Abstract
Abstract Background and Aims Chronic kidney disease (CKD) and kidney failure are connected to increased oxidative stress and vascular calcification, which are indicators for development of comorbidities and mortality outcome. Mitochondrial (mt)DNA copy number has been reported as independent predictor for frailty and mortality outcome of various cardiovascular diseases (CVD) and cancer. We aimed that mtDNA copy number in whole blood of kidney failure patients can be correlated to coronary artery media calcification score and coronary artery calcium (CAC) score and be used as an independent predictor for comorbidities and mortality outcome. Method Quantitative PCR (qPCR) with TaqMan® probes for three mtDNA genes (mtND1, mtND4 and mtCOX1) and two single locus genes on nuclear DNA (hemoglobin subunit beta and 18S), for normalization, is performed on DNA samples isolated from collected blood of 196 kidney transplant donors and 211 recipients at basal timepoint and 32 at 1-year-follow-up timepoint, included in the KaroKidney biobank. Resulting mtDNA copy number is investigated for correlation to CAC score, patient mortality outcome, biological age determined by skin autofluorescence and other clinical parameters. Results In our Swedish kidney transplant cohort we can see statistically significant difference in mtDNA copy number between kidney failure patients (recipients) and healthy controls (donors). No obvious difference between females and males was observed. mtDNA copy number correlates to biological age determined by skin autofluorescence, CAC score and Framingham CVD risk score. In the 32 1-year-follow-up samples we could see significant increase/recovery of mtDNA copy number for male patients compared to their baseline before receiving a transplant. Conclusion In this study we show that mtDNA copy number in kidney failure patients correlates to biological age and CAC score, affirming mtDNA copy number as an independent predictor of frailty in this Swedish cohort of CKD patients. Additionally, we can see that a kidney transplant can lead to a significant increase of mtDNA copy number in blood one year later, suggesting a general increase in health quality.
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