Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022672 (acute tubular necrosis)
 2,175 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tenofovir disoproxil fumarate (TDF) is effective against chronic hepatitis B (CHB) infection and its use is increasing rapidly worldwide. However, it has been established that TDF is associated with renal toxicity in human immunodeficiency virus-infected patients, while severe or symptomatic TDF-associated nephrotoxicity has rarely been reported in patients with CHB. Here we present two patients with TDF-associated nephrotoxicity who were being treated for CHB infection. The first patient was found to have clinical manifestations of proximal renal tubular dysfunction and histopathologic evidence of acute tubular necrosis at 5 months after starting TDF treatment. The second patient developed acute kidney injury at 17 days after commencing TDF, and he was found to have membranoproliferative glomerulonephritis with acute tubular injury. The renal function improved in both patients after discontinuing TDF. We discuss the risk factors for TDF-associated renal toxicity and present recommendations for monitoring renal function during TDF therapy.
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PMID:Tenofovir-associated nephrotoxicity in patients with chronic hepatitis B: two cases. 2737 11

Tenofovir disoproxil fumarate (TDF) is a commonly used antiretroviral drug for HIV, rarely causing Fanconi syndrome and acute kidney injury. We retrospectively analyzed the clinico pathological presentation of 20 cases of tenofovir-induced tubulopathy, and investigated the renal expression of the megalin and cubilin proteins, as well as the mitochondrial respiratory chain activity. Estimated glomerular filtration rate (eGFR) before TDF exposure was 92 ml/min/1.73m2, decreasing to 27.5 ml/min/1.73m2 at the time of biopsy, with 30% of patients requiring renal replacement therapy. Proximal tubular expression of megalin and cubilin was altered in 19 and 18 cases, respectively, whereas it was preserved in patients exposed to TDF without proximal tubular dysfunction and in HIV-negative patients with acute tubular necrosis. Loss of megalin/cubilin was correlated with low eGFR and high urine retinol binding protein at the time of biopsy, low eGFR at last follow-up, and was more severe in patients with multifactorial toxicity. Patients with additional nephrotoxic conditions promoting tenofovir accumulation showed a lower eGFR at presentation and at last follow-up, and more severe lesions of acute tubular necrosis, than those with isolated tenofovir toxicity. Altered mitochondrial COX activity in proximal tubules was observed and may be an early cellular alteration in tenofovir nephrotoxicity. In conclusion, altered megalin/cubilin expression represents a distinctive feature in tenofovir-induced tubulopathy, and its severity is correlated with urine retinol binding protein loss and is associated with a poor renal prognosis. Concomitant exposure to other nephrotoxic conditions severely impacts the renal presentation and outcome.
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PMID:Decreased expression of megalin and cubilin and altered mitochondrial activity in tenofovir nephrotoxicity. 2930 6