Close
New

Medscape is available in 5 Language Editions – Choose your Edition here.

 

Bartter Syndrome Treatment & Management

  • Author: Lynda A Frassetto, MD; Chief Editor: Vecihi Batuman, MD, FACP, FASN  more...
 
Updated: Aug 20, 2015
 

Approach Considerations

Since first described in 1962, several types of medical treatment have been used, including the following:

  • Sodium and potassium supplements - Used for the electrolyte imbalances
  • Aldosterone antagonists and diuretic spironolactone - Are mainstays of therapy
  • Angiotensin-converting enzyme (ACE) inhibitors - Used to counteract the effects of angiotensin II (ANG II) and aldosterone
  • Indomethacin - Used to decrease prostaglandin excretion
  • Growth hormone (GH) - Used to treat short stature
  • 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.[13] 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.

Next

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.

Previous
Next

Preemptive Surgery

One approach to the management of severe Bartter syndrome involves preemptive nephrectomy and renal transplantation.[28] 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.

Previous
Next

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.

Previous
Next

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.

Previous
 
 
Contributor Information and Disclosures
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, FACP, FASN Huberwald Professor of Medicine, Section of Nephrology-Hypertension, Tulane University School of Medicine; Chief, Renal Section, Southeast Louisiana Veterans Health Care System

Vecihi Batuman, MD, FACP, FASN is a member of the following medical societies: American College of Physicians, American Society of Hypertension, American Society of Nephrology, International Society of Nephrology

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

Disclosure: Nothing to disclose.

George R Aronoff, MD Director, Professor, Departments of Internal Medicine and Pharmacology, Section of Nephrology, Kidney Disease Program, University of Louisville School of Medicine

George R Aronoff, MD is a member of the following medical societies: American Federation for Medical Research, American Society of Nephrology, Kentucky Medical Association, and National Kidney Foundation

Disclosure: Nothing to disclose.

Prasad Devarajan, MD Louise M Williams Endowed Chair in Pediatrics, Professor of Pediatrics and Developmental Biology, Director of Nephrology and Hypertension, Director of Clinical Nephrology Laboratories, CEO of Dialysis Unit, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine

Prasad Devarajan, MD is a member of the following medical societies: American Heart Association, American Society of Nephrology, American Society of Pediatric Nephrology, National Kidney Foundation, and Society for Pediatric Research

Disclosure: Nothing to disclose.

Abubakr Imam, MD Assistant Professor of Pediatrics, Department of Pediatrics, Division of Pediatric Nephrology, Wayne State University School of Medicine, Children's Hospital of Michigan

Disclosure: Nothing to disclose.

Craig B Langman, MD The Isaac A Abt, MD, Professor of Kidney Diseases, Northwestern University, The Feinberg School of Medicine; Division Head of Kidney Diseases, Children's Memorial Hospital

Craig B Langman, MD is a member of the following medical societies: American Academy of Pediatrics, American Society of Nephrology, and International Society of Nephrology

Disclosure: NIH Grant/research funds None; Raptor Pharmaceuticals, Inc Grant/research funds None; Alexion Pharmaceuticals, Inc. Grant/research funds None

Adrian Spitzer, MD Clinical Professor Emeritus, Department of Pediatrics, Albert Einstein College of Medicine

Adrian Spitzer, MD is a member of the following medical societies: American Academy of Pediatrics, American Federation for Medical Research, American Pediatric Society, American Society of Nephrology, American Society of Pediatric Nephrology, International Society of Nephrology, and Society for Pediatric Research

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

References
  1. Lin SH, Yang SS, Chau T. A practical approach to genetic hypokalemia. Electrolyte Blood Press. 2010 Jun. 8(1):38-50. [Medline]. [Full Text].

  2. Seyberth HW. An improved terminology and classification of Bartter-like syndromes. Nat Clin Pract Nephrol. 2008 Oct. 4(10):560-7. [Medline].

  3. Watanabe S, Fukumoto S, Chang H, Takeuchi Y, Hasegawa Y, Okazaki R, et al. Association between activating mutations of calcium-sensing receptor and Bartter's syndrome. Lancet. 2002 Aug 31. 360(9334):692-4. [Medline].

