The biochemical diagnosis of Gitelman disease and the definition of "hypocalciuria"

Excerpt

Several years ago it was demonstrated that measurement of plasma renin activity, aldosterone and urinary prostaglandin E₂ is of little value for the diagnosis of normotensive renal hypokalemic alkalosis [1, 2]. In addition, we were able to confirm the suggestion of Rodríguez-Soriano et al. [3] and noted in a retrospective survey of a large number of subjects that those with normal or slightly reduced plasma magnesium levels and a molar urinary calcium/creatinine ratio ranging between 0.40 and 5.62 had a history of extracellular volume contraction or short stature at less than 4 years of age, mostly with a history of polyhydramnios or birth weight of less than 2.50 kg. Patients with hypomagnesemia and a molar urinary calcium/creatinine ratio between 0.01 and 0.10 are sometimes asymptomatic (Fig. 1). However, the latter patients are usually symptomatic and present with cramps and tetany (often with vomiting and diarrhea) at school age or even later. It was therefore concluded that low urinary calcium levels and hypomagnesemia characterize a rather benign variant of normotensive hypokalemic alkalosis, which is mostly referred to as Gitelman disease [3, 4, 5]. In patients with Gitelman disease the laboratory characteristics resemble those induced by thiazides, which bind to and inhibit the luminal sodium chloride cotransporter in the distal convoluted tubule. A defective sodium chloride carrier protein along the distal convoluted tubule is responsible for this tubulopathy [6]. Most reviews of Gitelman disease state that the biochemical features include a negative urinary screen for diuretics, absence of arterial hypertension, hypokalemia of renal origin, hyperbicarbonatemia, hypomagnesemia of renal origin, inappropriate urinary chloride excretion, and hypocalciuria [7, 8, 9].

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