Fanconi Syndrome and Antiretrovirals

Abstract

Antiretroviral medications such as tenofovir have been associated with Fanconi syndrome (FS) usually identified within the first 1-29 months after exposure to the medication. We present a case of life-threatening FS which developed in a 37-year-old woman with HIV after 8 years of asymptomatic tenofovir use. The patient was diagnosed with HIV in 1996 at 20 years of age, hepatitis C 10 years later, and Staphylococcus aureus sepsis with secondary osteomyelitis of the spine 3 years before admission for FS. She developed nausea, vomiting, diarrhea, and generalized weakness over a 2-week time period and presented to the hospital. In the emergency department, her serum potassium was 1.5 mEq/L, bicarbonate was 12 mEq/L, chloride was 111 mEq/L, phosphorus was 1.8 mg/dL, and creatinine was 1.95 mg/dL (baseline, 1.4). Arterial blood gas revealed a non-anion gap (hyperchloremic) metabolic acidosis. Type 2 renal tubular acidosis induced by antiretroviral therapy (ART) was suspected and the ART was discontinued with resolution of the renal abnormalities within 7 days. A non-tenofovir-containing ART regimen consisting of lamivudine/abacavir and efavirenz was begun, and over the next 8 months, the patient was without recurrence of the FS. This case report demonstrates the acute development of FS after prolonged exposure to tenofovir without exposure to additional nephrotoxins such as nonsteroidal medications or aminoglycosides. Tenofovir can cause FS at any time and should be considered in any patient presenting with renal tubular acidosis type 2 while on tenofovir regardless of the duration of drug exposure.

Renal Toxicity Presenting with a Fracture in an HIV Positive Adolescent

“…3 Renal toxicity resulting from tenofovir may occur at any time after its initiation-even up to 8 years after tenofovir was started. 4 In our patient, osteopenia, which was attributed to phosphate wasting from acquired Fanconi's syndrome became evident 2 years after starting tenofovir. It is important that patients on tenofovir are regularly screened for the development of side effects, given that acquired Fanconi's syndrome may occur at any time.…”

Acute kidney injury and other factors associated with mortality in hiv-infected patients

“…We believe that AKI was the primary cause of metabolic acidosis, but other factors may have contributed, such as drug toxicity by the nucleoside/nucleotide reverse transcriptase inhibitors (NRTI/NtRTIs) 22 . Several studies have demonstrated that drugs like stavudine, didanosine, zidovudine, lamivudine, abacavir, and tenofovir may cause acidosis through different mechanisms, such as mitochondrial dysfunction, Fanconi syndrome (proximal acidosis), and distal renal tubular acidosis 23,24 . In a previous study from our group with pediatric HIV patients, we observed that metabolic acidosis also happened as a consequence of HAART use 25 .…”

To err is…Drug? Patient? Doctor? Healthcare System?

“…The presentation of fanconi syndrome can be quite delayed also in a patient on tenofovir. 19 Therefore drug related adverse effect should be considered in any patient presenting with renal tubular acidosis type 2 while on tenofovir regardless of the duration of drug exposure.…”