Tenofovir-Associated Nephrotoxicty

Last updated April 10, 2015
Case Authors: 
Brian R. Wood, MD
Assistant Professor of Medicine
Division of Infectious Diseases
University of Washington School of Medicine
David H. Spach, MD's picture
David H. Spach, MD
Professor of Medicine
Division of Infectious Diseases
Clinical Director, Frontier AIDS Education and Training Center
University of Washington School of Medicine
Learning Objectives: 
  1. Identify factors that increase the risk of developing tenofovir-associated nephrotoxity.
  2. Summarize recommended monitoring for tenofovir-associated nephrotoxity.

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  1. Wyatt CM. Antiretroviral therapy and the kidney. Top Antivir Med. 2014;22:655-8.
  2. Hall AM, Bass P, Unwin RJ. Drug-induced renal Fanconi syndrome. QJM. 2013;107:261-9.
  3. Lucas GM, Ross MJ, Stock PG, et al. Clinical practice guideline for the management of chronic kidney disease in patients infected with HIV: 2014 update by the HIV Medicine Association of the Infectious Diseases Society of America. Clin Infect Dis. 2014;59:e96-138.
  4. Hall AM, Hendry BM, Nitsch D, Connolly JO. Tenofovir-associated kidney toxicity in HIV-infected patients: a review of the evidence. Am J Kidney Dis. 2011;57:773-80.
  5. Ryom L, Mocroft A, Kirk O, et al. Association between antiretroviral exposure and renal impairment among HIV-positive persons with normal baseline renal function: the D:A:D study. J Infect Dis. 2013;207:1359-69.
  6. Laprise C, Baril JG, Dufresne S, Trottier H. Association between tenofovir exposure and reduced kidney function in a cohort of HIV-positive patients: results from 10 years of follow-up. Clin Infect Dis. 2012;56:567-75.
  7. Scherzer R, Estrella M, Li Y, et al. Association of tenofovir exposure with kidney disease risk in HIV infection. AIDS. 2012;26:867-75.
  8. Horberg M, Tang B, Towner W, et al. Impact of tenofovir on renal function in HIV-infected, antiretroviral-naive patients. J Acquir Immune Defic Syndr. 2010;53:62-9.
  9. Herlitz LC, Mohan S, Stokes MB, Radhakrishnan J, D'Agati VD, Markowitz GS. Tenofovir nephrotoxicity: acute tubular necrosis with distinctive clinical, pathological, and mitochondrial abnormalities. Kidney Int. 2010;78:1171-7.
  10. Labarga P, Barreiro P, Martin-Carbonero L, et al. Kidney tubular abnormalities in the absence of impaired glomerular function in HIV patients treated with tenofovir. AIDS. 2009;23:689-96.
  11. Gervasoni C, Meraviglia P, Landonio S, et al. Low body weight in females is a risk factor for increased tenofovir exposure and drug-related adverse events. PLoS One. 2013;8:e80242.
  12. Mwafongo A, Nkanaunena K, Zheng Y, et al. Renal events among women treated with tenofovir/emtricitabine in combination with either lopinavir/ritonavir or nevirapine. AIDS. 2014;28:1135-42.
  13. Tourret J, Deray G, Isnard-Bagnis C. Tenofovir effect on the kidneys of HIV-infected patients: a double-edged sword? J Am Soc Nephrol. 2013;24:1519-27.
  14. Baxi SM, Greenblatt RM, Bacchetti P, et al. Common clinical conditions - age, low BMI, ritonavir use, mild renal impairment - affect tenofovir pharmacokinetics in a large cohort of HIV-infected women. AIDS. 2014;28:59-66.
  15. Goicoechea M, Liu S, Best B, et al. Greater tenofovir-associated renal function decline with protease inhibitor-based versus nonnucleoside reverse-transcriptase inhibitor-based therapy. J Infect Dis. 2008;197:102-8.
  16. Bonjoch A, Echeverría P, Perez-Alvarez N, et al. High rate of reversibility of renal damage in a cohort of HIV-infected patients receiving tenofovir-containing antiretroviral therapy. Antiviral Res. 2012;96:65-9.
