Xhakollari Liana, Jujic Amra, Molvin John, Nilsson Peter, Holm Hannes, Bachus Erasmus, Leosdottir Margret, Grubb Anders, Christensson Anders, Magnusson Martin
Department of Clinical Sciences, Lund University, Malmö, Sweden.
Department of Nephrology, Skåne University Hospital, Malmö, Sweden.
Proteomics Clin Appl. 2021 Jul;15(4):e2000089. doi: 10.1002/prca.202000089. Epub 2021 Mar 20.
The "Shrunken pore syndrome" (SPS) is characterized by a difference in renal filtration between cystatin C and creatinine, resulting in a low eGFR /eGFR -ratio. Studies have demonstrated a high risk for cardiovascular morbidity and mortality for patients with SPS. In this discovery study, we explored associations between SPS and proteins implicated in cardiovascular disease and inflammation in patients with heart failure.
Plasma samples from 300 individuals in HARVEST-Malmö trial hospitalized for the diagnosis of heart failure (mean age 74.9 ± 11.5 years; 30.0% female), were analyzed with a proximity extension assay consisting of 92 proteins. A Bonferroni-corrected p-value of 0.05/92 = 5.4 × 10 was considered significant in the initial age and sex-adjusted analyses. Presence of SPS was defined as eGFR ≤ 60% of eGFR .
SPS presented with significant associations (p < 5.4 × 10 ) in age and sex-adjusted logistic regressions with elevated levels of six proteins; scavenger receptor cysteine rich type 1 protein M130, tumor necrosis factor receptor 1, tumor necrosis factor receptor 2, osteoprotegerin, interleukin-2 receptor subunit alpha, and tyrosine-protein kinase receptor UFO. All proteins remained associated (p < 0.05) with SPS after multivariate adjustments.
In heart failure patients, SPS was associated with proteins linked to atherosclerosis and cell proliferation.
“收缩孔综合征”（SPS）的特征是胱抑素C和肌酐之间的肾滤过差异，导致估算肾小球滤过率（eGFR）/eGFR比值较低。研究表明，SPS患者发生心血管疾病和死亡的风险较高。在这项探索性研究中，我们探讨了SPS与心力衰竭患者心血管疾病和炎症相关蛋白之间的关联。
对因心力衰竭诊断而住院的HARVEST - 马尔默试验中的300名个体（平均年龄74.9±11.5岁；女性占30.0%）的血浆样本进行分析，采用包含92种蛋白质的邻位延伸分析方法。在初始的年龄和性别调整分析中，经Bonferroni校正的p值0.05/92 = 5.4×10被认为具有显著性。SPS的存在定义为eGFR≤eGFR的60%。
在年龄和性别调整的逻辑回归中，SPS与六种蛋白质水平升高存在显著关联（p < 5.4×10）；富含半胱氨酸的清道夫受体1蛋白M130、肿瘤坏死因子受体1、肿瘤坏死因子受体2、骨保护素、白细胞介素 - 2受体α亚基和酪氨酸蛋白激酶受体UFO。经过多变量调整后，所有蛋白质仍与SPS相关（p < 0.05）。
在心力衰竭患者中，SPS与动脉粥样硬化和细胞增殖相关的蛋白质有关。
