Renal Genetic Disorders Related to K⁺ and Mg²⁺

Abstract

The recent knowledge of the renal epithelial transport systems has exploded with the identification, cloning, and characterization of a large number of membrane transport proteins. The fundamental aspects of these transporters are beginning to emerge at the molecular level and are summarized in the accompanying contributions in this volume of the Annual Review of Physiology. The aim of my review is to integrate this body of knowledge with the understanding of the clinical disorders of human mineral homeostasis that accompany gain, loss, or dysregulation of function of these transport systems. The specific focus is on the best defined human clinical syndromes in which there are derangements in K(+) and Mg(2+) homeostasis.

Pregnancy in Inherited Hypokalemic Salt-Losing Renal Tubular Disorder

“…Affected patients present with normal or low blood pressure, hyperreninemia, metabolic alkalosis, and especially hypokalemia. [1][2][3] The disorder has been recently classified into three distinct phenotypes. [1][2][3] Antenatal Bartter syndrome, the most severe phenotype, is characterized by hydramnios, premature birth, life-threatening episodes of salt and water loss, and early onset of nephrocalcinosis.…”

“…[1][2][3] The disorder has been recently classified into three distinct phenotypes. [1][2][3] Antenatal Bartter syndrome, the most severe phenotype, is characterized by hydramnios, premature birth, life-threatening episodes of salt and water loss, and early onset of nephrocalcinosis. Classic Bartter syndrome, which presents in infancy or early childhood, is characterized by marked salt wasting and hypokalemia leading to polyuria and polydipsia.…”

“…Finally, Gitelman syndrome, the most common phenotype, is mostly asymptomatic until approximately age 5 years and presents with muscle weakness, muscle cramps, tetany, and hypomagnesemia. [1][2][3] The management of these patients has improved remarkably over the past two decades. In an increasing adult population, issues such as fertility, family planning, and pregnancy have become important for these patients.…”

Urinary Potassium Excretion and Sodium Sensitivity in Blacks

“…50 The hallmark of disorders that cause an increase in the activity of the ENaC is an increase in the urinary excretion of potassium. 51 Because blacks excrete less potassium in the urine than do whites, it is unlikely that sodium sensitivity in blacks is the result of an increase in the activity of the ENaC.…”

“…50 The hallmark of disorders that cause an increase in the activity of the ENaC is an increase in the urinary excretion of potassium. 51 Because blacks excrete less potassium in the urine than do whites, it is unlikely that sodium sensitivity in blacks is the result of an increase in the activity of the ENaC.A recent study by Pratt et al 38 showed that treatment with amiloride for 1 week caused a reduction in blood pressure in whites but a paradoxical increase in the blood pressure in blacks. Treatment with amiloride during this short time period reduced urinary potassium, with whites showing twice the reduction in potassium excretion as did blacks, although this ethnic difference was not statistically significant.…”