Pediatric Nephrology

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

Update on tenofovir toxicity in the kidney

Review

Abstract

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.

Keywords

Hepatitis B HIV Proximal tubule Renal Fanconi syndrome Tenofovir 

Abbreviations

AKI

Acute kidney injury

ART

Anti-retroviral therapy

CKD

Chronic kidney disease

CrCl

Creatinine clearance

eGFR

Estimated glomerular filtration rate

FGF 23

Fibroblast growth factor 23

FS

Renal Fanconi syndrome

HBV

Hepatitis B virus

MDRD

Modification of Diet in Renal Disease formula

MRP

Multidrug resistance-associated protein

MtDNA

Mitochondrial DNA

NaPi-IIa

Sodium-phosphate co-transporter subtype IIa

NRTI

Nucleoside reverse transcriptase inhibitor

OAT

Organic anion transporter

PI

Protease inhibitor

PPAR

Peroxisome proliferator-activated receptor

PT

Proximal tubule

TFV

Tenofovir

WHO

World Health Organization

Notes

Acknowledgments

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.

Disclosures

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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