Urinary mitochondrial DNA copy number identifies renal mitochondrial injury in renovascular hypertensive patients undergoing renal revascularization: A Pilot Study.
PTRA
mitochondria
mtDNA
renovascular hypertension
revascularization
Journal
Acta physiologica (Oxford, England)
ISSN: 1748-1716
Titre abrégé: Acta Physiol (Oxf)
Pays: England
ID NLM: 101262545
Informations de publication
Date de publication:
07 2019
07 2019
Historique:
received:
19
10
2018
accepted:
21
02
2019
pubmed:
26
2
2019
medline:
7
8
2020
entrez:
26
2
2019
Statut:
ppublish
Résumé
Patients with renovascular hypertension (RVH) exhibit elevated urinary mtDNA copy numbers, considered to constitute surrogate markers of renal mitochondrial injury. The modest success of percutaneous transluminal renal angioplasty (PTRA) in restoring renal function in RVH has been postulated to be partly attributable to acute reperfusion injury. We hypothesized that mitoprotection during revascularization would ameliorate PTRA-induced renal mitochondrial injury, reflected in elevated urinary mtDNA copy numbers and improve blood pressure and functional outcomes 3 months later. We prospectively measured urinary copy number of the mtDNA genes COX3 and ND1 using qPCR in RVH patients before and 24 hrs after PTRA, performed during IV infusion of vehicle (n = 8) or the mitoprotective drug elamipretide (ELAM, 0.05 mg/kg/h, n = 6). Five healthy volunteers (HV) served as controls. Urinary mtDNA levels were also assessed in RVH and normal pigs (n = 7 each), in which renal mitochondrial structure and density were studied ex-vivo. Baseline urinary mtDNA levels were elevated in all RVH patients vs HV and directly correlated with serum creatinine levels. An increase in urinary mtDNA 24 hours after PTRA was blunted in PTRA+ELAM vs PTRA+Placebo. Furthermore, 3-months after PTRA, systolic blood pressure decreased and estimated glomerular filtration rate increased only in ELAM-treated subjects. In RVH pigs, mitochondrial damage was observed using electron microscopy in tubular cells and elevated urinary mtDNA levels correlated inversely with renal mitochondrial density. PTRA leads to an acute rise in urinary mtDNA, reflecting renal mitochondrial injury that in turn inhibits renal recovery. Mitoprotection might minimize PTRA-associated mitochondrial injury and improve renal outcomes after revascularization.
Identifiants
pubmed: 30803138
doi: 10.1111/apha.13267
pmc: PMC6556125
mid: NIHMS1014044
doi:
Substances chimiques
DNA, Mitochondrial
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e13267Subventions
Organisme : NIH HHS
ID : HL123160
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL123160
Pays : United States
Organisme : NIH HHS
ID : DK106427
Pays : United States
Organisme : NIDDK NIH HHS
ID : K08 DK118120
Pays : United States
Organisme : NIH HHS
ID : DK104273
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK100081
Pays : United States
Organisme : NIDDK NIH HHS
ID : K08 DK106427
Pays : United States
Organisme : Stealth Biotherapeutics
Pays : International
Organisme : NIH HHS
ID : DK100081
Pays : United States
Organisme : NIDDK NIH HHS
ID : U01 DK104273
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK102325
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK120292
Pays : United States
Organisme : NIH HHS
ID : DK102325
Pays : United States
Organisme : NIH HHS
ID : DK118120
Pays : United States
Informations de copyright
© 2019 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.
Références
J Am Soc Nephrol. 1999 Jul;10(7):1455-65
pubmed: 10405201
Am J Physiol Renal Physiol. 2001 Oct;281(4):F630-8
pubmed: 11553509
J Vasc Surg. 2002 Sep;36(3):443-51
pubmed: 12218965
J Am Soc Nephrol. 2002 Nov;13 Suppl 3:S179-83
pubmed: 12466310
Nat Rev Mol Cell Biol. 2003 Jul;4(7):552-65
pubmed: 12838338
Toxicology. 2005 Feb 28;207(3):339-47
pubmed: 15664262
Arch Pathol Lab Med. 2009 Feb;133(2):181-8
pubmed: 19195962
Ann Intern Med. 2009 May 5;150(9):604-12
pubmed: 19414839
J Am Soc Nephrol. 2011 Jun;22(6):1041-52
pubmed: 21546574
Hypertension. 2012 Nov;60(5):1242-9
pubmed: 23045468
Circ Cardiovasc Interv. 2012 Oct;5(5):720-8
pubmed: 23048054
Kidney Int. 2013 Jan;83(1):28-40
pubmed: 23151953
Crit Care. 2013 Feb 06;17(1):R25
pubmed: 23388612
PLoS One. 2013 May 15;8(5):e64436
pubmed: 23691217
J Am Soc Nephrol. 2013 Jul;24(8):1250-61
pubmed: 23813215
Br J Pharmacol. 2014 Apr;171(8):2029-50
pubmed: 24117165
Br J Pharmacol. 2014 Apr;171(8):2017-28
pubmed: 24134698
N Engl J Med. 2014 Jan 2;370(1):13-22
pubmed: 24245566
Am J Physiol Renal Physiol. 2014 Feb 15;306(4):F379-88
pubmed: 24338822
Am J Respir Crit Care Med. 2014 Apr 15;189(8):932-9
pubmed: 24559465
Nephrol Dial Transplant. 2015 Mar;30(3):366-75
pubmed: 24723543
Hypertension. 2014 Jul;64(1):87-93
pubmed: 24752430
Cardiovasc Res. 2014 Sep 1;103(4):461-72
pubmed: 24947415
Hypertension. 2015 Aug;66(2):430-6
pubmed: 26077566
Nephrol Dial Transplant. 2016 Sep;31(9):1437-43
pubmed: 26908767
Hypertension. 2016 Aug;68(2):401-10
pubmed: 27324229
Transl Res. 2017 Jun;184:45-56.e9
pubmed: 28363084
Am J Hypertens. 2017 Nov 1;30(11):1112-1119
pubmed: 28641368
Circ Cardiovasc Interv. 2017 Sep;10(9):
pubmed: 28916603
J Cell Physiol. 2018 Aug;233(8):5926-5936
pubmed: 29243809