The clinical use of urinary mitochondrial DNA in adult surgical critical care patients with acute kidney injury. (14th January 2023)

• Record Type: Journal Article
• Authors: Abayasekara, Kiara; Sullo, Nikol
• Is Part Of: Clinical and experimental pharmacology and physiology. Volume 50:Number 4(2023)
• Page Start: 277
• Page End: 286
• Publication Date: 2023-01-14
• Subjects: acute kidney injury -- adult surgical critical care patients -- COX3 -- ND1 -- novel biomarkers -- UmtDNA; Clinical pharmacology -- Periodicals; Pharmacology, Experimental -- Periodicals; Physiology, Experimental -- Periodicals; Physiology, Pathological -- Periodicals; 615.1
• DOI: 10.1111/1440-1681.13746
• Languages: English
• ISSNs: 0305-1870

Abstract

Abstract: Acute kidney injury (AKI) affects 47% of adult surgical critical care patients (ASCCPs). AKI is induced through a common oxidative stress pathway resulting in mitochondrial and tubular cell injury with increased urinary mitochondrial DNA (UmtDNA) excretion. UmtDNA is an emerging and readily sampled novel biomarker for varied surgical critical care cohorts. This review aimed to determine the clinical use of UmtDNA genes (ND1 and COX3) in AKI in ASCCPs. PubMed, MEDLINE and Web of Science databases were searched. Eligibility criteria were based on the patient/problem, intervention, comparison and outcome framework. Methodological quality of studies was assessed with the Newcastle‐Ottawa Quality Assessment Scale. WebPlot Digitizer version 4.4 was used to extract UmtDNA data from graphs and UmtDNA ratios were statistically analysed with PRISM version 9.1.0 (GraphPad Software). Six human studies (n = 391) with three translational murine models (n = 112) satisfied inclusion criteria. One sample t test suggested significantly high UmtDNA‐ND1 ratios in progressive/severe AKI (or delayed renal transplant graft function) to no AKI (or immediate renal transplant graft function) and increased UmtDNA‐COX3 ratios approached significance. Sensitivities and specificities for UmtDNA ranged from 68% to 85% and 52% to 83.6%, respectively, comparable with new biomarkers, neutrophil gelatinase‐associated lipocalin and kidney injury molecule‐1. Weak correlation was observed with serum creatinine. These findings were complemented in translational murine AKI experiments with significantly elevated ND1 and COX3. From bench to clinical practice, UmtDNA appears to be a promising novel biomarker of progressive/severe AKI (or delayed graft function). Large prospective, multi‐centre studies reporting standardised UmtDNA findings should clarify use of UmtDNA in ASCCP‐AKI management. Abstract : mtDNA is an emerging biomarker of AKI. UmtDNA could be a plausible, readily obtained, minimally invasive, sensitive, and predictive NBM of Progressive/Severe AKI. Large prospective, multi‐centre studies reporting standardised UmtDNA findings should clarify utility of UmtDNA in AKI management.