balance in Nx rats.

Main Methods:

• Rats underwent 5/6 nephrectomy (Nx) or sham surgery.
• Renal ET-1 content and urinary ET-1 excretion were measured.
• In situ proximal and distal tubule bicarbonate reabsorption was assessed.
• The ET(A/B) receptor antagonist bosentan was administered orally to Nx rats.

Main Results:

• Nx animals showed significantly higher renal ET-1 content and urinary ET-1 excretion compared to controls.
• Despite similar urinary net acid excretion, Nx animals exhibited increased proximal and distal tubule bicarbonate reabsorption.
• Bosentan administration significantly decreased urinary net acid excretion and improved blood base excess in Nx animals.
• The effects of bosentan were attributed to reduced bicarbonate reabsorption in both proximal and distal tubules.

Conclusions:

• Endogenous endothelins mediate increased urinary acid excretion in remnant kidneys of Nx animals.
• ET receptor blockade with bosentan ameliorates acid retention in reduced renal mass models.
• Targeting the endothelin system may offer therapeutic potential for managing acid-base disorders in chronic kidney disease.