AUTHOR AND EDITOR INFORMATION

Section 1 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

INTRODUCTION

Section 2 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Background

In 1962, Frederic Bartter first observed the association of hyperplasia of the juxtaglomerular complex with hyperaldosteronism and hypokalemic metabolic alkalosis.¹ With the advent of polymerase chain reaction (PCR) and molecular genetic analysis techniques in the 1980s, it was found to be not one disease but several different abnormalities occurring in 4 transporters in 2 parts of the kidneys but with similar pathophysiologic consequences.

Bartter described this combination of juxtaglomerular hyperplasia, hyperaldosteronism, and hypokalemic alkalosis in 2 African American patients, a 25-year-old man with a long history of slow growth, weakness, and fatigue, and a 5-year-old boy. On high-sodium diets, both patients had normal blood pressure and high urinary aldosterone excretion associated with low plasma potassium levels and excessive sodium and chloride urinary excretion, resulting in hyperbicarbonatemia.

Initially, Bartter syndrome was considered a vascular disease. In the 1970s, when prostaglandins were discovered, patients with Bartter syndrome were discovered to overproduce prostaglandins. If treated with a prostaglandin inhibitor, aldosterone levels returned to normal, but plasma potassium levels did not. Subsequently, experimental potassium deficiency induced prostaglandin production and many of the symptoms of Bartter syndrome. This suggested that the problem was not an intravascular problem but a renal tubular problem.

Primarily through the work of Richard Lifton and colleagues, 4 areas of renal tubular defects have been described.^{2, 3, 4, 5} They are in the Na-K-2Cl transporter (now known as Bartter syndrome I), caused by mutations in the SLC12A1 gene; the apical potassium channel (Bartter syndrome II), caused by mutations in the ROMK1 gene; and two defects associated with the basal chloride channel in the thick ascending limb of Henle (TALH), one due to mutations in the CLCNKB gene (Bartter syndrome III) and another due to mutations in the CLCNKA (or BSDN) gene that alters a subunit protein named barttin, which is required for potassium-chloride membrane currents. 

A fifth defect results from loss-of-function mutations in the SLC12A3 gene that codes for the thiazide-sensitive Na-Cl cotransporter in the distal convoluted tubule (DCT). Known as Gitelman syndrome, mutations in this gene lead to similar but milder physiologic abnormalities in renal sodium, calcium, magnesium, and potassium handling.

The importance of the chloride channel in Bartter syndrome and Gitelman syndrome as well as some other nonrenal diseases, such as Dent disease, has been recognized, and it is now apparent that quite a few diseases, including cystic fibrosis, myotonia, deafness, and osteopetrosis, result from chloride channel disorders. The reviews by Jentsch et al and Veizis et al describe the detail of the various chloride channel mutations.^{6, 7}

Pathophysiology

Bartter and Gitelman syndromes are renal tubular salt-wasting disorders in which the kidneys cannot reabsorb chloride in the TALH or the DCT, depending on the mutation.

Chloride is passively absorbed along most of the proximal tubule but is actively transported in the TALH and the DCT. Failure to reabsorb chloride results in a failure to reabsorb sodium and leads to excessive sodium and chloride (salt) delivery to the distal tubules, leading to excessive salt and water loss from the body.

Other pathophysiologic abnormalities result from excessive salt and water loss. The renin-angiotensin-aldosterone system (RAAS) is a feedback system activated with volume depletion. Long-term stimulation may lead to hyperplasia of the juxtaglomerular complex.

Angiotensin II (ANG II) is directly vasoconstrictive, increasing both systemic and renal arteriolar constriction, which helps prevent systemic hypotension. It directly increases proximal tubular sodium reabsorption.

ANG II–induced renal vasoconstriction, along with potassium deficiency, produces a counterregulatory rise in vasodilating prostaglandin E (PGE) levels. High PGE levels are associated with growth inhibition in children.

