Snapshot A 2-year-old boy is brought to the pediatrician due to vomiting and frequent urination. His mother reports that he appears to be very thirsty. Obstetric history is significant for prematuritry and polyhydramnios noted on prenatal testing. Laboratory testing is significant for hypokalemia, hypochloremia, 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 in neonatal cases can be suspected before birth and diagnosed soon after birth in classic cases begins around 2 years of age or younger no race or sex predilection Risk factors family history Etiology Pathophysiology 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 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 both will present with hypokalemia metabolic alkalosis and have elevated urine chloride Gitleman syndrome Surreptitious vomiting Mineralocorticoid excess Cystic fibrosis Renal Tubular DefectsCategoryFanconi SyndromeBartter SyndromeGitelman SyndromeLiddle SyndromeDefect localizationProximal tubuleThick ascending loop of HenleDistal convoluted tubuleCollecting tubuleEtiologyWilson diseaseTyrosinemiaCystinosisMultiple myelomaGalactosemiaMitochondrial myopathiesMedicationsaminoglycosidescisplatinifosfamidevalproic acidHeavy metalsmercuryleadAutosomal recessive mutation involving the NKCC2 cotransporterAutosomal recessive mutationinvolving the Na+Cl- cotransporterAutosomal dominant mutation leading to increased activity of epithelial sodium channel (ENaC)FindingsHypophosphatemiaAminoaciduriaRenal glucosuriaTubular proteinuriaProximal renal tubular acidosisHypokalemiaHypochloremiaMetabolic alkalosisNormotensionElevated plasma renin levelHypokalemiaHypochloremiaMetabolic alkalosisHypomagnesemiaHypocalciuriaNormotensionHypertensionHypokalemiaMetabolic 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 Prognosis Can slowly progress to interstitial fibrosis resulting in chronic renal failure