Division of Nephrology and Hypertension, 1 Department of Internal Medicine, AHEPA Hospital, School of Medicine, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece.
Department of Microbiology, AHEPA Hospital, School of Medicine, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece.
Oxid Med Cell Longev. 2021 Oct 19;2021:2968869. doi: 10.1155/2021/2968869. eCollection 2021.
Diabetic kidney disease (DKD) is a highly heterogenous disease, including the proteinuric and the nonproteinuric pattern. Oxidized low-density lipoprotein (ox-LDL) is progressively increased in DKD and causes direct damage to kidney tubular epithelial cells through a mechanism similar to that underlying the deleterious effect of lipid peroxides in the vascular endothelium. We aimed to examine the association between plasma ox-LDL cholesterol and clinical endpoints in DKD patients. Ninety-one patients with established proteinuric DKD and diabetic retinopathy were enrolled and prospectively followed for 10 years or the occurrence of death, or at least 30% decline in eGFR, or progression to end-stage kidney disease (ESKD) requiring renal replacement therapy (primary outcome). At the end of the study, both eGFR and proteinuria were reassessed. Secondary outcomes of the study were the percentage change in eGFR and proteinuria over time for each patient. At baseline, patients were divided into 2 groups according to the median ox-LDL value (i.e., below or equal and above 66.22 U/L). Both Kaplan-Meier curves ( = 0.001, log-rank test) and univariate Cox regression analysis showed that high ox-LDL was associated with the primary outcome (HR = 3.42, 95%CI = 1.55 - 7.56, = 0.002). After adjustment for various well-known cofounders, multivariate Cox analysis showed that the association between increased circulating ox-LDL levels and the composite kidney endpoint remained significant (HR = 2.87, 95%CI = 1.14-7.20, = 0.025). Regarding the secondary outcome of eGFR decline, the assessment of areas under the curves (AUC) showed that ox-LDL outperformed several cofounding factors (AUC 71%, 95%CI = 0.59 - 0.83, = 0.001) and had better accuracy to predict deterioration of eGFR over time than baseline proteinuria (AUC 67%, 95%CI = 0.54 - 0.79, = 0.014). Increased ox-LDL might be associated with disease progression in proteinuric DKD.
糖尿病肾病（DKD）是一种高度异质性疾病，包括蛋白尿和非蛋白尿两种类型。氧化型低密度脂蛋白（ox-LDL）在 DKD 中逐渐增加，并通过类似于脂质过氧化物对血管内皮有害作用的机制直接损伤肾小管上皮细胞。我们旨在研究 DKD 患者血浆 ox-LDL 胆固醇与临床终点之间的关系。
纳入了 91 例已确诊的蛋白尿型 DKD 和糖尿病视网膜病变患者，并前瞻性随访 10 年或直至死亡、eGFR 至少下降 30%、进展至终末期肾病（ESKD）需要肾脏替代治疗（主要终点）。在研究结束时，重新评估了 eGFR 和蛋白尿。该研究的次要终点是每位患者随时间推移 eGFR 和蛋白尿的百分比变化。
在基线时，根据 ox-LDL 值的中位数（即低于或等于和高于 66.22U/L）将患者分为 2 组。Kaplan-Meier 曲线（=0.001，对数秩检验）和单变量 Cox 回归分析均表明，高 ox-LDL 与主要终点相关（HR=3.42，95%CI=1.55-7.56，=0.002）。
在校正各种已知混杂因素后，多变量 Cox 分析表明，循环 ox-LDL 水平升高与复合肾脏终点之间的关联仍然显著（HR=2.87，95%CI=1.14-7.20，=0.025）。
关于 eGFR 下降的次要终点，曲线下面积（AUC）的评估表明，ox-LDL 优于几个混杂因素（AUC 为 71%，95%CI=0.59-0.83，=0.001），并且比基线蛋白尿更能准确预测随时间推移 eGFR 的恶化（AUC 为 67%，95%CI=0.54-0.79，=0.014）。
升高的 ox-LDL 可能与蛋白尿型 DKD 的疾病进展有关。