High levels of aldosterone also enhance potassium and hydrogen exchange for sodium. Excessive intracellular hydrogen ion accumulation is associated with hypokalemia and intracellular renal tubule potassium depletion. This is because hydrogen is exchanged for potassium to maintain electrical neutrality. It may lead to intracellular citrate depletion because the alkali salt is used to buffer the intracellular acid and then lowers urinary citrate excretion. Hypocitraturia is an independent risk factor for renal stone formation.

Excessive distal sodium delivery increases distal tubular sodium reabsorption and exchange with the electrically equivalent potassium or hydrogen ion. This, in turn, promotes hypokalemia, while lack of chloride reabsorption promotes inadequate exchange of bicarbonate for chloride, and the combined hypokalemia and excessive bicarbonate retention lead to metabolic alkalosis.

Persons with Bartter syndrome often have hypercalciuria. Normally, reabsorption of the negative chloride ions promotes a lumen-positive voltage, driving paracellular positive calcium and magnesium absorption. Continued reabsorption and secretion of the positive potassium ions into the lumen of the TALH also promotes reabsorption of the positive calcium ions through paracellular channels. Dysfunction of the TAL chloride transporters prevents urine calcium reabsorption in the TALH. Excessive urine calcium excretion may be one factor in the nephrocalcinosis observed in these patients.

Calcium is usually reabsorbed in the DCT. Theoretically, chloride is reabsorbed through the thiazide-sensitive Na-Cl cotransporter and transported from the cell through a basolateral chloride channel, reducing intracellular chloride concentration. The net effect is increased activity of the voltage-dependent calcium channels and enhanced electrical gradient for calcium reabsorption from the lumen.

In Gitelman syndrome, dysfunction of the Na-Cl cotransporter NCCT leads to hypocalciuria and hypomagnesemia. In the last several years, the understanding of magnesium handling by the kidney has improved and advances in genetics have allowed the differentiation of a variety of magnesium-handling mutations.

While the variants that make up Bartter syndrome may or may not have hypomagnesemia, it is pathognomonic for Gitelman syndrome. The mechanism of the impaired magnesium reabsorption is still unknown; studies in NCCT knockout mice demonstrate increased apoptosis of DCT cells, which would then lead to diminished reabsorptive surface area.

Frequency

International

Estimates of prevalence vary from country to country.

In Costa Rica, the frequency of neonatal Bartter syndrome is approximately 1.2 cases per 100,000 live births and is higher if all preterm births are considered. No evidence of consanguinity was found in the Costa Rican cohort.

In Kuwait, the prevalence of consanguineous marriages or related families in patients with Bartter syndrome is higher than 50%, and prevalence in the general population is 1.7 cases per 100,000 persons.

In Sweden, the frequency has been calculated as 1.2 cases per 1 million persons. Of the 28 patients Rudin reported, 7 came from 3 families; the others were unrelated.⁸

Mortality/Morbidity

The severity and site of the mutation determines the age at which symptoms first develop. Completely dysfunctional mutations in the receptors and ion channels in the TALH are probably not compatible with life.

• Most cases of Bartter syndrome are discovered in infancy or early adolescence. Bartter syndrome can also be diagnosed prenatally, when the fetus develops polyhydramnios and intrauterine growth retardation. Many of the neonates are born prematurely. Children diagnosed early in life usually have more severe electrolyte disorders and symptoms. Because of Bartter syndrome's heterogeneity, patients with minimal symptomatology may be discovered relatively late.
• Patients with Gitelman syndrome tend to have milder symptoms than those with Bartter syndrome and to present in adolescence and early adulthood. Often, patients have minimal symptomatology and lead relatively normal lives. Of the 28 patients Rudin reported, 22 probably had Gitelman syndrome.⁸ Many had no symptoms. Electrolyte abnormalities were found when the patients presented for other problems.

Race

Bartter and Gitelman syndromes have no predilection for any racial or ethnic group.

Sex

Bartter and Gitelman syndromes are inherited as autosomal recessive syndromes. Neither syndrome has a predilection for either sex.

Age

• Bartter syndrome can be diagnosed antenatally, within the first few days of life, or during childhood or adolescence, depending on the severity of the disease.
• Gitelman syndrome is often not diagnosed until adolescence or early adulthood.

