Renal tubular disorders of electrolyte regulation in children

Abstract

In 1962, F. Bartter and coworkers described two African American patients presenting a new entity characterized by hypokalemic metabolic alkalosis, renal K+ wasting, hypertrophy and hyperplasia of the juxtaglomerular apparatus, and normotensive hyperaldosteronism [1]. The disorder also featured increased urinary excretion of prostaglandins, high plasma renin activity, and a resistance to the pressor effects of exogenous angiotensin II [1]. For decades, many similar cases and several phenotypic variants have been progressively identified and included in a group of hypokalemic salt-losing tubulopathies, referred to as Bartter-like syndromes [2]. All these disorders are recessively inherited and associated with hypokalemia and hypochloremic metabolic alkalosis due to stimulation of the renin–angiotensin–aldosterone system (RAAS). However, they differ in terms of age of onset, severity, presence of urinary concentrating defect and/or hypomagnesemia, and magnitude of urinary calcium excretion. Over the years, it became apparent that these tubulopathies affect salt handling in distinct nephron segments, based on the analogy between patient’s symptoms and the effects of loop and thiazide diuretics affecting the thick ascending limb (TAL) and the distal convoluted tubule (DCT), respectively.