Snapshot A 3-year-old boy is brought to the pediatrician due poor growth and increased urinary frequency. According to the mother, the child appears to be very thirsty. He was born prematurely and the mother states she was found to have polyhydramnios on ultrasonograpahy while pregnant. Laboratory testing is significant for hypokalemia, hypochloremia, mild hypomagnesemia, and metabolic alkalosis. Introduction Clinical definition a renal tubular disorder characterized by hypokalemia hypochloremia metabolic alkalosis normotension elevated plasma renin level Epidemiology incidence rare precise incidence is unknown demographics neonatal cases can be suspected before birth and diagnosed soon after birth classic cases begins around 2 years of age or younger no race or sex predilection risk factors family history Pathophysiology pathobiology mutation involving the Na+/K+/Cl- cotransporter (NKCC2) results in salt and water loss resulting in activation of the renin-angiotensin-aldosterone system secondary to volume depletion renal vasoconstriction due to angiotensin II and hypokalemia leads to an increase in prostaglandin E (PGE) Genetics inheritance pattern autosomal recessive Prognosis can slowly progress to interstitial fibrosis resulting in chronic renal failure Presentation Symptoms failure to thrive increased thirst polyuria polydipsia vomiting Physical exam clinical volume depletion maternal polyhydramnios growth retardation Studies Labs ↑ plasma renin and aldosterone ↓ serum potassium and chloride ↑ urine prostaglandin E genetic testing Differential Diuretic abuse Gitleman syndrome Surreptitious vomiting Mineralocorticoid excess Cystic fibrosis Renal Tubular Defects Category Fanconi Syndrome Bartter Syndrome Gitelman Syndrome Liddle Syndrome Defect localization Proximal tubule Thick ascending loop of Henle Distal convoluted tubule Collecting tubule Etiology Wilson disease Tyrosinemia Cystinosis Multiple myeloma Galactosemia Mitochondrial myopathies Medications aminoglycosides cisplatin ifosfamide valproic acid Heavy metals mercury lead Autosomal recessive mutation involving the NKCC2 cotransporter Autosomal recessive mutation involving the Na+Cl- cotransporter Autosomal dominant mutation leading to increased activity of epithelial sodium channel (ENaC) Findings Hypophosphatemia Aminoaciduria Renal glucosuria Tubular proteinuria Proximal renal tubular acidosis Hypokalemia Hypochloremia Metabolic alkalosis Normotension Elevated plasma renin level Hypokalemia Hypochloremia Metabolic alkalosis Hypomagnesemia Hypocalciuria Normotension Hypertension Hypokalemia Metabolic alkalosis Treatment Medical nonsteroidal anti-inflammatory drugs (NSAIDs) indication for patients with Bartter syndrome drugs indomethicin celecoxib potassium-sparring diuretics indication to treat hypokalemia and metabolic alkalosis in Bartter syndrome drugs spironolactone eplerenone amiloride potassium and magnesium supplementation indication to help improve potassium and magnesium levels in Bartter syndrome Complications Cardiac arrhythmia due to severe hypokalemia