Bartter Syndrome - Treatment and Medication
Treatment
Medical Care:- Since first described in 1962, several types of medical treatment have been used.
- Sodium and potassium supplements are used for the electrolyte imbalances, and aldosterone antagonists and diuretic spironolactone are mainstays of therapy.
- ACE inhibitors are used to counteract the effects of ANG II and aldosterone.
- Indomethacin is used to decrease prostaglandin excretion.
- Growth hormone (GH) is used to treat short stature.
- Calcium or magnesium supplements may occasionally be needed if tetany or muscle spasms are present.
Surgical Care:
- Bartter and Gitelman syndromes, by themselves, do not lead to chronic renal insufficiency; however, in patients with these syndromes who develop end-stage renal disease (ESRD) for other reasons, transplants from living relatives are an option and result in normal urinary handling of sodium, potassium, calcium, and magnesium.
- Reports of renal transplants from living relatives in ESRD patients with Bartter syndrome suggest that many endocrinologic abnormalities in Bartter syndrome improve or normalize after transplantation.
- Because the genetic abnormality in Bartter syndrome may be found only in the kidneys (which is certain in Na-K-Cl cotransporter but may not be the case for some of the other mutations), transplantation corrects the problem by replacing unhealthy kidneys with normal ones.
- Bartter syndrome is an autosomal recessive disorder. Both parents carry at least 1 gene for the disorder. Statistically, only 1 of 4 siblings is completely healthy.
- Whether carrying 1 gene for this abnormality leads to long-term problems late in life if 1 kidney is removed is unknown.
- Transplants from living unrelated persons or cadavers are options for patients with ESRD.
Consultations: Contact a nephrologist or pediatric nephrologist whenever a patient fitting the clinical picture of Bartter or Gitelman syndrome is identified.
Diet:
- Adequate salt and water intake are necessary to prevent hypovolemia.
- Adequate potassium intake is essential to replace urinary potassium losses.
- With growth retardation, adequate overall nutritional balance (protein-calorie intake) is important. Whether other diet supplements (eg, citrate, magnesium, vitamins) are helpful is not clear.
Medication
Salt and water depletion due to inability to conserve sodium in the TALH or DCT leads to activation of the RAAS and high aldosterone levels. This helps the kidneys retain sodium distal to the site of the mutation but at the expense of losing potassium.
Aldosterone inhibitors and ACE inhibitors help block the RAAS and help prevent potassium loss in the distal tubules. The body conserves potassium, and less oral potassium supplementation is needed.
Short stature and growth failure are common in Bartter syndrome. Exogenous GH increases the growth rate and helps patients with GH deficiency attain normal height. Although not well studied, at least 1 report describes a patient with low GH levels and Gitelman syndrome who was below the third percentile for height and whose growth rate improved 4-fold during GH treatment. Dose depends on brand used. Somatropin (up to 0.3 mg/kg/wk SC) and somatropin (rDNA origin, 0.1 mg/kg/d SC) have been used.
Drug Category: Potassium supplements -- Used to treat the hypokalemia associated with the syndrome.
| Potassium chloride (K-Dur, Gen-K, Klor-Con) -- Depends on degree of receptor dysfunction and hypokalemia. Serum potassium levels often run in the range of 2-3 mEq/L, which may require several hundred milliequivalents of potassium per day. | |
| Adult Dose | 100-200 mEq PO qd in divided doses; easier to take with meals |
|---|---|
| Pediatric Dose | 1-2 mEq/kg PO qd in divided doses; easier to take with meals |
| Contraindications | Hyperkalemia; renal failure; conditions in which potassium retention is present; oliguria or azotemia; crush syndrome; severe hemolytic reactions; anuria; adrenocortical insufficiency |
| Interactions | Concurrent use with ACE inhibitors may result in elevated serum concentrations; potassium-sparing diuretics and potassium-containing salt substitutes can produce severe hyperkalemia; in patients taking digoxin, hypokalemia may result in digoxin toxicity; caution if discontinuing administration in patients maintained on digoxin |
| Pregnancy | A - Safe in pregnancy |
| Precautions | Do not infuse rapidly; high plasma concentrations may cause death due to cardiac depression, arrhythmias, or arrest; plasma levels do not necessarily reflect tissue levels; monitor potassium replacement therapy whenever possible by continuous or serial ECG; when a concentration >40 mEq/L is infused, local pain and phlebitis may follow |
Drug Category: Potassium sparing diuretics -- These agents can increase potassium blood levels.
| Spironolactone (Aldactone) -- Aldosterone antagonist that competitively inhibits binding to the aldosterone receptor. It competes for receptor sites in the distal renal tubules, increasing water excretion while retaining potassium and hydrogen ions. | |
| Adult Dose | 25-100 mg PO divided bid/tid |
|---|---|
| Pediatric Dose | 3 mg/kg PO divided bid/tid to 100 mg total daily dose |
| Contraindications | Documented hypersensitivity; anuria; renal failure; hyperkalemia |
| Interactions | May decrease effect of anticoagulants; potassium and potassium-sparing diuretics may increase toxicity |
| Pregnancy | D - Unsafe in pregnancy |
| Precautions | Caution in renal and hepatic impairment |
Drug Category: Angiotensin-converting enzyme inhibitors -- Block the conversion of ANG I to ANG II and prevent the secretion of aldosterone from the adrenal cortex.
