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TDF associated renal tubular dysfunction: non-invasive assessment of mitochondrial injury

Lookup NU author(s): Professor John Sayer, Dr David Price, Dr Brendan Payne

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Abstract

Copyright © 2017 Wolters Kluwer Health, Inc. OBJECTIVE:: To determine whether TDF-associated renal tubular dysfunction is associated with evidence of mitochondrial injury in urine. DESIGN:: Single centre cross-sectional observational study of HIV positive outpatients. METHODS:: Biochemistry was performed on paired serum and urine samples. Mitochondrial DNA (mtDNA) was studied by real-time PCR and long-range PCR on cellular fractions of urine. RESULTS:: 48 subjects were enrolled of whom half were TDF-treated. Mean age was 43 years. 58% had eGFR ≥90, with no differences between ART treatment groups. Urinary phosphate wasting was common and independently associated with TDF exposure (p?=?0.02). No subjects had low molecular weight proteinuria. Cellular mtDNA content in urine was heavily influenced by the cellularity of the sample. The mtDNA ‘common deletion’ mutation (CD) was detectable significantly more commonly in the urine of TDF exposed subjects compared with unexposed (13/22 TDF+ subjects (59%), 4/21 TDF- (19%), p?=?0.01). CD levels were not associated with age, eGFR or urinary phosphate wasting. No mtDNA measures were associated with current or nadir CD4 lymphocyte counts, duration of disease or anti-retroviral therapy, or historical exposure to NRTIs with systemic mitochondrial toxicity. CONCLUSIONS:: The presence of mtDNA mutations in the context of TDF exposure adds weight to the hypothesis that TDF associated renal damage is at least in part mitochondrially-mediated. The assessment of mtDNA markers in urine may be a feasible non-invasive investigation for TDF-treated patients.


Publication metadata

Author(s): Samuels R, Bayerri CR, Sayer JA, Price DA, Payne BA

Publication type: Article

Publication status: Published

Journal: AIDS

Year: 2017

Volume: 31

Issue: 9

Pages: 1297-1301

Online publication date: 01/06/2017

Acceptance date: 02/03/2017

ISSN (print): 0269-9370

ISSN (electronic): 1473-5571

Publisher: Lippincott Williams and Wilkins

URL: http://doi.org/10.1097/QAD.0000000000001466

DOI: 10.1097/QAD.0000000000001466


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