Fanconi Syndrome Induced by Tenofovir Alafenamide in a Patient with Chronic Hepatitis B: A Case Report

Tenofovir-related nephrotoxicity is a well-known complication, particularly with tenofovir disoproxil fumarate (TDF). The newer formulation, tenofovir alafenamide (TAF), imposes a much lower burden on the kidneys through a mechanism that achieves high intracellular concentrations while maintaining low plasma tenofovir levels. Nonetheless, few reports have demonstrated that TAF can make kidney problem still.

A 60-year-old female has been on TAF for chronic hepatitis B for nearly 2 years. She reported progressive weakness, myalgia, and significant weight loss (8 kg) over 2 months. She has no prior history of kidney disease, diabetes, or hypertension. Initial vital signs recorded a blood pressure of 114/71 mmHg and a pulse rate of 89 beats/min. Laboratory results revealed elevated creatinine (1.76 mg/dL), a reduced eGFR (32.9mL/min/1.73m²), hemoglobin A1C (4.5%), low phosphate (1.8 mg/dL), potassium (2.7mmol/L), and decreased total CO2 (14mmol/L). Urinalysis showed glycosuria (3+), proteinuria (2+), and a urine protein to creatinine ratio of 1.6 g/g, with no red blood cells present. 

The kidney biopsy revealed with 70% tubular necrosis, characterized by pyknosis, hyperchromasia, and tubular cell damage. The interstitium demonstrated focal edema with moderate mononuclear cell infiltration. Globally sclerosed glomeruli constituted 10% and mild hypercellularity of mesangial cells. Epithelial foot processes showed moderate effacement. TAF-related ATN with Fanconi syndrome was inferred from laboratory and pathological results. Following cessation and supportive care, renal function and metabolic parameters improved over time (Table 1).

Table 1. Laboratory findings over time.

The mechanism of tenofovir-related renal issues is thought to involve mitochondrial toxicity in proximal tubular cells, resulting in tubular necrosis and disrupted reabsorption of key substances. The onset of TDF-associated nephrotoxicity varies across studies. They have been noted as soon as 3 to 7 weeks post-TDF initiation, whereas others arise after more than 8 years of use. In a cohort of 13 patients with confirmed ATN, the average onset time was 30.8 weeks. Although most patients recover upon discontinuation of the drug, some may sustain enduring kidney damage. Despite being rare, existing reports of TAF-related nephrotoxicity indicate that it, while reducing plasma tenofovir levels by 90% compared to TDF, does not entirely negate the risk of renal injury. Most reported cases involved the standard daily dosage of 25mg, with concomitant risk factors including CKD, prior TDF exposure, older age, diabetes and hypertension, HIV, and drugs influencing TAF metabolism (protease inhibitor). Additionally, the majority of nephrotoxicity cases manifest within months of TAF administration. In contrast, this case highlights TAF-induced nephrotoxicity that developed significantly later in a chronic hepatitis B patient without any notable risk factors aside from age. Although TAF is generally safer than TDF, nephrotoxicity remains a possibility. This toxicity can occur early or develop after an extended period. Consequently, regular monitoring of patients on tenofovir—including urinalysis, renal function assessments, and electrolyte balance evaluations—is essential for preventing kidney injury and maintaining renal health.