Pediatric Nephrology

, Volume 28, Issue 7, pp 1011–1023 | Cite as

Update on tenofovir toxicity in the kidney



Tenofovir (TFV) is a widely used and effective treatment for HIV infection. Numerous studies have shown that TFV exposure is associated with small but significant declines in estimated glomerular filtration rate (eGFR). However, TFV toxicity is targeted mainly at the proximal tubule (PT), and in severe cases can cause the renal Fanconi syndrome or acute kidney injury. Severe toxicity occurs in a minority of patients, but milder PT dysfunction is more common; the long-term significance of this on kidney and bone health is uncertain. Recent work suggests that changes in eGFR on TFV therapy might be explained by inhibition of PT creatinine secretion rather than actual alterations in glomerular function. Risk factors for nephrotoxicity include pre-existing kidney disease, increased age, and low body mass. Mitochondria in the PT are the targets of TFV toxicity, but the exact mechanisms remain unclear. Substantial improvement of renal function occurs in many patients with TFV toxicity upon stopping therapy, but function does not always return to baseline. In recent years, TFV usage has been extended to new clinical spheres, including pediatrics, resource-poor settings and treatment of Hepatitis B infection; theoretical reasons exist as to why some of these patients might be at higher or lower risk of TFV toxicity. Finally, strategies have been proposed to prevent TFV toxicity or enhance recovery.


Hepatitis B HIV Proximal tubule Renal Fanconi syndrome Tenofovir 



Acute kidney injury


Anti-retroviral therapy


Chronic kidney disease


Creatinine clearance


Estimated glomerular filtration rate

FGF 23

Fibroblast growth factor 23


Renal Fanconi syndrome


Hepatitis B virus


Modification of Diet in Renal Disease formula


Multidrug resistance-associated protein


Mitochondrial DNA


Sodium-phosphate co-transporter subtype IIa


Nucleoside reverse transcriptase inhibitor


Organic anion transporter


Protease inhibitor


Peroxisome proliferator-activated receptor


Proximal tubule




World Health Organization



Dr. Hall has received research funding from Kidney Research UK, St. Peter’s Trust for Kidney, Bladder and Prostate Research, The Academy of Medical Sciences, The British HIV Association, and The Wellcome Trust.


Dr. Hall previously has received a lectureship fee from Gilead Sciences, which markets tenofovir under the trade name Viread.


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Copyright information

© IPNA 2012

Authors and Affiliations

  1. 1.UCL Centre for Nephrology, Royal Free HospitalLondonUK

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