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Saudi Journal of Kidney Diseases and Transplantation
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Year : 2020  |  Volume : 31  |  Issue : 5  |  Page : 1144-1147
Acquired Bartter Syndrome in Primary Sjögren Syndrome

Department of Internal Medicine A, Charles Nicolle Hospital, Tunis, Tunisia

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Date of Web Publication21-Nov-2020


Renal tubular involvement in Sjögren's syndrome (SS) often described with renal tubular acidosis, nephrogenic diabetes insipidus, or rarely with Fanconi syndrome. SS presenting with clinical features of Bartter's syndrome or Gitelman's syndrome is rare. We report a case of a female patient who presented an acquired Bartter syndrome with a primary SS.

How to cite this article:
Fraj A, El Euch M, Jaziri F, Kefi A, Abdelghani KB, Turki S, Abdallah TB. Acquired Bartter Syndrome in Primary Sjögren Syndrome. Saudi J Kidney Dis Transpl 2020;31:1144-7

How to cite this URL:
Fraj A, El Euch M, Jaziri F, Kefi A, Abdelghani KB, Turki S, Abdallah TB. Acquired Bartter Syndrome in Primary Sjögren Syndrome. Saudi J Kidney Dis Transpl [serial online] 2020 [cited 2023 Feb 4];31:1144-7. Available from: https://www.sjkdt.org/text.asp?2020/31/5/1144/301185

   Introduction Top

Sjogren's syndrome (SS) is an autoimmune disease which predominantly affects middle-aged women, with a female-to-male ratio reaching 9:1[1] This disease is characterized by sicca symptoms (dryness of the eyes and mouth) caused by lymphoplasmacytic infiltration of the exocrine glands (salivary and lachrymal)[2] and production of antibodies. All tissues may be affected, including kidneys, gastrointestinal system, blood vessels, lungs, liver, pancreas, and nervous system.

The reported prevalence of renal involvement ranges from 2% to 67%.[3]One of the most common reported renal manifestation is interstitial nephritis.[3] Acquired Bartter syndrome associated with SS is rare, and only four cases were reported in the literature.[4],[5],[6],[7] We hereby report a patient with SS who presented with Bartter like syndrome.

   Case Report Top

Informed consent was obtained from the patient's relatives before publishing the case.

A 60-year-old female presented in our department with dry eye and mouth for six years. She developed weakness followed by lower limb neuropathic pain.

She did not report a history of fever, vomiting, diarrhea, or any drug abuse before the onset of the symptoms. She denied a suggestive family history of any autoimmune or renal disease.

On physical examination, the patient was conscious with Glasgow coma scale 15/15. Her body weight was 60 kg. Her blood pressure was 120/70 mm Hg. Her pulse was 70/min. The rest of the cardiovascular system and respiratory system examination was normal.

Neurological examination showed normal higher mental function and cranial nerves. Motor system examination showed hypotonia of lower limbs. All reflexes were present but diminished. There was no sensory and auto-nomic system involvement. Reduced tear break-up time was confirmed.

Laboratory tests were performed and revealed serum creatinine of 72 μmol/L, sodium 142 mmol/L, potassium 3.2 mmol/L, chloride 104 mmol/L, magnesium 0.75 mmol/L, calcium 2.5 mmol/L, phosphorus 0.75 mmol/L. Arterial blood pH was 7.52 and serum bicarbonate was 29 mmol/L. Plasma aldosterone and renin levels were in the normal range. Immunologic tests showed the positivity of antinuclear and anti-SSA antibodies.

Urinary microscopic analysis was normal. Urine protein was <0.5 mg/24 h, urinary metabolic levels were as follows: potassium 68 mmol/24 h, sodium 94 mmol/24 h, magnesium 4.29 mmol/24 h, and calcium was 7.74 mmol/ 24 h.

Ultrasound abdomen was normal, with no evidence of nephrocalcinosis. Electromyography disclosed a sensitive polyneuropathy. A minor salivary glands biopsy showed lymphocytic infiltration (grade 3 Chisholm).

Based on the clinical and histological findings, primary SS diagnosis was retained according to American-European Consensus Criteria for SS [Table 1].[8]
Table 1: American-European consensus group revised international classification criteria for Sjogren's syndrome.

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Since the combination of previous biochemical abnormalities, including hypokalemia, hyperchloremia, and metabolic acidosis, we suspected the diagnosis of Bartter syndrome.

She was treated with intravenously administered potassium supplementation. On the follow-up, her potassium increased gradually, and she was normokalemic after one month from starting treatment.

   Discussion Top

Bartter syndrome is a rare autosomal recessive disorder with a prevalence of one in 1,000,000 described by Bartter in 1962,[9] resulting from mutations affecting any of the five ion transport proteins in the apical membrane of thick ascending loop of Henle resulting a salt-wasting and hypokalemic metabolic alkalosis.

