Janssens Peter, Decuypere Jean-Paul, De Rechter Stéphanie, Breysem Luc, Van Giel Dorien, Billen Jaak, Hindryckx An, De Catte Luc, Baldewijns Marcella, Claes Kathleen B M, Wissing Karl M, Devriendt Koen, Bammens Bert, Meyts Isabelle, Torres Vicente E, Vennekens Rudi, Mekahli Djalila
PKD Research Group, Laboratory of Pediatrics, Department of Development and Regeneration, KU Leuven, Leuven, Belgium.
Department of Nephrology, University Hospitals Brussels, Brussels, Belgium.
Kidney Int Rep. 2021 Apr 6;6(6):1687-1698. doi: 10.1016/j.ekir.2021.03.893. eCollection 2021 Jun.
Autosomal dominant polycystic kidney disease (ADPKD) causes kidney failure typically in adulthood, but the disease starts . Copeptin, epidermal growth factor (EGF), and monocyte chemoattractant protein-1 (MCP-1) are associated with severity and hold prognostic value in adults but remain unstudied in the early disease stage. Kidneys from adults with ADPKD exhibit macrophage infiltration, and a prominent role of MCP-1 secretion by tubular epithelial cells is suggested from rodent models.
In a cross-sectional study, plasma copeptin, urinary EGF, and urinary MCP-1 were evaluated in a pediatric ADPKD cohort and compared with age-, sex-, and body mass index (BMI)-matched healthy controls. MCP-1 was studied in mouse collecting duct cells, human proximal tubular cells, and fetal kidney tissue.
Fifty-three genotyped ADPKD patients and 53 controls were included. The mean (SD) age was 10.4 (5.9) versus 10.5 (6.1) years ( = 0.543), and the estimated glomerular filtration rate (eGFR) was 122.7 (39.8) versus 114.5 (23.1) ml/min per 1.73 m ( = 0.177) in patients versus controls, respectively. Plasma copeptin and EGF secretion were comparable between groups. The median (interquartile range) urinary MCP-1 (pg/mg creatinine) was significantly higher in ADPKD patients (185.4 [213.8]) compared with controls (154.7 [98.0], = 0.010). Human proximal tubular cells with a heterozygous mutation and mouse collecting duct cells with a knockout exhibited increased MCP-1 secretion. Human fetal ADPKD kidneys displayed prominent MCP-1 immunoreactivity and M2 macrophage infiltration.
An increase in tubular MCP-1 secretion is an early event in ADPKD. MCP-1 is an early disease severity marker and a potential treatment target.
常染色体显性遗传性多囊肾病（ADPKD）通常在成年期导致肾衰竭，但该病始于……。 copeptin、表皮生长因子（EGF）和单核细胞趋化蛋白-1（MCP-1）与疾病严重程度相关，对成年人具有预后价值，但在疾病早期阶段仍未得到研究。成年ADPKD患者的肾脏表现出巨噬细胞浸润，并且从啮齿动物模型提示肾小管上皮细胞分泌MCP-1具有重要作用。
在一项横断面研究中，对儿科ADPKD队列中的血浆copeptin、尿EGF和尿MCP-1进行评估，并与年龄、性别和体重指数（BMI）匹配的健康对照进行比较。在小鼠集合管细胞、人近端肾小管细胞和胎儿肾脏组织中研究MCP-1。
纳入了53例基因分型的ADPKD患者和53例对照。患者的平均（标准差）年龄为10.4（5.9）岁，而对照为10.5（6.1）岁（P = 0.543），患者和对照的估计肾小球滤过率（eGFR）分别为122.7（39.8）和114.5（23.1）ml/min per 1.73 m²（P = 0.177）。两组间血浆copeptin和EGF分泌相当。ADPKD患者尿MCP-1（pg/mg肌酐）的中位数（四分位间距）显著高于对照（185.4 [213.8] 对比154.7 [98.0]，P = 0.010）。具有杂合PKD1突变的人近端肾小管细胞和具有Pkd1敲除的小鼠集合管细胞表现出MCP-1分泌增加。人胎儿ADPKD肾脏显示出显著的MCP-1免疫反应性和M2巨噬细胞浸润。
肾小管MCP-1分泌增加是ADPKD的早期事件。MCP-1是疾病早期严重程度的标志物和潜在的治疗靶点。
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