Tenofovir stems treatment-induced kidney toxicity in HBV-related chronic hepatitis

Jan 28 2015

By Lucy Piper, Senior medwireNews Reporter

Switching to tenofovir may stave further kidney and bone impairment in patients with hepatitis B virus-related chronic hepatitis taking adefovir-based therapy, retrospective study findings suggest.

But until prospective studies have been carried out to confirm their findings, the study researchers recommend clinicians monitor markers of kidney and bone toxicity in patients receiving tenofovir, especially following a switch from adefovir-based therapy, and pay particular attention to baseline values.

Lead researcher Paolo Maggi (Policlinico-University of Bari, Italy) and colleagues found a high prevalence of kidney and bone impairment in 60 patients who had taken lamivudine monotherapy followed by lamivudine plus adefovir for up to a mean of 114 months.

The average estimated glomerular filtration rate (eGFR) was 89.3 mL/min per 1.73 m² and 40% and 6.7% of patients had levels below 90 mL/min per 1.73 m² (representing chronic kidney disease [CKD] stage II) and 60 mL/min per 1.73 m² (CKD stage III), respectively. This compares with corresponding rates in the general population of 3.0% and 4.6%.

A total of 18.6% of patients had hypophosphataemia (<2.5 mg/dL), 26.9% had proteinuria (>200 mg/24 hours), 22.6% tested positive for microscopic haematuria and 29.6% had hyperparathyroidism (>65 pg/mL).

Also, suboptimal plasma levels of vitamin D (11–29 ng/mL) were present in 92.6% of the patients and more than half of the patients had reduced bone mineral density (BMD).

Switching to tenofovir monotherapy provoked a moderate decline in eGFR, which stabilised after 6 months showing no further progression at months 9 and 12. After 1-year of tenofovir treatment, the average eGFR was 82.6 mL/min per 1.73 m², reflecting a reduction of 7.5%. About half of the patients progressed from CKD stage I to II or from stage II to III, the team reports in the Journal of Antimicrobial Chemotherapy.

There was a worsening of serum phosphate and parathyroid hormone levels, haemoglobinuria and 24-hour proteinuria after 1 month of tenofovir treatment, but after 3 and 12 months levels of all these parameters had recovered to baseline levels.

“Although exposure to tenofovir has been associated with phosphate wasting and hypophosphataemia, we did not observe a worsening of the prevalence and magnitude of hypophosphataemia in the present study”, the researchers comment.

Vitamin D levels improved with tenofovir treatment and supplementation for those with hypovitaminosis D, with the percentage of patients with normal plasma levels increasing from about 7% to 30%.

The proportion of patients with reduced BMD increased to 77.8% after 6 months of tenofovir, but at 1 year the percentage had fallen to a level slightly above the baseline value. This transient effect of tenofovir on BMD was “perhaps in line with the relatively preserved phosphate and vitamin D homeostasis”, Maggi et al suggest.

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