| Captopril (Capoten) -- Prevents conversion of ANG I to ANG II, a potent vasoconstrictor, resulting in lower aldosterone secretion. Also helpful in preventing potassium loss. | |
| Adult Dose | 12.5-25 mg PO tid |
|---|---|
| Pediatric Dose | Not established |
| Contraindications | Documented hypersensitivity; renal impairment |
| Interactions | NSAIDs may reduce hypotensive effects; ACE inhibitors may increase digoxin, lithium, and allopurinol levels; rifampin decreases levels; probenecid may increase levels; hypotensive effects of ACE inhibitors may be enhanced when administered concurrently with diuretics |
| Pregnancy | C - Safety for use during pregnancy has not been established. |
| Precautions | Pregnancy category D in second and third trimesters; ensuring that women are not pregnant at time of initiation of therapy is extremely important; severe fetal toxicity can result from maternal ACE inhibitor treatment during second and third trimesters; all ACE inhibitors can cause coughing |
| Enalapril (Vasotec) -- Competitive inhibitor of ACE. Reduces ANG II levels, decreasing aldosterone secretion. | |
| Adult Dose | 2.5-20 mg PO qd |
|---|---|
| Pediatric Dose | Not established |
| Contraindications | Documented hypersensitivity |
| Interactions | NSAIDs may reduce hypotensive effects; ACE inhibitors may increase digoxin, lithium, and allopurinol levels; rifampin decreases levels; probenecid may increase levels; hypotensive effects of ACE inhibitors may be enhanced when administered concurrently with diuretics |
| Pregnancy | C - Safety for use during pregnancy has not been established. |
| Precautions | Pregnancy category D in second and third trimesters; caution in renal impairment, valvular stenosis, or severe congestive heart failure |
| Lisinopril (Prinivil, Zestril) -- Prevents conversion of ANG I to ANG II, a potent vasoconstrictor, resulting in lower aldosterone secretion. | |
| Adult Dose | 2.5-20 mg PO qd |
|---|---|
| Pediatric Dose | Not established |
| Contraindications | Documented hypersensitivity |
| Interactions | May increase digoxin lithium, and allopurinol levels; probenecid may increase levels; coadministration with diuretics increase hypotensive effects; hypotensive effects may be enhanced when administered concurrently with diuretics and NSAIDs |
| Pregnancy | C - Safety for use during pregnancy has not been established. |
| Precautions | Pregnancy category D in second and third trimesters; caution in renal impairment, valvular stenosis, or severe congestive heart failure |
Drug Category: Prostaglandin inhibitors -- Vascular action of ANG II also activates the phosphatidylinositol pathway, increasing release of diacylglycerol, which leads to the release of arachidonic acid and can increase the production of prostaglandins. Bartter syndrome is associated with an increase in the renal excretion of vasodilating PGE2, which may help mediate the vasoconstrictive effects of ANG II. Hypokalemia also induces prostaglandin production.
| Indomethacin (Indocin) -- NSAID used in Bartter syndrome to help improve growth and decrease urinary potassium excretion. | |
| Adult Dose | 25-100 mg PO qd/bid |
|---|---|
| Pediatric Dose | 0.5-3 mg/kg/d PO in divided doses |
| Contraindications | Documented hypersensitivity; GI bleeding; renal insufficiency |
| Interactions | Coadministration with aspirin increases risk of inducing serious NSAID-related adverse effects; may decrease effects of beta-blockers, hydralazine, and captopril; may decrease diuretic effects of furosemide and thiazides; coadministration with anticoagulants may prolong PT (monitor and watch for signs of bleeding); may increase risk of methotrexate toxicity, which can manifest as stomatitis, bone marrow suppression, or nephrotoxicity; coadministration may increase phenytoin levels; probenecid may increase toxicity of NSAIDs |
| Pregnancy | B - Usually safe but benefits must outweigh the risks. |
| Precautions | Pregnancy risk factor D if used longer than 48 hours or after 34-week gestation; although reports describe indomethacin in newborns with Bartter syndrome without problems, a study of 36 newborns treated with indomethacin for persistent patent ductus arteriosus reported 3 with necrotizing enterocolitis; a case report describes no complications following indomethacin use for a neonate with polyhydramnios who received the drug during weeks 26-31, and the indomethacin prevented further fluid accumulation; NSAIDs should be avoided in adult patients unless inadequate response to other agents occurs |
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Synonyms And Related Keywords
salt-wasting disorder, salt-losing nephropathy, Gitelman syndrome, hyperplasia, juxtaglomerular complex, chloride channel, hyperaldosteronism, hypokalemic metabolic alkalosis, hypercalciuria, hypomagnesemia, nephrocalcinosis, kidney transplant, kidney transplantation, renal transplant, renal transplantation, end-stage renal disease, ESRD, growth hormone, GH, short stature, growth failure, growth retardation, renin-angiotensin-aldosterone system, RAAS
