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tenofovir induced renal dysfunction

Christopher Loens, Sabine Amet, Corinne Isnard-Bagnis, Gilbert Deray, Jérôme Tourret
The remarkable improvement of the outcome of HIV infection came with the price of substantial toxicity of some antiretrovirals. The first molecules used to treat HIV included an important nephrotoxicity. Zalcitabine, stavudine and didanosine can induce severe lactic acidosis. Lactate production is enhanced and the renal capacity to regulate pH is overwhelmed. However, this side effect is not due to a direct dysfunction of the kidneys. Zalcitabine was withdrawn from the market because of this risk. Indinavir, a protease inhibitor, is soluble only in very acidic solutions...
February 2018: Néphrologie & Thérapeutique
Jeong Eun Lee, Shinwon Lee, Sang Heon Song, Ihm Soo Kwak, Sun Hee Lee
Background/Aims: Little is known about tenofovir disoproxil fumarate (TDF)-induced nephrotoxicity in human immunodeficiency virus (HIV)-infected patients in Korea. The objective of this study was to evaluate the incidence and risk factors of TDF-associated nephrotoxicity among HIV-infected patients in Korea. Methods: A single-center retrospective cohort study was conducted on HIVinfected patients in Korea. We included patients who had started TDF or abacavir (ABC)-based antiretroviral therapy (ART) between October 2006 and December 2014...
October 12, 2017: Korean Journal of Internal Medicine
Glenda Grossi, Alessandro Loglio, Floriana Facchetti, Marta Borghi, Roberta Soffredini, Enrico Galmozzi, Giovanna Lunghi, Anuj Gaggar, Pietro Lampertico
Tenofovir disoproxil fumarate (TDF) is a recommended first-line therapy for both naïve and experienced patients with chronic hepatitis B (CHB), although reduced estimated glomerular filtration rate (eGFR), hypophosphatemia, hyperphosphaturia and Fanconi syndrome have been reported in some patients. Entecavir (ETV) could be considered as a rescue therapy for TDF-treated patients developing renal dysfunction, though patients with prior history of treatment with lamivudine (LAM) can develop ETV resistance strains, which can lead to potentially severe hepatitis flares...
September 21, 2017: Journal of Hepatology
Jan Hajek, Simple Ouma, Juliya Hemmett, Rob Starko, Paska Apiyo
Millions of people worldwide take tenofovir disoproxil fumarate (TDF) for the treatment of human immunodeficiency virus (HIV) and/or hepatitis B infection. Although generally safe and well tolerated, clinicians need to be aware that TDF can cause proximal renal tubular dysfunction and loss of bone mineral density, especially in patients with concomitant renal disease or other risk factors. We present the case of a patient with chronic HIV infection and urethral stricture who developed TDF-related proximal renal tubular dysfunction with hypophosphatemia and osteomalacia, presenting with bone pains, skeletal deformity, and disability...
September 2017: Journal of the International Association of Providers of AIDS Care
Xinbin Zhao, Kun Sun, Zhou Lan, Wenxin Song, Lili Cheng, Wenna Chi, Jing Chen, Yi Huo, Lina Xu, Xiaohui Liu, Haiteng Deng, Julie A Siegenthaler, Ligong Chen
Despite the therapeutic success of tenofovir (TFV) for treatment of HIV-1 infection, numerous cases of nephrotoxicity have been reported. Mitochondrial toxicity has been purported as the major target of TFV-associated renal tubulopathy but the underlying molecular mechanism remains unclear. In this report, we use metabolomics and proteomics with HK-2 cells and animal models to dissect the molecular pathways underlying nephropathy caused by TFV and its more toxic analog, adefovir (ADV). Proteomic analysis shows that mitochondrial chaperone TRAP1 and mtDNA replicating protein SSBP1 were significantly down-regulated in TFV and ADV treated HK-2 cells compared with controls...
April 11, 2017: Scientific Reports
Rachel A Murphy, Reagan M Stafford, Brooke A Petrasovits, Megann A Boone, Monica A Valentovic
Tenofovir (TFV) is an antiviral drug approved for treating Human Immunodeficiency Virus (HIV) and Hepatitis B. TFV is administered orally as the prodrug tenofovir disoproxil fumarate (TDF) which then is deesterified to the active drug TFV. TFV induces nephrotoxicity characterized by renal failure and Fanconi Syndrome. The mechanism of this toxicity remains unknown due to limited experimental models. This study investigated the cellular mechanism of cytotoxicity using a human renal proximal tubular epithelial cell line (HK-2)...
March 1, 2017: International Journal of Molecular Sciences
H M Koh, K Suresh
BACKGROUND: Tenofovir (TDF) has been associated with renal function deterioration, but local data regarding the incidence and risk factors for this adverse event were lacking. OBJECTIVES: To determine the incidence of nephrotoxicity in HIV-infected patients on tenofovir-based regimens and to evaluate risk factors involved in tenofovir-associated renal function decline. METHODS: This is a single-centre retrospective cohort study of 440 HIV-infected adults who were started on tenofovirbased antiretroviral regimens...
