Table 1.

Studies suggesting circulating mtDNA-CN as a biomarker of kidney disease/renal function in the context of renal function and chronic kidney disease

Method of mtDNA-CN determination	Patient population (sample type/numbers)	Key points	Reference
Relative quantification delta CT method	T2D South Asian (cross-sectional study, whole blood n = 60)	MtDNA-CN higher in patients with T2DN relative to T2D no renal disease (no healthy controls, primers that co-amplify NUMTS)	Malik et al.[11]
Relative quantification deltaCT method	Community based general population study (leukocytes, n = 694))	The prevalence of microalbuminuria decreased progressively from lower to upper quartiles of mtDNA-CN	Lee et al.[37▪]
Absolute quantification using qPCR	Diabetes clinic London: T1D and T2D ± nephropathy (cross sectional study, whole blood, n = 169)	MtDNA-CN lower in patients with DKD, alongside increased mtDNA damage, reduced metabolic flexibility and altered mitochondrial RNAs.	Czajka et al.[35▪▪]
Affymetrix arrays; estimated mtDNA-CN	Atherosclerosis Risk in Communities Study Longitudinal study over 19.6 years, n = 9058	Higher e-mtDNA-CN associated with lower risk of incident CKD (highest versus lowest quartile: hazard ratio 0.65; 95% confidence interval, 0.56 to 0.75; P = 0.001)	Tin et al.[38▪▪]
Absolute quantification using plasmid based qPCR	German Chronic Kidney Disease (GCKD) study, n = 4812, cross sectional and longitudinal study	Lowest quartile of mtDNA-CN showed highest risk of mortality and infections, 4 years follow up	Fazzini et al.[39▪▪]
Illumina HumanOmni 1-Quad Array. Estimated mtDNA-CN	Chronic Renal Insufficiency Cohort study (CRIC) Longitudinal study N = 2943	Lowest tertile of e-mtDNA-CN showed the highest risk of progression, 6.5 years follow up	He et al.[40▪▪]
Relative mtDNA-CN Taqman probes (delta Ct method)	Type 2 diabetes patients with progressive stages of renal disease N = 180	Linked serum (and urinary) mtDNA to inflammatory status in patients with diabetic kidney disease	Petrica et al.[36]

Note: excludes studies reporting mtDNA-CN changes in AKI, IGA nephropathy and hemodialysis patients. Excludes studies reporting mtDNA mutations or measuring mtDNA in renal/other tissues.

AKI, acute kidney injury; CN, copy number.