Mechanisms of the effects of acidosis and hypokalemia on renal ammonia metabolism

Abstract

Renal ammonia metabolism is the predominant component of net acid excretion and new bicarbonate generation. Renal ammonia metabolism is regulated by acid-base balance. Both acute and chronic acid loads enhance ammonia production in the proximal tubule and secretion into the urine. In contrast, alkalosis reduces ammoniagenesis. Hypokalemia is a common electrolyte disorder that significantly increases renal ammonia production and excretion, despite causing metabolic alkalosis. Although the net effects of hypokalemia are similar to metabolic acidosis, molecular mechanisms of renal ammonia production and transport have not been well understood. This mini review summarizes recent findings regarding renal ammonia metabolism in response to chronic hypokalemia.

Keywords: acids; ammonia; hypokalemia; kidney.

Fig. 1

Ammonia Metabolism in the Proximal Tubule. GA, glutaminase; GDH, glutamine dehydrogenase; TCA, tricarboxylic acid cycle enzymes; PEPCK, phosphoenol pyruvate carboxykinase.

Fig. 2

Schematic Representation of the Ammonia Transport Mechanisms along the Nephron Segments. NHE3, Na⁺/H⁺ exchanger; NKCC2, Na⁺-K⁺(NH₄⁺)-2Cl^-cotransporter 2; NHE4, Na⁺-H⁺(NH₄⁺) exchanger 4.