JAIDS Journal of Acquired Immune Deficiency Syndromes:
Brief Report: Clinical Science
Renal Tubular Dysfunction Associated With Tenofovir Therapy: Report of 7 Cases
Peyrière, Hélène PharmD, PhD*; Reynes, Jacques MD, PhD†; Rouanet, Isabelle MD‡; Daniel, Nathalie MD§; de Boever, Corinne Merle MD†; Mauboussin, Jean-Marc MD‡; Leray, Hélène MD∥; Moachon, Laurence MD¶; Vincent, Denis MD, PhD‡; Salmon-Céron, Dominique MD, PhD§
From the *Department of Medical Pharmacology, Lapeyronie Hospital, CHU Montpellier, Montpellier; ∥Department of Nephrology, Lapeyronie Hospital, Montpellier; †Department of Infectious Diseases, Gui de Chauliac Hospital, CHU Montpellier, Montpellier; ‡Department of Internal Medicine A–Pneumology Department, Caremeau Hospital, Nîmes; and §Department of Internal Medicine and Infectious Diseases, and ¶Pharmacovigilance Center, Cochin Hospital, University Paris V, Paris, France.
Received for publication June 23, 2003; accepted November 24, 2003.
Reprints: Jacques Reynes, Department of Infectious Diseases, Gui de Chauliac Hospital, CHU Montpellier, F-34295 Montpellier, France (e-mail: firstname.lastname@example.org).
We describe 7 cases of renal tubular injury in HIV-infected patients receiving an antiretroviral regimen containing tenofovir. Our patients (5 women and 2 men) developed renal tubular dysfunction, with hypophosphatemia, normoglycemic glycosuria, proteinuria, and decrease of creatinine clearance. The first biologic signs of renal toxicity were observed after duration of tenofovir treatment from 5 weeks to 16 months, and they resolved less than 4 months after discontinuation of tenofovir. Six patients had a low body weight (<60 kg). Five patients received low doses of ritonavir, and 1 received didanosine. In 5 patients, the signs resolved with the discontinuation of only the tenofovir. A renal biopsy performed in 1 patient was consistent with tubulointerstitial injury. Proximal tubulopathy appears to be a rare adverse effect of long-term tenofovir therapy. In patients with low weight or mild preexisting renal impairment, regular monitoring of tubulopathy markers could lead to early detection of this dysfunction.
Tenofovir (Viread; Gilead, Foster City, CA) is a nucleotide analogue used in the treatment of HIV infection. 1 Tenofovir is extensively excreted by the renal route by means of glomerular filtration and active tubular secretion. 2 This drug is structurally close to adefovir and cidofovir, which are used in the treatment of hepatitis B infection and cytomegalovirus infection, respectively. 1,3 High doses of adefovir and cidofovir have been involved in renal injuries. 4 Moreover, 2 cases of Fanconi syndrome have been previously reported with cidofovir. 5,6 Until now, few cases of Fanconi syndrome and acute renal failure have been described with tenofovir. 7–10 We report 7 new cases of renal tubular injury in patients treated with tenofovir.
A 48-year-old HIV-infected woman had been treated with ritonavir/lopinavir, lamivudine, efavirenz, and tenofovir since August 2001. In addition, the patient received fenofibrate and pravastatin for dyslipidemia. Before starting tenofovir, her serum creatinine level was normal. In March 2002, laboratory tests showed phosphatemia at 0.39 mmol/L, proteinuria at 1.7 g/L, glycosuria at 27.5 mmol/L, and serum creatinine level at 88 μmol/L. Glycemia, creatine kinase, and aminotransferase levels were normal. One week later, the patient complained of paresthesia in the lower back and legs, leading to the discontinuation of pravastatin and fenofibrate. The pain persisted, however, and 1 week later, biologic test results remained abnormal. At that time, the tenofovir plasma level was 380 ng/mL (15 hours after drug administration). Urinary protein electrophoresis showed albumin of 26.3%, α1-glycoprotein of 24.5%, α2-glycoprotein of 24.7%, β-microglobulin of 10.8%, and γ-globulin of 13.7%. Chromatography of urinary amino acid showed severe hyperaminoaciduria with citrullinuria, compatible with tubulopathy. All antiretroviral agents were stopped. Clinical symptoms disappeared within 1 week, and laboratory abnormalities returned to baseline values within 3 months.
