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糖尿病肾病中的血清和尿颗粒蛋白前体

Serum and Urinary Progranulin in Diabetic Kidney Disease.

作者信息

Nicoletto Bruna Bellincanta, Krolikowski Thaiana Cirino, Crispim Daisy, Canani Luis Henrique

机构信息

Post Graduate Medical Sciences Program: Endocrinology, School of Medicine, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil.

Nutrition Course, School of Medicine, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil.

出版信息

PLoS One. 2016 Oct 24;11(10):e0165177. doi: 10.1371/journal.pone.0165177. eCollection 2016.

Abstract

Progranulin has been recognized as an adipokine related to obesity, insulin resistance and type 2 diabetes mellitus (T2DM). There are scarce data regarding progranulin and kidney disease, but there are some data linking diabetic kidney disease (DKD) and increased progranulin levels. We aimed to better describe the relationship between serum and urinary progranulin levels and DKD in T2DM. This is a case-control study including four groups of subjects: 1) Advanced DKD cases: T2DM patients with estimated glomerular filtration rate (eGFR) <60 mL/min/1.73m2; 2) Albuminuric DKD cases: T2DM patients with urinary albumin excretion (UAE) ≥30 mg/g creatinine and eGFR ≥60 mL/min/1.73m2; 3) Diabetic controls: T2DM patients with UAE <30 mg/g creatinine and eGFR ≥60 mL/min/1.73m2; and 4) Non-diabetic controls: individuals without T2DM. Progranulin was determined by enzyme-linked immunosorbent assay. One hundred and fourteen patients were included (23 advanced DKD cases, 25 albuminuric DKD cases, 40 diabetic controls and 26 non-diabetic controls). Serum progranulin was increased in advanced DKD compared to other groups [70.84 (59.04-83.16) vs. albuminuric cases 57.16 (42.24-67.38), diabetic controls 57.28 (42.08-70.47) and non-diabetic controls 44.54 (41.44-53.32) ng/mL; p<0.001]. Urinary progranulin was decreased in advanced DKD cases compared to albuminuric cases [10.62 (6.30-16.08) vs. 20.94 (12.35-30.22); diabetic controls 14.06 (9.88-20.82) and non-diabetic controls 13.51 (7.94-24.36) ng/mL; p = 0.017]. There was a positive correlation between serum progranulin and body mass index (r = 0.27; p = 0.004), waist circumference (r = 0.25; p = 0.007); body fat percentage (r = 0.20; p = 0.042), high-sensitive C reactive protein (r = 0.35; p<0.001) and interleukin-6 (r = 0.37; p<0.001) and a negative correlation with eGFR (r = -0.22; p = 0.023). Urinary progranulin was positively associated with albuminuria (r = 0.25; p = 0.010). In conclusion, progranulin is affected by a decrease in eGFR, being at a higher concentration in serum and lower in urine of DKD patients with T2DM and eGFR <60 mL/min/1.73m2. It is also associated with markers of obesity and inflammation.

摘要

颗粒蛋白前体已被公认为是一种与肥胖、胰岛素抵抗和2型糖尿病(T2DM)相关的脂肪因子。关于颗粒蛋白前体与肾脏疾病的数据很少,但有一些数据将糖尿病肾病(DKD)与颗粒蛋白前体水平升高联系起来。我们旨在更好地描述T2DM患者血清和尿颗粒蛋白前体水平与DKD之间的关系。这是一项病例对照研究,包括四组受试者:1)晚期DKD病例:估计肾小球滤过率(eGFR)<60 mL/min/1.73m²的T2DM患者;2)蛋白尿性DKD病例:尿白蛋白排泄量(UAE)≥30 mg/g肌酐且eGFR≥60 mL/min/1.73m²的T2DM患者;3)糖尿病对照组:UAE<30 mg/g肌酐且eGFR≥60 mL/min/1.73m²的T2DM患者;4)非糖尿病对照组:无T2DM的个体。通过酶联免疫吸附测定法测定颗粒蛋白前体。共纳入114例患者(23例晚期DKD病例、25例蛋白尿性DKD病例、40例糖尿病对照组和26例非糖尿病对照组)。与其他组相比,晚期DKD患者的血清颗粒蛋白前体升高[70.84(59.04 - 83.16)对蛋白尿性病例57.16(42.24 - 67.38)、糖尿病对照组57.28(42.�8 - 70.47)和非糖尿病对照组44.54(41.44 - 53.32)ng/mL;p<0.001]。与蛋白尿性病例相比,晚期DKD病例的尿颗粒蛋白前体降低[10.62(6.30 - 16.08)对20.94(12.35 - 30.22);糖尿病对照组14.06(9.88 - 20.82)和非糖尿病对照组13.51(7.94 - 24.36)ng/mL;p = 0.017]。血清颗粒蛋白前体与体重指数呈正相关(r = 0.27;p = 0.004)、腰围(r = 0.25;p = 0.007)、体脂百分比(r = 0.20;p = 0.042)、高敏C反应蛋白(r = 0.35;p<0.001)和白细胞介素 - 6(r = 0.37;p<0.001),与eGFR呈负相关(r = -0.22;p = 0.023)。尿颗粒蛋白前体与蛋白尿呈正相关(r = 0.25;p = 0.010)。总之,颗粒蛋白前体受eGFR降低的影响,在eGFR<60 mL/min/1.73m²的T2DM DKD患者中,血清浓度较高而尿中浓度较低。它还与肥胖和炎症标志物相关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5bdb/5077076/4d5e8430bab3/pone.0165177.g001.jpg

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