Zhang Hong, Gong Dawei, Ni Liqiang, Shi Lin, Xu Wendong, Shi Min, Chen Juan, Ai Yong, Zhang Xiangcheng
Departments of Endocrinology and ICU, the Affiliated Huaian No.1 People's Hospital of Nanjing Medical University, Huai'an, China.
Division of Endocrinology, Diabetes and Nutrition, Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland, USA.
Cell Physiol Biochem. 2018;48(3):1347-1354. doi: 10.1159/000492093. Epub 2018 Jul 26.
BACKGROUND/AIMS: Elabela (ELA) or Toddler is a recently identified hormone that plays a crucial role in embryonic development through the activation of the apelin receptor (APJ). Our previous study indicated that ELA is highly expressed in adult kidney and the ELA receptor signaling pathway is functional in mammalian systems. Whereas nothing is yet known regarding ELA and diabetic kidney disease (DKD). Here, we evaluated the relationship between serum ELA levels and albuminuria in patients with type 2 diabetes (T2D).
An observational study involving 80 patients divided into groups according to their baseline urinary albumin/creatinine ratio (ACR): Group 1 (ACR ≤ 29 mg/g), Group 2 (ACR = 30-299 mg/g), Group 3 (ACR ≥ 300 mg/g with normal serum creatinine), and Group 4 (ACR ≥ 300 mg/g with increased serum creatinine). The demographic, clinical, and biochemical variables including serum ELA were obtained or measured through disease history, physical examination, or laboratory evidence.
The results showed that the serum ELA levels decreased gradually with the deterioration of DKD from the stages of normal albuminuria, microalbuminuria, macroalbuminuria, to macroalbuminuria and elevated serum creatinine. In addition, ELA had a significantly negative correlation with ACR (r = -0.561, P < 0.001), retinopathy (r = -0.424, P < 0.001), serum creatinine (r = -0.269, P = 0.016), SBP (r = -0.249, P = 0.026), DBP (r = -0.261, P = 0.020) and a positive correlation with eGFR (r = 0.318, P = 0.004). Furthermore, stepwise multiple linear regression analysis showed that ACR, retinopathy, and LDL-C were considered the most relevant variables to ELA, and ELA, retinopathy, eGFR, and age were important predictors for ACR (t = -4.546, P = 0.000).
To our knowledge, this is the first study to explore the clinical relationship between ELA levels and CKD. Decreased serum ELA levels might be a significant clinical predictor in patients with DKD or even as a promising agent for treating CKD patients.
背景/目的：埃拉贝肽（ELA）或托德林蛋白是一种最近发现的激素，通过激活血管紧张素原受体（APJ）在胚胎发育中起关键作用。我们之前的研究表明，ELA在成年肾脏中高表达，且ELA受体信号通路在哺乳动物系统中发挥作用。然而，关于ELA与糖尿病肾病（DKD）的关系尚无定论。在此，我们评估了2型糖尿病（T2D）患者血清ELA水平与蛋白尿之间的关系。
一项观察性研究，纳入80例患者，根据其基线尿白蛋白/肌酐比值（ACR）分组：第1组（ACR≤29mg/g），第2组（ACR = 30 - 299mg/g），第3组（ACR≥300mg/g且血清肌酐正常），第4组（ACR≥300mg/g且血清肌酐升高）。通过病史、体格检查或实验室检查获取或测量包括血清ELA在内的人口统计学、临床和生化变量。
结果显示，随着DKD从正常蛋白尿、微量白蛋白尿、大量白蛋白尿发展到大量白蛋白尿且血清肌酐升高，血清ELA水平逐渐降低。此外，ELA与ACR（r = -0.561，P < 0.001）、视网膜病变（r = -0.424，P < 0.001）、血清肌酐（r = -0.269，P = 0.016）、收缩压（r = -0.249，P = 0.026）、舒张压（r = -0.261，P = 0.020）呈显著负相关，与估算肾小球滤过率（eGFR）呈正相关（r = 0.318，P = 0.004）。此外，逐步多元线性回归分析表明，ACR、视网膜病变和低密度脂蛋白胆固醇（LDL-C）被认为是与ELA最相关的变量，而ELA、视网膜病变、eGFR和年龄是ACR的重要预测因素（t = -4.546，P = 0.000）。
据我们所知，这是第一项探讨ELA水平与慢性肾脏病（CKD）临床关系的研究。血清ELA水平降低可能是DKD患者的一个重要临床预测指标，甚至可能成为治疗CKD患者的一种有前景的药物。