A 56-year-old HIV-infected woman had been treated with ritonavir/lopinavir, lamivudine, efavirenz, and tenofovir since May 2001. In addition, she received fenofibrate for dyslipidemia. Before starting tenofovir, her serum creatinine level was normal. In March 2002, the patient complained of pains in the legs and elbows. Laboratory tests showed phosphatemia at 0.72 mmol/L, proteinuria at 1.59 g/L, glycosuria at 7.7 mmol/L, and serum creatinine level at 78 μmol/L. Glycemia, creatine kinase, and aminotransferase levels were normal. Urinary protein electrophoresis showed albumin of 39.8%, α1-glycoprotein of 18.8%, β2-glycoprotein of 21.8%, β-microglobulin of 9%, and γ-globulin of 10.6%, compatible with renal tubulopathy. Only the tenofovir was stopped. The pains disappeared within 1 week, and laboratory abnormalities returned to baseline values within 3 months.
A 49-year-old man had been treated with didanosine, lamivudine, ritonavir, amprenavir, and tenofovir since August 2001. Before starting tenofovir, his serum creatinine level was normal. In May 2002, laboratory tests showed phosphatemia at 0.41 mmol/L, proteinuria at 1.15 g/L, glycosuria at 0.8 mmol/L, and serum creatinine level at 101 μmol/L. Glycemia and aminotransferase levels were normal. Urinary protein electrophoresis showed albumin of 47.4%, α1-glycoprotein of 10%, α2-glycoprotein of 21.1%, β-microglobulin of 9.2%, and γ-globulin of 12.3%. Only the tenofovir was stopped. Within 3 months, laboratory abnormalities normalized.
A 35-year-old HIV-infected woman, coinfected with hepatitis C virus (HCV), had been followed for Crohn disease since 1983. In May 2001, a new treatment combined abacavir, tenofovir, and ritonavir/lopinavir. When this tritherapy was started, the patient presented with persistent diarrhea related to her Crohn disease, her body weight was 38 kg, and her serum creatinine level was normal. With the new antiretroviral regimen, she presented a gain of body weight of 9 kg (47 kg). In April 2002, laboratory tests showed proteinuria at 1.86 g per 24 hours, glycosuria at 8.2 mmol/L, and serum creatinine level at 349 μmol/L. Only the tenofovir was stopped and replaced by lamivudine. Within 4 months, biologic parameters returned to normal values.
A 42-year-old HIV-infected woman had been treated with abacavir, ritonavir/lopinavir, lamivudine, and tenofovir since November 2001. Before starting tenofovir, her serum creatinine level was normal. Since the start of tenofovir, phosphatemia progressively decreased to a value of 0.23 mmol/L in September 2002, which led to phosphorus supplementation. Concomitantly, neurologic symptoms related to HIV gradually worsened. In March 2003, laboratory tests showed proteinuria at 0.78 g/L, normoglycemic glycosuria at 19.2 mmol/L, and serum creatinine level at 135 μmol/L. Within 10 months, the body weight of the patient decreased to 38 kg. At that time, the tenofovir plasma level, measured 16 hours after administration, was 1159 ng/mL. Only the tenofovir was stopped. Within 3 months, laboratory abnormalities significantly improved, and a body weight gain of 11 kg was observed.
A 41-year-old HIV-infected woman coinfected with HCV had received abacavir, nevirapine, and tenofovir since November 2001. Before starting tenofovir, her serum creatinine level was normal. In August 2002, the patient started treatment against HCV infection with ribavirin and pegylated (PEG)-interferon. In March 2003, the patient complained of paresthesia and myalgia in her lower limbs. Laboratory parameters showed phosphatemia at 0.51 mmol/L, proteinuria at 0.56 g/L, normoglycemic glycosuria at 0.3 mmol/L, and serum creatinine level at 84 μmol/L. In addition, anemia was observed with hemoglobinemia at 7.5 g/dL. Within 10 months, the body weight of the patient decreased to 40 kg. Urinary protein electrophoresis showed albumin of 29.1%, compatible with renal tubular injury. At that time, the tenofovir plasma level, measured 16 hours after administration, was 804 ng/mL. Only the tenofovir was stopped. Within 2 weeks, laboratory abnormalities normalized and a body weight gain of 4 kg was observed.
