Context: Our understanding of inherited salt-losing tubulopathies has improved with recent advances in molecular genetics. However, the terminology of Bartter syndrome and Gitelman syndrome does not always accurately reflect their pathophysiological basis or clinical presentation, and some patients are difficult to diagnose from their clinical presentations.
Objective: In the present study, we conducted molecular analysis and diuretic tests for patients with inherited salt-losing tubulopathies to clarify the pharmacological characteristics of these disorders.
Patients: We detected mutations and subsequently conducted diuretic tests using furosemide and thiazide for 16 patients with salt-losing tubulopathies (two with SLC12A1; two with KCNJ1; nine with CLCNKB; and three with SLC12A3).
Results: Patients with SLC12A1 mutations showed no response to furosemide, whereas those with SLC12A3 mutations showed no response to thiazide. However, patients with CLCNKB mutations showed no response to thiazide and a normal response to furosemide, and those with KCNJ1 mutations showed a good response to both diuretics. This study revealed the following characteristics of these disorders: 1) subjects with CLCNKB mutations showed one or more biochemical features of Gitelman syndrome (including hypomagnesemia, hypocalciuria, and fractional chloride excretion insensitivity to thiazide administration); and 2) subjects with KCNJ1 mutations appeared to show normal fractional chloride excretion sensitivity to furosemide and thiazide administration.
Conclusions: These results indicate that these disorders are difficult to distinguish in some patients, even when using diuretic challenge. This clinical report provides important findings that can improve our understanding of inherited salt-losing tubulopathies and renal tubular physiology.