  17. Cao Y, Han Y, Xie J, et al. Impact of a tenofovir disoproxil fumarate plus ritonavir-boosted protease inhibitor-based regimen on renal function in HIV-infected individuals: a prospective, multicenter study. BMC Infect Dis. 2013;13:301.
  18. Kerr SJ, Punyawudho B, Thammajaruk N, et al. Factors associated with daily tenofovir exposure in thai subjects taking combination antiretroviral therapy. AIDS Res Hum Retroviruses. 2014;31:368-74.
  19. Moss DM, Neary M, Owen A. The role of drug transporters in the kidney: lessons from tenofovir. Front Pharmacol. 2014;5:248.
  20. Nishijima T, Komatsu H, Higasa K, et al. Single nucleotide polymorphisms in ABCC2 associate with tenofovir-induced kidney tubular dysfunction in Japanese patients with HIV-1 infection: a pharmacogenetic study. Clin Infect Dis. 2012;55:1558-67.
  21. Pushpakom SP, Liptrott NJ, Rodríguez-Nóvoa S, et al. Genetic variants of ABCC10, a novel tenofovir transporter, are associated with kidney tubular dysfunction. J Infect Dis. 2011;204:145-53.
  22. Giacomet V, Cattaneo D, Viganò A, et al. Tenofovir-induced renal tubular dysfunction in vertically HIV-infected patients associated with polymorphisms in ABCC2, ABCC4 and ABCC10 genes. Pediatr Infect Dis J. 2013;32:e403-5.
  23. Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. Department of Health and Human Services. Baseline evaluation. May 1, 2014.
  24. Aberg JA, Gallant JE, Ghanem KG, et al. Primary care guidelines for the management of persons infected with HIV: 2013 update by the HIV Medicine Association of the Infectious Diseases Society of America. Clin Infect Dis. 2014;58:1-10.
  25. Liamis G, Milionis HJ, Elisaf M. Medication-induced hypophosphatemia: a review. QJM. 2010;103:449-59.
  26. Subramanian R, Khardori R. Severe hypophosphatemia. Pathophysiologic implications, clinical presentations, and treatment. Medicine (Baltimore). 2000;79:1-8.
  27. Del Palacio M, Romero S, Casado JL. Proximal tubular renal dysfunction or damage in HIV-infected patients. AIDS Rev. 2012;14:179-87.
  28. Oboho I, Abraham AG, Benning L, et al. Tenofovir use and urinary biomarkers among HIV-infected women in the Women's Interagency HIV Study (WIHS). J Acquir Immune Defic Syndr. 2013;62:388-95.
  29. Post FA, Wyatt CM, Mocroft A. Biomarkers of impaired renal function. Curr Opin HIV AIDS. 2010;5:524-30.
  30. Gutiérrez F, Fulladosa X, Barril G, Domingo P. Renal tubular transporter-mediated interactions of HIV drugs: implications for patient management. AIDS Rev. 2014;16:199-212.
  31. Holt SG, Gracey DM, Levy MT, et al. A consensus statement on the renal monitoring of Australian patients receiving tenofovir based antiviral therapy for HIV/HBV infection. AIDS Res Ther. 2014;11:35.
  32. Hamada Y, Nishijima T, Watanabe K, et al. High incidence of renal stones among HIV-infected patients on ritonavir-boosted atazanavir than in those receiving other protease inhibitor-containing antiretroviral therapy. Clin Infect Dis. 2012;55:1262-9.
  33. Yoshino M, Yagura H, Kushida H, et al. Assessing recovery of renal function after tenofovir disoproxil fumarate discontinuation. J Infect Chemother. 2011;18:169-74.
  34. Post F. Adverse events: ART and the kidney: alterations in renal function and renal toxicity. J Int AIDS Soc. 2014;17:19513.
  35. Sax PE, Zolopa A, Brar I, et al. Tenofovir alafenamide vs. tenofovir disoproxil fumarate in single tablet regimens for initial HIV-1 therapy: a randomized phase 2 study. J Acquir Immune Defic Syndr. 2014;67:52-8.