A 57-year-old HIV-infected man had been treated with lamivudine, abacavir, and tenofovir since June 2003. Before starting tenofovir, the patient received atazanavir with the same nucleoside reverse transcriptase inhibitors (NRTIs) but stopped after 3 months because of hyperglycemia. His serum creatinine level was normal. The patient received metformin and glibenclamide for hyperglycemia, rilmenidine for hypertension, and cotrimoxazole for Pneumocystis prophylaxis. Five weeks after initiation of the tenofovir, the patient suddenly developed acute renal failure, with serum creatinine level at 376 μmol/L, proteinuria at 2.7 g/L, (6.2 g per 24 hours) and hematuria. Other laboratory tests showed phosphatemia at 0.57 mmol/L, metabolic acidosis, and normoglycemic glycosuria at 31 mmol/L. A renal biopsy revealed tubulointerstitial nephropathy with a primarily lymphocytic infiltrate. Glomeruli were normal. All drugs were discontinued. One month later, serum creatinine level was at 193 μmol/L, with persistent proteinuria and glycosuria. Within 3 months, laboratory abnormalities significantly improved.
Demographic data are reported in Table 1, and biologic data are summarized in Table 2.
We present 7 cases of renal injury associated with tenofovir therapy. Some renal disorders observed in our patients are consistent with Fanconi syndrome, including proximal renal tubular acidosis, normoglycemic glycosuria, hypophosphatemia, hypouricemia, hypokalemia, generalized aminoaciduria, and proteinuria. 11 In some cases, acute renal failure may be observed.
Tenofovir, like cidofovir and adefovir, is an acyclic nucleoside phosphonate. 4 The 3 drugs are excreted by glomerular filtration and active tubular secretion. In the proximal tubule, cidofovir and adefovir interact with more than 1 renal transporter. They enter the renal cells on human renal organic anion transporter 1 (hOATI) and exit on multidrug resistance-associated protein 2 (Mrp-2). 3,11 Cidofovir and high-dose adefovir have been previously involved in renal dysfunction, and hOAT1 seems to play an active role in nephrotoxicity associated with these drugs. 4,12 Although efficiently transported by hOAT1, tenofovir shows weak cytotoxicity in isolated human proximal tubular cells. 4,13 In addition, a recent study showed that tenofovir does not seem to interfere with mitochondrial function, as suggested previously in studies relating nephrotoxicity to adefovir. 14,15 Finally, in a clinical trial, the safety profile of tenofovir was reported to be similar to that of placebo. 16
Our 7 patients had been treated with tenofovir for 5 to 64 weeks when the first symptoms of renal dysfunction occurred. In all patients, laboratory abnormalities rapidly improved after stopping the tenofovir. It seems unlikely that other drugs were responsible for renal dysfunction, because in 5 patients, only the tenofovir was discontinued.
A median decrease in creatinine clearance of 46% (range: 20%–78%) was observed. At baseline, some patients presented a decrease in creatinine clearance (calculated with the formula of Cockroft and Gault), despite serum creatinine levels showing normal ranges (see Table 2). Six patients had a low body weight. With these lightweight patients, serum creatinine level seems a poor parameter by which to evaluate renal function, and we recommend systematically calculating creatinine clearance.
Pharmacokinetics of tenofovir in HIV-infected patients showed median steady-state peak concentrations of 326 ng/mL and a trough value of about 40 ng/mL. 1 Plasma levels of tenofovir were measured in 3 patients at the time of renal dysfunction. Results showed high values (ie, 380 ng/mL, 1159 ng/mL, and 804 ng/mL [about 16 hours after drug administration], respectively). In animal models, nephrotoxicity seems to be dose dependent. Thus, this dose dependence could be one of the potential mechanisms of tenofovir-related renal complications.
In recent publications, 4 cases of Fanconi syndrome, 2 cases of acute renal failure, and 1 case of nephrogenic insipidus diabetes have been reported. 7–10,17 The time lapse between initiation of tenofovir and the onset of renal abnormalities is variable: 4 to 7 weeks in some cases 8,9,17 and several months in others. 7,10
A renal biopsy was performed in some published cases and showed acute tubular necrosis with normal glomeruli. 7–10 In our cases, only 1 renal biopsy was performed in patient 7. Results were in accordance with data reported in the literature (ie, tubulointerstitial nephropathy with normal glomeruli). In this patient, conventional immunofluorescence with anti-immunoglobulin and anti-C3 antibodies was negative. Furthermore, mild “tubular” proteinuria and glycosuria observed in other cases were consistent with a tubular source rather than with a glomerular leak.
