Herath Sanjeeva, Au Amy Y M, Taylor Kylie M, Kapoor-Kaushik Natasha, Endre Zoltán H, Erlich Jonathan H
School of Clinical Medicine, Faculty of Medicine and Health, University of New South Wales, Sydney, NSW 2052, Australia.
Department of Nephrology, Prince of Wales Hospital, Sydney, NSW 2031, Australia.
Int J Mol Sci. 2025 May 12;26(10):4616. doi: 10.3390/ijms26104616.
Subclinical chronic kidney disease (sCKD) predisposes one to acute kidney injury (AKI) and chronic kidney disease (CKD). Reduced kidney functional reserve (KFR) detects sCKD in preclinical studies and predicts AKI after cardiac surgery. We evaluated renal protection in a rat model of kidney injury where ischaemia-reperfusion injury (IRI) was induced after sCKD. Dual treatment boosting nicotinamide adenine dinucleotide (NAD) by nicotinamide riboside (NR) combined with the mitochondria-targeted antioxidant SkQR1 protected the KFR and reduced structural kidney damage, including markers of vascular integrity and the relative blood volume (rBV). The dual treatment upregulated and increased the nuclear localisation of the mitochondrial biogenesis regulator PGC-1α and the mitochondrial protein marker COX4, and upregulated the antioxidant gene . These observations suggest mitochondrial protection and modulation of the cellular redox state provided long-term structural and functional protection against kidney injury superimposed on background sCKD.
亚临床慢性肾脏病（sCKD）使人易患急性肾损伤（AKI）和慢性肾脏病（CKD）。肾脏功能储备（KFR）降低在临床前研究中可检测出sCKD，并可预测心脏手术后的AKI。我们在一个肾损伤大鼠模型中评估了肾脏保护作用，该模型在sCKD后诱导缺血再灌注损伤（IRI）。通过烟酰胺核糖苷（NR）增强烟酰胺腺嘌呤二核苷酸（NAD）的双重治疗与线粒体靶向抗氧化剂SkQR1联合使用，可保护KFR并减少肾脏结构损伤，包括血管完整性标志物和相对血容量（rBV）。双重治疗上调了线粒体生物发生调节因子PGC-1α和线粒体蛋白标志物COX4的表达并增加了其核定位，还上调了抗氧化基因。这些观察结果表明，线粒体保护和细胞氧化还原状态的调节为叠加在背景sCKD上的肾损伤提供了长期的结构和功能保护。
