The clinical and pathological features of adefovir dipivoxil-related renal impairment

Clin Nephrol. 2019 Mar;91(3):180-186. doi: 10.5414/CN109574.

Abstract

Aims: To investigate the clinicopathological features and outcomes of adefovir dipivoxil (ADV)-related renal impairment in Chinese patients.

Materials and methods: Clinical, pathological, and follow-up data from 15 patients with ADV-related renal impairment were studied. Proximal renal tubular dysfunction (PRTD) was defined by the presence of at least two of the following four abnormalities: hypophosphatemia, hypouricemia, nondiabetic glucosuria, and proteinuria.

Results: All patients were treated for 3 - 15 (mean 6.7) years with daily ADV of 10 mg. Renal impairment manifested as PRTD (12, 80%), elevated serum creatinine (12, 80%), and hematuria (2, 13.3%). Mild to moderate tubulointerstitial injury primarily affecting the proximal tubules by light microscopy, and enlarged, dysmorphic mitochondria with loss and disorientation of cristae by electron microscope were identified in all of our cases. Four patients had pathological evidence of IgA nephropathy. The phosphorus, serum uric acid, and creatinine levels were normalized after ADV cessation in 66.7% (8/12) of affected patients, 27.3% (3/11) of affected patients, and 25% (3/12) of affected patients, respectively; proteinuria was eliminated in 7 of 13 affected patients (53.8%); and glucosuria and hematuria both disappeared in all affected patients. These abnormalities had hardly any recovery, and even aggravated with new-onset glucosuria, new-onset hematuria in 3 patients who replaced ADV with tenofovir.

Conclusion: Nephrotoxicity developed in patients undergoing long-term ADV treatment and was partially reversible after drug cessation. Tubulointerstitial lesions and heteromorphic mitochondria were the predominant pathological changes. Patients with ADV-induced renal impairment should replace ADV with other antiviral agents other than tenofovir. .

MeSH terms

  • Adenine / adverse effects
  • Adenine / analogs & derivatives*
  • Adult
  • Antiviral Agents / adverse effects*
  • Creatinine / blood
  • Female
  • Glycosuria / chemically induced
  • Hematuria / chemically induced
  • Hepatitis B, Chronic / drug therapy
  • Humans
  • Hypophosphatemia / chemically induced
  • Kidney Tubules, Proximal / pathology
  • Kidney Tubules, Proximal / physiopathology
  • Male
  • Middle Aged
  • Mitochondria / pathology
  • Organophosphonates / adverse effects*
  • Phosphorus / blood
  • Proteinuria / chemically induced
  • Renal Insufficiency / chemically induced*
  • Renal Insufficiency / pathology*
  • Renal Insufficiency / physiopathology
  • Uric Acid / blood

Substances

  • Antiviral Agents
  • Organophosphonates
  • Uric Acid
  • Phosphorus
  • Creatinine
  • Adenine
  • adefovir dipivoxil