Guidelines Summary

In 2021, the European Rare Kidney Disease Reference Network published guidelines for the diagnosis and management of Bartter syndrome. Because of the rarity of the syndrome, the guidelines are based on the expert consensus of the organization's Working Group for Tubular Disorders.^[49]

Diagnosis

Key recommendations for the diagnosis of Bartter syndrome include the following^[49]:

Prenatal diagnosis should be considered in the presence of a polyhydramnios of fetal origin; polyhydramnios due to excessive fetal polyuria is virtually always caused by Bartter syndrome.
Prenatal molecular genetic testing should be done according to country-specific ethical and legal standards and with appropriate genetic counseling.
If genetic testing is unavailable, consider the assessment of the “Bartter index” (alpha fetoprotein [AFP] × total protein) in the amniotic fluid for prenatal diagnosis.
The assessment of electrolytes and/or aldosterone from amniotic fluid for prenatal diagnosis is not recommended.
Postnatal diagnosis should be considered in patients with renal salt wasting, polyuria, rapid weight loss, and signs of dehydration.
Failure to thrive, recurrent vomiting, repeated fever, hypochloremic and hypokalemic metabolic alkalosis, and nephrocalcinosis beyond the neonatal period should raise suspicion of Bartter syndrome.

The guidelines recommend the following approach in the initial postnatal workup for Bartter syndrome^[49]:

Medical history focus : Polyhydramnios, premature birth, growth failure, and family history
Biochemical panel: Serum electrolytes (sodium, chloride, potassium, calcium, magnesium), acid-base status, renin, aldosterone, creatinine, fractional excretion of chloride, and urinary calcium-creatinine ratio
Kidney ultrasound:Evidence of medullary nephrocalcinosis and/or kidney stones

The diagnosis should be confirmed by genetic testing where available and genetic counseling should be offered. The following genes should be included in genetic testing for Bartter syndrome^[49]:

SLC12A1
KCNJ1
CLCNKB
CLCNKA
BSND
MAGED2
SLC12A3
CASR
KCNJ10
SLC26A3
CLDN10
SCNN1A
SCNN1B
SCNN1G
NR3C2

Tubular function tests with furosemide or thiazides are not recommended if genetic testing is available.^[49]

Management

Key recommendations for the management of Bartter syndrome include the following^[49]:

Prenatal therapy aimed at reduction of amniotic fluid volume should be undertaken only after weighing the potential risks for the fetus, such as premature closure of the ductus arteriosus or necrotizing enterocolitis. A multidisciplinary team including maternal-fetal medicine specialist, neonatologist, pediatric nephrologist, and pediatric cardiologist should be consulted.
Sodium chloride supplementation should be considered for postnatal treatment.
Potassium chloride is preferred for potassium supplementation; complete normalization of plasma potassium levels is not recommended.
If needed, provide oral magnesium supplements.
Salt and electrolyte supplements should be spread out throughout the day as much as possible.
In symptomatic patients, consider treatment with nonsteroidal anti-inflammatory drugs (NSAIDs).
Use gastric acid inhibitors together with nonselective cyclooxygenase inhibitors.
Use of potassium-sparing diuretics, angiotensin-converting enzyme (ACE) inhibitors, or angiotensin receptor blockers (ARBs) is not recommended.
Use of thiazides to reduce hypercalciuria are not recommended.

Medication

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Media Gallery

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).
Type I neonatal Bartter syndrome. Mutations in the sodium chloride/potassium chloride cotransporter gene result in defective reabsorption of sodium, chloride, and potassium.
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.
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.

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Author

Lynda A Frassetto, MD Clinical Professor, Department of Internal Medicine, University of California, San Francisco, School of Medicine

Lynda A Frassetto, MD is a member of the following medical societies: American College of Physicians, American Society of Nephrology

Disclosure: Nothing to disclose.

Coauthor(s)

Lowell J Lo, MD Assistant Clinical Professor, Division of Nephrology, Department of Medicine, University of California, San Francisco, School of Medicine; Renal Ambulatory Service and Practice Chief, Medical Director, Mount Zion Dialysis Unit

Lowell J Lo, MD is a member of the following medical societies: American College of Physicians, American Medical Association, American Society of Nephrology, National Kidney Foundation

Disclosure: Nothing to disclose.

Chief Editor

Vecihi Batuman, MD, FASN Professor of Medicine, Section of Nephrology-Hypertension, Deming Department of Medicine, Tulane University School of Medicine

Vecihi Batuman, MD, FASN is a member of the following medical societies: American College of Physicians, American Society of Hypertension, American Society of Nephrology, Southern Society for Clinical Investigation

Disclosure: Nothing to disclose.

Acknowledgements

Uri S Alon, MD Director of Bone and Mineral Disorders Clinic and Renal Research Laboratory, Children's Mercy Hospital of Kansas City; Professor, Department of Pediatrics, Division of Pediatric Nephrology, University of Missouri-Kansas City School of Medicine

Uri S Alon, MD is a member of the following medical societies: American Federation for Medical Research