Tenofovir renal safety in HIV-infected patients: Results from the SCOLTA Project

Madeddu, Giordano; Bonfanti, Paolo; Socio, Giuseppe Vittorio De; Carradori, Silvia; Grosso, Carmela; Marconi, Patrizia; Penco, Giovanni; Rosella, Elena; Miccolis, Sebastiano; Melzi, Sara; Mura, María Stella; Landonio, Simona; Ricci, Elena; Quirino, Tiziana

doi:10.1016/j.biopha.2007.04.008

Cited by 61 publications

(58 citation statements)

References 28 publications

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“…However, a European population study did not find female gender as a predictor of renal damage [24]. Age was associated with renal toxicity in similarity with other studies [18,25]. It is well known that there is a strong relationship between increased age and presence of a low baseline creatinine clearance, which gradually decreases with age [26].…”

Section: Resultssupporting

confidence: 72%

Incidence and Risk Factors of Renal Impairment in Hiv-1 Infected Patients Receiving Tenofovir Based Antiretroviral Therapy in a South Indian Hospital

Kumar

Parthasarathi

Sudheer

et al. 2017

Int J Pharm Pharm Sci

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Objective: To identify the incidence and risk factors of tenofovir (TDF) induced nephrotoxicity among People Living with HIV/AIDS (PLHA) receiving TDF-based anti-retroviral therapy (ART) in a South Indian Hospital.Methods: A retrospective cohort study was conducted among HIV-infected ART naïve patients taking TDF as part of either a first-line or second-line ART between July 2013 and June 2015 at Asha kirana Hospital Mysore, India.Results: A total of 380 patients have been initiated on TDF-based ART. Out of these, 335 patients were on tenofovir+lamivudine+efavirenz, 30 patients were on the tenofovir+lamivudine+nevirapine regimen and 25 patients were on tenofovir+lamivudine+atazanavir/ritonavir regimen. Renal impairment was documented for 35 patients with 9.21% incidence. 34% of renal impaired patients had a severe impairment with eGFR<30 ml/min. Elderly patients (>61 y) had higher chances of developing TDF toxicity compared to adult patients (P=0.0018). Other possible risk factors for TDF-induced renal impairment was CD4>200 (P=0.003). TDF was withdrawn and substituted with Nucleoside Reverse Transcriptase Inhibitor (NRTI) drug following the diagnosis of renal impairment.Conclusion: TDF-associated renal impairment was not uncommon in real-life practice and considered as a frequent complication during treatment with TDF. Risk factors for developing renal impairment include increasing age and CD4>200 cells.

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Section: Resultssupporting

confidence: 72%

Incidence and Risk Factors of Renal Impairment in Hiv-1 Infected Patients Receiving Tenofovir Based Antiretroviral Therapy in a South Indian Hospital

Kumar

Parthasarathi

Sudheer

et al. 2017

Int J Pharm Pharm Sci

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“…In addition, NSAIDs can independently reduce glomerular filtration and thus potentially further contribute to the development of renal injury. In a few cases, acute onset of TFV-associated nephrotoxicity has been reported in patients with previously stable renal function associated with the concomitant use of NSAIDs [15][16][17][18][19]. The purpose of this study was to determine the frequency of and risk factors for acute renal failure and proximal tubular dysfunction after initiation of NSAID therapy in HIV-infected patients receiving cART.…”

Section: Introductionmentioning

confidence: 99%

Acute kidney injury caused by tenofovir disoproxil fumarate and diclofenac co‐administration

