Can Tenofovir (antiretroviral medication) cause renal failure?

Can Tenofovir Cause Renal Failure?

Yes, tenofovir disoproxil fumarate (TDF) can cause renal failure, including acute renal failure and Fanconi syndrome, though this occurs in a minority of patients (1-2% develop treatment-limiting tubulopathy). 1, 2

Mechanism and Clinical Manifestations

Tenofovir causes nephrotoxicity primarily through proximal tubular dysfunction, which can manifest as: 1, 2

• Fanconi syndrome with normoglycemic glycosuria, hypophosphatemia, proteinuria, and metabolic acidosis from bicarbonate wasting 1
• Acute renal failure requiring discontinuation of therapy 3, 4
• Low-level proteinuria and phosphaturia progressing to eGFR decline in 1-2% of cases 2

The FDA label explicitly warns that "renal impairment, including cases of acute renal failure and Fanconi syndrome (renal tubular injury with severe hypophosphatemia), has been reported with the use of tenofovir disoproxil fumarate." 3

Timeline of Onset

Renal failure can occur at two distinct timepoints: 4

• Early onset (within 8 weeks): 27% of reported cases developed renal failure within 2 months of starting tenofovir, with some cases occurring as early as 3-5 weeks 4, 5
• Late onset (5-26 months): 73% of cases occurred months after therapy initiation 4

High-Risk Populations Requiring Enhanced Monitoring

You must identify patients at increased risk before prescribing tenofovir: 2, 6

• Pre-existing renal dysfunction (CrCl <50 mL/min): Patients with mild renal dysfunction have 4.8-fold increased risk of nephrotoxicity, while those with moderate dysfunction have 15-fold increased risk 6
• Concurrent nephrotoxic medications, especially ritonavir-boosted protease inhibitors, cobicistat, or didanosine, which increase tenofovir plasma levels 1, 2
• Advanced immunodeficiency 2
• Diabetes mellitus or hypertension 2
• Hepatitis B or C co-infection (2-3 fold increased CKD risk) 2

Mandatory Monitoring Protocol

The FDA and multiple guidelines require specific monitoring: 3, 1, 2

• Before initiation: Estimated creatinine clearance, serum phosphorus, urine glucose, and urine protein 3, 2
• During therapy:
  • Routine monitoring of creatinine clearance, serum phosphorus, urine glucose, and urine protein 3
  • Twice-yearly monitoring for patients on tenofovir plus ritonavir or cobicistat 1
  • Monitor for glycosuria, phosphaturia (with hypophosphatemia), and proteinuria as early signs of tubulopathy 1, 2

Immediate Management When Nephrotoxicity Occurs

Discontinue tenofovir immediately upon diagnosis of Fanconi syndrome or significant renal dysfunction. 2 The National Kidney Foundation and Kidney International guidelines are unequivocal on this point. 1, 2

Switch to safer alternatives: 2

• First-line alternatives: Tenofovir alafenamide (TAF) or abacavir 1, 2
• TAF has significantly lower renal toxicity than TDF and switching from TDF to TAF improves kidney function 2
• Do not continue TDF when TAF, abacavir, or darunavir are available for patients with CKD, rapid eGFR decline (>3-5 mL/min/1.73 m²/year), or high CKD risk 2

Dose Adjustment Requirements

For patients who must continue tenofovir with renal impairment, the FDA mandates dose adjustments: 3

• CrCl 30-49 mL/min: 300 mg every 48 hours 3
• CrCl 10-29 mL/min: 300 mg every 72-96 hours 3
• Hemodialysis patients: 300 mg every 7 days following dialysis 3
• No adjustment needed for CrCl 50-80 mL/min, but routine monitoring still required 3

Critical Pitfalls to Avoid

Avoid concurrent nephrotoxic agents, particularly: 2, 3

• High-dose or multiple NSAIDs (cases of acute renal failure requiring hospitalization and renal replacement therapy have been reported) 3
• Ritonavir-boosted protease inhibitors, cobicistat, and didanosine (significantly increase tenofovir exposure) 2, 7

Watch for subtle early signs: Persistent bone pain, pain in extremities, fractures, or muscular weakness may indicate proximal renal tubulopathy and warrant immediate renal function evaluation. 3