A 55-year-old man was admitted to the department of nephrology for the diagnosis of persistent proteinuria. He has been treated with tenofovir disoproxil fumarate (TDF) due to hepatitis B since 2019 (245 mg/day).

The patient reported weakness, gradual weight loss, chronic nausea, vomiting, lack of appetite, and bone pain increasing with movement. Physical examination revealed cachexia, chest deformation, and swelling of the lower limbs.

In October 2021, cancer had been suspected. Bone scintigraphy showed numerous lesions in the skeleton that could correspond to multiple myeloma (Figure 1). However, after hematologic workup, multiple myeloma was excluded. Prostate cancer was also ruled out, and no potential starting point for neoplastic disease was found.

Figure 1. Whole-body bone scintigraphy showing multiple foci of increased radiotracer uptake in the sternum, shoulder blades, ribs, spine (at all levels), pelvic bones, left humerus, right tibia, and mandible

Laboratory workup performed at the local nephrology department in May 2022 showed persistence of the abnormalities present in the medical records provided by the patient: increased serum creatinine (2 mg/dl; reference range [RR], 0.7–1.2 mg/dl) with estimated glomerular filtration rate of 37 ml/min/1.73 m2, hypophosphatemia (1.4 mg/dl; RR, 2.6–4.5 mg/dl), hypouricemia (2.9 mg/dl; RR, 3.4–7 mg/dl), hypokalemia (2.7 mmol/l; RR, 3.6–4.8 mmol/l), and elevated alkaline phosphatase levels (191 U/l; RR, 40–129 U/l), with normal serum calcium (8.9 mg/dl; RR, 8.6–10.2 mg/dl), parathyroid hormone (26.9 pg/ml; RR, 15–65 pg/ml) and 25-hydroxyvitamin D concentrations (33.1 ng/ml; RR, 20–80 ng/ml). Results of the venous blood gas analysis showed characteristics of hyperchloremic (Cl, 119 mmol/l; RR, 95–105 mmol/l) metabolic acidosis, with pH of 7.22 and HCO3 of 17.1 mmol/l.

Urinalysis showed slight proteinuria (30 mg/dl) and normoglycemic glucosuria (500 mg/dl). Proteinuria in a 24-hour urine collection was 0.5 g (RR <⁠125 mg); urinary excretion of β-2-microglobulin was significantly increased (50.3 µg/ml; RR <⁠0.2 µg/ml). Markedly decreased tubular reabsorption of phosphate (34%; RR >85%) confirmed the presence of a complex proximal tubule defect.

Positron emission tomography / computed tomography did not reveal foci of increased uptake that would indicate a metabolically active proliferative process.

Fanconi syndrome complicated by osteomalacia was diagnosed. The secondary nature of the changes was considered to be associated with chronic treatment with TDF.

After consultation with infectious disease specialists, it was decided to discontinue TDF and include entecavir (1 mg every other day). Nine months after the treatment modification, the previously reported symptoms resolved; moreover, weight gain was observed. Follow-up test results showed a significant improvement in renal parameters (creatinine, 1.2 mg/dl) and normalization of phosphatemia (2.7 mg/dl), which allowed for discontinuation of phosphate supplementation.

TDF is the first-choice treatment for a wide group of patients with chronic hepatitis B.1 In HIV-infected patients, the use of TDF was associated with the occurrence of kidney diseases, in particular dysfunction of the proximal renal tubules, as in Fanconi syndrome.2 TDF nephrotoxicity in hepatitis B is estimated at 5.1%.3 Acquired Fanconi syndrome accompanied by osteomalacia is a rare complication of long-term TDF treatment in hepatitis B, although close monitoring of renal parameters and phosphate levels during such therapy is currently recommended.1,4

In the case of renal complications, changing the treatment to tenofovir alafenamide or entecavir should be considered,1 which was performed in the presented patient.