In 5 cases, ritonavir was associated with antiretroviral regimens. This drug has been previously involved in acute renal failure. 18 Moreover, coadministration of ritonavir and lopinavir is known to increase pharmacokinetic parameters of tenofovir (maximum concentration [Cmax], +31%; minimum concentration [Cmin], +29%; area under the curve [AUC], +34%). 19 Ritonavir has been shown to be a potent inhibitor of Mrp-2–mediated transport. 20 As shown for adefovir and cidofovir, we suggest that Mrp-2 transports tenofovir outside renal tubules. Inhibition of Mrp-2 by ritonavir in patients taking tenofovir could be an explanation of the tubular dysfunction observed.
One patient (no. 3) has taken didanosine associated with tenofovir. Didanosine alone may be nephrotoxic, because 1 case of Fanconi syndrome has been reported. 21 Pharmacokinetic data showed a significant increase of bioavailability of didanosine when it is taken with tenofovir. 22 A recent publication reports the case of an HIV-infected patient with chronic renal insufficiency who developed acute renal failure and severe lactic acidosis when tenofovir was added to his antiretroviral regimen, including didanosine. 17
All our patients were extensively pretreated with NRTIs, which are known to induce mitochondrial defects. Even if an in vitro study showed that tenofovir does not induce mitochondrial toxicity, we speculate that after several months of therapy, tenofovir could worsen latent tubular injury in patients with a mitochondrial defect caused by previous treatment with NRTIs.
According to data presented here, occurrence of renal toxicity seems to focus on patients (1) with low body weight or altered renal function (low creatinine clearance) at baseline, (2) extensively pretreated with NRTIs and/or all nephrotoxic drugs, or (3) receiving ritonavir.
In conclusion, intensive renal monitoring, including creatinine clearance, proteinuria, and glycosuria, is essential at baseline and during treatment with tenofovir. Risk factors of nephrotoxicity and pertinence of therapeutic drug monitoring of tenofovir should be evaluated in prospective safety studies.
The authors thank Gilbert Deray, MD (Hôpital Pitié-Salpétrière, Paris), for his helpful comments and Gilles Peytavin, PharmD (Hôpital Bichat, Paris), for the measurement of tenofovir plasma levels.
1. Barditch-Crovo P, Deeks SG, Collier A, et al. Phase I/II trial of the pharmacokinetics, safety and antiretroviral activity of tenofovir disoproxil fumarate in human immunodeficiency virus-infected adults. Antimicrob Agents Chemother. 2001; 45:2733–2739.
2. Antoniou T, Park-Wyllie LY, Tseng AL. Tenofovir: a nucleotide analog for the management of human immunodeficiency virus infection. Pharmacotherapy. 2003; 23:29–43.
3. Cundy KC. Clinical pharmacokinetics of the antiviral nucleotide analogues cidofovir and adefovir. Clin Pharmacokinet. 1999; 36:127–143.
4. Cihlar T, Ho ES, Lin DC, et al. Human renal organic anion transporter 1 (hOAT1) and its role in the nephrotoxicity of antiviral nucleotide analogs. Nucleosides Nucleotides Nucleic Acids. 2001; 20:641–648.
5. Vittecoq D, Dumitrescu L, Beaufils H, et al. Fanconi syndrome associated with cidofovir therapy. Antimicrob Agents Chemother. 1997; 41:1846.
6. Purohit N, Durr J, Lopez R. Cidofovir induced Fanconi syndrome and nephrogenic diabetes insipidus. Am J Kidney Dis. 2002; 39:26.
7. Verhelst D, Monge M, Meynard JL, et al. Fanconi syndrome and renal failure induced by tenofovir: a first case report. Am J Kidney Dis. 2002; 40:1331–1333.
8. Coca S, Perazella MA. Acute renal failure associated with tenofovir: evidence of drug-induced nephrotoxicity. Am J Med Sci. 2002; 324:342–344.
9. Créput C, Gonzalez-Canali G, Hill G, et al. Renal lesions in HIV-1-positive patient treated with tenofovir. AIDS. 2003; 17:935–937.
10. Karras A, Lafaurie M, Furco A, et al. Tenofovir-related nephrotoxicity in human immunodeficiency virus-infected patients: three cases of renal failure, Fanconi syndrome, and nephrogenic diabetes insipidus. Clin Infect Dis. 2003; 36:1070–1073.
11. Izzedine H, Launay-Vacher V, Isnard-Bagnis C, et al. Drug-induced Fanconi's syndrome. Am J Kidney Dis. 2003; 41:292–309.
12. Ho ES, Lin DC, Mendel DB, et al. Cytotoxicity of antiviral nucleotides adefovir and cidofovir is induced by the expression of human renal organic anion transporter 1. J Am Soc Nephrol. 2000; 11:383–393.
