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Tenofovir-Related Fanconi Syndrome In HIV Positive Patients: The Role Of Interaction With Other Antiretroviral Drugs
Abstract Content:
Introduction: Despite the absence of renal toxicity observed in major clinical trials of tenofovir (TDF), several case reports suggest nephrotoxicity. TDF with IPs interact with renal organic anion transporters, leading to nephrotoxic tubular concentrations of TDF and systemic accumulation of ddI. We reviewed cases of nephrotoxicity in patients on ddI-TDF regimen.
Methods: Renal toxicity was retrospective review on 97 elegible patients on ddI (250 mg/day) and TDF, between Sep 2002 and Dec 2004. Fanconi syndrome was diagnosed on the basis of metabolic acidosis, glycosuria, hypophosphatemia, and tubular proteinuria.
Results: Case 1: A 34-year-old HIV-infected women started ddI/TDF/LPV-rit. Weight 45 kg. CD4 37 cells/mm3. 11 months after TDF: abdominal pain, emesis and polyuria. Laboratory : metabolic acidosis (HCO3- , 11.5 mmol/L), hypophosphatemia (2,3 mg/dL) , proteinuria, glycosuria, serum creatinine: 4.96 mg/dL. All antiretroviral were discontinued. Favourable outcome. Case 2: A 32-year-old HIV-infected man started ddI/TDF/Trizivir/LPV-rit. Weight 59 kg. CD4 40 cells/mm3. 7 months after TDF appeared polyuria. Laboratory: metabolic acidosis (HCO3-, 19 mmol/L), ypophosphatemia (0.7 mg/dL), glycosuria and microalbuminuria, serum creatinine: 1.68 mg/dL. ddI and TDF were discontinued. Favourable outcome. Case 3: A 42-year-old HIV-infected woman started ddI/TDF/LPV-rit. Weight 53 kg. CD4 137 cells/mm3. 16 months after TDF: bone pain and weight loss. Laboratory: metabolic acidosis (HCO3-,18 mmol/L), hypophosphatemia (1.8 mg/dL), glycosuria and proteinuria , serum creatinine: 1.5 mg/dL. All antiretroviral were discontinued. Favourable outcome. Case 4: A 44-year-old HIV and HVC coinfected man started ddI/TDF/LPV-rit. Weight 67 kg. CD4 49 cells/mm3. 11 months after TDF, laboratory parameters revealed metabolic acidosis (HCO3-, 13 mmol/L), hypophosphatemia (1.5 mg/dL), glycosuria and microalbuminuria, serum creatinine: 2.45 mg/dL. All antiretroviral were discontinued. Favourable outcome.
Conclusions: Patients receiving TDF, ddI and PIs, must be monitored closely for early signs of tubulopathy. Clinicians should anticipate that TDF-ddI and LPV-rit may precipitate acute renal failure or Fanconi syndrome.
Methods: Renal toxicity was retrospective review on 97 elegible patients on ddI (250 mg/day) and TDF, between Sep 2002 and Dec 2004. Fanconi syndrome was diagnosed on the basis of metabolic acidosis, glycosuria, hypophosphatemia, and tubular proteinuria.
Results: Case 1: A 34-year-old HIV-infected women started ddI/TDF/LPV-rit. Weight 45 kg. CD4 37 cells/mm3. 11 months after TDF: abdominal pain, emesis and polyuria. Laboratory : metabolic acidosis (HCO3- , 11.5 mmol/L), hypophosphatemia (2,3 mg/dL) , proteinuria, glycosuria, serum creatinine: 4.96 mg/dL. All antiretroviral were discontinued. Favourable outcome. Case 2: A 32-year-old HIV-infected man started ddI/TDF/Trizivir/LPV-rit. Weight 59 kg. CD4 40 cells/mm3. 7 months after TDF appeared polyuria. Laboratory: metabolic acidosis (HCO3-, 19 mmol/L), ypophosphatemia (0.7 mg/dL), glycosuria and microalbuminuria, serum creatinine: 1.68 mg/dL. ddI and TDF were discontinued. Favourable outcome. Case 3: A 42-year-old HIV-infected woman started ddI/TDF/LPV-rit. Weight 53 kg. CD4 137 cells/mm3. 16 months after TDF: bone pain and weight loss. Laboratory: metabolic acidosis (HCO3-,18 mmol/L), hypophosphatemia (1.8 mg/dL), glycosuria and proteinuria , serum creatinine: 1.5 mg/dL. All antiretroviral were discontinued. Favourable outcome. Case 4: A 44-year-old HIV and HVC coinfected man started ddI/TDF/LPV-rit. Weight 67 kg. CD4 49 cells/mm3. 11 months after TDF, laboratory parameters revealed metabolic acidosis (HCO3-, 13 mmol/L), hypophosphatemia (1.5 mg/dL), glycosuria and microalbuminuria, serum creatinine: 2.45 mg/dL. All antiretroviral were discontinued. Favourable outcome.
Conclusions: Patients receiving TDF, ddI and PIs, must be monitored closely for early signs of tubulopathy. Clinicians should anticipate that TDF-ddI and LPV-rit may precipitate acute renal failure or Fanconi syndrome.