Based on the different underlying disease-causing genes, Bartter syndrome was classified into five types:[10],[11],[12],[13],[14]

  1. Type I results from mutations in the SLC12A1 gene and due to defective function of the Na-K-2Cl cotransporter
  2. Type II is caused by mutations in the KCNJ1 gene and due to defective function of the renal potassium channel (ROMK)
  3. Type III results from mutations in the CLCNKB gene and due to defective function of the renal chloride channel (CIC-kb)
  4. Type IV is caused by mutations in the BSND gene or from a combination of mutations in the CLCNKA and CLCNKB genes and due to reduced activity of both ClC-Ka and ClC-Kb transporters
  5. Type V is caused by mutations in the calcium-sensing receptor (CASR) gene and due to defects in the CaSR in the basolateral membrane of the thick ascending limb.

The laboratory criteria of Bartter syndrome can include hypokalemia with hyperkaliuria, hyponatremia, hypochloremia, metabolic alkalosis, mild hypomagnesemia, hypercalciuria, hyperaldosteronism, hyperreninemia with normal blood pressure. Most of these abnormalities (hypokalemia, hyperkaliuria, hyperchloremia, hypercalciuria, metabolic acidosis) were found in our patient.

The nephrocalcinosis which is a potential complication of hypercalciuria, can evolve into renal failure.[15] Fortunately, it was not found in our patient.

The Bartter syndrome occurs most commonly in antenatal or neonatal period.[16] Very few cases of acquired Bartter syndrome have been reported in the literature and they have been mostly associated with tuberculosis, diabetes, sarcoidosis, some drugs such as colistin, aminoglycosides (netilmicin, gentamicin, kanamycin) [Table 2].[17],[18],[19],[20],[21],[22],[23]
Table 2: Acquired causes of Bartter's syndrome.

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Our case reported primary SS associated with acquired Bartter syndrome, which is, until now to our knowledge the 5th published case in the literature.[4],[5],[6],[7] The 1st association was reported in 1979 in Japan.[7]

The mechanism underlying acquired Bartter syndrome associated with primary SS is not furthermore clear. There have been some previous reports describing the possible mechanism of acquired tubular dysfunction [distal renal tubular acidosis (RTA)] associated with SS.[24] Walsh et al found that the pathogenesis of primary and acquired distal RTA is different. Although altered expression and location of anion exchanger 1 and vacuolar proton pump (vH-ATPase) were observed in patients with primary distal RTA, no protein could be detected in patients with acquired distal RTA.[24] Bastani et al in other report detected auto-antibodies against vH+-ATPase in a patient with distal RTA in SS.[25] However, until now, no test has been reported to determine the pathophysiological state of acquired Bartter syndrome in patients with primary SS.

In contrast to Bartter syndrome, Gitelman syndrome is a disorder affecting the distal tubule and is caused by mutation in the SLC12A3 gene, which encodes the thiazide-sensitive NaCl cotransporter. This disorder is associated with hypokalemic, metabolic alkalosis, hypocalciuria, and hypomagnesemia.[26]

Regarding therapy, lifelong potassium supplementation is the therapy of choice. Potassium-sparing agents such as spironolactone could be an effective additive to supplementation to reduce the loss of potassium but could further increase the hypercalciuria. Prostaglandin synthetase inhibitors (e.g. indomethacin) are another principal group of drugs recommended in Bartter syndrome. The aim of this drug is the correction of urine concentration, decreasing salt wasting, and hypokalemic alkalosis. The recommended dose of indomethacin is 1.5–2.5 mg/kg/day.[27]

   Conclusion Top

Bartter syndrome is often an inherited disease. However, it can be acquired in patients with autoimmune diseases, especially SS. This association was rarely described, and our patient illustrated until now the 5th reported case worldwide. Fortunately, the prognosis of Bartter syndrome is favorable and all reported patients recovered under potassium correction, which must be continued lifelong.

Conflict of interest: None declared.