13. Cihlar T, Birkus G, Greenwalt DE, et al. Tenofovir exhibits low cytotoxicity in various human cell types: comparison with other nucleoside reverse transcriptase inhibitors. Antiviral Res. 2002; 54:37–45.
14. Tanji N, Tanji K, Kambham N, et al. Adefovir nephrotoxicity: possible role of mitochondrial DNA depletion. Hum Pathol. 2001; 32:734–740.
15. Birkus G, Hitchcock MJ, Cihlar T, et al. Assessment of mitochondrial toxicity in human cells treated with tenofovir: comparison with other nucleoside reverse transcriptase inhibitors. Antimicrob Agents Chemother. 2002; 46:716–723.
16. Schooley RT, Ruane P, Myers RA, et al. Tenofovir DF in antiretroviral-experienced patients: results from a 48-weeks, randomized, double-blind study. AIDS. 2002; 16:1257–1263.
17. Murphy MD, O'Hearn M, Chou S. Fatal lactic acidosis and acute renal failure after addition of tenofovir to an antiretroviral regimen containing didanosine. Clin Infect Dis. 2003; 36:1082–1085.
18. Deray G, Bochet M, Katlama C, et al. Néphrotoxicité du ritonavir. Presse Med. 1998; 27:1801–1803.
19. Kearney BP, Flaherty J, Wolf J, et al. Lack of clinically relevant drug-drug interactions between tenofovir DF and efavirenz, indinavir, lamivudine and lopinavir/ritonavir in healthy subjects. Presented at the 8th European Conference on Clinical Aspects and Treatment of HIV-Infection, Athens, 2001.
20. Gutmann H, Fricker G, Drewe J, et al. Interactions of HIV protease inhibitors with ATP-dependent drug export proteins. Mol Pharmacol. 1999; 56:383–389.
21. Crowther MA, Callaghan W, Hodsman AB, et al. Dideoxyinosine-associated nephrotoxicity. AIDS. 1993; 7:131–132.
22. Flaherty J, Kearney B, Wolf J, et al. Coadministration of tenofovir DF (TDF) and didanosine (ddI): a pharmacokinetic (PK) and safety evaluation [abstract I-1729]. Presented at the 41st Interscience Conference on Antimicrobial Agents and Chemotherapy, Chicago, December 2001.
This article has been cited 105 time(s).
Internal MedicineAbacavir/Lamivudine versus Tenofovir/Emtricitabine with Atazanavir/Ritonavir for Treatment-naive Japanese Patients with HIV-1 Infection: A Randomized Multicenter TrialInternal Medicine
AIDS Research and TherapyRenal safety of tenofovir containing antiretroviral regimen in a Singapore cohortAIDS Research and Therapy
Hiv Clinical Trials
Serious renal impairment occurs rarely with use of tenofovir
Hiv Clinical Trials, 7(2):
Clinical Pharmacology & TherapeuticsThe effect of lopinavir/ritonavir on the renal clearance of tenofovir in HIV-infected patientsClinical Pharmacology & Therapeutics
Tenofovir-related acute kidney injury and proximal tubule dysfunction precipitated by diclofenac: a case of drug-drug interaction
Clinical Nephrology, 71(5):
Evaluation of hypophosphataemia in tenofovir disoproxil fumarate (TDF)-exposed and TDF-unexposed HIV-infected out-patients receiving highly active antiretroviral therapy
Hiv Medicine, 7(7):
Journal of General Internal MedicineAcquired Fanconi's syndrome associated with tenofovir therapyJournal of General Internal Medicine
Tenofovir use is associated with a reduction in calculated glomerular filtration rates in the Swiss HIV Cohort Study
Antiviral Therapy, 12(8):
HautarztThe side effects of antiretroviral therapyHautarzt
Expert Opinion on Drug Metabolism & ToxicologyTenofovir disoproxil fumarate for the treatment of HIV infectionExpert Opinion on Drug Metabolism & Toxicology
ThescientificworldjournalEarly onset of tenofovir-induced renal failure: Case report and review of the literatureThescientificworldjournal
Effect of tenofovir on renal glomerular and tubular function
Clinical Drug Investigation
Renal safety of tenofovir in HIV-infected children - A prospective, 96-week longitudinal study
Clinical Drug Investigation, 27(8):
Expert Opinion on Drug SafetyNephrotoxicity associated with antiretroviral therapy in HIV-infected patientsExpert Opinion on Drug Safety
Qjm-An International Journal of MedicineRenal function and mitochondrial cytopathy (MC): more questions than answersQjm-An International Journal of Medicine
Clinical Infectious DiseasesPredictors of Kidney Tubular Dysfunction in HIV-Infected Patients Treated with Tenofovir: A Pharmacogenetic StudyClinical Infectious Diseases
