Fanconi-like syndrome and rhabdomyolysis in a person with HIV infection on highly active antiretroviral treatment including tenofovir

Callens, Steven

doi:10.1016/s0163-4453(03)00082-3

Cited by 33 publications

(18 citation statements)

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“…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.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2005

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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...

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Section: Introductionmentioning

confidence: 99%

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

et al. 2005

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“…For example, severe liver toxicity has been described for PIs like indinavir, nelfinavir, and ritonavir and for NNRTIs like nevirapine and efavirenz and different NRTIs like lamivudine (Carr et al, 2001;Clark et al, 2002). Nephrotoxicity is a common side effect of the NRTI tenofovir (Callens et al, 2003), and combination therapy leads to an aggravation of toxic reactions (Zimmermann et al, 2006).…”

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confidence: 99%

Relevance of the Organic Cation Transporters 1 and 2 for Antiretroviral Drug Therapy in Human Immunodeficiency Virus Infection

Jung

Lehmann²,

Rubbert³

et al. 2008

Drug Metab Dispos

132

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ABSTRACT:Carrier-mediated transport across cell membranes is an important determinant of activity, resistance, and toxicity of chemotherapeutic agents including antiretroviral (ARV) drugs (ARDs). The organic cation transporters (OCTs) 1 and 2 have been implicated in the translocation of different cationic drugs but so far were insufficiently tested for interactions with ARDs. Here, we assessed among cationic drugs commonly used in human immunodeficiency virus (HIV) therapy inhibitors and substrates of OCTs, and analyzed the tissue distribution of OCTs and their expression in lymph nodes (LNs), the primary intracellular target of HIV and ARDs. Inhibitors were identified by measuring the attenuated uptake of the radiolabeled model substrate 1-methyl-4-phenylpyridinium into OCTtransfected human embryonic kidney-293 cells in the presence of ARDs. Substrates were identified by measuring OCT-specific intracellular accumulation using liquid chromatography/tandem mass spectrometry. Inhibitory drugs were (in order of increasing potency): nelfinavir < ritonavir < saquinavir < indinavir < trimethoprim < pentamidine, with consistently lower IC 50 values determined for OCT1. Substrates with highest transport efficacy (V max /K m ) were lamivudine (OCT1, 8 l/mg protein/min; OCT2, 4.4 l/mg protein/min) and zalcitabine (OCT1, 4.1 l/mg protein/min; OCT2, 2.6 l/mg protein/min). Using quantitative real-time polymerase chain reaction, a marked expression level of OCT1 was detected in human samples of liver, ovary, prostate, and testis, and of OCT2 in kidney, colon, heart, skeletal muscle, and testis. Expression of OCTs in LNs was low in HIV-negative control individuals but dramatically increased in HIV-infected persons. These data suggest that drug interactions about the OCTs may be relevant for the ARV therapy, in particular by influencing drug accession to infected tissues and hepatic or renal elimination.

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“…18,20,21 To the best of our knowledge, there is only one reported case of a 47-year-old HIVpositive female on HAART, including tenofovir, developing symptomatic rhabdomyolysis, evidence of proximal tubular dysfunction, and AKI. 22 However, this episode of AKI was not severe enough to necessitate hemodialysis. An asymptomatic rise in CK level in a HIV-infected patient taking tenofovir has also been reported, 23 but the previous case highlights a symptomatic presentation.…”

Section: Discussionmentioning

confidence: 95%

Severe recurrent rhabdomyolysis-induced acute kidney injury in a HIV-infected patient on antiretroviral therapy

2013

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Antiretroviral medications, specifically tenofovir, have been linked to acute tubular necrosis in humans with a suggested mechanism of direct tubular injury. Rhabdomyolysis has rarely been described in patients on highly active antiretroviral therapy (HAART). To the best of our knowledge, severe recurrent rhabdomyolysis-induced acute kidney injury (AKI) in a HIV-infected patient on two different triple antiretroviral regimens has not been reported. We present a HIV-positive patient who first developed heme pigment-induced oliguric AKI due to non-traumatic rhabdomyolysis, 5 days after initiation of triple antiretroviral therapy. Renal function normalized 2 months after discontinuation of antiretroviral therapy. Two weeks after reinitiating a different HAART regimen, our patient developed a recurrent episode of severe rhabdomyolysis-induced AKI. Both rhabdomyolysis and AKI resolved after discontinuation of the second antiretroviral regimen. First tenofovir and subsequently abacavir seem to be the likely culprits in our case. We also briefly discuss tenofovir nephrotoxicity followed by a literature review on rhabdomyolysis in HIV-infected patients.

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Fanconi-like syndrome and rhabdomyolysis in a person with HIV infection on highly active antiretroviral treatment including tenofovir

Cited by 33 publications

References 5 publications

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

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

Relevance of the Organic Cation Transporters 1 and 2 for Antiretroviral Drug Therapy in Human Immunodeficiency Virus Infection

Severe recurrent rhabdomyolysis-induced acute kidney injury in a HIV-infected patient on antiretroviral therapy

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