Murakoshi Maki, Gohda Tomohito, Sakuma Hiroko, Shibata Terumi, Adachi Eri, Kishida Chiaki, Ichikawa Saki, Koshida Takeo, Kamei Nozomu, Suzuki Yusuke
Department of Nephrology, Faculty of Medicine, Juntendo University, Tokyo, Japan.
Department of Endocrinology and Metabolism, Hiroshima Red Cross Hospital and Atomic-Bomb Survivors Hospital, Hiroshima, Japan.
Front Endocrinol (Lausanne). 2022 Apr 1;13:849457. doi: 10.3389/fendo.2022.849457. eCollection 2022.
Progranulin (PGRN), a growth factor, is abundantly expressed in a broad range of tissues and cell types with pleiotropic functions including inflammation, neurodegeneration, and facilitating lysosome acidification. PGRN binds to TNF receptors (TNFR) and inhibits downstream inflammatory signaling pathways. TNFR is a well-known predictor of glomerular filtration rate (GFR) decline in a variety of diseases. Therefore, we measured circulating PGRN in addition to TNFR using an enzyme-linked immunosorbent assay and explored whether it predicted renal prognosis in 201 Japanese patients with type 2 diabetes. During a median follow-up of 7.6 years, 21 participants reached primary renal endpoint, which involves a decline of at least 57% in eGFR from baseline, or the onset of end-stage renal disease. Univariate Cox regression analysis revealed that classical renal measures (GFR and albuminuria), two TNF-related biomarkers (PGRN and TNFR), and BMI were associated with this outcome. Multivariate analysis demonstrated that high levels of PGRN [HR 2.50 (95%CI 2.47-2.52)] or TNFR1 [HR 5.38 (95%CI 5.26-5.50)] were associated with this outcome after adjusting for relevant covariates. The high levels of PGRN as well as TNFR1 were associated with a risk of primary renal outcome in patients with type 2 diabetes after adjusting for established risk factors.
颗粒蛋白前体（PGRN）是一种生长因子，在多种组织和细胞类型中大量表达，具有多效性功能，包括炎症、神经退行性变以及促进溶酶体酸化。PGRN与肿瘤坏死因子受体（TNFR）结合并抑制下游炎症信号通路。TNFR是多种疾病中肾小球滤过率（GFR）下降的一个众所周知的预测指标。因此，我们使用酶联免疫吸附测定法除了检测TNFR之外还检测了循环中的PGRN，并探讨其是否能预测201例2型糖尿病日本患者的肾脏预后。在中位随访7.6年期间，21名参与者达到了主要肾脏终点，即估算肾小球滤过率（eGFR）较基线下降至少57%，或出现终末期肾病。单因素Cox回归分析显示，经典的肾脏指标（GFR和蛋白尿）、两种与肿瘤坏死因子相关的生物标志物（PGRN和TNFR）以及体重指数与这一结果相关。多因素分析表明，在调整相关协变量后，高水平的PGRN [风险比（HR）2.50（95%置信区间[CI] 2.47 - 2.52）]或TNFR1 [HR 5.38（95%CI 5.26 - 5.50）]与这一结果相关。在调整既定风险因素后，高水平的PGRN以及TNFR1与2型糖尿病患者发生主要肾脏结局的风险相关。
