Journal of Postgraduate Medicine
 Open access journal indexed with Index Medicus & ISI's SCI  
Users online: 292  
Home | Subscribe | Feedback | Login 
About Latest Articles Back-Issues Articlesmenu-bullet Search Instructions Online Submission Subscribe Etcetera Contact
 :: Next article
 :: Previous article 
 :: Table of Contents
 ::  Similar in PUBMED
 ::  Search Pubmed for
 ::  Search in Google Scholar for
 ::Related articles
 ::  Article in PDF (44 KB)
 ::  Citation Manager
 ::  Access Statistics
 ::  Reader Comments
 ::  Email Alert *
 ::  Add to My List *
* Registration required (free) 

  IN THIS Article
 ::  Abstract
 ::  Case Report
 ::  Discussion
 ::  References
 ::  Article Tables

 Article Access Statistics
    PDF Downloaded174    
    Comments [Add]    
    Cited by others 20    

Recommend this journal


Year : 2009  |  Volume : 55  |  Issue : 3  |  Page : 208-210

Amikacin-induced type 5 Bartter-like syndrome with severe hypocalcemia

Department of Medicine II, Christian Medical College, Vellore, India

Date of Submission16-Sep-2008
Date of Decision10-Apr-2009
Date of Acceptance20-Jul-2009
Date of Web Publication2-Nov-2009

Correspondence Address:
A Chrispal
Department of Medicine II, Christian Medical College, Vellore
Login to access the Email id

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0022-3859.57407

Rights and Permissions

 :: Abstract 

Aminoglycoside-induced renal toxicity is well known and may manifest with nonoliguric renal failure or renal tubular dysfunction. Aminoglycoside-induced renal tubular dysfunction could result in diffuse damage or manifest as a Fanconi-like syndrome, Bartter-like syndrome, or distal renal tubular acidosis. We discuss a patient who developed severe renal tubular dysfunction secondary to short-term therapy with Amikacin, resulting in refractory hypokalemia, hypocalcemia, hypomagnesemia, metabolic alkalosis, and polyuria. This constellation of biochemical abnormalities mimic Type 5 Bartter's syndrome, where there is activating mutation of the calcium sensing receptor in the thick ascending loop of Henle and the distal tubule. In this case this activation of the calcium sensing receptor was triggered by amikacin. This phenomenon has been described with gentamicin though never with amikacin. Recovery of the tubular dysfunction took 15 days following cessation of the offending drug, Amikacin.

Keywords: Aminoglycoside, amikacin, Bartter′s syndrome, calcium sensing receptor, nephrotoxicity

How to cite this article:
Chrispal A, Boorugu H, Prabhakar A T, Moses V. Amikacin-induced type 5 Bartter-like syndrome with severe hypocalcemia. J Postgrad Med 2009;55:208-10

How to cite this URL:
Chrispal A, Boorugu H, Prabhakar A T, Moses V. Amikacin-induced type 5 Bartter-like syndrome with severe hypocalcemia. J Postgrad Med [serial online] 2009 [cited 2023 Mar 22];55:208-10. Available from:

Aminoglycosides are commonly used antibiotics with excellent renal parenchymal penetration. Their clinical effectiveness is counterbalanced with the risk of renal toxicity, which develops in a dose-dependent fashion. The toxic potential of individual aminoglycosides is directly related to their ability to bind and disrupt plasma membranes - in this regard Amikacin is less toxic than Gentamicin. [1] Aminoglycoside-induced renal tubular dysfunction may present as a Bartter-like syndrome and this has been reported with Gentamicin. [2],[3] We present a case of a man who developed severe refractory electrolyte abnormalities, suggestive of diffuse renal tubular dysfunction, following treatment with Amikacin. To the best of our knowledge this is the first case report of Type 5 Bartter-like syndrome with severe hypocalcemia, associated with Amikacin.

 :: Case Report Top

A 39-year-old male underwent a colostomy and suprapubic cystostomy for the management of pelvic fracture with membranous urethral injury sustained due to a road traffic accident. After remaining well for six years following the procedure, he developed high grade intermittent fever for three days. Suspecting urinary tract infection (UTI), the local practitioner initiated treatment with Amikacin injection of 750 mg intravenously once daily (15 mg/kg body weight) for seven days. On the fourth day of treatment the patient became progressively drowsy, although his fever had subsided. He presented to the Emergency Department of our hospital after the seventh dose of Amikacin, with persistent altered sensorium. There was no history of significant vomiting, diarrhea, or use of any other medication during this period. On initial examination he was drowsy. His blood pressure was 100/70 mmHg, pulse rate was 104/minute and central venous pressure (CVP) was low (2 cm H 2 O), with features of dehydration. He was afebrile. General and systemic examination was otherwise unremarkable. Within a few hours of presentation, he developed recurrent episodes of generalized tonic-clonic seizures, for which he was initiated on anti-epileptics and required mechanical ventilation.

