Two Cases of Gitelman's Syndrome Diagnosed by Renal Clearance Study

Gitelman's syndrome is an autosomal recessive disorder characterized by hypokalemic metabolic alkalosis, hypomagnesemia, and hypocalciuria that has recently been reported to be linked to thiazide-sensitive Na-Cl cotransporter gene mutation. In this study, we performed renal clearance studies to differentiate Gitelman's from Bartter's syndrome and to confirm the diagnosis in two patients clinically diagnosed with Gitelman's syndrome. Each patient was hydrated by 20 mL/kg body weight of oral water within 30 minutes, which was followed by intravenous half saline. When urinary flow reached 10 mL/min, samples of urine and serum were obtained to calculate the osmolar clearance, free water clearance, chloride clearance, and distal fractional chloride reabsorption. Subsequently, furosemide or hydrochlorothiazide was administered. Samples were collected and the same parameters were calculated. In our patients, chloride clearance was increased more than 10 times after furosemide administration(2.1:25.7 and 2.2:27.4 mL/min/100 mL GFR), but not increased after hydrochlorothiazide treatment(2.1:1.6 and 2.2:2.6 mL/min/100 mL GFR). And the distal fractional chloride reabsorption was significantly decreased by furosemide injection (73%:15% and 75%:4.6%), whereas hydrochlorothiazide had no effect on it(73%:63% and 75%:78%). These findings indicate that our patients have a defect in thiazide-sensitive Na-Cl cotransporter in the distal tubule, which is compatible with the pathophysiology of Gitelman's syndrome.

Two Cases of Gitelman's Syndrome Diagnosed by Renal Clearance Study / 대한신장학회잡지

We have experienced two patients who had hypokalemic metabolic alkalosis as well as hypomagnesemia and hypocalciuria with elevated plasma renin activity. We have performed renal clearance study after water loading, administration of furosemide and thiazide in two patients and two normal controls. Maximal free water clearance per 100 mL glomerular filtration rate(CH2O) and distal fractional chloride reabsorption[CH2O/(CH2O+CCl)] in our patients were reduced than the controls. Chloride clearance(CCl) was increased after furosemide administration but not after thiazide administration. Distal fractional chloride reabsorption[CH2O/(CH2O+CCl)] was dramatically decreased by furosemide administration in our patients, whereas thiazide had little effect on it. Fractional excretion of sodium, chloride, magnesium, calcium was increased by furosemide administration, whereas thiazide administration had little effect on this parameters. These findings suggested the presence of a defect in the distal convoluted tubule rather than in the thick ascending loop of Henle. Herein, we report two cases of Gitelman's syndrome diagnosed by renal clearace study after water loading, administration of furosemide and thiazide.