Nature Reviews Nephrology ( IF 28.6 ) Pub Date : 2024-04-25 , DOI: 10.1038/s41581-024-00837-x Heidi Noels 1, 2, 3 , Vera Jankowski 1, 2 , Stefan J Schunk 4 , Raymond Vanholder 5, 6 , Sahir Kalim 7 , Joachim Jankowski 1, 2, 8
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Patients with chronic kidney disease (CKD) are at an increased cardiovascular risk compared with the general population, which is driven, at least in part, by mechanisms that are uniquely associated with kidney disease. In CKD, increased levels of oxidative stress and uraemic retention solutes, including urea and advanced glycation end products, enhance non-enzymatic post-translational modification events, such as protein oxidation, glycation, carbamylation and guanidinylation. Alterations in enzymatic post-translational modifications such as glycosylation, ubiquitination, acetylation and methylation are also detected in CKD. Post-translational modifications can alter the structure and function of proteins and lipoprotein particles, thereby affecting cellular processes. In CKD, evidence suggests that post-translationally modified proteins can contribute to inflammation, oxidative stress and fibrosis, and induce vascular damage or prothrombotic effects, which might contribute to CKD progression and/or increase cardiovascular risk in patients with CKD. Consequently, post-translational protein modifications prevalent in CKD might be useful as diagnostic biomarkers and indicators of disease activity that could be used to guide and evaluate therapeutic interventions, in addition to providing potential novel therapeutic targets.
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肾脏疾病和相关心血管风险的翻译后修饰
与普通人群相比,慢性肾脏病 (CKD) 患者的心血管风险更高,这至少部分是由与肾脏疾病独特相关的机制驱动的。在 CKD 中,氧化应激和尿毒症潴留溶质(包括尿素和晚期糖基化终产物)水平升高,增强非酶翻译后修饰事件,例如蛋白质氧化、糖基化、氨甲酰化和胍基化。 CKD 中还检测到酶促翻译后修饰的改变,例如糖基化、泛素化、乙酰化和甲基化。翻译后修饰可以改变蛋白质和脂蛋白颗粒的结构和功能,从而影响细胞过程。在 CKD 中,有证据表明翻译后修饰的蛋白质可能导致炎症、氧化应激和纤维化,并诱导血管损伤或促血栓形成效应,这可能导致 CKD 进展和/或增加 CKD 患者的心血管风险。因此,除了提供潜在的新治疗靶点外,CKD 中普遍存在的翻译后蛋白修饰可能可用作诊断生物标志物和疾病活动指标,可用于指导和评估治疗干预措施。