tenofovir induced renal dysfunction

Background/Objectives: Currently, there are insufficient data to recommend the treatment of patients with hepatitis B e antigen (HBeAg)-negative chronic infection who have normal ALT and low HBV DNA, since the prognosis is generally regarded as favorable. The aim of this pilot study was to determine whether the use of tenofovir disoproxil fumarate (TDF) 300 mg/day for 3 years was able to achieve functional cure (HBsAg loss) and HBsAg seroconversion in HBeAb-positive individuals. Methods: Fifty patients not on antiviral therapy (40% men, mean age 48...

Tenofovir, as nucleotide reverse transcriptase inhibitors (NRTIs), is used to prevent and cure HIV/AIDS. Ample evidence confirmed that the nephrotoxicity of tenofovir has been linked to mitochondrial dysfunction. It seems that transplantation with healthy mitochondria instead of damaged mitochondria may be a beneficial approach to therapy. Therefore, it decided to investigate the impact of mitotherapy on tenofovir against renal proximal tubular cells (RPTCs) toxicity by measurement of oxidative stress and cytotoxicity biomarkers and restoring of mitochondrial function on isolated mitochondria...

During the drug development process, organ toxicity leads to an estimated failure of one-third of novel chemical entities. Drug-induced toxicity is increasingly associated with mitochondrial dysfunction, but identifying the underlying molecular mechanisms remains a challenge. Computational modeling techniques have proven to be a good tool in searching for drug off-targets. Here, we aimed to identify mitochondrial off-targets of the nephrotoxic drugs tenofovir and gentamicin using different in silico approaches (KRIPO, ProBis and PDID)...

Lactic acidosis is a rare but serious side effect in individuals receiving nucleoside reverse transcriptase inhibitors. An underweight woman with HIV was admitted to our hospital because of nausea and diffuse myalgia. Her antiretroviral regimen had been changed to tenofovir disoproxil fumarate (TDF)/emtricitabine and darunavir/cobicistat 3 months prior, after which her renal function had gradually declined. After admission, she was diagnosed with lactic acidosis, and a liver biopsy suggested mitochondrial damage...

Tenofovir disoproxil fumarate (TDF) is an antiretroviral drug widely used as part of antiretroviral therapy (ART) to treat human immunodeficiency virus (HIV-1) infection. Negative effects of tenofovir include impaired kidney function, especially with long-term use. In studies conducted among HIV-positive individuals, we found evidence of extensive kidney damage associated with TDF use. Despite the therapeutic importance of this consequence, its continued use in ART regimens was not contraindicated. The therapeutic and long-term effects of TDF are a major concern...

Fanconi syndrome is a rare disease of generalized proximal tubule dysfunction which can be acquired secondary to certain medications, including tenofovir, a commonly used hepatitis B treatment. Signs and symptoms of ensuing renal wasting can be severe but vague, leading to potentially avoidable invasive investigations and delays in diagnosis. We present a case of a 62-year-old female with chronic hepatitis B on tenofovir treatment who was found to have subacute weakness, anorexia, and weight loss. She underwent extensive investigations including computed tomography (CT) imaging, bronchoscopy, upper and lower endoscopy, and psychiatric evaluation...

BACKGROUND: The incidence of tenofovir disoproxil fumarate (TDF)-induced nephrotoxicity ranges from 15.8 to 19.3 percent. Following cessation of TDF, approximately one-half of patients with nephrotoxicity regained full renal functions. This study aimed to determine the incidence and risk factors for nephrotoxicity, as well as the complete recovery of renal function, in human immunodeficiency virus (HIV)-infected patients receiving TDF regimens. MATERIALS AND METHODS: This was a retrospective case-control study of HIV-positive patients who received TDF regimens from 2 tertiary hospitals between 2012 and 2018...

SUMMARY: Tenofovir-induced osteomalacia secondary to proximal renal tubular dysfunction is not an uncommon complication known to occur. A 46-year-old woman was referred for the evaluation of osteoporosis which was diagnosed elsewhere. She had polyarthralgia, bony pains and proximal muscle weakness of 1 year duration. She was diagnosed to have HIV infection and was on antiretroviral therapy that consisted of tenofovir, lamivudine and efavirenz for the past 12 years. She had attained menopause 5 years back...

INTRODUCTION: Tenofovir Disoproxil Fumarate (TDF) is the most widely used Anti-Retroviral Therapy (ART) drug due to its potency, safety profile and World Health Organization (WHO) recommendation. TDF causes proximal tubular renal dysfunction (PTRD) leading to Fanconi syndrome, acute kidney injury and chronic kidney disease. Modest rates (2-4%) of TDF related toxicity based on estimated Glomerular Filtration Rate (GFR) have been described, while TDF-induced PTRD has been reported to be 22%...

Background: Tenofovir disoproxil fumarate (TDF), a widely prescribed component in antiretroviral regimens, has been associated with nephrotoxicity. Nebivolol is a third generation selective β-1 adrenergic receptor blocker and may protect renal structure and function through the suppression of oxidative stress and enhancement of nitric oxide (NO) synthesis. We aimed to investigate whether nebivolol could be an effective therapeutic strategy to mitigate tenofovir-induced nephrotoxicity...

