Hashad Doaa, Elgohry Iman, Dwedar Fatma
Clin Lab. 2016 Nov 1;62(11):2149-2154. doi: 10.7754/Clin.Lab.2016.160329.
Chronic kidney disease (CKD) is characterized by progressive irreversible deterioration of renal functions. Advanced stages of CKD are associated with oxidative stress due to the imbalance between oxidant production and antioxidant defense mechanisms. Survival of patients with end stage renal diseases is maintained on variable forms of renal replacement therapies (RRT) which include peritoneal dialysis, hemodialysis, and sometimes renal transplantation. In humans, Nuclear Respiratory Factor 1 (NRF-1) gene encodes for a transcription factor that, together with the transcriptional co-activator encoded by Peroxisome Proliferator activated Receptor Gamma coactivator 1 Alpha (PGC1-a) gene, stimulates the expression of a broad set of nuclear genes (as COX6C) which are involved in mitochondrial biogenesis and functions. As mitochondria are considered a major source of reactive oxidant species, the objective of the present study was to assess mitochondrial oxidative dysregulation occurring in chronic kidney disease patients undergoing hemodialysis employing NRF-1 and COX6C genes' expression as an indicator of mitochondrial oxidative metabolism.
Forty-nine chronic kidney disease patients undergoing intermittent hemodialysis were included in the present study. A group of thirty-three age- and gender- matched healthy volunteers served as a control group. Assessment of expression of NRF-1 and COX6C genes was performed using quantitative real-time PCR technique.
NRF-1 and COX6C expression showed a statistically significant difference between both studied groups being down-regulated in CKD patients. In addition, malondialdehyde (MDA) levels were higher in patients on hemodialysis indicating lipid peroxidation. A negative correlation was detected between MDA level and expression of both NRF-1 and COX6C genes.
Chronic kidney disease patients undergoing hemodialysis might be subjected to potential mitochondrial oxidative dysregulation with subsequent possible vascular and tissue injury.
慢性肾脏病（CKD）的特征是肾功能进行性不可逆恶化。CKD晚期与氧化应激有关，这是由于氧化剂生成与抗氧化防御机制之间的失衡所致。终末期肾病患者通过多种形式的肾脏替代疗法（RRT）维持生存，这些疗法包括腹膜透析、血液透析，有时还包括肾移植。在人类中，核呼吸因子1（NRF-1）基因编码一种转录因子，该转录因子与过氧化物酶体增殖物激活受体γ共激活因子1α（PGC1-α）基因编码的转录共激活因子一起，刺激一组广泛的核基因（如COX6C）的表达，这些基因参与线粒体生物发生和功能。由于线粒体被认为是活性氧物种的主要来源，本研究的目的是评估接受血液透析的慢性肾脏病患者中发生的线粒体氧化失调，采用NRF-1和COX6C基因的表达作为线粒体氧化代谢的指标。
本研究纳入了49例接受间歇性血液透析的慢性肾脏病患者。一组33名年龄和性别匹配的健康志愿者作为对照组。使用定量实时PCR技术评估NRF-1和COX6C基因的表达。
NRF-1和COX6C的表达在两个研究组之间存在统计学显著差异，在CKD患者中下调。此外，血液透析患者的丙二醛（MDA）水平较高，表明存在脂质过氧化。MDA水平与NRF-1和COX6C基因的表达之间存在负相关。
接受血液透析的慢性肾脏病患者可能存在潜在的线粒体氧化失调，随后可能导致血管和组织损伤。
