Approach Considerations
Since the first description of Bartter syndrome in 1962, several types of medical treatment have been used, including the following:
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Sodium and potassium supplements - Used for the electrolyte imbalances
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Aldosterone antagonists and diuretic spironolactone - Are mainstays of therapy
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Angiotensin-converting enzyme (ACE) inhibitors - Used to counteract the effects of angiotensin II (ANG II) and aldosterone
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Indomethacin or ibuprofen [45] - Used to decrease prostaglandin excretion
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Growth hormone (GH) - Used to treat short stature
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Calcium or magnesium supplements - May occasionally be needed if tetany or muscle spasms are present
Pregnancy-related considerations
Reports associated with Bartter syndrome in pregnant women are limited because Bartter syndrome is a rare disease. Complications related to electrolyte loss (eg, hypokalemia, hypomagnesemia) responded well to supplementation. Fetuses were unaffected and carried to term.
In Rudin's report of 28 pregnant patients, no problems were noted except asymptomatic hypokalemia. [26] In another study, of 40 patients, 30 reported normal pregnancies and terminated by normal parturition; however, many of the patients who were pregnant probably had Gitelman syndrome.
Renal Transplantation
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.
Donors
Bartter syndrome is an autosomal recessive disorder. Both parents carry at least 1 gene for the disorder. Statistically, only 1 of 4 siblings will be 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.
Preemptive Surgery
One approach to the management of severe Bartter syndrome involves preemptive nephrectomy and renal transplantation. [46] The rationale for this approach lies in the fact that Bartter syndrome is an incurable genetic disease, and the poorly controlled forms may result in frequent life-threatening episodes of dehydration and electrolyte imbalances. Preemptive bilateral nephrectomies and successful kidney transplantation prior to the onset of ESRD has resulted in correction of metabolic abnormalities and excellent graft function.
Special Surgical Concerns
Electrolytes
Special attention should be paid to correcting electrolyte abnormalities when patients with Bartter syndrome undergo surgical procedures.
Anesthesia
The multiple biochemical abnormalities that occur in patients with Bartter syndrome may present a challenge to anesthesiologists when general anesthesia is used. Potential problems include difficulties in fluid and electrolyte management, acid-base abnormalities, and a decreased response to vasopressors.
Renal function must be monitored carefully, and dose adjustments must be made for drugs dependent on renal excretion if renal function declines. Moreover, metabolic alkalosis has been reported to alter drug protein binding for some anesthetic agents.
Patients with Bartter syndrome may also have platelet dysfunction if routinely treated with nonsteroidal anti-inflammatory agents.
Diet and Activity
Diet
Adequate salt and water intake is necessary to prevent hypovolemia, and adequate potassium intake is essential to replace urinary potassium losses. Patients should consume foods and drinks that contain high levels of potassium (eg, tomatoes, bananas, orange juice).
With growth retardation, adequate overall nutritional balance (protein-calorie intake) is important. Whether other dietary supplements (eg, citrate, magnesium, vitamins) are helpful is not clear.
Activity
No restriction on general activity is required, but precautions against dehydration should be taken. Patients should avoid strenuous exercise avoided because of the danger of dehydration and functional cardiac abnormalities secondary to potassium imbalance.
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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 |
