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(Hypertension. 2003;41:1000.)
© 2003 American Heart Association, Inc.

Brief Reviews

Altered Renal Handling of Sodium in Human Hypertension

Short Review of the Evidence

From the Department of Clinical and Experimental Medicine, Unit of Clinical Genetics and Pharmacology, Hypertension and Mineral Metabolism, Federico II University of Naples Medical School (P.S., F.G.), Naples, Italy; and Epidemiology and Population Genetics, Institute of Food Science, National Research Council (G.B.), Avellino, Italy.

Correspondence to P. Strazzullo, MD, Department of Clinical and Experimental Medicine, "Federico II" University of Naples Medical School, Via S. Pansini, 5, 80131 Naples, Italy. E-mail strazzul{at}unina.it

A pathogenic role of the kidney in hypertension has been strongly supported by experimental studies by Guyton and Dahl since the 1960s. In the early 1980s, de Wardener and MacGregor proposed that in hypertensive patients the ability of the kidneys to excrete a sodium load could be genetically impaired. Since then, "sodium-sensitive" hypertension has been the object of numerous studies, mostly on animal models because of the difficulty to investigate the renal handling of sodium in humans. More recently, considerable progress in this field has been made thanks to the in vivo study of segmental renal tubular function by the clearance of lithium and to the growing knowledge of the genetics of renal tubular sodium transport systems. The scope of this review is to briefly review the most relevant information gathered by the investigation of segmental renal tubular sodium handling in humans as related to blood pressure regulation and hypertension. In aggregate, the results of these studies strongly support the association between altered renal sodium handling and high blood pressure and suggest a causal role of genetic, nutritional, metabolic, and neurohormonal factors. All of these factors, alone or in combination, may be able to impair the normal renal tubular sodium handling and influence blood pressure homeostasis. The paradigm of the pathogenic role of the kidney in hypertension is thus relentlessly shifting toward the definition of inherited as well as acquired renal tubular defects and molecular alterations, providing a plausible explanation for the alteration in blood pressure levels.

Key Words: sodium • kidney • hypertension, essential • hypertension, sodium-dependent • genetics

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