CLINICAL

Section 3 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

History

Bartter described 2 patients. The first was a boy aged 4 years 10 months with tetany and dwarfism. He had been hospitalized at age 4 months for vomiting, diarrhea, dehydration, and generalized convulsions. Although otherwise healthy, the boy's growth lagged, and he had polydipsia, which caused him to drink 10-12 glasses of fluid daily. The other patient was a 25-year-old man who presented with a long history of enuresis, slow growth, weakness, and fatigue. He had been hospitalized several times (once in a semicomatose condition) with vomiting, abdominal and leg cramps, and dehydration.

• Because Bartter and Gitelman syndromes result from a mutation in 1 of 5 transporters or subunits, age at onset of symptoms and severity of symptoms vary, depending on the severity of the mutation.
• Patients with antenatal Bartter syndrome often present with polyhydramnios and growth retardation and were delivered prematurely.
• The inability of the kidney tubules to retain salt and water results in urinary fluid loss, so polyuria is common.
• The resulting volume depletion increases thirst, and the normal response is to increase fluid intake.
• If patients cannot receive sufficient salt and water, dehydration and altered mental status can occur.
• In severe cases of Bartter syndrome, vomiting is not uncommon, producing further volume depletion.
• Inability of the kidney tubules to retain potassium, calcium, or magnesium can lead to muscle weakness, spasms, tetany, or palpitations. In Rudin's report of 28 patients, 22 had hypomagnesemia, but most denied any of these symptoms.⁸
• A few patients with severe cases of antenatal Bartter syndrome have also had mental retardation.

Physical

• Untreated patients tend to be very short.
• Most patients have low or low-to-normal blood pressure. They may show signs of volume depletion.
• Tetany, muscle spasms, and Chvostek and Trousseau signs may be observed in patients with hypokalemia, hypocalcemia, and hypomagnesemia. In the older literature, rickets was occasionally reported.
• In 1997, Madrigal and colleagues described a type of this syndrome in Costa Rica in 16 of 20 patients, each with "a peculiar facies distinguished by a triangularly shaped face, large eyes, and protruding ears."⁹ 
• • Strabismus was found in 9 of the patients.
  • Another 8 patients had sensorineural hearing loss determined by audiometry. Sensorineural hearing loss is reported in other series.
  • This sensorineural loss has now been linked to mutations in the barttin subunit in Bartter syndrome IV.

Causes

Both familial and sporadic forms of Bartter and Gitelman syndromes exist. Bartter and Gitelman syndromes are inherited as autosomal recessive syndromes.

DIFFERENTIALS

Section 4 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Other Problems to be Considered

Diuretic abuse
Gitelman syndrome
Hyperprostaglandin E syndrome
Familial hypomagnesemia with hypercalciuria/nephrocalcinosis
Activating mutations of the CaSR calcium sensing receptor

WORKUP

Section 5 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Lab Studies

• Consider possible renal tubular disorder if patients, especially dehydrated infants and young children, are found to have hypokalemia and a high serum bicarbonate concentration that do not correct with potassium and chloride replacement treatment.
• Initiate timed urine collection to determine potassium levels.  
• • In hypokalemia, normal kidneys retain potassium.
  • Elevated urinary potassium levels with low blood potassium levels suggest the kidneys are having problems retaining potassium.
• Next, initiate timed urine collection to determine aldosterone levels.  
• • Aldosterone levels should be low in volume-replete patients.
  • If urinary aldosterone levels are high despite volume replacement, there is an abnormal stimulation of aldosterone.
  • Patients with primary hyperaldosteronism in a volume-replete state usually have normal-to-high blood pressure.
  • Low or low-normal blood pressure with high aldosterone excretion suggests the primary problem is something else, and the aldosterone response is secondary to the undiagnosed primary abnormality.
• Then, initiate a timed urine collection to determine chloride levels.  
• • Extrarenal volume depletion is a possible reason for low blood pressure, high aldosterone excretion, and potassium loss. In this case, the kidneys retain sodium and chloride, and urinary chloride concentrations should be low.
  • High urine chloride levels with low blood pressure, high aldosterone secretion, and high urinary potassium levels are found only with long-term diuretic use and Bartter or Gitelman syndrome.
  • If diuretic abuse is suspected, a urine screen for diuretics can be ordered. Otherwise, the diagnosis is Bartter or Gitelman syndrome.
• Mutations in the different transporters cause Bartter syndrome. Mutations can be determined in the following ways:  
• • The older methods require more detailed physiologic investigations, including determination of serum magnesium levels and further urine collections to assess calcium, magnesium, and PGE2 levels.
  • In Bartter syndrome, urine calcium excretion is high, leading to nephrocalcinosis, while serum magnesium levels are normal.
  • With the transporter mutations that cause Gitelman syndrome, hypomagnesemia is common and is accompanied by hypocalciuria.
  • More recently, genetic analysis has become the preferred methodology for determining if a mutation in one of the transporters has occurred. Some mutations lead to marked loss of function, while others do not.^{10, 11}

