Treatment-limiting renal tubulopathy in patients treated with tenofovir disoproxil fumarate

Hamzah, Lisa; José, Sophie; Booth, John; Hegazi, Aseel; Rayment, Michael; Bailey, Angela; Williams, D I; Hendry, Bruce M.; Hay, Phillip; Jones, Rachael; Levy, Jeremy; Chadwick, David; Johnson, Margaret; Sabin, Caroline; Post, FA

doi:10.1016/j.jinf.2017.01.010

Cited by 49 publications

(49 citation statements)

References 51 publications

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“…This may have resulted in the inclusion of several patients with 'softer' phenotypes in the trial. Although most would probably have developed severe PRT with continued TDF exposure, [5] others might not have progressed beyond subclinical renal tubular dysfunction [17]. It should be noted, however, that the observed fasting urine osmolality, eGFR and TmPO4/GFR values were considerably lower than their expected values, [23] suggesting that we enrolled a population with (residual) renal dysfunction who may be at risk of adverse renal effects from even low-level tubular tenofovir diphosphate exposure as typically achieved with TAF.…”

Section: Baselinementioning

confidence: 99%

“…PRT is characterized by normoglycaemic glycosuria, proteinuria, renal phosphate wasting and/or metabolic acidosis which may progress to Fanconi syndrome and be accompanied by reductions in bone mineral density, osteomalacia and/or fragility fractures . Based on data from the UK Collaborative HIV Cohort, the incidence of renal toxicity with TDF use is estimated to be around 5% and the incidence of treatment‐limiting PRT around 0.4% . Reported risk factors for PRT include older age, white ethnicity, immunodeficiency, more prolonged exposure to TDF and co‐exposure to didanosine or ritonavir‐ and cobicistat‐boosted agents .…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Early safety of tenofovir alafenamide in patients with a history of tubulopathy on tenofovir disoproxil fumarate: a randomized controlled clinical trial

Hamzah

Williams²,

Bailey

et al. 2019

HIV Medicine

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Objectives The aim of the study was to assess the effect of tenofovir alafenamide (TAF) on kidney and bone biomarkers in patients who developed proximal renal tubulopathy (PRT) while receiving tenofovir disoproxil fumarate (TDF). Methods Individuals with a history of TDF‐associated PRT and currently suppressed HIV infection on a tenofovir‐sparing regimen were randomized 1:1 to continue current antiretroviral therapy or initiate emtricitabine (F)/TAF with discontinuation of nucleoside reverse transcriptase inhibitors (NRTIs) as appropriate. Renal and bone biomarkers were analysed at baseline, week 4 and week 12. The primary outcome was the mean difference between study arms in urine retinol‐binding protein:creatinine ratio (RBPCR) change from baseline to week 12. Data were analysed using linear regression, with robust standard errors (primary outcome), and repeated measures mixed effects models (secondary outcomes). The trial was registered under European Union Drug Regulating Authorities Clinical Trials Database 2016‐003345‐29. Results We randomized 31 individuals [mean age 52.4 (standard deviation 0.3) years; 97% male; 90% white); all completed the study. At 12 weeks, there was no difference in change in RBPCR (β 19.6; 95% confidence interval −35.3, 74.5; P = 0.47), and no difference in change in estimated glomerular filtration rate (eGFR) (based on creatinine or cystatin C), albuminuria, proteinuria, renal phosphate or urea handling, (fasting) urine osmolality, parathyroid hormone and bone turnover markers in the control versus the F/TAF exposed groups. No cases of PRT were observed. Conclusions In people with a history of proximal renal tubulopathy while on TDF, 12‐week exposure to TAF did not adversely affect renal tubular function. These data support continued evaluation of the long‐term safety of TAF in this group of patients.

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Section: Baselinementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Early safety of tenofovir alafenamide in patients with a history of tubulopathy on tenofovir disoproxil fumarate: a randomized controlled clinical trial

Hamzah

Williams²,

Bailey

et al. 2019

HIV Medicine

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“…Tenofovir is widely used as one component of a nucleoside backbone in ART and has been recommended by the World Health Organization. Tenofovir has been associated with renal toxicity ranging from Fanconi's syndrome, acute kidney injury (AKI), and reduction in estimated glomerular filtration rate (eGFR), sometimes progressing to CKD . There is limited information on the incidence and risk factors associated with renal dysfunction among PLHIV in Asia.…”

