Department of Gastroenterology and Hepatology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
Department of Internal Medicine, Division of Nephrology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
Redox Biol. 2024 Nov;77:103408. doi: 10.1016/j.redox.2024.103408. Epub 2024 Oct 22.
BACKGROUND: Chronic Kidney Disease (CKD), is often detected late due to its asymptomatic nature in the early stage of the disease. Overproduction of reactive oxygen species contributes to various pathological processes through oxidative stress (OS), impacting on cellular structures and functions with previous studies suggesting a link between OS and CKD progression. This study investigated the association between serum peroxiredoxin-4 (Prx4), a biomarker of oxidative stress, and the development of CKD in the general population. METHODS: This study featured data from the Prevention of REnal and Vascular ENd-stage Disease (PREVEND) cohort, involving 5341 participants without CKD at baseline who underwent extensive prospective health evaluations. Serum Prx4 levels were quantified using an immunoluminometric assay. The primary outcome was new-onset CKD as defined by the composite of urinary albumin excretion (UAE) > 30 mg/24-h, an estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m, or both. RESULTS: Baseline median Prx4 level was 0.65 [interquartile range (IQR): 0.42-1.04] U/L, median eGFR was 98 [IQR: 87-108] mL/min/1.73 m, and median UAE was 8.1 [IQR: 6.0-12.1] mg/L. During a median follow-up of 10.4 [IQR: 6.3-11.4] years, 867 (16.2 %) patients developed new-onset CKD. Higher Prx4 levels were significantly associated with an increased risk of CKD (hazard ratio (HR) per doubling: 1.29 [95 % confidence interval (CI): 1.21-1.37], p < 0.001), also after adjustment for risk factors including sex, smoking status, systolic blood pressure, high-sensitive C-reactive protein, chronic heart failure, diabetes mellitus and dyslipidemia (HR per doubling: 1.16 [1.06-1.24], p < 0.001). Sensitivity analyses confirmed the robustness of these findings. CONCLUSIONS: This study supports the hypothesis that systemic oxidative stress, reflected by higher serum Prx4 levels, is significantly associated with the risk of developing CKD in the general population. These findings suggest that Prx4 could be a valuable biomarker for early risk stratification and prevention strategies in CKD management.
背景：慢性肾脏病（CKD）在疾病早期通常无症状，因此往往检测较晚。活性氧（ROS）的过度产生通过氧化应激（OS）导致各种病理过程，先前的研究表明 OS 与 CKD 进展之间存在关联。本研究旨在调查一般人群中血清过氧化物酶 4（Prx4）作为氧化应激生物标志物与 CKD 发展之间的关系。
方法：本研究的数据来自预防肾脏和血管终末期疾病（PREVEND）队列，共纳入 5341 名基线时无 CKD 的参与者，他们接受了广泛的前瞻性健康评估。采用免疫发光法测定血清 Prx4 水平。主要结局为新诊断的 CKD，定义为尿白蛋白排泄（UAE）>30mg/24h、估算肾小球滤过率（eGFR）<60ml/min/1.73m 或两者兼有的复合结果。
结果：基线时 Prx4 中位数为 0.65[四分位距（IQR）：0.42-1.04]U/L，eGFR 中位数为 98[IQR：87-108]ml/min/1.73m，UAE 中位数为 8.1[IQR：6.0-12.1]mg/L。在中位数为 10.4[IQR：6.3-11.4]年的随访期间，867 名（16.2%）患者出现新发 CKD。Prx4 水平较高与 CKD 风险增加显著相关（每翻倍 HR：1.29[95%可信区间（CI）：1.21-1.37]，p<0.001），即使在校正了包括性别、吸烟状况、收缩压、高敏 C 反应蛋白、慢性心力衰竭、糖尿病和血脂异常等危险因素后也是如此（每翻倍 HR：1.16[1.06-1.24]，p<0.001）。敏感性分析证实了这些发现的稳健性。
结论：本研究支持了这样一种假设，即全身性氧化应激，反映在较高的血清 Prx4 水平上，与一般人群发生 CKD 的风险显著相关。这些发现表明 Prx4 可能是 CKD 管理中早期风险分层和预防策略的有价值的生物标志物。
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