Mitochondrial DNA copy number is a biomarker of mitochondrial function, which has been hypothesized to contribute to pathogenesis of CKD through podocyte injury, tubular epithelial cell damage, and endothelial dysfunction. The prospective association of mitochondrial DNA copy number with CKD progression has not been previously evaluated.

Chronic Renal Insufficiency Cohort study participants had serum levels of mitochondrial DNA copy number calculated from probe intensities of mitochondrial single nucleotide polymorphisms genotyped on the Illumina HumanOmni 1-Quad Array. CKD progression was defined as kidney failure or halving of eGFR from baseline. Cox proportional hazards models were used to calculate hazard ratios for mitochondrial DNA copy number and risk of CKD progression.

Among 2943 participants, mean age was 58 years, 45% were women, and 48% self-identified as Black. There were 1077 patients who experienced CKD progression over a median follow-up of 6.5 years. The incidence rate of CKD progression was highest for those in the lowest tertile of mitochondrial DNA copy number (tertile 1, 58.1; tertile 2, 50.8; tertile 3, 46.3 per 1000 person-years). Risk for CKD progression was higher for participants with lower levels of mitochondrial DNA copy number after adjustment for established risk factors (for tertile 1 versus 3, hazard ratio, 1.28 [95% confidence interval, 1.10 to 1.50]; for tertile 2 versus 3, hazard ratio, 0.99 [95% confidence interval, 0.85 to 1.16]; trend P=0.002). Similar results were seen among those with albuminuria (for tertile 1 versus 3, hazard ratio, 1.24; 95% confidence interval, 1.05 to 1.47), but there were no statistically significant associations among individuals without albuminuria (for tertile 1 versus 3, hazard ratio, 1.04; 95% confidence interval, 0.70 to 1.53; interaction P<0.001).

These findings suggest lower mitochondrial DNA copy number is associated with higher risk of CKD progression, independent of established risk factors among patients with CKD.

线粒体 DNA 拷贝数是线粒体功能的生物标志物，据推测，线粒体 DNA 拷贝数通过足细胞损伤、肾小管上皮细胞损伤和内皮功能障碍促进 CKD 的发病机制。线粒体 DNA 拷贝数与 CKD 进展的前瞻性关联尚未得到评估。

慢性肾功能不全队列研究参与者的线粒体 DNA 拷贝数血清水平是根据 Illumina HumanOmni 1-Quad Array 上基因分型的线粒体单核苷酸多态性的探针强度计算得出的。 CKD 进展定义为肾衰竭或 eGFR 较基线减半。 Cox 比例风险模型用于计算线粒体 DNA 拷贝数和 CKD 进展风险的风险比。

在 2943 名参与者中，平均年龄为 58 岁，45% 是女性，48% 自认为是黑人。在中位随访 6.5 年中，有 1077 名患者经历了 CKD 进展。线粒体 DNA 拷贝数最低三分位数的人的 CKD 进展发生率最高（每 1000 人年，1 分位数为 58.1；2 分位数为 50.8；3 分位数为 46.3）。在调整既定风险因素后，线粒体 DNA 拷贝数水平较低的参与者的 CKD 进展风险较高（对于三分位数 1 与 3，风险比为 1.28 [95% 置信区间，1.10 至 1.50]；对于三分位数 2 与 3，风险比，0.99 [95% 置信区间，0.85 至 1.16]；趋势P = 0.002）。在蛋白尿患者中也观察到类似的结果（对于三分位数 1 与 3，风险比为 1.24；95% 置信区间为 1.05 至 1.47），但在没有蛋白尿的个体中没有统计学上显着的关联（对于三分位数 1 与 3，风险比，1.04；95% 置信区间，0.70 至 1.53；交互作用P <0.001）。

这些发现表明，线粒体 DNA 拷贝数较低与 CKD 进展风险较高相关，与 CKD 患者中已确定的危险因素无关。