Which type of tenofovir (Tenofovir Disoproxil Fumarate (TDF) or Tenofovir Alafenamide (TAF)) is more related to renal injury?

Tenofovir Disoproxil Fumarate (TDF) is More Related to Renal Injury Than Tenofovir Alafenamide (TAF)

Tenofovir Disoproxil Fumarate (TDF) has significantly higher nephrotoxic potential compared to Tenofovir Alafenamide (TAF), with TDF causing more renal tubular dysfunction, decline in estimated glomerular filtration rate (eGFR), and risk of Fanconi syndrome. 1

Comparative Renal Effects

• TDF is generally safe but has important potential for cumulative nephrotoxicity, with approximately 1-2% of recipients developing treatment-limiting tubulopathy 1
• TAF demonstrates superior renal safety with significantly less impact on kidney function compared to TDF in multiple clinical trials 1
• In clinical studies comparing TAF to TDF, significant differences in eGFR decline were observed:
  • In HBeAg-positive patients: 0.6 ml/min vs. 5.4 ml/min decline (p<0.0001) 1
  • In HBeAg-negative patients: 1.8 ml/min vs. 4.8 ml/min decline (p=0.004) 1

Mechanisms of Renal Injury

• TDF causes higher plasma tenofovir concentrations, which is directly linked to its nephrotoxic potential 2, 3
• TAF has 90% lower plasma tenofovir concentrations while maintaining similar antiviral efficacy 3
• TDF-associated renal toxicity manifests as:
  • Subclinical proximal tubular dysfunction (low-level proteinuria and excessive phosphaturia) 1
  • Decreased eGFR or creatinine clearance 1
  • Fanconi syndrome in severe cases 1, 2
  • Potential progression to osteomalacia and pathological fractures 1

Risk Factors for TDF-Related Nephrotoxicity

• Aging and immunodeficiency 1
• Pre-existing diabetes 1, 2
• Prolonged exposure to TDF 1, 4
• Concomitant use with ritonavir-boosted protease inhibitors or cobicistat (increases tenofovir exposure) 1
• Hypertension 2, 4
• Lower baseline eGFR 2, 4

Clinical Evidence for Improved Renal Outcomes with TAF

• Switching from TDF to TAF has been associated with improved kidney function 1, 3, 5
• In HIV-positive patients who switched from TDF to TAF:
  • Mean eGFR improved from 81.2 ml/min/1.73m² to 90.9 ml/min/1.73m² (p<0.001) 3
  • 57.9% of patients recovered from renal dysfunction after switching to TAF 3
  • Tubulopathy rates decreased from 45.0% to 15.0% (p=0.002) 3
• In chronic hepatitis B patients with eGFR <60 ml/min, 76% experienced improved renal function after switching from TDF to TAF (p=0.009) 5

Monitoring Recommendations

• Assess renal function using creatinine-based eGFR before initiating TDF, at 1-3 months after starting, and then every 6-12 months if stable 2
• More frequent monitoring is required for patients with:
  • Established CKD (eGFR <50 ml/min/1.73m²) 2
  • Risk factors for kidney disease 1, 2
• Monitor for tubular dysfunction using serum phosphate levels in patients on TDF 1
• Consider switching from TDF to TAF in patients who develop:
  • Decline in eGFR to <60 ml/min/1.73m² 1
  • Rapid eGFR decline (>3-5 ml/min/1.73m² per year) 1
  • New onset or worsening proteinuria 2

Clinical Implications and Recommendations

• In settings where both options are available, TAF is preferred over TDF for patients with:
  • Existing renal impairment 1
  • Risk factors for kidney disease 1, 2
  • Osteopenia or osteoporosis 1
• Prompt discontinuation of TDF among patients developing mild renal impairment may prevent further progression of renal damage 4
• For patients who develop renal dysfunction on TDF, switching to TAF can lead to improvement in kidney function in the majority of cases 3, 5