Fanconi syndrome and renal failure induced by tenofovir: A first case report

Verhelst, David; Monge, Matthieu; Meynard, Jean-Luc; Fouqueray, Bruno; Mougenot, B; Girard, Pierre‐Marie; Ronco, Pierre; Rossert, Jérôme

doi:10.1053/ajkd.2002.36924

Cited by 316 publications

(210 citation statements)

References 11 publications

Supporting

Mentioning

195

Contrasting

Unclassified

Order By: Relevance

“…Indinavir-associated renal dysfunction is well documented and there is also growing evidence of an association between tenofovir use and loss of renal function. [22][23][24][25][26][27] In a recent meta-analysis that included 17 studies to assess the renal safety of tenofovir in HIV-infected patients, a statistically significant greater loss in creatinine clearance was observed among tenofovir recipients compared to control subjects, as well as a significantly greater risk of acute renal failure among tenofovir recipients. 22 Of subjects on ARVs at the time of AKI, 45% were receiving indinavir or tenofovir-containing regimens, reflecting evolving drug availability and prescribing practices during the study period.…”

Section: Discussionmentioning

confidence: 99%

Incidence and Predictors of Acute Kidney Injury in an Urban Cohort of Subjects with HIV and Hepatitis C Virus Coinfection

Garg

Hoenig

Edwards

et al. 2011

AIDS Patient Care and STDs

View full text Add to dashboard Cite

Coinfection with hepatitis C (HCV) significantly increases the risk of acute and chronic renal disease in HIVinfected individuals. However, the burden of acute kidney injury (AKI) directly attributable to HIV among HCV-infected individuals and associated risk factors are not well understood. Within a prospective cohort, AKI episodes were identified by a rise in creatinine of 0.5 mg/dL. Incidence of first AKI events was calculated for HIV/HCV coinfected versus HCV monoinfected subjects, and multivariable analyses using Cox proportional hazards were performed to identify predictors of AKI. Throughout the study period, 35% HIV/HCV coinfected and 17% HCV monoinfected subjects developed AKI, with incidence of 8. (HR 2.06 [1.15, 3.71]) were independently associated with AKI. HCV genotype, HCV viral load, hazardous drinking, and heroin use were not associated with AKI. Study limitations included potential misclassification bias of HCV-infected individuals as serial HIV antibody testing was not routinely performed after study entry, and inability to adjust for tenofovir use in multivariable analysis. In conclusion, among subjects with HCV infection, decompensated cirrhosis, HIV coinfection, and cocaine use are associated with increased risk of AKI. These findings highlight the importance of preventing and treating cirrhosis, controlling HIV coinfection, and reducing cocaine use in HIV/HCV coinfected persons.

show abstract

Section: Discussionmentioning

confidence: 99%

Incidence and Predictors of Acute Kidney Injury in an Urban Cohort of Subjects with HIV and Hepatitis C Virus Coinfection

Garg

Hoenig

Edwards

et al. 2011

AIDS Patient Care and STDs

View full text Add to dashboard Cite

show abstract

“…However, there are mounting numbers of anecdotal reports describing Fanconi's syndrome and renal insufficiency induced by TDF therapy [8][9][10][11][12][13][14][15][16][17][18]. Predisposing factors for the development of acute renal failure with the use of TDF remain obscure.…”

Section: Introductionmentioning

confidence: 99%

Minor changes in calculated creatinine clearance and anion‐gap are associated with tenofovir disoproxil fumarate‐containing highly active antiretroviral therapy

et al. 2006

View full text Add to dashboard Cite

BackgroundTenofovir disoproxil fumarate (Tenofovir DF, TDF), the first nucleotide reverse transcriptase inhibitor approved for the treatment of HIV disease, has been associated with renal dysfunction in isolated cases. The aim of this study was to assess changes in renal parameters in individuals receiving TDFand non-TDF-containing highly active antiretroviral therapy (HAART). MethodsAll individuals on HAART attending our clinic were included in the analysis. Time-weighted changes in serum creatinine, calculated creatinine clearance (CCrCl) and anion-gap were assessed for individuals on TDF-and non-TDF HAART. ResultsOf 948 individuals on HAART, 290 (31%) and 618 (65%) were on TDF-and non-TDF HAART, with 40 (4%) having ceased TDF HAART. Baseline values for serum creatinine, CCrCl and anion-gap were similar for those on TDF-and non-TDF HAART. In a multivariate analysis, statistically significant differences were observed in time-weighted change from baseline in anion-gap and CCrCl between individuals on TDF-and non-TDF HAART [mean difference in change between groups: anion-gap 0.78 mmol/L (standard error, 0.19) and CCrCl À 6.80 (standard error 2.2); P 5 0.005 and P 5 0.032, respectively] after adjusting for baseline anion-gap and CCrCl, respectively. Two cases of TDF-associated renal failure were observed. ConclusionOvert renal failure with TDF HAART is rare. However, subtle but statistically significant changes in anion-gap and CCrCl were observed which were associated with TDF HAART. These parameters may be of use in monitoring individuals on HAART. Cidofovir and adefovir, compounds structurally related to TDF, have been associated with an increased risk of acute renal insufficiency. In particular, a dose-and timedependent development of a Fanconi-like syndrome has been reported [5,6]. In pivotal studies assessing the safety and efficacy of TDF, renal safety profiles were found to be similar in individuals receiving and in those not receiving TDF-containing highly active antiretroviral therapy (HAART) [2][3][4]. In addition, a recent large cohort has described no significant evidence of renal dysfunction with the use of TDF in clinical practice [7]. However, there are mounting numbers of anecdotal reports describing Fanconi's syndrome and renal insufficiency induced by TDF therapy [8][9][10][11][12][13][14][15][16][17][18]. Predisposing factors for the development of acute renal failure with the use of TDF remain obscure.Several groups reporting no significant evidence of renal dysfunction with the use of TDF have relied on serum creatinine as a marker of renal function [7]. A recent report utilizing glomerular filtration rate (GFR) calculated on the basis of a 24-h urine collection has observed a lower GFR associated with TDF treatment [19].The aim of this study was to investigate changes in anion-gap and calculated creatinine clearance (CCrCl) in a large cohort of HIV-1-infected individuals receiving TDFand non-TDF-containing HAART. Methods Study designAll individuals currently on HAART attending the Departmen...