Section: Introductionmentioning

confidence: 99%

“…Tenofovir has been associated with renal toxicity ranging from Fanconi's syndrome, acute kidney injury (AKI), and reduction in estimated glomerular filtration rate (eGFR), sometimes progressing to CKD. [3][4][5][6] There is limited information on the incidence and risk factors associated with renal dysfunction among PLHIV in Asia. We previously reported an incidence of TDF-associated renal dysfunction of 1.75 per 100 years in the TREAT Asia HIV Observational Database (TAHOD) cohort.…”

mentioning

confidence: 99%

Changes in renal function with long‐term exposure to antiretroviral therapy in HIV‐infected adults in Asia

Joshi¹,

Boettiger

Kerr

et al. 2018

Pharmacoepidemiology and Drug

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Introduction: Renal disease is common amongst people living with HIV. However, there is limited information on the incidence and risk factors associated with renal dysfunction among this population in Asia. Methods: We used data from the TREAT Asia HIV Observational Database. Patients were included if they started antiretroviral therapy (ART) during or after 2003, had a serum creatinine measurement at ART initiation (baseline) and had at least two follow-up creatinine measurements taken ≥3 months apart. Patients with a baseline estimated glomerular filtration rate (eGFR) ≤60ml/min/1.73m2 were excluded. Chronic kidney disease was defined as two consecutive eGFR values ≤60ml/min/1.73m2 taken ≥3 months apart. Generalized estimating equations were used to identify factors associated with eGFR change. Competing risk regression adjusted for study site, age and sex, and cumulative_incidence plots were used to evaluate factors associated with CKD. Results: Of 2,547 patients eligible for this analysis, tenofovir was being used by 703 (27.6%) at baseline. Tenofovir use, high baseline eGFR, advanced HIV disease stage and low nadir CD4 were associated with a decrease in eGFR during follow up. CKD occurred at a rate of 3.4 per 1000 patient/years. Factors associated with CKD were tenofovir use, old age, low baseline eGFR, low nadir CD4, and protease inhibitor use. Conclusions: There is an urgent need to enhance renal monitoring and management capacity among at-risk groups in Asia and improve access to less nephrotoxic antiretrovirals.

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“…TDF-induced nephrotoxicity is characterized by Fanconi syndrome, manifesting as low molecular weight proteinuria, phosphaturia, uricosuria, normoglycemic glucosuria, and metabolic acidosis 13,56,61 ; however, the full syndrome is seen only in a minority of TDF users, with a reported incidence of 0.4% over a median duration of 44 months. 80,81 However, milder forms of tubular damage occur commonly among TDF users. 12,76,[82][83][84][85][86] Among ART-naïve patients, those who initiated TDF versus non-TDF regimens had a 5.2-fold higher risk of developing proximal tubular dysfunction after 2 years of follow-up.…”

Section: Art Nephrotoxicitymentioning

confidence: 99%

Kidney Disease in HIV: Moving beyond HIV-Associated Nephropathy

Jotwani

Atta²,

Estrella

2017

JASN

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In developed countries, remarkable advances in antiretroviral therapy have transformed HIV infection into a chronic condition. As a result, HIV-associated nephropathy, the classic HIV-driven kidney lesion among individuals of African descent, has largely disappeared in these regions. However, HIV-positive blacks continue to have much higher rates of ESRD than HIV-positive whites, which could be attributed to the renal risk variants. Additionally, HIV-positive individuals face adverse consequences beyond HIV itself, including traditional risk factors for CKD and nephrotoxic effects of antiretroviral therapy. Concerns for nephrotoxicity also extend to HIV-negative individuals using tenofovir disoproxil fumarate-based pre-exposure prophylaxis for the prevention of HIV infection. Therefore, CKD remains an important comorbid condition in the HIV-positive population and an emerging concern among HIV-negative persons receiving pre-exposure prophylaxis. With the improved longevity of HIV-positive individuals, a kidney transplant has become a viable option for many who have progressed to ESRD. Herein, we review the growing knowledge regarding the renal risk variants in the context of HIV infection, antiretroviral therapy-related nephrotoxicity, and developments in kidney transplantation among HIV-positive individuals.

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Treatment-limiting renal tubulopathy in patients treated with tenofovir disoproxil fumarate

Cited by 49 publications

References 51 publications

Early safety of tenofovir alafenamide in patients with a history of tubulopathy on tenofovir disoproxil fumarate: a randomized controlled clinical trial

Early safety of tenofovir alafenamide in patients with a history of tubulopathy on tenofovir disoproxil fumarate: a randomized controlled clinical trial

Changes in renal function with long‐term exposure to antiretroviral therapy in HIV‐infected adults in Asia

Kidney Disease in HIV: Moving beyond HIV-Associated Nephropathy

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