The role of growth factors and ammonia in the genesis of hypokalemic nephropathy

Hypokalemia is a common electrolyte abnormality encountered in clinical practice. It can be identified in an asymptomatic patient undergoing routine electrolyte screening or can manifest itself as part of a number of functional abnormalities in a variety of organs and systems. Among the most commonly recognized complications are profound effects on the cardiovascular and neuromuscular systems, together with abnormalities in acid–base regulation. In humans, hypokalemia contributes to the development of hypertension and predisposes patients to a variety of ventricular arrhythmias, including ventricular fibrillation. Commonly recognized neuromuscular complications include weakness, cramping, and myalgia. Hypokalemia also affects systemic acid–base homeostasis by interfering with multiple components of the renal acid–base regulation and is a frequent cause of metabolic alkalosis. Less known, however, is the role of potassium deficiency in causing progressive renal failure. In animals, potassium deficiency stimulates renal enlargement because of cellular hypertrophy and hyperplasia. If potassium deficiency persists, interstitial infiltrates appear in the renal interstitial compartment, and eventually tubulointerstitial fibrosis develops. In humans, longstanding hypokalemia is associated with the development of renal cysts, chronic interstitial nephritis, and progressive loss of renal function, the so-called hypokalemic nephropathy. This review focuses on the potential mechanisms involved in the development of the hypokalemic nephropathy with emphasis on the role of ammonia and growth factors in its pathogenesis.