Investigations revealed profound electrolyte abnormalities [Table 1]. CSF analysis was normal. An MRI of the brain showed bilateral, symmetric, long TR hyperintensities involving the basal ganglia, central and dorsal midbrain, which, in the setting of electrolyte abnormalities, was suggestive of metabolic encephalopathy. The seizures were attributed to severe hypocalcemia and/or hyponatremia. As the patient had leucocytosis (20,000 cells/cu mm), preceding fever, and suspected UTI, he was initiated on treatment with Ceftriaxone injection 2 gm IV twice daily; Amikacin was discontinued.

During the first 24 hours of hospital stay, polyuria (urine output > 6 L/d) with minimal colostomy loss was noted. In view of clinically evident dehydration, low CVP, increased serum osmolarity (310 mOsm/kg), normal urine osmolarity (348 mOsm/kg) with polyuria, and hyponatremia with natriuresis, a diagnosis of severe renal salt wasting with resultant depletional hyponatremia and defective renal tubular concentrating ability was made. He was hydrated (3 liters of normal saline in the first 24 hours) and the serum sodium levels were corrected over the first 72 hours. 8 am Serum cortisol (27 mcg/dL) and TSH (3.32 uIU/ml) levels were normal.

He had persistent hypokalemia and kaliuresis associated with metabolic alkalosis (Blood pH 7.473). Hypocalcemia with inappropriate calciuria, hypomagnesemia, and hypophosphatemia were documented. Serum parathyroid hormone levels were elevated (198 pg/ml [normal 8-74 pg/ml]). This constellation of electrolyte abnormalities was suggestive of a global renal tubular dysfunction. Acute proximal tubule dysfunction was evident by virtue of polyuria, renal salt wasting, and hypophosphatemia. Hypokalemia, metabolic alkalosis, hypocalcemia, hypercalciuria, and hypomagnesemia were consistent with an acquired Bartter-like syndrome. Based on the temporal profile these phenomena were due to Amikacin-related tubular toxicity (Naranjo score 7; probable adverse drug reaction). [4]

These abnormalities normalized 15 days after the last dose of Amikacin. However, on day 10, he developed ventilator-associated pneumonia with  Pseudomonas aeruginosa Scientific Name Search pticemia. Despite appropriate treatment for the same, the patient steadily deteriorated and he expired on the twenty-third day of hospitalization.

 :: Discussion Top

Nonoliguric renal failure is the commonest manifestation of aminoglycoside-induced renal toxicity. The susceptibility of the kidney to aminoglycoside-induced toxicity is due to the exclusive excretion of the antibiotic by this organ. Once filtered, a small but significant fraction (< 5%) of the drug is taken up by receptor mediated endocytosis at the apical surface of the proximal convoluted tubule (PCT) and accumulates in a dose-dependent manner. [5] Histopathological studies have supported the concept that patchy tubular necrosis is the primary cause of functional toxicity. [6] Aminoglycoside accumulation in the PCT cells results in lysosomal swelling and impaired generation of adenosine triphosphate, which in turn results in cell destruction. [1] Aminoglycoside-induced renal tubular dysfunction can result in diffuse damage and can be divided into Fanconi-like syndrome (FS), Bartter-like syndrome (BS), and distal renal tubular acidosis. [2] It is hypothesized that mitochondrial dysfunction underlies the abnormalities in all parts of the renal tubule.

Aminoglycoside-induced Bartter-like syndrome is less clearly understood and may involve a transporter defect situated in the thick ascending loop of the renal tubule that is similar to the hereditary variant of Bartter's disease. Certain patients with the hereditary variant of Bartter's syndrome have the features of potassium wasting, hypokalemia, metabolic alkalosis associated with hypocalcemia, and hypomagnesemia. These patients denoted as Bartter's syndrome type 5, appear to have a gain-in-function mutation in the calcium sensing receptor. Activation of this receptor results in the inhibition of the luminal potassium channel, in the thick ascending limb. It is possible that aminoglycosides directly activates the calcium sensing receptor in the thick ascending loop of Henle and the distal tubule, resulting in hypokalemia, metabolic alkalosis, hypomagnesemia with hypermagnesuria, and hypercalciuria. [2],[3]

