Tenofovir-induced renal tubular dysfunction presenting with hypocalcaemia

Jd, Williams; Chadwick, David

doi:10.1016/j.jinf.2005.07.014

Cited by 17 publications

(8 citation statements)

References 11 publications

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“…42,61,[64][65][66][67][68][69][70][71][72] The failure of renal proximal tubular cells to reabsorb filtered bicarbonate from the urine would result in urinary bicarbonate wasting and subsequent acidemia and a more general dysfunction of the proximal tubular cells -called Fanconi's syndrome. Commonly observed conditions in Fanconi syndrome include aminoaciduria, glycosuria, tubular proteinuria, and uricosuria.…”

Section: Dovepressmentioning

confidence: 99%

Tenofovir-associated bone density loss

Mansky¹

2009

TCRM

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Section: Dovepressmentioning

confidence: 99%

Tenofovir-associated bone density loss

Mansky¹

2009

TCRM

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“…However, several case reports and series show patients treated with TDF may present with acute renal failure, Fanconi syndrome and diabetes insipidus. These reports suggested that TDF could cause renal tubular injury and decline in creatinine clearance (CL Cr ) [8-14]. A meta-analysis of prospective studies comparing TDF-containing with non-TDF containing ARV regimens showed that TDF use was associated with statistically significant loss of renal function and the clinical effect was modest [15].…”

Section: Introductionmentioning

confidence: 99%

Renal safety of tenofovir containing antiretroviral regimen in a Singapore cohort

et al. 2012

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“…Common features of most reports of TFV-related kidney toxicity were an advanced stage of HIV-1 infection and extensive pretreatment with antiretrovirals and other potentially nephrotoxic drugs before TFV was prescribed. The patients were receiving second, third, or even more advanced treatment regimens, which included in most cases lopinavir/ritonavir (LPV/RTV) and/or didanosine (ddI) in addition to TFV (3,10,16,18,[24][25][26]32,[36][37][38]40,43,46,49,51,53,55,[58][59][60][61]66,67).…”

mentioning

confidence: 99%

In Vitro Cytotoxicity and Mitochondrial Toxicity of Tenofovir Alone and in Combination with Other Antiretrovirals in Human Renal Proximal Tubule Cells

Vidal

Domingo

Guallar

et al. 2006

Antimicrob Agents Chemother

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We assessed the in vitro toxicity of tenofovir (TFV) and compared it with those of zidovudine (AZT), didanosine (ddI), ritonavir (RTV), and lopinavir (LPV) alone and in combination in human renal proximal tubule epithelial cells (RPTECs). The cells were treated with various concentrations and combinations of the tested antiretrovirals for up to 22 days, and cytotoxicity was determined. In addition, we assessed the levels of mitochondrial DNA (mtDNA) and cytochrome oxidase II (COII) mRNA in RPTECs treated with reverse transcriptase inhibitors. TFV alone was not associated with significant cytotoxicity. ddI showed pronounced cytotoxicity that was greater than those of AZT (P ‫؍‬ 0.002) and TFV (P ‫؍‬ 0.0001). The combination of 10 M RTV and 40 M LPV significantly reduced RPTEC viability (P < 0.0001), and TFV tended to partially reduce this effect. TFV alone affected neither mtDNA nor COII mRNA levels, whereas ddI caused a profound depletion of mtDNA and a parallel reduction in COII mRNA expression. The effects of ddI, but not those of AZT, on mtDNA and COII mRNA were further enhanced in the presence of TFV, a finding consistent with the inhibition of ddI clearance by TFV. The addition of TFV to ddI or AZT appeared to slightly increase the COII mRNA/mtDNA ratio relative to that in cells treated with ddI or AZT alone. Together, these in vitro results indicate that combination with other antiretrovirals does not significantly increase the toxic potential of TFV in RPTECs.Tenofovir disoproxil fumarate (TDF) is an oral prodrug of tenofovir (TFV), an acyclic nucleotide analogue reverse transcriptase inhibitor that is widely used for the treatment of human immunodeficiency virus type 1 (HIV-1) infection (42). Controlled clinical studies in humans found TDF to be safe, with the incidence of TDF-associated renal impairment (elevated serum creatinine or hypophosphatemia) being 1 to 3% and with minimal differences from comparative non-TDF arms (22,23,29,30,34,50,62). However, several reports have reassessed the renal safety of TFV, and presently there is a progressively growing subset of TFV-treated patients presenting with acute renal failure, with Fanconi syndrome and/or nephrogenic diabetes insipidus, attributed to this drug (3, 10, 16, 18, 24-26, 32, 36-38, 40, 43, 46, 49, 51, 53, 55, 58-61, 66, 67). In the majority of cases the kidney damage was reversed upon discontinuation of TFV (71). Many of these case reports have suggested different mechanisms to explain the link between this drug and its attributed kidney toxicity, but at present this still remain largely elusive. Common features of most reports of TFV-related kidney toxicity were an advanced stage of HIV-1 infection and extensive pretreatment with antiretrovirals and other potentially nephrotoxic drugs before TFV was prescribed. The patients were receiving second, third, or even more advanced treatment regimens, which included in most cases lopinavir/ritonavir (LPV/RTV) and/or didanosine (ddI) in addition to TFV (3,10,16,18,[24][25][26]32,[36][37][38]40,43,46,...

show abstract

Tenofovir-induced renal tubular dysfunction presenting with hypocalcaemia

Cited by 17 publications

References 11 publications

Tenofovir-associated bone density loss

Tenofovir-associated bone density loss

Renal safety of tenofovir containing antiretroviral regimen in a Singapore cohort

In Vitro Cytotoxicity and Mitochondrial Toxicity of Tenofovir Alone and in Combination with Other Antiretrovirals in Human Renal Proximal Tubule Cells

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