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Serum Copeptin, NLPR3, and suPAR Levels among Patients with Autosomal-Dominant Polycystic Kidney Disease with and without Impaired Renal Function
Cardiorenal Medicine ( IF 2.4 ) Pub Date : 2020-11-17 , DOI: 10.1159/000510834
Vasileios Raptis 1 , Charalampos Loutradis 1 , Afroditi K Boutou 2 , Danai Faitatzidou 1 , Athanasios Sioulis 3 , Charles J Ferro 4 , Aikaterini Papagianni 1 , Pantelis A Sarafidis 5
Affiliation  

Background: The pathophysiology of renal disease progression in autosomal-dominant polycystic kidney disease (ADPKD) involves not only cystogenesis but also endothelial dysfunction, leading to the activation of inflammatory and fibrotic pathways. This study evaluated the levels of biomarkers related to osmoregulation, immune system activation, and tubular injury in ADPKD patients with impaired or preserved renal function. Methods: This study included 26 ADPKD patients with modestly impaired renal function (estimated glomerular filtration rate [eGFR] 45–70 mL/min/1.73 m2; Group A), 26 age- and sex-matched ADPKD patients with relatively preserved renal function (eGFR #x3e;70 mL/min/1.73 m2; Group B), and 26 age- and sex-matched controls (Group C). Serum levels of copeptin, the inflammasome nucleotide-binding and oligomerization domain-like receptors pyrin domain-containing protein 3 (NLRP3), and soluble urokinase-type plasminogen activator receptor (suPAR) were measured with ELISA techniques. Results: Patients in Group A had higher levels of copeptin (median [interquartile range]: 50.44 [334.85] pg/mL), NLRP3 (5.86 [3.89] ng/mL), and suPAR (390.05 [476.53] pg/mL) compared to patients in Group B (32.38 [58.33], p = 0.042; 2.42 [1.96], p #x3c; 0.001; and 313.78 [178.85], p = 0.035, respectively) and Group C (6.75 [6.43]; 1.09 [0.56]; and 198.30 [28.53], respectively; p #x3c; 0.001 for all comparisons). Levels of all studied markers were also significantly higher in Group B patients compared to controls (p #x3c; 0.001), despite having similar eGFR. In patients with ADPKD, all studied biomarkers were correlated positively with asymmetric-dimethylarginine (ADMA) and endocan levels, and negatively with eGFR. ADMA and endocan levels were the only parameters independently associated with increased copeptin levels. Conclusions: This study showed that ADPKD patients with impaired and preserved renal function had higher copeptin, NLRP3, and suPAR levels than controls. Such findings support that cystogenesis and inflammation are associated with endothelial dysfunction, even in the early stages of ADKPD.
Cardiorenal Med


中文翻译:

伴有和不伴有肾功能受损的常染色体显性多囊肾病患者的血清和肽素、NLPR3 和 suPAR 水平

背景:常染色体显性多囊肾病 (ADPKD) 肾脏疾病进展的病理生理学不仅涉及囊肿发生,还涉及内皮功能障碍,导致炎症和纤维化途径的激活。本研究评估了肾功能受损或保留的 ADPKD 患者中与渗透压调节、免疫系统激活和肾小管损伤相关的生物标志物水平。方法:本研究包括 26 名肾功能中度受损的 ADPKD 患者(估计肾小球滤过率 [eGFR] 45-70 mL/min/1.73 m 2;A 组),26 名年龄和性别匹配且肾功能相对保留的 ADPKD 患者(eGFR #x3e;70 mL/min/1.73 m 2; B 组)和 26 名年龄和性别匹配的对照(C 组)。用ELISA技术测量和肽素、炎性体核苷酸结合和寡聚结构域样受体pyrin结构域蛋白3 (NLRP3)和可溶性尿激酶型纤溶酶原激活物受体(suPAR)的血清水平。结果:与 A 组患者相比,A 组患者的和肽素水平更高(中位数 [四分位距]:50.44 [334.85] pg/mL)、NLRP3(5.86 [3.89] ng/mL)和 suPAR(390.05 [476.53] pg/mL) B 组(32.38 [58.33],p = 0.042;2.42 [1.96],p #x3c;0.001;和 313.78 [178.85],p = 0.035)和 C 组(6.75 [6.43];1.09 [0.56] ];和 198.30 [28.53];p#x3c; 所有比较均为 0.001)。尽管具有相似的 eGFR,但B 组患者的所有研究标志物水平也显着高于对照组 ( p #x3c; 0.001)。在患有 ADPKD 的患者中,所有研究的生物标志物都与不对称二甲基精氨酸 (ADMA) 和 endocan 水平呈正相关,与 eGFR 呈负相关。ADMA 和 endocan 水平是与和肽素水平升高独立相关的唯一参数。结论:本研究表明,肾功能受损和保留的 ADPKD 患者的和肽素、NLRP3 和 suPAR 水平高于对照组。这些发现支持囊肿形成和炎症与内皮功能障碍有关,即使在 ADKPD 的早期阶段也是如此。
心肾医学
更新日期:2020-11-17
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