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| ADR REPORT |
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| Year : 2009 | Volume
: 55
| Issue : 3 | Page : 208-210 |
Amikacin-induced type 5 Bartter-like syndrome with severe hypocalcemia
A Chrispal, H Boorugu, AT Prabhakar, V Moses
Department of Medicine II, Christian Medical College, Vellore, India
| Date of Submission | 16-Sep-2008 |
| Date of Decision | 10-Apr-2009 |
| Date of Acceptance | 20-Jul-2009 |
| Date of Web Publication | 2-Nov-2009 |
Correspondence Address:
A Chrispal
Department of Medicine II, Christian Medical College, Vellore
India
 Source of Support: None, Conflict of Interest: None  | Check |
DOI: 10.4103/0022-3859.57407
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: https://www.jpgmonline.com/text.asp?2009/55/3/208/57407 |
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 | |  |
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  pticemia. Despite appropriate treatment for the same, the patient steadily deteriorated and he expired on the twenty-third day of hospitalization.
| :: Discussion | | |
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 | | |
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| 2. | Hung CC, Guh JY, Kuo MC, Lai YH, Chen HC. Gentamicin-induced diffuse renal tubular dysfunction. Nephrol Dial Transplant 2006;21:547. [PUBMED] [FULLTEXT] |
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| 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. |
| 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. [PUBMED] [FULLTEXT] |
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