December 2016: Medical Journal of Malaysia
Laura Milazzo, Cristina Gervasoni, Felicia Stefania Falvella, Dario Cattaneo, Cristina Mazzali, Paola Ronzi, Francesca Binda, Stefania Cheli, Salvatore Sollima, Spinello Antinori
The human immunodeficiency virus (HIV)/hepatitis B virus (HBV) co-infection is likely to be associated with an increased risk of kidney disease, due to the additional factors that may affect renal function in the HIV population. We aimed to evaluate renal toxicity in HIV/HBV and HBV mono-infected patients on long-term therapy with tenofovir (TDF) and to explore the association of polymorphisms in ATP-binding cassette (ABCC)2, ABCC4, ABCC10 with the development of renal dysfunction. From September 2006 to November 2014, 44 HIV/HBV co-infected and 34 HBV mono-infected patients were commenced on TDF...
February 2017: Clinical and Experimental Pharmacology & Physiology
Yusuke Kunimoto, Hiroshi Ikeda, Satoshi Fujii, Manabu Kitagawa, Kieko Yamazaki, Hiromasa Nakata, Norimasa Noda, Tadao Ishida, Atsushi Miyamoto
BACKGROUND: Plasma tenofovir (TFV) trough concentrations may be relevant for tenofovir disoproxil fumarate (TDF)-induced renal dysfunction. The purpose of this study was to determine the association between plasma TFV trough concentrations and TDF-induced renal dysfunction in Japanese patients with human immunodeficiency virus (HIV) infection. METHODS: A 48-week, retrospective cohort study was performed with Japanese patients with HIV infection who started a TDF-containing combination antiretroviral therapy regimen...
2016: Journal of Pharmaceutical Health Care and Sciences
Takeshi Nishijima, Takuma Kurosawa, Noriko Tanaka, Yohei Kawasaki, Yoshimi Kikuchi, Shinichi Oka, Hiroyuki Gatanaga
OBJECTIVE: In nephrotoxicity induced by tenofovir disoproxil fumarate (TDF), tubular dysfunction precedes the decline in GFR, suggesting that tubular markers are more sensitive than estimated glomerular filtration rate (eGFR). The hypothesis that urinary β2 microglobulin (β2 M), a tubular function marker, can predict TDF-renal dysfunction in HIV-1-infected patients was tested. DESIGN: A single-center observational study. METHODS: The inclusion criteria were: HIV-1-infected patients who started TDF-containing antiretroviral therapy from 2004 to 2013, urinary β2 M after and closest to the day of TDF initiation within 180 days (termed 'β2 M after TDF') was measured...
June 19, 2016: AIDS
Fabio Conti, Giovanni Vitale, Carmela Cursaro, Mauro Bernardi, Pietro Andreone
 Tenofovir disoproxil fumarate (TDF) is a nucleotide reverse transcriptase inhibitor indicated for treatment of patients with chronic hepatitis B virus (CHB) and human immunodeficiency virus (HIV) infections. Despite the good safety profile of the drug, Fanconi syndrome is a possible adverse reaction of TDF treatment, especially in HIV-infected patients. Only a few cases have been reported in patients with CHB-monoinfections. This report presents a case of a 58-year-old man with mild HBeAg-negative CHB who was exposed to TDF and developed drug-induced Fanconi syndrome...
March 2016: Annals of Hepatology
Sirirat Likanonsakul, Bussakorn Suntisuklappon, Ravee Nitiyanontakij, Wisit Prasithsirikul, Emi E Nakayama, Tatsuo Shioda, Chariya Sangsajja
BACKGROUND: In Thailand, the combined generic anti-retroviral drug stavudine/lamivudine/nevirapine (d4T/3TC/NVP) has been used to treat human immunodeficiency virus (HIV)-infected individuals since 2001. Due to relatively frequent adverse effects, d4T gradually has been replaced with tenofovir disoproxil fumarate (TDF). Although the frequency of adverse drug effects with TDF is lower than that with d4T, TDF is known to induce kidney dysfunction, especially in the proximal tubules. It has been reported that renal tubular transporters, including members of the multi-drug resistant (MDR) protein family, are implicated in tenofovir extrusion and may, therefore, confer susceptibility to TDF-induced kidney tubular dysfunction (KTD)...
2016: PloS One
Sana Waheed, Doaa Attia, Michelle M Estrella, Yousuf Zafar, Mohamed G Atta, Gregory M Lucas, Derek M Fine
BACKGROUND: Tenofovir disoproxil fumarate (TDF) may cause acute kidney injury and proximal tubular dysfunction. However, no detailed studies document urinary phosphate wasting as a marker of TDF-induced tubulopathy. METHODS: Records of HIV-infected patients with presumed TDF toxicity were reviewed. We describe the characteristics and clinical course of 15 patients who had documented elevated (>20%) fractional excretion of phosphate (FEphos). RESULTS: Patients were predominantly Caucasian and male (73 and 80%, respectively), with a mean age of 56 years (range 38-76)...
