eMedicine Specialties > Nephrology > Hereditary Kidney Disorders

Bartter Syndrome: Follow-up

Author: Lynda A Frassetto, MD, Associate Clinical Professor, Department of Internal Medicine, University of California at San Francisco School of Medicine
Contributor Information and Disclosures

Updated: Sep 18, 2009

Follow-up

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

Medicolegal 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.11 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.
 


More on Bartter Syndrome

Overview: Bartter Syndrome
Differential Diagnoses & Workup: Bartter Syndrome
Treatment & Medication: Bartter Syndrome
Follow-up: Bartter Syndrome
References
Further Reading
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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].

  4. 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. Oct 1996;14(2):152-6. [Medline].

  5. 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. Jan 1996;12(1):24-30. [Medline].

  6. 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. Aug 2009;85(2):273-80. [Medline].

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

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

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

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

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

  12. 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). Jan-Feb 2009;3(1):57-68. [Medline]. [Full Text].

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

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

  15. 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].

  16. 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. Apr 2007;31(2):149-53. [Medline].

  17. 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].

  18. Abdel-al YK, Badawi MH, Yaeesh SA, Habib YQ, al-Khuffash FA, al-Ghanim MM, et al. Bartter's syndrome in Arabic children: review of 13 cases. Pediatr Int. Jun 1999;41(3):299-303. [Medline].

  19. Aurell M, Rudin A. Effect of captopril on blood pressure, renal function, the electrolyte balance and the renin-angiotensin system in Bartter's syndrome. Nephron. 1983;33(4):274-8. [Medline].

  20. Brimacombe JR, Breen DP. Anesthesia and Bartter's syndrome: a case report and review. AANA J. Apr 1993;61(2):193-7. [Medline].

  21. Clementsen P, Hoegholm A, Hansen CL, Damkjaer M, Christensen P, Giese J. Bartter's syndrome--treatment with potassium, spironolactone and ACE-inhibitor. J Intern Med. Feb 1989;225(2):107-10. [Medline].

  22. Dillon MJ, Shah V, Mitchell MD. Bartter's syndrome: 10 cases in childhood. Results of long-term indomethacin therapy. Q J Med. Jul 1979;48(191):429-46. [Medline].

  23. Gitelman HJ, Graham JB, Welt LG. A new familial disorder characterized by hypokalemia and hypomagnesemia. Trans Assoc Am Physicians. 1966;79:221-35. [Medline].

  24. Jest P, Pedersen KE, Klitgaard NA, Thomsen N, Kjaer K, Simonsen E. Angiotensin-converting enzyme inhibition as a therapeutic principle in Bartter's syndrome. Eur J Clin Pharmacol. 1991;41(4):303-5. [Medline].

  25. Kleta R, Bockenhauer D. Bartter syndromes and other salt-losing tubulopathies. Nephron Physiol. 2006;104(2):p73-80. [Medline].

  26. Konrad M, Leonhardt A, Hensen P, Seyberth HW, Köckerling A. Prenatal and postnatal management of hyperprostaglandin E syndrome after genetic diagnosis from amniocytes. Pediatrics. Mar 1999;103(3):678-83. [Medline].

  27. 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].

  28. 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].

  29. O'Sullivan E, Monga M, Graves W. Bartter's syndrome in pregnancy: a case report and review. Am J Perinatol. Jan 1997;14(1):55-7. [Medline].

  30. Scheinman SJ, Guay-Woodford LM, Thakker RV, Warnock DG. Genetic disorders of renal electrolyte transport. N Engl J Med. Apr 15 1999;340(15):1177-87. [Medline].

  31. Schlingmann KP, Konrad M, Seyberth HW. Genetics of hereditary disorders of magnesium homeostasis. Pediatr Nephrol. 2004;19:13-25.

  32. Yokoyama T. [Endocrinological analysis before and after living-related renal transplantation in a patient of Bartter's syndrome]. Nippon Jinzo Gakkai Shi. Oct 1995;37(10):580-6. [Medline].

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Further Reading

Related eMedicine topics:
Bartter Syndrome [Pediatrics: General Medicine]
Hypercalciuria [Pediatrics: General Medicine]
Hypercalciuria [Urology]
Hypokalemia [Emergency Medicine]
Hypokalemia [Nephrology]
Hypokalemia [Pediatrics: Cardiac Disease and Critical Care Medicine]
Hypomagnesemia [Emergency Medicine]
Hypomagnesemia [Nephrology]
Hypomagnesemia [Pediatrics: General Medicine]

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Keywords

Bartter syndrome, Bartter’s syndrome, hypomagnesemia, hypercalciuria, nephrocalcinosis, hypokalemia, Gitelman syndrome, Gitelman’s syndrome, salt wasting, salt-wasting syndrome, salt-wasting disorder, salt-losing nephropathy, hyperplasia, juxtaglomerular complex, chloride channel, hyperaldosteronism, hypokalemic metabolic alkalosis, renin-angiotensin-aldosterone system, RAAS

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Contributor Information and Disclosures

Author

Lynda A Frassetto, MD, Associate Clinical Professor, Department of Internal Medicine, University of California at San Francisco School of Medicine
Lynda A Frassetto, MD is a member of the following medical societies: American College of Physicians and American Society of Nephrology
Disclosure: Nothing to disclose.

Medical Editor

Frank C Brosius III, MD, Nephrology Program Director, Professor of Internal Medicine and Physiology, Department of Internal Medicine, Division of Nephrology, University of Michigan School of Medicine
Frank C Brosius III, MD is a member of the following medical societies: Alpha Omega Alpha, American Diabetes Association, American Society of Nephrology, and Phi Beta Kappa
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

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.

CME Editor

Rebecca J Schmidt, DO, FACP, FASN, Professor of Medicine, Section Chief, Department of Medicine, Section of Nephrology, West Virginia University School of Medicine
Rebecca J Schmidt, DO, FACP, FASN is a member of the following medical societies: American College of Osteopathic Internists, American College of Physicians, American Medical Association, American Society of Nephrology, International Society of Nephrology, National Kidney Foundation, Renal Physicians Association, and West Virginia State Medical Association
Disclosure: Abbott Grant/research funds Speaking and teaching; Genzyme Honoraria Consulting; Amgen Honoraria Speaking and teaching; Ortho Biotech Honoraria Speaking and teaching

Chief Editor

Vecihi Batuman, MD, FACP, FASN, Professor of Medicine, Section of Nephrology-Hypertension, Tulane University School of Medicine; Chief, Medicine Service, 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, and International Society of Nephrology
Disclosure: Nothing to disclose.

 
 
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