Bartter's syndrome: clinical findings, genetic causes and therapeutic approach.

BACKGOUND: Bartter's syndrome (BS) is a rare group of salt losing tubulopathies due to the impairment of transport mechanisms at the thick ascending limb of the Henle's loop. DATA SOURCES: Literature reviews and original research articles were collected from database, including PubMed and Scopus. RESULTS: According to the time of onset and symptoms, BS can be classified into antenatal and classic BS. Molecular studies have identified different subtypes of BS. BS types I, II and III are caused by mutations on genes encoding the luminal Na+-K+-2Cl- co-transporter, the luminal K+ channel ROMK, and the basolateral chloride channel ClC-Kb (CLCNKB), respectively. Loss-of-function mutations of Barttin CLCNK type accessory beta subunit cause BS type IVa. Simultaneous mutations of CLCNKB and CLCNKA cause BS type IVb. BS type V consists in a novel transient form characterized by antenatal presentation due to mutations in the MAGE family member D2. Severe gain-of-function mutations of the extracellular calcium sensing receptor gene can result in an autosomal dominant condition of BS. Main clinical and biochemical alterations in BS include polyuria, dehydration, hypokalemia, hypochloremic metabolic alkalosis, hyperreninemia, high levels of prostaglandins, normal or low blood pressure, hypercalciuria and failure to thrive. Treatment focuses mainly at correcting dehydration and electrolyte disturbances and in measures to reduce polyuria, including the use of nonsteroidal anti-inflammatory medications to control excessive renal prostaglandin E2 production. CONCLUSIONS: Early diagnosis and treatment of BS may prevent long-term consequences such as growth failure, nephrocalcinosis and end-stage renal disease.

Distal renal tubular acidosis: genetic causes and management.

BACKGROUND: Distal renal tubular acidosis (dRTA) is a kidney tubulopathy that causes a state of normal anion gap metabolic acidosis due to impairment of urine acidification. This review aims to summarize the etiology, pathophysiology, clinical findings, diagnosis and therapeutic approach of dRTA, with emphasis on genetic causes of dRTA. DATA SOURCES: Literature reviews and original research articles from databases, including PubMed and Google Scholar. Manual searching was performed to identify additional studies about dRTA. RESULTS: dRTA is characterized as the dysfunction of the distal urinary acidification, leading to metabolic acidosis. In pediatric patients, the most frequent etiology of dRTA is the genetic alteration of genes responsible for the codification of distal tubule channels, whereas, in adult patients, dRTA is more commonly secondary to autoimmune diseases, use of medications and uropathies. Patients with dRTA exhibit failure to thrive and important laboratory alterations, which are used to define the diagnosis. The oral alkali and potassium supplementation can correct the biochemical defects, improve clinical manifestations and avoid nephrolithiasis and nephrocalcinosis. CONCLUSIONS: dRTA is a multifactorial disease leading to several clinical manifestations. Clinical and laboratory alterations can be corrected by alkali replacement therapy.