Assessment of renal abnormalities in 107 HIV patients treated with tenofovir
Antimicrobial Agents and ChemotherapyBiological effects of short-term or prolonged administration of 9-[2-(phosphonomethoxy)propyl]adenine (tenofovir) to newborn and infant rhesus macaquesAntimicrobial Agents and Chemotherapy
Antiretrovirals, part II: Focus on non-protease inhibitor antiretrovirals (NRTIs, NNRTIs, and fusion inhibitors)
Clinical Infectious Diseases
Changes in renal function associated with tenofovir disoproxil fumarate treatment, compared with nucleoside reverse-transcriptase inhibitor treatment
Clinical Infectious Diseases, 40(8):
The impact of human genetic variation on HIV disease in the era of HAART
AIDS Reviews, 8(2):
Antimicrobial Agents and ChemotherapyIn vitro cytotoxicity and mitochondrial toxicity of tenofovir alone and in combination with other antiretrovirals in human renal proximal tubule cellsAntimicrobial Agents and Chemotherapy
Enfermedades Infecciosas Y Microbiologia ClinicaAssessment and management of kidney disease in the HIV-1-infected patient. A practical reviewEnfermedades Infecciosas Y Microbiologia Clinica
Hiv Clinical Trials
Hepatic and renal safety profile of tenofovir in HIV-infected patients with hepatitis C, including patients on interferon plus ribavirin
Hiv Clinical Trials, 6(5):
Journal of Antimicrobial ChemotherapyEffectiveness and safety of didanosine, lamivudine and efavirenz versus zidovudine, lamivudine and efavirenz for the initial treatment of HIV-infected patients from the Spanish VACH cohortJournal of Antimicrobial Chemotherapy
AIDS Patient Care and StdsRenal Function in Patients with Preexisting Renal Disease Receiving Tenofovir-Containing Highly Active Antiretroviral Therapy in the HIV Outpatient StudyAIDS Patient Care and Stds
Minor changes in calculated creatinine clearance and anion-gap are associated with tenofovir disoproxil fumarate-containing highly active antiretroviral therapy
Hiv Medicine, 7(2):
Journal of Infectious Diseases
Toward a pharmacogenetic understanding of nucleotide and nucleoside analogue toxicity
Journal of Infectious Diseases, 194():
Amprenavir and didanosine are associated with declining kidney function among patients receiving tenofovir
Renal disease in patients with HIV infection - Epidemiology, pathogenesis and management
Osteoporosis InternationalRisk factors for decreased bone density and effects of HIV on bone in the elderlyOsteoporosis International
American Journal of Kidney DiseasesSubclinical Tubular Injury in HIV-Infected Individuals on Antiretroviral Therapy: A Cross-sectional AnalysisAmerican Journal of Kidney Diseases
Improvement in dyslipidaemia after switching stavudine to tenofovir and replacing protease inhibitors with efavirenz in HIV-infected children
Antiviral Therapy, 10(8):
Pediatric NephrologyNephrotoxicity in a child with perinatal HIV on tenofovir, didanosine and lopinavir/ritonavirPediatric Nephrology
Current Medicinal Chemistry
Treating chronic hepatitis B: Today and tomorrow
Current Medicinal Chemistry, 13():
Iatrogenic cushing's syndrome and polyuria-polydipsia in an HIV-infected patient treated with ritonavir
Acta Endocrinologica-Bucharest, 4(3):
Hiv MedicineFactors associated with renal dysfunction within an urban HIV-infected cohort in the era of highly active antiretroviral therapyHiv Medicine
Clinical Infectious Diseases
Tenofovir-associated acute and chronic kidney disease: A case of multiple drug interactions
Clinical Infectious Diseases, 42(2):
Current Pharmaceutical Design
Current HIV treatment guidelines - An overview
Current Pharmaceutical Design, 12(9):
Current Pharmaceutical Design
Understanding and avoiding antiretroviral adverse events
Current Pharmaceutical Design, 12(9):
Clinical Journal of the American Society of NephrologyHighly active antiretroviral therapy and the kidney: An update on antiretroviral medications for nephrologistsClinical Journal of the American Society of Nephrology
Journal of Antimicrobial ChemotherapyGlomerular filtration rates in HIV-infected patients treated with and without tenofovir: a prospective, observational studyJournal of Antimicrobial Chemotherapy
PharmacogenomicsPharmacogenetics of tenofovir treatmentPharmacogenomics
