Monogenic Forms of Low-Renin Hypertension

Vesna D Garovic; Anthony A Hilliard; Stephen T Turner


Nat Clin Pract Nephrol. 2006;2(11):624-630. 

In This Article

Gordon's Syndrome

Recently identified mutations of WNK1 and WNK4 (members of a family of serine-threonine kinases) have been shown to cause the rare familial autosomal dominant disease, Gordon's syndrome (also known as pseudohypoaldosteronism type II).[22] Wild-type WNK1 and WNK4 inhibit the thiazide-sensitive Na-Cl co-transporter in the distal tubule. Mutations of these proteins are associated with gain of function (Figure 3Da) and increased co-transporter activity, excessive chloride and sodium reabsorption, and volume expansion.[23] This syndrome is characterized by short stature, intellectual impairment, dental abnormalities, muscle weakness, severe hypertension by the third decade of life, low fractional excretion of sodium, normal renal function, hyperchloremic metabolic acidosis, and low renin and aldosterone levels. Hyperkalemia, another hallmark of this syndrome, might be a function of diminished sodium delivery to the cortical collecting tubule (sodium reabsorption provides the driving force for potassium excretion, which is mediated by the renal outer medullary potassium channel ROMK). Alternatively, the same mutations in WNK4 that result in a gain of function of the Na-Cl co-transporter, might inhibit ROMK activity (Figure 3Db), resulting in hyperkalemia, as suggested by recent genetic studies.[24] Treatment consists of either a low-salt diet or thiazide diuretics, aimed at decreasing chloride intake and blocking Na-Cl co-transporter activity, respectively.


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