tenofovir induced renal dysfunction

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...

 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...

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)...

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)...

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...

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...

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...

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...

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.

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...

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...

We describe a case of 68-year-old Japanese man with HIV-1 infection who developed acute kidney injury with prominent tubular dysfunction immediately after starting tenofovir-containing antiretroviral therapy. Antiretroviral therapy was discontinued in two weeks but renal function, as well as tubular function, did not shown full recovery even at a 3-year follow-up examination. Acute tubular necrosis, a rare but well-known side effect of tenofovir, was suspected, but kidney biopsy confirmed interstitial nephritis...

BACKGROUND: Tenofovir is a widely used antiretroviral drug although it can cause kidney tubular dysfunction (KTD). The aim of this study was to determine the association between polymorphisms in genes encoding drug transporters and KTD in Japanese patients treated with tenofovir. METHODS: The association between tenofovir-induced KTD and 14 single nucleotide polymorphisms (SNPs) in the ABCC2, ABCC4, ABCC10, SCL22A6, and ABCB1 genes was investigated in 190 Japanese patients...

Tenofovir disoproxil fumerate (TDF) is an effective nucleoside reverse transcriptase inhibitor for HIV infection but it is potentially nephrotoxic. A selective mithochondrial toxicity has been hypothesized. To assess early markers of renal toxicity, we evaluated a cohort of antiretroviral (ARV)-experienced HIV patients who had been switched from a thymidinic backbone to either a TDF/emtricitabine regimen (TDF; 73 patients) or an abacavir/lamivudine (ABV) regimen (28 patients). Markers of mitochondrial toxicity (cytochrome c, Cyc) or cytosolic (α-glutathione S transferase, α-GST) together with common indicators of renal damage were assessed at baseline (T0) and after 1 (T1), 3 (T2), 6 (T3), and 12 (T4) months of patient exposure to therapy...

Highly active antiretroviral therapy (HAART) and other medical therapies for HIV-related infections have been associated with toxicities. Antiretroviral therapy can contribute to renal dysfunction directly by inducing acute tubular necrosis, acute interstitial nephritis, crystal nephropathy, and renal tubular disorders or indirectly via drug interactions. With the increase in HAART use, clinicians must screen patients for the development of kidney disease especially if the regimen employed increases risk of kidney injury...

To better evaluate the renal safety profile of tenofovir, we performed a retrospective study of HIV-infected antiretroviral-naïve patients starting a first antiretroviral therapy between July 2004 and July 2008, and followed-up for 24 months. The glomerular filtration rate (GFR) was calculated using the MDRD formula, and tubular dysfunction was diagnosed with 2 or more of the following: proteinuria, glucosuria, hypouricemia, hypophosphatemia and hypokalemia. Overall, 324 patients were enrolled: 201 were tenofovir-exposed and were compared with 123 tenofovir-unexposed subjects...

Two male patients with HIV, aged 61 and 58 years, presented with slowly progressive renal failure. Both had been treated with highly active antiretroviral therapy (HAART) for several years. Additional laboratory investigations showed hypophosphatemia, hypouricemia, metabolic acidosis and normoglycemic glucosuria. These results are an indication of proximal tubular dysfunction (PTD). Complete PTD is also known as Fanconi syndrome. Other laboratory abnormalities in Fanconi syndrome include aminoaciduria, phosphaturia and β2-microglobulinuria...

BACKGROUND: In many preclinical AIDS research studies, antiretroviral therapy (ART) is administered to experimentally simian immunodeficiency (SIV)-infected rhesus macaques for reduction of viral load to undetectable levels. Prolonged treatment of macaques with a high dose of PMPA (9-[2-(r)-(phosphonomethoxy) propyl] adenine or tenofovir; 30 mg/kg of body weight subcutaneously once daily) can result in proximal renal tubular dysfunction, a Fanconi-like syndrome characterized by glucosuria, aminoaciduria, hypophosphatemia, and bone pathology...

The antiretroviral agent tenofovir can cause hypophosphatemic osteomalacia due to renal phosphate wasting. The potential role for Fibroblast Growth Factor 23 (FGF23), a phosphaturic hormone is unknown. We evaluated FGF23 plasma concentrations in an HIV-positive patient with neurofibromatosis in whom hypophosphatemia developed during tenofovir therapy. This patient presented with diffuse pain, hypophosphatemia and tubular dysfunction with inadequate phosphate reabsorption. The full recovery after tenofovir discontinuation indicates that the hypophosphatemia was related to tenofovir and not to von Recklinghausen disease...

BACKGROUND: Tenofovir-containing antiviral therapy might result in acute renal failure and is able to induce tubular dysfunction with hypocalcemia. On the other hand, hypercalcemia induced by intoxication with colecalciferol has been described to induce renal failure in HIV-positive individuals as well. Here, the authors describe the unusual case of reversible renal failure due to hypercalcemia in a patient with low-dose colecalciferol substitution treated with tenofovir. CASE REPORT: A 31-year-old HIV-positive female, CDC stage C3, was admitted to the authors' hospital with progressive renal failure and hypercalcemia...