Tenofovir-Associated Kidney Toxicity in HIV-Infected Patients: A Review of the Evidence

• Published in: American journal of kidney diseases Vol. 57; no. 5; pp. 773 - 780
• Main Authors: Hall, Andrew M., MD, PhD, Hendry, Bruce M., MD, PhD, Nitsch, Dorothea, MD, MSc, Connolly, John O., MD, PhD
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.05.2011; Elsevier
• Subjects: Adenine - adverse effects; Adenine - analogs & derivatives; Animals; Biological and medical sciences; Fanconi syndrome; Fanconi Syndrome - chemically induced; Fanconi Syndrome - physiopathology; Glomerular Filtration Rate - drug effects; Glomerular Filtration Rate - physiology; HIV Infections - complications; HIV Infections - physiopathology; Human viral diseases; Humans; Infectious diseases; Kidney; Kidney Diseases - chemically induced; Kidney Diseases - etiology; Kidney Diseases - physiopathology; Kidney Tubules, Proximal - drug effects; Kidney Tubules, Proximal - physiopathology; Medical sciences; Nephrology; Nephrology. Urinary tract diseases; Nephropathies. Renovascular diseases. Renal failure; Organophosphonates - adverse effects; Risk Factors; Tenofovir; toxicity; Tubulopathies; Viral diseases; Viral diseases of the lymphoid tissue and the blood. Aids; Tenofovir; toxicity; Fanconi syndrome; Kidney; De Toni-Debré-Fanconi syndrome; Antiretroviral agent; Nephrology; RNA-directed DNA polymerase; Toxicity; Tubulopathy; Nucleotide analog; Review; Enzymopathy; Urology; Reverse transcriptase inhibitor; Nucleoside analog; Antiviral; Aminoacid disorder; Kidney disease; Immunopathology; Purine nucleotide; Acyclic nucleotide; Urinary system disease; Enzyme; Transferases; Enzyme inhibitor; Metabolic diseases; AIDS; Organic phosphonate; Immune deficiency; Genetic disease; Infection; Nucleotidyltransferases; Urinary system; Viral disease; Nephrotoxicity; Bibliographic review; Aminoaciduria
• ISSN: 0272-6386; 1523-6838
• DOI: 10.1053/j.ajkd.2011.01.022

Tenofovir (TDF) is an effective and widely used treatment for both human immunodeficiency virus (HIV) and hepatitis B virus infection. Although studies suggest that TDF has a low overall toxicity profile and only a modest effect on estimated glomerular filtration rate, numerous case reports have since appeared in the literature describing TDF-associated renal tubular dysfunction, and this is now a significant source of HIV-related referrals to nephrologists. The main target of toxicity appears to be the proximal tubule, and in severe cases, patients can develop renal Fanconi syndrome. We review findings from recent studies in this area performed by ourselves and others and discuss our direct experience as practicing nephrologists. In particular, we discuss: (1) the nature and extent of TDF-associated kidney toxicity in the HIV-infected population, (2) potential underlying mechanisms of toxicity in the proximal tubule, (3) risk factors for developing tubular dysfunction, and (4) suggested strategies to monitor patients on TDF therapy.