Renal tubular dysfunction secondary to aminoglycosides is related to a prolonged and inappropriately high-dose use. However, there appears to be recovery after two to six weeks after cessation of the antibiotic. Defects in the thick ascending loop of Henle may be caused by drugs like Furosemide, Cisplatin, carbenicillin, cyclosporine, amphotericin, prolonged administration of Gentamicin, Capreomycin, and Streptomycin. [7],[8],[9] To the best of our knowledge this is the first report of a Bartter-like syndrome with hypocalcemia associated with amikacin. Urine chloride, vitamin D, and prostaglandin E2 levels were not measured in this patient - this was a limitation and if available would have augmented the diagnosis. Interestingly, the patient described received an appropriate dose and short duration of therapy prior to developing refractory metabolic abnormalities due to tubular toxicity.

 :: References Top

1.Zahid M, Kamal F, Qamar MZ, Bhatti SA, Insari NI. Morphological changes produced by aminoglycoside induced nephrotoxicity: An experimental study. Annals 2007;13:234-7.  Back to cited text no. 1      
2.Hung CC, Guh JY, Kuo MC, Lai YH, Chen HC. Gentamicin-induced diffuse renal tubular dysfunction. Nephrol Dial Transplant 2006;21:547.  Back to cited text no. 2  [PUBMED]  [FULLTEXT]  
3.Chou CL, Chen YH, Chau T, Lin SH. Acquired Bartter-like syndrome associated with gentamicin administration. Am J Med Sci 2005;329:144-9.  Back to cited text no. 3  [PUBMED]  [FULLTEXT]  
4.Naranjo CA, Busto U, Sellers EM, Sandor P, Ruiz I, Roberts EA, et al. A method for estimating the probability of adverse drug reactions. Clin Pharmacol Ther 1981;30:239-45.  Back to cited text no. 4  [PUBMED]  [FULLTEXT]  
5.Mingeot-Leclercq MP, Tulkens PM. Aminoglycosides: Nephrotoxicity. Antimicrobial Agents Chemother 1999;43:1003-12.  Back to cited text no. 5      
6.Moir JP, Viotte G, Vandewalle A, Van Hoof A, Tulkens P, Fillastre JP. Gentamicin-induced nephrotoxicity: A cell biology approach. Kidney Int 1980;18:583-90.  Back to cited text no. 6      
7.Steiner RW, Omachi AS. A Bartter's-like syndrome from capreomycin and a similar gentamicin tubulopathy. Am J Kidney Dis 1986;7:245-9.  Back to cited text no. 7  [PUBMED]  [FULLTEXT]  
8.Landau D, Kher KK. Gentamicin-induced Bartter-like syndrome. Pediatr Nephrol 1997;11:737-40.  Back to cited text no. 8  [PUBMED]  [FULLTEXT]  
9.Shetty AK, Rogers NL, Mannick EE, Aviles DH. Syndrome of hypokalemic metabolic alkalosis and hypomagnesemia associated with gentamicin therapy: Case reports. Clin Pediatr 2000;39:529-33.  Back to cited text no. 9      


  [Table 1]

