Urinary β-2 Microglobulin Levels Sensitively Altered in an Osteomalacia Patient Receiving Add-on Adefovir Dipivoxil Therapy for Hepatitis B Virus Infection

Takagi, Junko; Morita, Hiroyuki; Ito, Kiyoaki; Ohashi, Tomohiko; Hirase, Sho; Itö, Tatsuo; Morishima, Takkan; Otake, Kazuo; Yoneda, Masashi

doi:10.2169/internalmedicine.55.6301

Cited by 7 publications

(4 citation statements)

References 18 publications

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“…After cessation of ADV and long-term follow-up, patient 1 and patient 4 were still found to have high urine β 2 -MG levels. Urine β 2 -MG is a sensitive marker of renal tubular injury 17,18. This indicated that proximal renal tubular function could not be completely restored in patient 1 and patient 4.…”

Section: Discussionmentioning

confidence: 98%

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

Qian

Dai

Ruan

et al. 2019

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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.

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Section: Discussionmentioning

confidence: 98%

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

Qian

Dai

Ruan

et al. 2019

DDDT

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“…The urinary β2-microglobulin level has been suggested to be a biomarker of kidney injury among chronic HBV patients treated with low-dose ADV (24). Takagi et al reported the sensitive change in the urinary β2-microglobulin level after dose reduction of ADV (25). Thus, a careful evaluation of the urinary β2-microglobulin level is mandatory for the early recognition of ADV-induced tubular damage.…”

Section: Discussionmentioning

confidence: 99%

Hypophosphatemic Osteomalacia Associated with Adefovir-induced Fanconi Syndrome Initially Diagnosed as Diabetic Kidney Disease and Vitamin D Deficiency

et al. 2019

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A 68-year-old man with type 2 diabetes mellitus and chronic hepatitis B infection was referred to the nephrology department before planned surgery for hepatocellular carcinoma. He had been receiving low-dose adefovir dipivoxil (ADV) for 11 years. Laboratory findings revealed impaired re-absorption in the proximal renal tubules. He had been diagnosed with diabetic kidney disease and osteomalacia due to vitamin D deficiency; thus, ADV was not discontinued until he was referred to us. In this case, concomitant diabetes mellitus and vitamin D deficiency might have prevented the early diagnosis of ADV-induced Fanconi syndrome.

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“…It has been reported that β2-microglobulin is detected clearly in patients with ADV-induced hypophosphatemic osteoporosis, and hence can be used as an indicator of renal function in these particular patients. 18 …”

Section: Discussionmentioning

confidence: 99%

Clinical features of hypophosphatemic osteomalacia induced by long-term low-dose adefovir dipivoxil

Sheng

Yang

Gao

et al. 2017

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ObjectiveTo investigate the predictors of hypophosphatemic osteomalacia induced by adefovir dipivoxil (ADV) and to monitor for early detection.Patients and methodsHospitalized patients who were diagnosed with ADV-related hypo-phosphatemic osteomalacia were recruited and retrospectively analyzed in our hospital from January 2012 to December 2016. A telephone interview was conducted at 1, 3, 6, 9, 12, and 24 months after cessation of ADV.ResultsIn the 8 patients enrolled in the study, the hypophosphatemic osteomalacia symptoms developed at an average of 5.14 (4–7) years since ADV treatment (10 mg/d). The average alkaline phosphatase (ALP) level was 279.50 (137–548) U/L, which was significantly higher than the normal level (45–125 U/L). The serum phosphorus level was an average of 0.59 (0.43–0.69) mmol/L, which was lower than the normal range (2.06–2.60 mmol/L). Serum calcium levels of the enrolled patients remained within normal limits. Reduced estimated glomerular filtration rate (eGFR <29 mL/min/1.73 m2) was seen in 4 cases. The clinical manifestations were mainly progressive systemic bone and joint pain, frequent fractures, trouble in walking, height reduction (4–6 cm), and so on. After cessation of ADV, symptoms like bone pain resolved gradually. Serum phosphorus level restored to normal in 4.5 months after the withdrawal of ADV. However, in 4 patients, renal function failed to return to normal in 24 months.ConclusionMore attention should be paid to the duration of ADV treatment. The level of serum phosphorus and ALP, as well as renal function, should be monitored for early detection of potential adverse drug reactions.

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Urinary β-2 Microglobulin Levels Sensitively Altered in an Osteomalacia Patient Receiving Add-on Adefovir Dipivoxil Therapy for Hepatitis B Virus Infection

Cited by 7 publications

References 18 publications

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

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

Hypophosphatemic Osteomalacia Associated with Adefovir-induced Fanconi Syndrome Initially Diagnosed as Diabetic Kidney Disease and Vitamin D Deficiency

Clinical features of hypophosphatemic osteomalacia induced by long-term low-dose adefovir dipivoxil

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Urinary β-2 Microglobulin Levels Sensitively Altered in an Osteomalacia Patient Receiving Add-on Adefovir Dipivoxil Therapy for Hepatitis B Virus Infection

Cited by 7 publications

References 18 publications

<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>

<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>

Hypophosphatemic Osteomalacia Associated with Adefovir-induced Fanconi Syndrome Initially Diagnosed as Diabetic Kidney Disease and Vitamin D Deficiency

Clinical features of hypophosphatemic osteomalacia induced by long-term low-dose adefovir dipivoxil

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

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