Imaging Studies

• Antenatal Bartter syndrome can be diagnosed best by ultrasonography. The fetus may have polyhydramnios and intrauterine growth retardation. Amniotic chloride levels may be elevated.¹²
• After birth, especially if the disease is diagnosed in older patients who have hypercalciuria, consider a renal ultrasound or flat plate of the abdomen for nephrocalcinosis.  
• • Sonographic findings include diffusely increased echogenicity, hyperechoic pyramids, and interstitial calcium deposition.
  • Because continued calcium loss may affect bones, dual-energy x-ray absorptiometry (DEXA) scans to determine bone mineral density may be advisable in older patients.
• Nephrocalcinosis can occur and is often associated with hypercalciuria. It can be diagnosed with abdominal radiographs, intravenous pyelograms (IVPs), renal ultrasonograms, or spiral CT scans.

Other Tests

• An analysis of the genes for the transporters shows multiple problems leading to abnormal gene function, including missense, frame-shift, loss-of-function, and large deletion mutations.
• For a more detailed review, refer to the reports by Simon and colleagues (see References).^{2, 3, 4, 5}

TREATMENT

Section 6 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

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

Section 7 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

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.

Drug Category: Potassium sparing diuretics

These agents can increase potassium blood levels.

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.

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.

FOLLOW-UP

Section 8 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Further Inpatient Care

• For patients initially diagnosed in the hospital, the goal is to stabilize the patient sufficiently for discharge. This includes stabilization of potassium and other electrolytes, volume, and, perhaps, acid-base parameters.

Further Outpatient Care

• Patients initially need frequent outpatient follow-up care until the metabolic abnormalities caused by the renal tubular transporter mutation are stabilized with medications.
• The length of time to stability depends on the severity of the mutation and the degree of patient compliance.

Complications

• Nephrocalcinosis: A review of 61 cases of Bartter syndrome reported 29 with nephrocalcinosis. This is often associated with hypercalciuria.
• Sensorineural deafness
• • Sensorineural deafness associated with Bartter syndrome IV is due to defects in the barttin subunit of the ClC-Ka and CIC-Kb channels.
  • The ClC-Kb channel is found in the basolateral membrane of the TALH, while the ClC-Ka and ClC-Kb subunits are found in the basolateral membrane of the marginal cells of the cochlear stria vascularis.
  • In the inner ear, a Na-K-2Cl pump, called NKCC1, on the basolateral membrane increases intracellular levels of sodium, potassium, and chloride. Potassium excretion across the apical membrane against a concentration gradient produces the driving force for the depolarizing influx of potassium through the ion channels of the sensory hair cells required for hearing. The sodium ion is excreted across the basolateral membrane by the Na-K-ATPase pump, and the ClC-K channels allow the chloride ion to exit to maintain electroneutrality.
  • Mutations in only the ClC-Kb subunit causes Bartter syndrome without sensorineural deafness (Bartter syndrome III).
• Renal failure
• • Renal failure is fairly uncommon in Bartter syndrome.
  • In a review of 63 patients, 5 developed progressive renal disease requiring dialysis or transplantation.
  • In 2 reports of patients who underwent biopsies before developing ESRD, 1 patient had interstitial nephritis, and the other had mesangial and interstitial fibrosis.
  • One report relates the case of a patient developing reversible acute renal failure from rhabdomyolysis due to hypokalemia.
• Short stature/growth retardation
• • Nearly all patients with Bartter syndrome have growth retardation. In a review of 66 patients, 62 had growth retardation, often severe (below the fifth percentile for age).
  • Treatment with potassium, indomethacin, and GH has been effective.

