<p>Low-dose adefovir dipivoxil&ndash;induced hypophosphatemia osteomalacia in five chronic hepatitis B virus&ndash;infected patients. Is low-dose adefovir dipivoxil&ndash;induced nephrotoxicity completely reversible?</p>

Abstract

Adefovir dipivoxil (ADV) is one of the most important nucleostide analogues currently in use for the treatment of chronic hepatitis B virus (HBV) infection. Low-dose ADV-induced nephrotoxicity in most cases was reported to be reversible after the discontinuation of ADV or by decreasing the dose of ADV. In our study, we have 5 documented cases of low-dose ADV-induced hypophosphatemia osteomalacia with or without Fanconi syndrome which were diagnosed in our hospital between 2010 and 2017. Three patients were observed to have a full recovery after the discontinuation of ADV. Two patients had persistently elevated urine β 2 -microglobulin levels and out of these two patients, one patient had persistent hypophosphatemia after the cessation of ADV. These cases illustrated that the use of low-dose ADV increased the risk of nephrotoxicity, and in some patients, low-dose ADV-induced nephrotoxicity was not completely reversible. Patients of East Asian origin, especially those with a low body mass index, were prone to a relatively higher risk of developing low-dose ADV-induced nephrotoxicity; therefore, it was worth paying attention to the side effects caused by low-dose ADV.

Osteomalacia and renal failure due to Fanconi syndrome caused by long-term low-dose Adefovir Dipivoxil: a case report

“…Factors identified as predictive of kidney damage and Fanconi syndrome [17] include: age over 40 years, rural environment, renal injury, eGFR < 90 ml/min/1.73 m 2 , hypertension, diabetes, cirrhosis, and ADV treatment exceeding 24 months. Many cases of hypophosphatemic osteomalacia induced by low-dose adefovir (10 mg daily) have been reported [6,7], especially in Asian countries [18][19][20].…”

Fanconi syndrome induced by adefovir dipivoxil: a case report and clinical review

“…The main characteristics of 32 patients with ADV-induced FS, including eight patients in our institution and 24 published cases, are summarized in Table 4 . 5 , 18 , 22 , 23 , 36 – 43 …”

“… 52 However, some recent studies indicated that renal damage induced by ADV may be irreversible. 18 , 23 , 29 , 34 However, it may be not sufficient to evaluate renal function using only β2-M. 18 Thus, further comprehensive research using longer treatment periods and considering eGFR, β2-M, RBP, and other potential biomarkers is needed to clarify whether renal dysfunction induced by ADV is completely recoverable. Moreover, a study using a 6‐month follow‐up period found that patients with chronic kidney disease and tubule acidosis have a poor prognosis.…”

“… 13 – 16 However, more than 150 cases of hypophosphatemia osteomalacia (HO) or FS induced by low-dose ADV have been reported since 2002, when ADV was first introduced for long-term HBV treatment. 17 , 18 As the life expectancy of HBV-infected individuals has increased, the long-term adverse effects of antiviral therapies have increasingly emerged, 19 and nephrotoxicity is one of the most severe adverse effects of ADV. Investigators 20 conducted a retrospective study of 687 HBV-infected patients who received long-term ADV treatment.…”

“…Therefore, ADV-induced FS can easily be misdiagnosed, and it may seriously decrease the quality of life of patients and lead to bone fractures and even disability. 7 , 18 Therefore, more attention must be paid to FS induced by ADV.…”