Mitochondrial DNA copy number decreases with adenine-induced CKD in rat kidney tissue

Abstract

v, 26 p.Chronic kidney disease (CKD) is associated with increased morbidity and mortality, and cases are on the rise globally due to the increasing prevalence of risk factors. Despite its growing prevalence as an international health issue, a major problem with CKD diagnosis is that clinical symptoms do not appear until after severe kidney damage has occurred. The proximal tubule is the major cell type in the kidney cortex, necessitating a large number of mitochondria to satisfy its metabolic demands. Chronic kidney disease is associated with proximal tubule injury, which can lead to reduced mitochondrial function and decreased mitochondrial number. Direct measurement of mitochondrial DNA copy number (mt-CN) in the kidney is a potential biomarker of proximal tubule function and CKD progression because it reflects capacity for oxidative phosphorylation. However, most research focuses on mt-CN quantification in blood samples using insensitive methods like qPCR. It is unclear if mt-CN levels in blood are related to mt-CN in the kidney, or if methods like qPCR are sufficiently accurate. This paper utilizes kidney tissue samples and the adenine-induced model of CKD (with diets of 0%, 0.25%, 0.50%, and 0.75% adenine) as well as dPCR for quantification of mt-CN using mitochondrial-specific loci overlapping ND1 and ND4. Low mt-CN in the kidney was significantly associated with adenine-induced CKD for both loci (p < 0.0001). mt-CN did not significantly differ between the 0.25%, 0.50%, and 0.75% diets. Additionally, there was an age-dependent decrease in mt-CN. The results of this study validate mt-CN as a potential biomarker of CKD, and the absolute quantification of mt-CN may have prognostic value in screening and monitoring CKD in the clinical setting