AIDS Research and Human Retroviruses
Urinary beta(2)-microglobulin as a possible sensitive marker for renal injury caused by tenofovir disoproxil furnarate
AIDS Research and Human Retroviruses, 22(8):
Clinical Infectious DiseasesSevere renal dysfunction and risk factors associated with renal impairment in HIV-infected adults in Africa initiating antiretroviral therapyClinical Infectious Diseases
Journal of VirologyA Simian Immunodeficiency Virus-Infected Macaque Model To Study Viral Reservoirs That Persist during Highly Active Antiretroviral TherapyJournal of Virology
Clinical Infectious Diseases
Guidelines for the management of chronic kidney disease in HIV-infected patients: Recommendations of the HIV Medicine Association of the Infectious Diseases Society of America
Clinical Infectious Diseases, 40():
Incidence of and risk factors for tenofovir-induced nephrotoxicity: a retrospective cohort study
Hiv Medicine, 6(4):
PediatricsTenofovir disoproxil fumarate and an optimized background regimen of antiretroviral agents as salvage therapy for pediatric HIV infectionPediatrics
Antiretroviral treatment associated life-threatening adverse events
Medicina Clinica, 126():
The safety of tenofovir disoproxil fumarate for the treatment of HIV infection in adults: the first 4 years
Expert Opinion on PharmacotherapyExperience with tenofovir disoproxil fumarate for antiretroviral therapyExpert Opinion on Pharmacotherapy
Hiv MedicineComparison of glomerular filtration rate estimates vs. 24-h creatinine clearance in HIV-positive patientsHiv Medicine
Antimicrobial Agents and ChemotherapyPopulation pharmacokinetics of tenofovir in human immunodeficiency virus-infected patients taking highly active antiretroviral therapyAntimicrobial Agents and Chemotherapy
Clinical Infectious Diseases
HIV-associated renal diseases and highly active antiretroviral therapy-induced nephropathy
Clinical Infectious Diseases, 42():
Journal of InfectionIs tenofovir involved in hypophosphatemia and decrease of tubular phosphate reabsorption in HIV-positive adults?Journal of Infection
HepatologyTenofovir disoproxil fumarate: Role in hepatitis B treatmentHepatology
Renal safety of tenofovir disoproxil fumarate
AIDS Reader, 17(2):
Future VirologyRole of tenofovir in the treatment of chronic HBV infectionFuture Virology
Nature Reviews Drug DiscoveryAcyclic nucleoside phosphonates: A key class of antiviral drugsNature Reviews Drug Discovery
Current Pharmaceutical Design
Limitations of current antiretroviral agents and opportunities for development
Current Pharmaceutical Design, 12(9):
Expert Opinion on Drug SafetyCardiovascular & renal - Antiretroviral therapy and the kidney: balancing benefit and risk in patients with HIV infectionExpert Opinion on Drug Safety
Hypokalemia in HIV patients on tenofovir
Renal function in antiretroviral-experienced patients treated with tenofovir disoproxil fumarate associated with atazanavir/ritonavir
Antiviral Therapy, 12(1):
Virchows ArchivAcute interstitial nephritis of HIV-positive patients under atazanavir and tenofovir therapy in a retrospective analysis of kidney biopsiesVirchows Archiv
Mitochondrial toxicity of tenofovir, emtricitabine and abacavir alone and in combination with additional nucleoside reverse transcriptase inhibitors
Antiviral Therapy, 12(7):
Seminars in NephrologyAntiretroviral NephrotoxicitiesSeminars in Nephrology
Journal of VirologyAdjunctive passive immunotherapy in human immunodeficiency virus type 1-infected individuals treated with antiviral therapy during acute and early infectionJournal of Virology
Journal of Infectious DiseasesTenofovir nephrotoxicity: Focusing research questions and putting them into clinical contextJournal of Infectious Diseases
AIDS Research and Human RetrovirusesProgressive Renal Tubular Dysfunction Associated with Long-Term Use of Tenofovir DFAIDS Research and Human Retroviruses
Hiv MedicineTenofovir-associated renal and bone toxicityHiv Medicine
Journal of Infectious DiseasesSimian Immunodeficiency Virus-Infected Macaques Treated with Highly Active Antiretroviral Therapy Have Reduced Central Nervous System Viral Replication and Inflammation but Persistence of Viral DNAJournal of Infectious Diseases
