Letters
Infectious diseases Urology
Volume 196 - Issue 2

An unrecognised case of tenofovir-associated Fanconi syndrome

Authors:  David M Gracey, Mangalee Fernando, John Ziegler, Christopher P White and Jeffrey J Post

Med J Aust 2012; 196 (2): 111-112. || doi: 10.5694/mja11.11122
Published online: 6 February 2012
Download PDF (355 KB)
Share: Share on Blue Sky Share on Facebook Share on LinkedIn Share by email

To the Editor: Tenofovir disoproxil fumarate is a nucleotide analogue reverse transcriptase inhibitor that is used in Australia as first-line antiviral treatment for HIV infection.1,2 Tenofovir may be nephrotoxic, particularly affecting proximal tubular function.3 We report a case of tenofovir-associated Fanconi syndrome, which demonstrates the need for vigilance in patients taking tenofovir.

A 17-year-old rurally residing boy with perinatally acquired HIV infection presented to a tertiary referral hospital with renal impairment. His serum creatinine level had been normal 4 years previously. He had had severe leg pain and weakness for over a year, and was unable to mobilise without a walking frame. Because of his illness, he had stopped studying. He had commenced antiretroviral therapy in 1996, when he was 3 years old, and at presentation was taking tenofovir plus emtricitabine and lopinavir plus ritonavir. Follow-up with his local clinician was intermittent.

The patient’s HIV viral load was undetectable, and he had a CD4 count of 0.62 × 109 cells/L. His serum creatinine level was 150 μmol/L (reference interval, 60–110 μmol/L) and his estimated glomerular filtration rate (eGFR) was 52 mL/min/1.73 m2 (normal value, > 90 mL/min/1.73 m2). He had all the features of Fanconi syndrome — hypophosphataemia with renal phosphate wasting, glycosuria, aminoaciduria, a reduced serum uric acid level and proteinuria (1.93 g/day). He also had hypokalaemia and acidosis, and his urine tested positive for β2-microglobulin. Histological analysis of a renal biopsy specimen showed proximal tubular abnormalities (Box). In addition, he had severely reduced bone mineral density, elevated bone turnover markers and vitamin D deficiency.

The patient’s tenofovir therapy was ceased, he was started on an alternative antiretroviral regimen, and he was given phosphate, potassium, bicarbonate and calcium supplementation plus vitamin D and calcitriol therapy. Two months later, his serum creatinine level was 130 μmol/L, his eGFR was > 60 mL/min/1.73 m2, and his proteinuria, glycosuria and aminoaciduria had resolved. His leg pain and weakness resolved within another month. He has since been able to recommence full-time study.

The persistent biochemical and renal abnormalities in this patient may have been a result of delayed recognition of Fanconi syndrome leading to prolonged illness. Risk factors for tenofovir-associated nephrotoxicity include a GFR of less than 90 mL/min/1.73 m2, use of nephrotoxic medications, comorbidities (eg, diabetes and hypertension) and use of some protease inhibitors. Patients on tenofovir should be screened at least 6-monthly for eGFR, serum phosphate levels, proteinuria and glycosuria.4 Three-monthly testing is also suggested in the initial year, due to the occurrence of tenofovir-associated nephrotoxicity without risk factors.5 Urinary protein to creatinine ratio is usually increased in tenofovir-associated nephrotoxicity, and tests for some urinary proteins may be useful in subtle cases of the condition.3 Testing for albuminuria (a marker of glomerular disease) and sole reliance on eGFR are insufficient for detecting tenofovir-associated tubular dysfunction.3

Due to potential renal toxicity, optimal outcomes for patients on tenofovir require careful monitoring of patients and close liaison between treating practitioners.

Renal biopsy specimens showing proximal tubular abnormalities in a patient with tenofovir-associated Fanconi syndrome

A: Prominent changes of acute tubular necrosis (haematoxylin and eosin stain; original magnification, × 4). B: Acute tubular necrosis with proximal tubular eosinophillic inclusions (arrows) representing giant mitochondria visible by light microscopy (haematoxylin and eosin stain; original magnification, × 10).

Authors

  • David M Gracey1
  • Mangalee Fernando2
  • John Ziegler3
  • Christopher P White2
  • Jeffrey J Post2
  • 1. Royal Prince Alfred Hospital, Sydney, NSW.
  • 2. Prince of Wales Hospital, Sydney, NSW.
  • 3. Sydney Children’s Hospital, Sydney, NSW.

Correspondence: david.gracey@sswahs.nsw.gov.au

Competing interests

No relevant disclosures.

References

View this article on Wiley Online Library

More like this

View more