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(Hypertension. 2008;51:588.)
© 2008 American Heart Association, Inc.

Brief Reviews

WNK Kinases and Renal Sodium Transport in Health and Disease

An Integrated View

From the Division of Nephrology and Hypertension and Heart Research Center, Department of Medicine (J.A.M., C.-L.Y., D.H.E.), and Department of Physiology and Pharmacology (D.H.E.), Oregon Health and Science University, Portland; and the Veterans’ Affairs Medical Center (C.-L.Y., D.H.E.), Portland, Ore.

Correspondence to David H. Ellison, Division of Nephrology and Hypertension, Department of Medicine, Oregon Health and Science University, PP262, 3314 SW US Veterans Hospital Rd, Portland, OR 97239. E-mail ellisond@ohsu.edu

An extract of the first 250 words of the full text is provided, because this article has no abstract.

	Introduction

 
Hypertension affects 25% of the adult population in the developed world and is a major independent risk factor for stroke, myocardial infarction, and heart and kidney failure. Although many genetic and environmental contributors are involved, the kidney plays a dominant role, both in animal models,¹ and in human essential hypertension.² Most monogenic hypertensive syndromes result from increased Na⁺ transport along the aldosterone-sensitive distal nephron.³ The majority of these, however, are associated with hypokalemia, indicating that activation of the epithelial Na⁺ channel, ENaC, is a primary pathophysiologic process. In contrast, familial hyperkalemic hypertension (FHHt; also known as Gordon’s syndrome or type II pseudohypoaldosteronism) is characterized by hypertension with hyperkalemia, indicating that stimulated ENaC cannot be the primary event. FHHt was first described in 1964⁴ and later shown to be inherited in an autosomal dominant manner.^5,6 Patients with FHHt all exhibit hyperkalemia, which seems to be the most consistent feature of the disease. Hypertension, although commonly present and sometimes severe, often appears later in the natural history. Other characteristic features include mild metabolic acidosis, suppressed plasma renin activity, and aldosterone levels that are lower than would be expected, considering the hyperkalemia. Infusing the chloride salt of Na⁺ (NaCl) does not increase urinary potassium excretion in patients with FHHt, as it does in the normal individual, whereas infusing nonchloride salts of Na⁺ does increase K⁺ excretion in FHHt patients to normal levels.^7,8 Patients are often remarkably sensitive to thiazide diuretics, which can correct both the hyperkalemia and hypertension, in many cases.⁹

	WNK Kinases and FHHt

 
In 2001, . . . [Full Text of this Article]

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