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J Infect Dis. 2014 Aug 1;210(3):363-73. doi: 10.1093/infdis/jiu107. Epub 2014 Feb 28.

Incomplete reversibility of estimated glomerular filtration rate decline following tenofovir disoproxil fumarate exposure.

Author information

1
Research Department of Infection and Population Health, University College London.
2
Kings College Hospital National Health Service (NHS) Foundation Trust and King's College London School of Medicine.
3
Brighton and Sussex University Hospitals NHS Trust, Brighton.
4
The Lothian University Hospitals NHS Trust, Edinburgh.
5
Mortimer Market Centre, University College Medical School.
6
Imperial College Healthcare NHS Trust.
7
Chelsea and Westminster NHS Foundation Trust.
8
St George's Healthcare NHS Trust.
9
Royal Free Hampstead NHS Trust.
10
South Tees Hospitals NHS Foundation Trust, Middlesbrough, United Kingdom.
11
London School of Hygiene and Tropical Medicine, London.

Abstract

BACKGROUND:

Tenofovir disoproxil fumarate (TDF) has been linked to renal impairment, but the extent to which this impairment is reversible is unclear. We aimed to investigate the reversibility of renal decline during TDF therapy.

METHODS:

Cox proportional hazards models assessed factors associated with discontinuing TDF in those with an exposure duration of >6 months. In those who discontinued TDF therapy, linear piecewise regression models estimated glomerular filtration rate (eGFR) slopes before initiation of, during, and after discontinuation of TDF therapy. Factors associated with not achieving eGFR recovery 6 months after discontinuing TDF were assessed using multivariable logistic regression.

RESULTS:

We observed declines in the eGFR during TDF exposure (mean slopes, -15.7 mL/minute/1.73 m(2)/year [95% confidence interval {CI}, -20.5 to -10.9] during the first 3 months and -3.1 mL/minute/1.73 m(2)/year [95% CI, -4.6 to -1.7] thereafter) and evidence of eGFR increases following discontinuation of TDF therapy (mean slopes, 12.5 mL/minute/1.73 m(2)/year [95% CI, 8.9-16.1] during the first 3 months and 0.8 mL/minute/1.73 m(2)/year [95% CI, .1-1.5] thereafter). Following TDF discontinuation, 38.6% of patients with a decline in the eGFR did not experience recovery. A higher eGFR at baseline, a lower eGFR after discontinuation of TDF therapy, and more-prolonged exposure to TDF were associated with an increased risk of incomplete recovery 6 months after discontinuation of TDF therapy.

CONCLUSIONS:

This study shows that a decline in the eGFR during TDF therapy was not fully reversible in one third of patients and suggests that prolonged TDF exposure at a low eGFR should be avoided.

KEYWORDS:

eGFR; eGFR slopes; highly active antiretroviral therapy; kidney; renal function; tenofovir

PMID:
24585896
PMCID:
PMC4091582
DOI:
10.1093/infdis/jiu107
[Indexed for MEDLINE]
Free PMC Article
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