  4. Chen YH, Lin JJ, Jeansonne BG, et al. Analysis of claudin genes in pediatric patients with Bartter's syndrome. Ann N Y Acad Sci. 2009 May. 1165:126-34. [Medline].

  5. Deschênes G, Fila M. Primary molecular disorders and secondary biological adaptations in bartter syndrome. Int J Nephrol. 2011. 2011:396209. [Medline]. [Full Text].

  6. Janssen AG, Scholl U, Domeyer C, et al. Disease-causing dysfunctions of barttin in Bartter syndrome type IV. J Am Soc Nephrol. 2009 Jan. 20(1):145-53. [Medline]. [Full Text].

  7. Kitanaka S, Sato U, Maruyama K, Igarashi T. A compound heterozygous mutation in the BSND gene detected in Bartter syndrome type IV. Pediatr Nephrol. 2006 Feb. 21(2):190-3. [Medline].

  8. Zaffanello M, Taranta A, Palma A, Bettinelli A, Marseglia GL, Emma F. Type IV Bartter syndrome: report of two new cases. Pediatr Nephrol. 2006 Jun. 21(6):766-70. [Medline].

  9. Birkenhäger R, Otto E, Schürmann MJ, et al. Mutation of BSND causes Bartter syndrome with sensorineural deafness and kidney failure. Nat Genet. 2001 Nov. 29(3):310-4. [Medline].

  10. García-Nieto V, Flores C, Luis-Yanes MI, Gallego E, Villar J, Claverie-Martín F. Mutation G47R in the BSND gene causes Bartter syndrome with deafness in two Spanish families. Pediatr Nephrol. 2006 May. 21(5):643-8. [Medline].

  11. Krämer 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. 2008 Jan. 4(1):38-46. [Medline].

  12. Gunn IR, Gaffney D. Clinical and laboratory features of calcium-sensing receptor disorders: a systematic review. Ann Clin Biochem. 2004 Nov. 41:441-58. [Medline].

  13. Rudin A. Bartter's syndrome. A review of 28 patients followed for 10 years. Acta Med Scand. 1988. 224(2):165-71. [Medline].

  14. Fallen K, Banerjee S, Sheehan J, et al. The Kir channel immunoglobulin domain is essential for Kir1.1 (ROMK) thermodynamic stability, trafficking and gating. Channels (Austin). 2009 Jan-Feb. 3(1):57-68. [Medline]. [Full Text].

  15. Dane B, Dane C, Aksoy F, Cetin A, Yayla M. Antenatal Bartter syndrome: analysis of two cases with placental findings. Fetal Pediatr Pathol. 2010. 29(3):121-6. [Medline].

  16. Matsunoshita N, Nozu K, Shono A, Nozu Y, Fu XJ, Morisada N, et al. Differential diagnosis of Bartter syndrome, Gitelman syndrome, and pseudo-Bartter/Gitelman syndrome based on clinical characteristics. Genet Med. 2015 Apr 16. [Medline].

  17. Assadi F. Diagnosis of hypokalemia: a problem-solving approach to clinical cases. Iran J Kidney Dis. 2008 Jul. 2(3):115-22. [Medline]. [Full Text].

  18. 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. 1997 Oct. 17(2):171-8. [Medline].

  19. 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. 1996 Jun. 13(2):183-8. [Medline].

  20. Simon DB, Karet FE, Rodriguez-Soriano J, Hamdan JH, DiPietro A, et al. Genetic heterogeneity of Bartter's syndrome revealed by mutations in the K+ channel, ROMK. Nat Genet. 1996 Oct. 14(2):152-6. [Medline].

  21. Simon DB, Nelson-Williams C, Bia MJ, Ellison D, Karet FE, Molina AM, et al. Gitelman's variant of Bartter's syndrome, inherited hypokalaemic alkalosis, is caused by mutations in the thiazide-sensitive Na-Cl cotransporter. Nat Genet. 1996 Jan. 12(1):24-30. [Medline].

  22. Adachi M, Asakura Y, Sato Y, Tajima T, Nakajima T, Yamamoto T, et al. Novel SLC12A1 (NKCC2) mutations in two families with Bartter syndrome type 1. Endocr J. 2007. 54(6):1003-7. [Medline].