show abstract

“…Furthermore, the renal safety profile of TDF was similar to that of stavudine over 144 weeks of followup in study However, post-marketing experience with TDF has raised the possibility that nephrotoxicity may be an uncommon but important adverse effect of this agent. Several case reports describing nephrotoxicity attributable to TDF have been published, with manifestations of Fanconi syndrome, nephrogenic diabetes insipidus and acute renal failure being reported [3][4][5][6][7][8][9][10][11][12][13][14]. To better describe the incidence of and potential risk factors for TDF-associated nephrotoxicity in routine clinical care, we performed a retrospective review of patients enrolled in the TDF Expanded Access Programme (EAP) in Toronto, Canada.…”

mentioning

confidence: 99%

Incidence of and risk factors for tenofovir‐induced nephrotoxicity: a retrospective cohort study

et al. 2005

View full text Add to dashboard Cite

ObjectivesDespite the recent publication of case reports describing various manifestations of tenofovir-related nephrotoxicity, data regarding the incidence of and risk factors for this adverse effect are currently lacking. MethodsA retrospective cohort study of patients from four centres in Toronto, Canada, enrolled in the tenofovir expanded access programme with a minimum of 3 months follow up, was carried out. ResultsA total of 172 patients receiving tenofovir disoproxil fumarate (TDF) for a median of 16 months (range 3-25 months) were included in the study. Seven (4%) patients developed grade 1 (444 mmol/ L from baseline) increases in serum creatinine (SCr) during follow up; no patient developed grade 2 or higher nephrotoxicity. Fifteen (8.7%) patients had an increase in SCr of greater than 1.5 times baseline values during follow up. Four (2.3%) patients discontinued TDF because of an increase in SCr and/or abnormal urinalysis. Of 62 patients with a urinalysis, grade 1 or higher proteinuria (o 3 g/L) was observed in 27 (43%) patients. Only baseline SCr [odds ratio (OR) 5 0.51 per 10 mmol/L increase; P 5 0.0005] and baseline creatinine clearance (1.26 per 10 mL/min increase; P 5 0.01) were significantly associated with ever having a 1.5-fold increase in serum creatinine. Twenty-eight (16%) and 11 (6%) patients developed grade 1 (serum phosphorus 0.71 mmol/L) and grade 2 (serum phosphorus 0.61 mmol/L) hypophosphataemia during follow-up, respectively. ConclusionsAlthough slight increases in SCr did occur after starting TDF, clinically significant nephrotoxicity was rare. The clinical significance of TDF-related hypophosphataemia and proteinuria requires further study.Keywords: adverse effects, anti-HIV agents, creatinine, kidney, tenofovir IntroductionTenofovir disoproxil fumarate (TDF) is the only nucleotide analogue currently available for the management of HIV infection. The efficacy of TDF was initially established in two clinical trials with antiretroviral (ARV)-experienced patients, in which the addition of TDF to stable background therapy resulted in a significant decrease in viral load relative to placebo, with a similar incidence of adverse effects [1]. In addition, study GS-903 established TDF as a comparable alternative to stavudine when used in combination with lamivudine and efavirenz in ARV-naive patients, while eliciting less mitochondrial and metabolic toxicity [2]. The convenience of once-daily administration coupled with a favourable toxicity profile has rendered TDF a welcome addition to the ARV arsenal. Importantly, unlike structurally related nucleotide analogues such as cidofovir and adefovir, clinically significant nephrotoxicity did not emerge as a treatment-limiting adverse effect of TDF in the clinical trials. Furthermore, the renal safety profile of TDF was similar to that of stavudine over 144 weeks of followup in study However, post-marketing experience with TDF has raised the possibility that nephrotoxicity may be an uncommon but important adverse effect of this agent. Several c...

show abstract

Fanconi syndrome and renal failure induced by tenofovir: A first case report

Cited by 316 publications

References 11 publications

Incidence and Predictors of Acute Kidney Injury in an Urban Cohort of Subjects with HIV and Hepatitis C Virus Coinfection

Incidence and Predictors of Acute Kidney Injury in an Urban Cohort of Subjects with HIV and Hepatitis C Virus Coinfection

Minor changes in calculated creatinine clearance and anion‐gap are associated with tenofovir disoproxil fumarate‐containing highly active antiretroviral therapy

Incidence of and risk factors for tenofovir‐induced nephrotoxicity: a retrospective cohort study

Contact Info

Product

Resources

About