August 2015: Clinical Kidney Journal
Shubhanker Mitra, Rupali Priscilla, Karthik Rajeev, Sarkar Sauradeep, S Rajkumar, Abraham O Cherian
OBJECTIVE: To describe the i ncidence a nd cha racteristics of Tenofovir (TDF) induced nephrotoxicity among people living with HIV AIDS (PLHA) receiving TDF based anti-retroviral therapy (ART) at Christian Medical College, Vellore. METHOD: Medical record review of all the PLHA who is being enrolled and followed up at the ART clinic at CMC, Vellore. RESULTS: From 2006-11, a total of 274 PLHA have been initiated on TDF based ART. 10 (3.6%) patients developed TDF induced renal dysfunction after a mean duration of 42...
July 2014: Journal of the Association of Physicians of India
Daisuke Mizushima, Junko Tanuma, Nguyen Thi Dung, Nguyen Hoai Dung, Nguyen Vu Trung, Nguyen Tien Lam, Hiroyuki Gatanaga, Yoshimi Kikuchi, Nguyen Van Kinh, Shinichi Oka
BACKGROUND: The use of tenofovir has been rapidly increasing in Vietnam. Several studies identified low body weight as a risk factor for tenofovir-induced nephrotoxicity. However, little is known about the impact of tenofovir on renal function in HIV-infected Vietnamese with generally low weight. METHODS: An observational single-center cohort of adult HIV-infected patients on antiretroviral therapy at National Hospital of Tropical Diseases, Hanoi. Patients on tenofovir or with creatinine clearance ≤60 ml/min at baseline were excluded...
December 2014: Journal of Infection and Chemotherapy: Official Journal of the Japan Society of Chemotherapy
Hemalatha Ramamoorthy, Premila Abraham, Bina Isaac
The long-term use of tenofovir, a commonly used anti-HIV drug, can result in renal damage. The mechanism of tenofovir disoproxil fumarate (TDF) nephrotoxicity is not clear, although it has been shown to target proximal tubular mitochondria. In the present study, the effects of chronic TDF treatment on the proximal tubular function, renal mitochondrial function, and the activities of the electron transport chain (ETC) complexes were studied in rats. Damage to proximal tubular mitochondria and proximal tubular dysfunction was observed...
June 2014: Journal of Biochemical and Molecular Toxicology
A M Hall, P Bass, R J Unwin
A number of therapeutic drugs are toxic to the kidney proximal tubule (PT) and can cause the renal Fanconi syndrome (FS). The most frequently implicated drugs are cisplatin, ifosfamide, tenofovir, sodium valproate and aminoglycoside antibiotics, and the new oral iron chelator deferasirox has also recently been associated with FS. The incidence of full or partial FS is almost certainly under-estimated due to a lack of appropriate systematic studies, variations in definitions of tubular dysfunction and under-reporting of adverse events...
April 2014: QJM: Monthly Journal of the Association of Physicians
Vania Giacomet, Dario Cattaneo, Alessandra Viganò, Pilar Nannini, Valeria Manfredini, Giulia Ramponi, Emilio Clementi, Gian Vincenzo Zuccotti
Tenofovir disoproxyl fumarate is a known cause of kidney tubular dysfunction in HIV-infected patients. Recent studies reported significant association between specific allelic variants in ABCC2, ABCC4 and/or ABCC10 genes and the development of kidney tubular dysfunction in HIV-infected adults. We describe the first 2 cases of vertically HIV-infected patients affected by kidney tubular dysfunction associated with polymorphisms in the ABCC genes.
October 2013: Pediatric Infectious Disease Journal
Premila Abraham, Hemalatha Ramamoorthy, Bina Isaac
BACKGROUND: Nephrotoxicity is a dose limiting side effect of tenofovir, a reverse transcriptase inhibitor that is used for the treatment of HIV infection. The mechanism of tenofovir nephrotoxicity is not clear. Tenofovir is specifically toxic to the proximal convoluted tubules and proximal tubular mitochondria are the targets of tenofovir cytotoxicity. Damaged mitochondria are major sources of reactive oxygen species and cellular damage is reported to occur after the antioxidants are depleted...
2013: Journal of Biomedical Science
Isabelle Poizot-Martin, Caroline Solas, Julie Allemand, Véronique Obry-Roguet, Vincent Pradel, Sylvie Bregigeon, Olivia Faucher, Bruno Lacarelle
OBJECTIVE: Tenofovir disoproxil fumarate (TDF) is known to induce renal dysfunction in HIV-infected patients. The aim of this retrospective study was to evaluate the correlation between TDF trough concentration (Ctrough-TDF) and glomerular filtration rate (GFR) in a cohort of patients on antiretroviral therapy. METHODS: A total of 163 patients with at least one determination of Ctrough-TDF between 17-24 hours were retrospectively selected from a computerized database and distributed into 3 groups defined by TDF concentrations <40 (11...
April 1, 2013: Journal of Acquired Immune Deficiency Syndromes: JAIDS
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