Medication Summary
Salt and water depletion due to an inability to conserve sodium in the thick ascending limb of the loop of Henle (TALH) or the distal convoluted tubule (DCT) leads to activation of the renin-angiotensin-aldosterone system (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 angiotensin-converting enzyme (ACE) inhibitors help to block the RAAS and to 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 growth hormone (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 weekly SC) and somatropin (rDNA origin, 0.1 mg/kg daily SC) have been used.
Potassium Supplements
Class Summary
These are used to treat hypokalemia associated with Bartter syndrome. Correction of hypokalemia is the most important goal of medical therapy.
Potassium chloride (K-Dur, Klor-Con, Micro K)
Dosage depends on the 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.
Potassium can be administered in various formulations, but chloride salt is recommended because of coexisting chloride deficiencies in patients with Bartter syndrome. Potassium is essential for the transmission of nerve impulses, the contraction of cardiac muscle, the maintenance of intracellular tonicity, skeletal and smooth muscles, and the maintenance of normal renal function.
Diuretics, Potassium-Sparing
Class Summary
These medications enhance the effect of potassium supplementation by decreasing urinary potassium losses.
Spironolactone (Aldactone)
Spironolactone is a specific antagonist of aldosterone, primarily by competitively binding to receptors at the aldosterone-dependent sodium-potassium exchange site in the DCT. This agent increases water excretion while retaining potassium and hydrogen ions.
Amiloride
Amiloride inhibits sodium reabsorption at the DCT, cortical collecting tubule, and collecting duct. This decreases the net negative potential of the tubular lumen and reduces potassium and hydrogen secretion and their subsequent excretion.
Triamterene (Dyrenium)
Triamterene interferes with potassium/sodium exchange (active transport) in the distal tubule, cortical collecting tubule, and collecting duct by inhibiting sodium/potassium adenosine triphosphatase (ATPase). This agent decreases calcium excretion and increases magnesium loss.
ACE Inhibitors
Class Summary
ACE inhibitors block the conversion of angiotensin I (ANG I) to ANG II and prevent the secretion of aldosterone from the adrenal cortex.
Captopril
Captopril prevents the conversion of ANG I to ANG II, a potent vasoconstrictor, resulting in lower aldosterone secretion. It is also helpful in preventing potassium loss.
Enalapril (Vasotec)
Enalapril is a competitive inhibitor of ACE. It reduces ANG II levels, decreasing aldosterone secretion.
Lisinopril (Prinivil, Zestril)
Lisinopril prevents the conversion of ANG I to ANG II, a potent vasoconstrictor, resulting in lower aldosterone secretion.
Benazepril (Lotensin)
Benazepril prevents conversion of angiotensin I to angiotensin II, a potent vasoconstrictor, resulting in increased levels of plasma renin and a reduction in aldosterone secretion.
When pediatric patients are unable to swallow tablets or the calculated dose does not correspond with tablet strength, an extemporaneous suspension can be compounded. Combine 300 mg (15 tablets of 20-mg strength) in 75 mL of Ora-Plus suspending vehicle, and shake well for at least 2 minutes. Let the tabs sit and dissolve for at least 1 hour, then shake again for 1 minute. Add 75 mL of Ora-Sweet. The final concentration is 2 mg/mL, with a total volume of 150 mL. The expiration time is 30 days with refrigeration.
Fosinopril
Fosinopril is a competitive ACE inhibitor. It prevents conversion of angiotensin I to angiotensin II, a potent vasoconstrictor, resulting in increased levels of plasma renin and a reduction in aldosterone secretion. It decreases intraglomerular pressure and glomerular protein filtration by decreasing efferent arteriolar constriction.
Quinapril (Accupril)
Quinapril is a competitive ACE inhibitor. It reduces angiotensin II levels, decreasing aldosterone secretion.
NSAIDs
Class Summary
These medications blunt prostaglandin overproduction, which is responsible for the pressor resistance to ANGII and norepinephrine, hyperreninemia, and increased sympathoadrenal activity. By inhibiting PGE2 synthesis, these agents also contribute to the correction of the hemoconcentration defect.
Indomethacin (Indocin)
Indomethacin is a nonsteroidal drug with anti-inflammatory, antipyretic, and analgesic properties that are thought to be mediated by its potent prostaglandin inhibitory effect; ensuing hyporeninemic hypoaldosteronism is thought to be responsible for potassium retention.
Naproxen (Anaprox, Aleve, Naprosyn, Naprelan)
Naproxen is used for the relief of mild to moderate pain. It inhibits inflammatory reactions and pain by decreasing the activity of the enzyme cyclo-oxygenase (COX), which results in prostaglandin synthesis.
Sulindac (Clinoril)
Sulindac decreases COX activity and, in turn, inhibits prostaglandin synthesis. This results in decreased formation of inflammatory mediators.
Meloxicam (Mobic)
Meloxicam decreases COX activity and this, in turn, inhibits prostaglandin synthesis. These effects decrease the formation of inflammatory mediators.
Ketoprofen
Ketoprofen is used for relief of mild to moderate pain and inflammation. Small dosages are indicated initially in small patients, elderly patients, and patients with renal or liver disease. Doses higher than 75 mg do not increase the therapeutic effects. Administer high doses with caution, and closely observe the patient's response.
Flurbiprofen
Flurbiprofen may inhibit COX, thereby, in turn, inhibiting prostaglandin biosynthesis. These effects may result in analgesic, antipyretic, and anti-inflammatory activities.
Ibuprofen (Motrin, Advil, Ultraprin, Addaprin)
Ibuprofen inhibits inflammatory reactions and pain by decreasing prostaglandin synthesis.
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Normal transport mechanisms in the thick ascending limb of the loop of Henle. Reabsorption of sodium chloride is achieved with the sodium chloride/potassium chloride cotransporter, which is driven by the low intracellular concentrations of sodium, chloride, and potassium. Low concentrations are maintained by the basolateral sodium pump (sodium-potassium adenosine triphosphatase), the basolateral chloride channel (ClC-kb), and the apical potassium channel (ROMK).
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Type I neonatal Bartter syndrome. Mutations in the sodium chloride/potassium chloride cotransporter gene result in defective reabsorption of sodium, chloride, and potassium.
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Type II neonatal Bartter syndrome. Mutations in the ROMK gene result in an inability to recycle potassium from the cell back into the tubular lumen, with resultant inhibition of the sodium chloride/potassium chloride cotransporter.
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Classic Bartter syndrome. Mutations in the ClC-kb chloride channel lead to an inability of chloride to exit the cell, with resultant inhibition of the sodium chloride/potassium chloride cotransporter.
Tables
Bartter Syndrome Genotype-Phenotype Correlations |
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Genetic Type |
Defective Gene |
Clinical Type |
Bartter type I |
NKCC2 |
Neonatal |
Bartter type II |
ROMK |
Neonatal |
Bartter type III |
CLCNKB |
Classic |
Bartter type IV |
BSND |
Neonatal with deafness |
Bartter type IVb |
CLCNKB and CLCNKA |
Neonatal with deafness |
Bartter type V |
CaSR |
Classic |
