Evidence for a tubular defect in the loop of Henle

Early clearance studies suggested a defect in chloride transport in the TALH to be the proximal event in BS. [9] [10] In later studies, however, the combined use of clearance methods and diuretics revealed an impaired thiazide-sensitive salt reabsorption, suggesting that the distal convoluted tubule is the segment primarily affected in GS [13] and BS. [12] [15] Recently mutations in the thiazide-sensitive NaCl-cotransporter gene were detected in patients with GS. [49] Chaimovitz et al. [50] described a boy with “Bartter syndrome” who had a normal response to thiazides. This observation was probably the result of an incomplete characterization of the patient, who had typical features of HPS such as isosthenuria and severe failure to thrive. [50] Unfortunately no data referring to calcium and magnesium excretion were given in this case. Two of our children with HPS did show a normal response to hydrochlorothiazide (l mg/kg per day) during a treatment period of 1 week (unpublished observations).

In summary the classification of inborn hypokalemic tubular disorders into distinct entities could be confirmed by the use of furosemide administration. In HPS the markedly impaired response to furosemide revealed a tubular defect in the TALH. The beneficial effect of indomethacin treatment underscores the important pathophysiologic role of concomitant PGE2 overproduction in HPS. In contrast, patients with BS or GS had normal sensitivity to furosemide, indicating an intact function of the TALH in these disorders.

We thank Dr. Klaus Ehlenz for performing plasma renin activity and aldosterone assays, Dr. Horst Schweer for mass spectrometric analysis of urinary prostaglandins, and Bernhard Watzer for measuring the drug levels. We thank the nursing staff for their assistance in urine collections.

Supported by grant No. Se 263/11-1 from the Deutsche Forschungsgemeinschaft.

Presented in part at the International Congress of Nephrology, Madrid, Spain, July 2-6, 1995.

Submitted for publication Jan. 29, 1996; accepted May 23, 1996.Copyright ? 1996 by Mosby-Year Book, Inc.


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