et al. 2013

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ObjectivesThe renal elimination of tenofovir (TFV) may be subject to renal drug−drug interactions that may increase the risk of kidney injury. Case reports indicated that diclofenac might increase TFV-associated nephrotoxicity via a drug−drug interaction, leading to an increased intracellular TFV concentration in proximal tubular cells. MethodsA retrospective analysis of data for all patients from the Frankfurt HIV Cohort (FHC) who had diclofenac prescriptions between January 2008 and June 2012 was carried out. ResultsAmong 89 patients with diclofenac use, 61 patients (68.5%) were treated with tenofovir disoproxil fumarate (TDF) and 28 patients (31.5%) were treated with TDF-sparing combination antiretroviral therapy (cART). Thirteen patients (14.6%) developed acute kidney injury (AKI) shortly after initiating diclofenac treatment. AKI occurred exclusively in TDF-treated patients, although all had previously stable renal function. All cases were accompanied by new onset of at least two parameters indicating proximal tubular damage, such as normoglycaemic-glucosuria and hypophosphataemia. TFV-associated nephrotoxicity was demonstrated by renal biopsy in four cases. Additionally, 11.5% of patients on TDF treatment developed new-onset proximal tubular damage, while having a preserved glomerular filtration rate. In contrast, diclofenac did not affect renal function in patients with TDF-sparing cART, as only one case of isolated hypophataemia was observed in these patients. In univariate analysis, risk factors for AKI were TDF-containing cART (P = 0.0076) and pre-existing hypophosphataemia (P = 0.0086). ConclusionsDrug−drug interaction caused by diclofenac could exacerbate TFV-associated nephrotoxicity. Diclofenac should be used with caution in patients on TDF therapy, especially in those with hypophosphataemia. Our findings need to be confirmed in larger studies.Keywords: acute kidney injury, drug−drug interaction, Fanconi syndrome, HIV, nonsteroidal anti-inflammatory drugs, tenofovir IntroductionAcute kidney injury (AKI) is a common, often reversible complication with an estimated incidence of 2.7 to 5.9 per 100 person-years in HIV-infected out-patients [1][2][3][4] [3,7,8].Renal toxicity related to TFV is caused by proximal tubular injury that may present with various manifestations (hypophosphataemia, normoglycaemic-glucosuria, hypouricaemia, proteinuria and/or metabolic acidosis, including partial or complete Fanconi syndrome) attributable to impaired reabsorption of glomerular filtrate and nephrogenic diabetes insipidus, as well as AKI [9][10][11][12]. Tenofovir disoproxil fumarate (TDF) is a prodrug which is rapidly metabolized to TFV in plasma. TFV is eliminated unchanged by glomerular filtration (70-80%) as well as proximal tubular secretion (20-30%). TFV enters the proximal renal tubular cells via human organic anion transporter 1 (hOAT1) and is then actively secreted into the urine by the multidrug-resistance protein (MRP), mainly MRP4 [10,11,13,14].Nonsteroidal anti-inflammatory drugs (NSAIDs) inhibit dru...

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“…Observational studies suggest that older age and lower baseline eGFR are risk factors, all of which are well-known risk factors for progression to chronic kidney disease in the general population, with arterial hypertension not being so clearly related [10,12,14]. We only found these three risk factors as significant predictors of CRDRF onset in the multivariate model.…”

Section: Discussionmentioning

confidence: 57%

“…Moreover, large clinical trials with long follow-up periods of more than 144 weeks in naïve patients have shown a renal safety profile of ART containing TDF, either similar to other ART without it, or with small significant declines in the estimated glomerular filtration rate (eGFR) of clinical implications difficult to ascertain [7][8][9]. Observational studies with longer follow-up periods suggest a more deleterious effect on the renal function, and point that TDF is associated with a higher incidence of chronic kidney disease [10][11][12][13][14][15][16][17]. Overall, these results have shown either a modest or absent decline in renal function associated with TDF use after short follow-up periods of months or very few years, while studies with longer follow-up periods suggest a more relevant decrease in renal function [13][14][15][16][17].…”

Section: Introductionmentioning

confidence: 99%

Long-term comparative and prospective cohort study of renal function in patients with HIV infection treated with tenofovir disoproxil fumarate

Calle¹,

Pulido²,

Sánchez-Conde³

et al. 2017

HIV & AIDS Review

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Tenofovir renal safety in HIV-infected patients: Results from the SCOLTA Project

Cited by 61 publications

References 28 publications

Incidence and Risk Factors of Renal Impairment in Hiv-1 Infected Patients Receiving Tenofovir Based Antiretroviral Therapy in a South Indian Hospital

Incidence and Risk Factors of Renal Impairment in Hiv-1 Infected Patients Receiving Tenofovir Based Antiretroviral Therapy in a South Indian Hospital

Acute kidney injury caused by tenofovir disoproxil fumarate and diclofenac co‐administration

Long-term comparative and prospective cohort study of renal function in patients with HIV infection treated with tenofovir disoproxil fumarate

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