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BOSTON -- One week after starting canagliflozin (Invokana) off-label, a 41-year-old woman with type 1 diabetes presented with a slew of kidney problems, said researchers here.
This was the first case of canagliflozin-linked Fanconi syndrome, they said. The researchers found that the woman had anion gap metabolic acidosis, and she had been vomiting and was nauseated and fatigued. She also had uricosuria and new-onset proteinuria, among other problems.
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She stayed in the intensive care unit for 1 week and was taken off canagliflozin before her condition improved, reported , of TriHealth Good Samaritan Hospital in Cincinnati, at the annual spring clinical meeting of the National Kidney Foundation.
"We initially thought that she had diabetic ketoacidosis, but after we corrected her anion gap and put her on insulin her acidosis persisted," Shawwa told 鶹ý in an interview. "And she was also found to have hypophosphatemia. Upon further investigation, she was also found to have proteinuria and also increased fractional excretion of phosphate in the urine, which is not expected if the patient is hyp0phosphatemic."
The patient did not have a history of diabetic ketoacidosis, chronic metabolic acidosis, non-anion gap metabolic acidosis, proteinuria, albuminuria, or hypophosphatemia. "The fact that these findings are new and occurred a week after canagliflozin was started suggests that they were likely due to canagliflozin," wrote Shawwa and colleagues in their poster.
When the patient was in the hospital, she required a very large amount of bicarbonate and phosphate to correct her losses, they added. And even though she had hypophosphatemia, she had a fractional excretion of phosphorous of 90%, a realization that -- along with other findings like new proteinuria and positive urine anion gap -- suggested dysfunction of the proximal tubule.
Canagliflozin, a sodium-glucose co-transporter 2 inhibitor, affects glucose reabsorption by the kidneys via the proximal tubule, leading the researchers to think that the condition and the drug were linked. After the patient was taken off canagliflozin -- which she was taking for weight loss -- she still had persistent glucosuria 1 week later, even though her blood glucose was normal, reported the authors.
But by 2 weeks she had returned to normal, they said. "This is the first reported case, we think," said Shawwa in the interview. "But we don't really don't know the mechanism -- only that canagliflozin functions at that particular portion of the kidney."
They added that the suggested managment in similar cases would be to stop the drug and to replace the electrolytes. "We suggest that the expected course for such an event to be self-limited and resolution within one week if the offending agent was promptly discontinued," they wrote. In addition, the patient should be monitored by checking total protein to creatinine ratio, urine glucose, and the patients' metabolic profile, with an emphasis on bicarbonates and phosphates.
, at the Albert Einstein College of Medicine in New York, said it was an interesting case report of off-label use. He was not associated with the study. In an email, he told 鶹ý that the exact prevalence of Fanconi syndrome isn't known, but it is not very common. It can refer to any general defect in the function of the proximal tubules and can be inherited or acquired later.
"In this case, it is possible that Fanconi was 'unmasked' by canagliflozin," he wrote.
He added that there are a number of other medications -- including tetracycline, aminoglycosides, cisplatin, ifosfamide, 6-mercaptopurine, valproic acid, tenofovir, adefovir dipivoxil (ADV), rifampin, and deferasirox -- that have been associated with Fanconi syndrome. And some diseases have been identified as the cause of Fanconi syndrome in adults, he added, like multiple myeloma, and amyloidosis.
"The practical recommendation is that clinicians need to obtain a good history and examination and discuss with patients the pros and cons of taking the drug, including possible side effects, and follow the patient carefully," he wrote.
Disclosures
The authors disclosed no relationships with industry.
Primary Source
National Kidney Foundation
Shawwa, K et al "A case of Fanconi syndrome in a patient taking canagliflozin for diabetes: A previously unreported catastrophic adverse effect" NKF 2016; Poster 140.