Prognosis

• Bartter and Gitelman syndromes are both autosomal recessive disorders. Neither is curable.
• The degree of disability depends on the severity of the receptor dysfunction.
• Gitelman syndrome is often not diagnosed until adolescence or early adulthood.
• Prognosis in many cases is good, with patients able to lead fairly normal lives.

Patient Education

• Patients and their parents must understand that no cure exists for the constellation of mutations that causes these syndromes.
• • This chronic condition requires taking medications consistently, as prescribed, which is often difficult for children and adolescents.
  • Patients tend to become volume depleted if they are sodium and water restricted. Adequate fluid and electrolyte replacement should be available, especially in hot weather and during exercise.
• Both Bartter and Gitelman syndromes are autosomal recessive disorders, ie, mutations are required on each allele in the chromosome pair. Offspring carry at least 1 mutated allele. In consanguineous marriages or between closely related families, genetic counseling might be advisable.
• For excellent patient education resources, visit eMedicine's Growth Hormone Deficiency Center. Also, see eMedicine's patient education articles Growth Hormone Deficiency, Growth Failure in Children, Growth Hormone Deficiency in Children, and Growth Hormone Deficiency FAQs.

MISCELLANEOUS

Section 9 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical/Legal Pitfalls

• Failure to offer renal transplantation to patients with Bartter or Gitelman syndromes who develop ESRD
• Failure to consult with a nephrologist or pediatric nephrologist whenever a patient fitting the clinical picture of Bartter or Gitelman syndrome is found
• Failure to provide outpatient follow-up care until the metabolic abnormalities caused by the renal tubular transporter mutation are stabilized with medications
• Failure to provide treatment for patients with short stature or growth retardation
• Failure to provide adequate patient education regarding the syndrome

Special Concerns

• Pregnancy  
• • Reports associated with pregnancy 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 patients, no problems were noted except asymptomatic hypokalemia.⁸ 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.
• Anesthesia  
• • The multiple biochemical abnormalities present 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.
  • Metabolic alkalosis has also 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.

REFERENCES

Section 10 of 10

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

1. Bartter FC, Pronove P, Gill JR. Hyperplasia of the juxtaglomerular complex with hyperaldosteronism and hypokalemic alkalosis. American Journal of Medicine. 1962;33:811-828.
2. Simon DB, Bindra RS, Mansfield TA, Nelson-Williams C, Mendonca E, Stone R, et al. Mutations in the chloride channel gene, CLCNKB, cause Bartter's syndrome type III. Nat Genet. Oct 1997;17(2):171-8. [Medline].
3. Simon DB, Karet FE, Hamdan JM, DiPietro A, Sanjad SA, Lifton RP. Bartter's syndrome, hypokalaemic alkalosis with hypercalciuria, is caused by mutations in the Na-K-2Cl cotransporter NKCC2. Nat Genet. Jun 1996;13(2):183-8. [Medline].
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22. Kramer BK, Bergler T, Stoelcker B, Waldegger S. Mechanisms of Disease: the kidney-specific chloride channels ClCKA and ClCKB, the Barttin subunit, and their clinical relevance. Nat Clin Pract Nephrol. Jan 2008;4(1):38-46. [Medline].
23. Mackie FE, Hodson EM, Roy LP, Knight JF. Neonatal Bartter syndrome--use of indomethacin in the newborn period and prevention of growth failure. Pediatr Nephrol. Dec 1996;10(6):756-8. [Medline].
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Article Last Updated: May 16, 2008