Management of TDF-induced Fanconi Syndrome
The management of Tenofovir Disoproxil Fumarate (TDF)-induced Fanconi syndrome requires immediate discontinuation of TDF and switching to an alternative medication with less nephrotoxic potential. 1
Immediate Management
- Discontinue TDF immediately upon diagnosis of Fanconi syndrome, as continued exposure can lead to worsening renal function and irreversible damage 1
- Monitor electrolytes closely, particularly phosphate, potassium, and bicarbonate levels, as Fanconi syndrome causes significant electrolyte wasting 1
- Provide electrolyte supplementation as needed, especially phosphate and calcitriol if hypophosphatemia and secondary osteomalacia are present 2
- Assess for complications of Fanconi syndrome including osteomalacia, bone fractures, and metabolic acidosis 2, 3
Alternative Treatment Options
For HIV Patients:
- Switch to Tenofovir Alafenamide (TAF) if creatinine clearance is above 30 mL/min, as it has less renal toxicity while maintaining antiviral efficacy 1
- Switch to Abacavir in patients with significant renal impairment, as it does not require dose adjustment in renal disease 1
- Consider Dolutegravir or Raltegravir plus TAF/emtricitabine as these regimens have fewer renal adverse effects 1
For Hepatitis B Patients:
- Switch to Entecavir as it has minimal renal toxicity and is effective for HBV treatment 1
- Switch to TAF if available, as it provides similar efficacy with reduced renal and bone toxicity 1, 3
- Consider Besifovir (where available) as an alternative based on previous treatment history 1
Monitoring After Treatment Change
- Monitor renal function with eGFR, urinalysis, and testing for glycosuria, albuminuria or proteinuria every 6 months 1
- Assess for resolution of tubular dysfunction by checking for normalization of phosphate, glucose, and amino acid wasting 1, 4
- Evaluate bone health if osteomalacia was present, as recovery may take several months 2, 3
- Continue monitoring viral load to ensure efficacy of the alternative treatment 1, 5
Special Considerations
- TAF should not be initiated in patients with creatinine clearance below 30 mL/min 1
- For patients with active TDF-associated proximal tubulopathy, TAF should ideally be initiated only after tubulopathy has resolved, with monitoring for recurrence 1
- Patients with multidrug resistance may require combination therapy (e.g., entecavir plus TAF) to maintain viral suppression 1
- Risk factors for TDF-induced nephrotoxicity include concurrent use of ritonavir-boosted protease inhibitors, preexisting renal disease, and previous exposure to adefovir 1, 5, 4
Prognosis
- Most cases of TDF-induced Fanconi syndrome show improvement or resolution of renal function after TDF discontinuation, though complete normalization may not always occur 2, 3, 5
- The timeline for recovery varies, with most patients showing significant improvement within 3-6 months after TDF withdrawal 6, 4
- Early detection and management are critical to prevent permanent renal damage and complications such as osteomalacia and fractures 3, 6