Incidence and risk factors for tenofovir-associated renal toxicity in HIV-infected patients

Quesada, P Rodriguez; Esteban, L López; Garcia, Jimena Ramon; Vázquez-Sánchez, R; García, T Molina; Alonso-Vega, G. Gaspar; Ferrández, Javier Sánchez-Rubio

doi:10.1007/s11096-015-0132-1

Cited by 39 publications

(35 citation statements)

References 45 publications

(48 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Renal TFV toxicity in humans is characterized by Fanconi Syndrome, and depending on the dose, development of irreversible impaired renal function. There is a positive correlation between increased TFV plasma concentration, renal toxicity and the duration that patients were treated with TFV [20,21]. Because treatment with TFV is chronic, examination of the mechanism of renal toxicity is clinically relevant.…”

Section: Discussionmentioning

confidence: 99%

Establishment of HK-2 Cells as a Relevant Model to Study Tenofovir-Induced Cytotoxicity

Murphy

Stafford

Petrasovits

et al. 2017

IJMS

View full text Add to dashboard Cite

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). HK-2 cells were grown for 48 h followed by 24 to 72 h exposure to 0–28.8 μM TFV or vehicle, phosphate buffered saline (PBS). MTT (MTT, 3-(4,5-dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide) and Trypan blue indicated that TFV diminished cell viability at 24–72 h. TFV decreased ATP levels at 72 h when compared to vehicle, reflecting mitochondrial dysfunction. TFV increased the oxidative stress biomarkers of protein carbonylation and 4-hydroxynonenol (4-HNE) adduct formation. Tumor necrosis factor alpha (TNFα) was released into the media following exposure to 14.5 and 28.8 μM TFV. Caspase 3 and 9 cleavage was induced by TFV compared to vehicle at 72 h. These studies show that HK-2 cells are a sensitive model for TFV cytotoxicity and suggest that mitochondrial stress and apoptosis occur in HK-2 cells treated with TFV.

show abstract

Section: Discussionmentioning

confidence: 99%

Establishment of HK-2 Cells as a Relevant Model to Study Tenofovir-Induced Cytotoxicity

Murphy

Stafford

Petrasovits

et al. 2017

IJMS

View full text Add to dashboard Cite

show abstract

“…Several reports from Japan have shown the importance of low body weight and body mass index (BMI) for developing TDF-associated renal dysfunction defined as a ≥25% decline in estimated glomerular filtration rate (eGFR) 181920. However, in studies conducted in Europe and North America, body weight or BMI was not related to the development of TDF-induced renal insufficiency, as evaluated with decreased eGFR 115172122…”

Section: Introductionmentioning

confidence: 99%

Change in Renal Function among HIV-Infected Koreans Receiving Tenofovir Disoproxil Fumarate-Backbone Antiretroviral Therapy: A 3-Year Follow-Up Study

Lee

et al. 2017

Yonsei Med J

View full text Add to dashboard Cite

PurposeTenofovir disoproxil fumarate (TDF) is commonly prescribed as a fixed-dose, co-formulated antiretroviral drug for HIV-1 infection. The major concern of long-term TDF use is renal dysfunction. However, little is known about the long-term patterns of changes in renal function in HIV-infected Koreans receiving TDF.Materials and MethodsWe prospectively followed 50 HIV-infected Koreans, performing laboratory tests every 3 months during the first year and every 6 months for the next 2 years. Urine N-acetyl-β-D-glucosaminidase (NAG) and plasma cystatin-C were measured using samples collected in the first year. Data on renal function were retrospectively collected on HIV-infected patients receiving first-line TDF (n=40) and in antiretroviral therapy (ART)-naïve patients (n=24) for 3 years. Renal function was evaluated as estimated glomerular filtration rate (eGFR) from serum creatinine [Modification of Diet in Renal Disease (MDRD)] and cystatin-C.ResultsThe eGFR (cystatin-C) showed significant changes from 0 to 48 wks (p=0.002), with the lowest levels at 24 wks (84.3±18.8 mL/min vs. 90.3±22.5 mL/min, p=0.021 by post hoc test). Urine NAG levels did not differ at 0, 12, 24, and 48 wks, although eGFR (MDRD) significantly decreased from 0 (98.7±18.9 mL/min/1.73 m2) to 144 wks (89.0±14.7 mL/min/1.73 m2) (p=0.010). The first-line TDF group had significantly lower eGFR (MDRD) than the ART-naïve group at 144 wks (89.7 mL/min/1.73 m2 vs. 98.4 mL/min/1.73 m2, p=0.036). Thirteen (26%) participants experienced a decrease in renal impairment of 10 mL/min/1.73 m2 in eGFR (MDRD) at 144 wks.ConclusionThese data suggest that clinically meaningful renal injury can develop in HIV-infected Koreans receiving long-term TDF.

show abstract

“…Against this in the study by Queseda et al, increasing age was listed amongst the risk factors 18 . Overall, among the possible causes of renal impairment prior to cART initiation in our study, HIV infection was the known common factor.…”

Section: Discussionmentioning

confidence: 95%

“…As such, TDF is a probable cause of the decline in CrCl. However, as Queseda et al, and Chaisiri et al, discuss, the plausible synergy between TDF and ritonavir (RTV) as a risk factor for renal impairment cannot be overlooked 17,18 . At the time of data collection, all these patients were receiving TDF containing second line regimens, which means that they had not experienced TDF-associated acute renal impairment such as the Fanconi Syndrome.…”

Section: Discussionmentioning

confidence: 99%

Untitled

Kalemeera

Oberholster

Segamwenge³

et al. 2018

IJPSR

View full text Add to dashboard Cite

Introduction and Aims: Combination antiretroviral therapy (cART) has improved morbidity and mortality in patients with HIV across countries including countries in sub-Sahara Africa. However, cART is associated with renal impairment. The lack of pre-cART data in a recently published study limited the discussion on renal-based treatment outcomes with cART, which could have important clinical implications. Consequently, the aim of this paper is to correct this. Methods: Longitudinal retrospective study, with renal function assessed pre-cART and at various time points on cART using the Cockcroft-Gault method. The data source was the patients' care booklets. Results: 71 patients were included. The majority were adults and female. Before cART initiation, 70.4% and 29.6% had abnormal and normal CrCl, respectively. CrCl was normalised in 24% of patients, while abnormal in the remainder. The mean (median) time to normalisation was 47.4 (33.7) months, observed more in paediatric than adult patients (p = 0.014). However, in paediatric patients, normalisation took longer than in adult patients. The reduction in CrCl, was observed at variable time points. 9/16 patients experienced a decline during first-line cART and 7 of these were receiving TDF. 7/16 experienced this during second-line cART and 6 were receiving TDF. Conclusion: HIV is typically the cause of renal impairment prior to cART, with TDF likely to be the cause of renal impairment during cART. Consequently, co-administration of TDF with other nephrotoxic drugs should be undertaken with caution if unavoidable. Overall, improvement in renal impairment was faster in adults.

show abstract

Incidence and risk factors for tenofovir-associated renal toxicity in HIV-infected patients

Cited by 39 publications

References 45 publications

Establishment of HK-2 Cells as a Relevant Model to Study Tenofovir-Induced Cytotoxicity

Establishment of HK-2 Cells as a Relevant Model to Study Tenofovir-Induced Cytotoxicity

Change in Renal Function among HIV-Infected Koreans Receiving Tenofovir Disoproxil Fumarate-Backbone Antiretroviral Therapy: A 3-Year Follow-Up Study

Untitled

Contact Info

Product

Resources

About