Tenofovir disproxil fumarate (TDF) is a highly effective HIV antiviral drug approved for treating Human Immunodeficiency Virus and Hepatitis B. It is one of the first line drugs used to treat HIV and is efficacious in both novel and treatment-experienced patients. The prodrug is administered orally and deesterified to the active drug TFV. TFV is associated with nephrotoxicity. However, the precise mechanisms for cytotoxicity remain unknown. Our hypothesis is that TFV causes mitochondrial dysfunction including diminished ATP formation and oxidative stress...

A 46-year-old female with a history of generalized anxiety disorder was admitted after intentional ingestion of an unknown amount of emtricitabine/tenofovir alafenamide (Descovy®) in a suicidal attempt. Patient was emergently intubated secondary to severe agitation and inability to protect airways. Patient developed severe lactic acidosis early in the admission, secondary as to a possible mitochondrial toxicity. Failed attempts to fluid resuscitation with Lactate Ringer®, eventually warranted to start the patient on norepinephrine infusion...

BACKGROUND AND AIM: Urinary β2-microglobulin (β2-M) is a marker for renal tubular dysfunction. The current study aimed to assess urinary β2-M as a reliable marker for early prediction of tenofovir disoproxil fumarate (TDF)-related nephrotoxicity among hepatitis B virus (HBV) patients. METHODS: Forty-two HBV patients who were a candidate for TDF therapy or have recently started it (for less than 6 months) were enrolled and subjected to demographic, clinical, laboratory assessment, abdominal ultrasound and transient elastography...

A population pharmacokinetic (PopPK) model of delamanid in patients with pulmonary multidrug-resistant tuberculosis (MDR-TB) was developed using data from four delamanid clinical trials. The final PopPK dataset contained 20,483 plasma samples from 744 patients with MDR-TB receiving an optimized background regimen (OBR). Delamanid PK was adequately described for all observed dosing regimens and subpopulations by a two-compartment model with first-order elimination and absorption, an absorption lag time, and decreased relative bioavailability with increasing dose...

Tenofovir disoproxil fumarate (TDF) is the most preferred antiretroviral medicine in treating human immunodeficiency virus (HIV) and hepatitis B virus (HBV) infections. Recent clinical trials have reported conflicting results on renal toxicity and safety in TDF-treated patients, but reference animal studies, testing high-doses of TDF for renal toxicity, are scarce. In this preclinical study, we investigated whether daily oral TDF administration (200, 500, or 800 mg/kg/d, p . o .) for four weeks induces renal insufficiency in C57BL/6 mice, by evaluating changes in body weight, urine micro-total protein, urinary microalbumin, serum blood urea nitrogen (BUN), and creatinine levels, along with histological examination of kidney samples...

BACKGROUND: Individuals of African descent are at higher risk of developing kidney disease than their European counterparts, and HIV infection is associated with increased risk of nephropathy. Despite a safe renal profile in the clinical trials, long-term use of tenofovir disoproxil fumarate (TDF) has been associated with proximal renal tubulopathy although the underlying mechanisms remain undetermined. We aim to establish the prevalence of and risk factors for TDF-induced kidney tubular dysfunction (KTD) among HIV-I and II individuals treated with TDF in south-west Nigeria...

Long-term use of tenofovir disoproxil fumarate (TDF) can induce renal dysfunction that requires TDF dose reduction. Previous studies showed that systemic drug use exerts a threefold higher risk of moderate renal impairment. This study aimed to compare viral control between two tenofovir dose reduction regimens in chronic hepatitis B (CHB) patients with moderate renal impairment from TDF-induced renal dysfunction. This noninferiority, randomized controlled study was conducted at the Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand...

Tenofovir disoproxil fumarate (TDF) is the foundation nucleotide reverse-transcriptase inhibitor in the recommended first-line regimen for all naive human immunodeficciency virus-1 (HIV-1) patients whose age is more than 10 years and body weight is more than 30 kg. Although it has a good safety profile overall, nephrotoxicity is a concern and its overall incidence is 1-6% with a long period of clinical latency. Nephrotoxicity may manifest as either proximal renal tubule dysfunction in the form of a partial or complete Fanconi syndrome or as decreased renal function leading to acute or chronic kidney injury...

Purpose: Tenofovir disoproxil fumarate is accepted as an effective and tolerable drug for treatment of HBV, similar to entecavir. However, there are some concerns about the nephrotoxicity of tenofovir. The aim of this study is to compare the renal-function change of liver recipients who received tenofovir or entecavir for HBV. Methods: Among 468 patients with HBV who underwent liver transplantation at Samsung Medical Center between January 2008 and December 2015, the patients treated with tenofovir (n = 39) or entecavir (n = 429) were reviewed retrospectively...

BACKGROUND: Tenofovir disoproxil fumarate (TDF)-induced nephrotoxicity is related to high plasma tenofovir concentrations. Tenofovir alafenamide (TAF) is a tenofovir prodrug with 90% lower plasma tenofovir concentrations. The aim of this study was to evaluate changes in tenofovir-induced nephrotoxicity in Human Immunodeficiency Virus (HIV)-positive patients who switched from TDF to TAF. MATERIALS AND METHODS: We identified all HIV-positive patients who switched from elvitegravir/cobicistat/emtricitabine/TDF to elvitegravir/cobicistat/emtricitabine/TAF at a tertiary hospital...