This article has been cited by
1 Colistin-induced Bartter-like Syndrome: Ponder Before Treatment!
Himanshu Verma, Poonam Gupta, Anju Kumari, Ajay Kumar, Preeti Thakur, Kavish Sharma
Indian Journal of Critical Care Medicine. 2022; 26(2): 239
[Pubmed] | [DOI]
2 An overview of diagnosis and management of drug-induced hypomagnesemia
George Liamis, Ewout J. Hoorn, Matilda Florentin, Haralampos Milionis
Pharmacology Research & Perspectives. 2021; 9(4)
[Pubmed] | [DOI]
3 Transient Bartter-like syndrome in a child with extensively drug-resistant tuberculosis: Answers
Vishrutha Sujith Poojari, Ira Shah, Naman S. Shetty, Akanksha Jaiswal
Pediatric Nephrology. 2021; 36(7): 1975
[Pubmed] | [DOI]
4 Use of Urine Electrolytes and Urine Osmolality in the Clinical Diagnosis of Fluid, Electrolytes, and Acid-Base Disorders
Kamel S. Kamel, Mitchell L. Halperin
Kidney International Reports. 2021; 6(5): 1211
[Pubmed] | [DOI]
5 Differential diagnosis of perinatal Bartter, Bartter and Gitelman syndromes
Oluwatoyin Fatai Bamgbola, Youssef Ahmed
Clinical Kidney Journal. 2021; 14(1): 36
[Pubmed] | [DOI]
6 Electrolyte and Acid-Base Disorders Triggered by Aminoglycoside or Colistin Therapy: A Systematic Review
Martin Scoglio, Gabriel Bronz, Pietro O. Rinoldi, Pietro B. Faré, Céline Betti, Mario G. Bianchetti, Giacomo D. Simonetti, Viola Gennaro, Samuele Renzi, Sebastiano A. G. Lava, Gregorio P. Milani
Antibiotics. 2021; 10(2): 140
[Pubmed] | [DOI]
7 Molecular Basis, Diagnostic Challenges and Therapeutic Approaches of Bartter and Gitelman Syndromes: A Primer for Clinicians
Laura Nuńez-Gonzalez, Noa Carrera, Miguel A. Garcia-Gonzalez
International Journal of Molecular Sciences. 2021; 22(21): 11414
[Pubmed] | [DOI]
8 Review on the Antimicrobial Resistance of Pathogens from Tracheal and Endotracheal Aspirates of Patients with Clinical Manifestations of Pneumonia in Bacolod City in 2013
Alain C. Juayang,Dominador G. Maestral,Gemma B. de los Reyes,Michael Angelo D. Acosido,Christine T. Gallega
International Journal of Bacteriology. 2015; 2015: 1
[Pubmed] | [DOI]
9 Hypercalcemia-Induced Hypokalemic Metabolic Alkalosis in a Multiple Myeloma Patient: The Risk of Furosemide Use
Ira W. Reiser, Slamat Ali, Vladimir Gotlieb, Samuel Spitalewitz
Case Reports in Oncology. 2015; 8(3): 389
[Pubmed] | [DOI]
10 Molecular pathophysiology of Bartter’s and Gitelman’s syndromes
Efstathios Koulouridis,Ioannis Koulouridis
World Journal of Pediatrics. 2015; 11(2): 113
[Pubmed] | [DOI]
11 Acquired bartter-like syndrome associated with colistin use in a preterm infant
Cakir, U. and Alan, S. and Zeybek, C. and Erdeve, O. and Atasay, B. and Yalcinkaya, F. and Arsan, S.
Renal Failure. 2013; 35(3): 411-413
12 Acquired Bartter-Like Syndrome Associated with Colistin Use in a Preterm Infant
Ufuk Cakir,Serdar Alan,Cengiz Zeybek,Omer Erdeve,Begum Atasay,Fatma Yalcinkaya,Saadet Arsan
Renal Failure. 2013; 35(3): 411
[Pubmed] | [DOI]
13 Acquired Bartter-like syndrome association with netilmicin therapy in an extremely low birth weight infant
Gonca Sandal,Senay Akbay,Metehan Ozen
Renal Failure. 2013; : 1
[Pubmed] | [DOI]
14 Primary Molecular Disorders and Secondary Biological Adaptations in Bartter Syndrome
Georges Deschęnes, Marc Fila
International Journal of Nephrology. 2011; 2011: 1
[VIEW] | [DOI]
15 Miscellaneous antibacterial drugs
Corti, N. and Taegtmeyer, A. and Imhof, A.
Side Effects of Drugs Annual. 2011; 33(1): 509-540
16 Bartter- and Gitelman-like syndromes: salt-losing tubulopathies with loop or DCT defects
Hannsjörg W. Seyberth, Karl P. Schlingmann
Pediatric Nephrology. 2011;
[VIEW] | [DOI]
17 Drug-induced hypomagnesaemia
Hassam, R. and Arulanantham, N.
Adverse Drug Reaction Bulletin. 2010; (262): 1007-1010
18 Current awareness: Pharmacoepidemiology and drug safety
Pharmacoepidemiology and Drug Safety. 2010; 19(12): i
[VIEW] | [DOI]
19 Drug-induced hypomagnesaemia :
Rabia Hassam, Nirmalan Arulanantham
Adverse Drug Reaction Bulletin. 2010; &na;(262): 1007
[VIEW] | [DOI]
20 Familial hypercalcemia and hypophosphatemia: Importance in differential diagnosis of disorders in calcium-phosphate metabolism | [Familiární hyperkalcemie a hypofosfatemie a jejich význam v diferenciální diagnostice poruch kalcium-fosfátového metabolizmu]
Žofková, I.
Vnitrni Lekarstvi. 2010; 56(5): 397-401


Print this article  Email this article
Previous article Next article
Online since 12th February '04
© 2004 - Journal of Postgraduate Medicine
Official Publication of the Staff Society of the Seth GS Medical College and KEM Hospital, Mumbai, India
Published by Wolters Kluwer - Medknow