  23. Aoi N, Nakayama T, Tahira Y, Haketa A, Yabuki M, Sekiyama T, et al. Two novel genotypes of the thiazide-sensitive Na-Cl cotransporter (SLC12A3) gene in patients with Gitelman's syndrome. Endocrine. 2007 Apr. 31(2):149-53. [Medline].

  24. Colussi G, Bettinelli A, Tedeschi S, De Ferrari ME, Syrén ML, Borsa N, et al. A thiazide test for the diagnosis of renal tubular hypokalemic disorders. Clin J Am Soc Nephrol. 2007 May. 2 (3):454-60. [Medline]. [Full Text].

  25. Jiang L, Peng X, Ma J, Yuan T, Qin Y, Wang O, et al. NORMOMAGNESEMIC GITELMAN SYNDROME PATIENTS EXHIBIT A STRONGER REACTION TO THIAZIDE THAN HYPOMAGNESEMIC PATIENTS. Endocr Pract. 2015 Jun 29. [Medline].

  26. Walsh SB, Unwin E, Vargas-Poussou R, Houillier P, Unwin R. Does hypokalaemia cause nephropathy? An observational study of renal function in patients with Bartter or Gitelman syndrome. QJM. 2011 Nov. 104(11):939-44. [Medline].

  27. Dane B, Yayla M, Dane C, Cetin A. Prenatal diagnosis of Bartter syndrome with biochemical examination of amniotic fluid: case report. Fetal Diagn Ther. 2007. 22(3):206-8. [Medline].

  28. Chaudhuri A, Salvatierra O Jr, Alexander SR, Sarwal MM. Option of pre-emptive nephrectomy and renal transplantation for Bartter's syndrome. Pediatr Transplant. 2006 Mar. 10(2):266-70. [Medline].

  29. Bartter FC, Pronove P, Gill JR. Hyperplasia of the juxtaglomerular complex with hyperaldosteronism and hypokalemic alkalosis. American Journal of Medicine. 1962. 33:811-828.

  30. Bichet DG, Fujiwara TM. Reabsorption of sodium chloride--lessons from the chloride channels. N Engl J Med. 2004 Mar 25. 350(13):1281-3. [Medline].

  31. Estévez R, Boettger T, Stein V, Birkenhäger R, Otto E, Hildebrandt F, et al. Barttin is a Cl- channel beta-subunit crucial for renal Cl- reabsorption and inner ear K+ secretion. Nature. 2001 Nov 29. 414(6863):558-61. [Medline].

  32. Jentsch TJ, Maritzen T, Zdebik AA. Chloride channel diseases resulting from impaired transepithelial transport or vesicular function. J Clin Invest. 2005 Aug. 115(8):2039-46. [Medline].

  33. Lee EH, Heo JS, Lee HK, Han KH, Kang HG, Ha IS, et al. A case of Bartter syndrome type I with atypical presentations. Korean J Pediatr. 2010 Aug. 53(8):809-13. [Medline]. [Full Text].

  34. Madrigal G, Saborio P, Mora F, Rincon G, Guay-Woodford LM. Bartter syndrome in Costa Rica: a description of 20 cases. Pediatr Nephrol. 1997 Jun. 11(3):296-301. [Medline].

  35. Puricelli E, Bettinelli A, Borsa N, Sironi F, Mattiello C, Tammaro F, et al. Long-term follow-up of patients with Bartter syndrome type I and II. Nephrol Dial Transplant. 2010 Sep. 25(9):2976-81. [Medline].

  36. Riazuddin S, Anwar S, Fischer M, et al. Molecular basis of DFNB73: mutations of BSND can cause nonsyndromic deafness or Bartter syndrome. Am J Hum Genet. 2009 Aug. 85(2):273-80. [Medline]. [Full Text].

  37. Veizis IE, Cotton CU. Role of kidney chloride channels in health and disease. Pediatr Nephrol. 2007 Jun. 22(6):770-7. [Medline]. [Full Text].

 
Previous
Next
 
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.
Table 1. Bartter Syndrome Genotype-Phenotype Correlations
Bartter Syndrome Genotype-Phenotype Correlations
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
Previous
Next
 
 
 
 
 
All material on this website is protected by copyright, Copyright © 1994-2016 by WebMD LLC. This website also contains material copyrighted by 3rd parties.