Molecular Basis, Diagnostic Challenges and Therapeutic Approaches of Bartter and Gitelman Syndromes: A Primer for Clinicians.

Gitelman and Bartter syndromes are rare inherited diseases that belong to the category of renal tubulopathies. The genes associated with these pathologies encode electrolyte transport proteins located in the nephron, particularly in the Distal Convoluted Tubule and Ascending Loop of Henle. Therefore, both syndromes are characterized by alterations in the secretion and reabsorption processes that occur in these regions. Patients suffer from deficiencies in the concentration of electrolytes in the blood and urine, which leads to different systemic consequences related to these salt-wasting processes. The main clinical features of both syndromes are hypokalemia, hypochloremia, metabolic alkalosis, hyperreninemia and hyperaldosteronism. Despite having a different molecular etiology, Gitelman and Bartter syndromes share a relevant number of clinical symptoms, and they have similar therapeutic approaches. The main basis of their treatment consists of electrolytes supplements accompanied by dietary changes. Specifically for Bartter syndrome, the use of non-steroidal anti-inflammatory drugs is also strongly supported. This review aims to address the latest diagnostic challenges and therapeutic approaches, as well as relevant recent research on the biology of the proteins involved in disease. Finally, we highlight several objectives to continue advancing in the characterization of both etiologies.

The congenital "magnesium-losing kidney". Report of two patients.

A 39-year-old man with a lifelong history of tetany and hypocalcaemia was found to have hypomagnesaemia (0.29 mmol/l) due to renal magnesium loss. His asymptomatic 29-year-old brother had a similar disorder. Both were infertile and had severe oligospermia but normal endocrine function. They had medullary nephrocalcinosis and glomerular filtration rate was reduced. Renal biopsy showed patchy interstitial fibrosis and some glomerular sclerosis. Electron microscopy showed thickened basement membranes in damaged glomeruli and in tubules in areas of fibrosis. Tests of renal tubule function were normal. Hypocalcaemia and tetany were corrected by oral magnesium supplements which raised the serum magnesium level to around 0.54 mmol/l.