   References Top

Mavragani CP, Moutsopoulos HM. The geoepidemiology of Sjögren's syndrome. Autoimmun Rev 2010;9:305-10.  Back to cited text no. 1
Bloch KJ, Buchanan WW, Wohl MJ, Bunim JJ. Sjögren's syndrome. A clinical, pathological, and serological study of sixty-two cases. 1965. Medicine (Baltimore) 1992;71: 386-401.  Back to cited text no. 2
Luo J, Huo YW, Wang JW, Guo H. High-Risk Indicators of renal involvement in primary Sjogren's Syndrome: A clinical study of 1002 cases. J Immunol Res 2019;2019:3952392.  Back to cited text no. 3
Casatta L, Ferraccioli GF, Bartoli E. Hypokalaemic alkalosis, acquired Gitelman's and Bartter's syndrome in chronic sialoadenitis. Br J Rheumatol 1997;36:1125-8.  Back to cited text no. 4
Higashi K, Kawaguchi Y, Suzuki K, Nakamura H. Sjögren's syndrome associated with hypokalemic myopathy due to Bartter's syndrome. J Rheumatol 1997;24:1663-4.  Back to cited text no. 5
Pedro-Botet J, Tomas S, Soriano JC, Coll J. Primary Sjögren's syndrome associated with Bartter's syndrome. Clin Exp Rheumatol 1991; 9:210-2.  Back to cited text no. 6
Shibasaki T, Kimura Y, Abe T, Suzuki T, Miyajima M, Sakai S, et al. Bartter's syndrome in a patient with Sjögren's syndrome (author's transl). Nihon Naika Gakkai Zasshi 1979;68: 642-7.  Back to cited text no. 7
Baer AN, Walitt B. Sjögren Syndrome and other causes of sicca in older adults. Clin Geriatr Med 2017;33:87-103.  Back to cited text no. 8
Cunha TD, Heilberg IP. Bartter syndrome: Causes, diagnosis, and treatment. Int J Nephrol Renovasc Dis 2018;11:291-301.  Back to cited text no. 9
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 co-transporter NKCC2. Nat Genet 1996;13:183-8.  Back to cited text no. 10
Simon DB, Karet FE, Hamdan JM, DiPietro A, Sanjad SA, Lifton RP. Genetic heterogeneity o Bartter's syndrome revealed by mutations in the K+ channel, ROMK. Nat Genet 1996;14: 152.  Back to cited text no. 11
Simon DB, Bindra RS, Mansfield TA, et al. Mutations in the chloride channel gene, CLCNKB, cause Bartter's syndrome type III. Nat Genet 1997;17:171-8.  Back to cited text no. 12
Konrad M, Vollmer M, Lemmink HH, et al. Mutations in the chloride channel gene CLCNKB as a cause of classic Bartter syndrome. J Am Soc Nephrol 2000;11:1449- 59.  Back to cited text no. 13
Schlingmann KP, Konrad M, Jeck N, et al. Salt wasting and deafness resulting from mutations in two chloride channels. N Engl J Med 2004; 350:1314-9.  Back to cited text no. 14
Gadwalkar SR, Murthy PR, Raghavendra, Nandini K, Deepa DV. Acquired bartter-like phenotype. J Assoc Physicians India 2015;63: 78-9.  Back to cited text no. 15
Sakalli H, Bucak Hİ. Type IV neonatal Bartter syndrome complicated with congenital chloride diarrhea. Am J Case Rep 2012;13: 230-3.  Back to cited text no. 16
Workeneh B, Sangsiraprapha W, Addison D, Longfield E. A novel case of persistent Bartters-like syndrome associated with gentamicin exposure. Saudi J Kidney Dis Transpl 2013;24:144-6.  Back to cited text no. 17
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Mussche M, Thiels H. Schwartz-Bartter syndrome in a patient with pulmonary tuberculosis and tuberculous meningitis. Ned Tijdschr Geneeskd 1972;116:603-7.  Back to cited text no. 19
Cakir U, Alan S, Zeybek C, et al. Acquired bartter-like syndrome associated with colistin use in a preterm infant. Ren Fail 2013;35:411- 3.  Back to cited text no. 20
Sandal G, Akbay Ş, Ozen M. Acquired Bartter-like syndrome association with netilmicin therapy in an extremely low birth weight infant. Ren Fail 2014;36:123-5.  Back to cited text no. 21
Yu TM, Lin SH, Ya-Wen C, et al. A syndrome resembling Bartter's syndrome in sarcoidosis. Nephrol Dial Transplant 2009;24:667-9.  Back to cited text no. 22
Dalugama C, Pathirage M, Kularatne SA. Bartter syndrome-like phenotype in a patient with diabetes: A case report. J Med Case Rep 2018;12:222.  Back to cited text no. 23
Walsh S, Turner CM, Toye A, et al. Immunohistochemical comparison of a case of inherited distal renal tubular acidosis (with a unique AE1 mutation) with an acquired case secondary to autoimmune disease. Nephrol Dial Transplant 2007;22:807-12.  Back to cited text no. 24
Bastani B, Underhill D, Chu N, Nelson RD, Haragsim L, Gluck S. Preservation of intercalated cell H(+)-ATPase in two patients with lupus nephritis and hyperkalemic distal renal tubular acidosis. J Am Soc Nephrol 1997;8:1109-17.  Back to cited text no. 25
Kim YK, Song HC, Kim YS, Choi EJ. Acquired gitelman syndrome. Electrolyte Blood Press 2009;7:5-8.  Back to cited text no. 26
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Correspondence Address:
Fatima Jaziri
Department of Internal Medicine A, Charles Nicolle Hospital, Tunis
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/1319-2442.301185

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