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Urinary mitochondrial DNA copy number identifies renal mitochondrial injury in renovascular hypertensive patients undergoing renal revascularization: A Pilot Study
Author(s) -
Eirin A.,
Herrmann S. M.,
Saad A.,
Abumoawad A.,
Tang H.,
Lerman A.,
Textor S. C.,
Lerman L. O.
Publication year - 2019
Publication title -
acta physiologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.591
H-Index - 116
eISSN - 1748-1716
pISSN - 1748-1708
DOI - 10.1111/apha.13267
Subject(s) - renovascular hypertension , urinary system , blood pressure , renal function , kidney , urology , creatinine , medicine , biology , endocrinology , cardiology
Aims Patients with renovascular hypertension ( RVH ) exhibit elevated urinary mt DNA 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 mt DNA copy numbers and improve blood pressure and functional outcomes 3 months later. Methods We prospectively measured urinary copy number of the mt DNA genes COX 3 and ND 1 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 mt DNA levels were also assessed in RVH and normal pigs (n = 7 each), in which renal mitochondrial structure and density were studied ex‐vivo. Results Baseline urinary mt DNA levels were elevated in all RVH patients vs HV and directly correlated with serum creatinine levels. An increase in urinary mt DNA 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 mt DNA levels correlated inversely with renal mitochondrial density. Conclusions PTRA leads to an acute rise in urinary mt DNA , reflecting renal mitochondrial injury that in turn inhibits renal recovery. Mitoprotection might minimize PTRA –associated mitochondrial injury and improve renal outcomes after revascularization.