Sex differences in antiretroviral therapy-associated intolerance and adverse events
Drug Safety, 28():
Nephrology Dialysis TransplantationPrevalence of chronic kidney disease in Chinese HIV-infected patientsNephrology Dialysis Transplantation
European Journal of PediatricsHypercalciuria is the main renal abnormality finding in Human Immunodeficiency Virus-infected children in VenezuelaEuropean Journal of Pediatrics
Tenofovir use is associated with an increase in serum alkaline phosphatase in the Swiss HIV Cohort Study
Antiviral Therapy, 13(8):
Proximal Tubular Dysfunction Associated With Tenofovir and Didanosine Causing Fanconi Syndrome and Diabetes Insipidus: A Report of 3 Cases
AIDS Reader, 19(3):
Tenofovir Nephrotoxicity-The Disconnect Between Clinical Trials and Real-World Practice
AIDS Reader, 19(3):
Nephrologie & TherapeutiqueKidney diseases in HIV-infected patientsNephrologie & Therapeutique
Journal of Chromatography B-Analytical Technologies in the Biomedical and Life SciencesQuantification of seven nucleoside/nucleotide reverse transcriptase inhibitors in human plasma by high-performance liquid chromatography with tandem mass-spectrometryJournal of Chromatography B-Analytical Technologies in the Biomedical and Life Sciences
Tenofovir for the Treatment of Hepatitis B Virus
Tenofovir disoproxil fumarate - A review of its use in the management of HIV infection
Expert Opinion on PharmacotherapyEfavirenz/emtricitabine/tenofovir disoproxil fumarate fixed-dose combination: first-line therapy for all?Expert Opinion on Pharmacotherapy
AIDS Patient Care and StdsKidney disease in the HIV-infected patientAIDS Patient Care and Stds
Expert Opinion on Drug SafetyTenofovir-induced kidney injuryExpert Opinion on Drug Safety
Plos OneRenal Function Declines More in Tenofovir-than Abacavir-Based Antiretroviral Therapy in Low-Body Weight Treatment-Naive Patients with HIV InfectionPlos One
Transplant Infectious DiseaseEfficacy of combined antiviral therapy with lamivudine and tenofovir in a liver transplanted girl with de novo hepatitis B virus infectionTransplant Infectious Disease
Journal of Biomedical ScienceDepletion of the cellular antioxidant system contributes to tenofovir disoproxil fumarate - induced mitochondrial damage and increased oxido-nitrosative stress in the kidneyJournal of Biomedical Science
Expert Opinion on Drug SafetyRenal toxicity associated with tenofovir useExpert Opinion on Drug Safety
Future VirologyCurrent assays for HIV-1 diagnostics and antiretroviral therapy monitoring: challenges and possibilitiesFuture Virology
Pediatric NephrologyUpdate on tenofovir toxicity in the kidneyPediatric Nephrology
Plos OneSwitching Tenofovir/Emtricitabine plus Lopinavir/r to Raltegravir plus Darunavir/r in Patients with Suppressed Viral Load Did Not Result in Improvement of Renal Function but Could Sustain Viral Suppression: A Randomized Multicenter TrialPlos One
JAIDS Journal of Acquired Immune Deficiency SyndromesImpact of Tenofovir on Renal Function in HIV-Infected, Antiretroviral-Naive PatientsJAIDS Journal of Acquired Immune Deficiency Syndromes
JAIDS Journal of Acquired Immune Deficiency SyndromesClinical and Genetic Determinants of Intracellular Tenofovir Diphosphate Concentrations in HIV-Infected PatientsJAIDS Journal of Acquired Immune Deficiency Syndromes
AIDSMetabolic bone disease in HIV infectionAIDS
tenofovir; tubular injury; nephropathy; HIV; Fanconi syndrome
© 2004 Lippincott Williams & Wilkins, Inc.
What does "Remember me" mean?
By checking this box, you'll stay logged in until you logout. You'll get easier access to your articles, collections,
media, and all your other content, even if you close your browser or shut down your
To protect your most sensitive data and activities (like changing your password),
we'll ask you to re-enter your password when you access these services.
What if I'm on a computer that I share with others?
If you're using a public computer or you share this computer with others, we recommend
that you uncheck the "Remember me" box.
Highlight selected keywords in the article text.
Data is temporarily unavailable. Please try again soon.
Readers Of this Article Also Read