Department of Medicine, MetroWest Medical Center/Tufts Medical School, Framingham, Massachusetts, United States.
Department of Neurology, University of Massachusetts Medical Center, Worcester, Massachusetts, United States.
Can J Diabetes. 2022 Feb;46(1):69-74. doi: 10.1016/j.jcjd.2021.06.001. Epub 2021 Jun 7.
Our aim in this study was to characterize clinical associations between peripheral blood immune populations and diabetic kidney disease (DKD) in patients with type 2 diabetes mellitus.
We queried hospital records from an outpatient diabetes primary care clinic between 2018 and 2019 for clinical and laboratory data, including complete blood counts with differentials, serum albumin and globulin, glycated hemoglobin (A1C) and urine albumin-to-creatinine ratio. One hundred ninety-eight patients had complete cross-sectional data with temporally proximate complete blood counts and urine albumin-to-creatinine ratios. After univariable correlation assessment, we used a forward multivariable linear regression model to test the hypothesis that higher numbers of circulating innate immune populations would be associated with DKD, while accounting for known demographic, clinical and laboratory risk factors. We defined DKD as an albumin-to-creatinine ratio of >3 mg/mmol or an estimated glomerular filtration rate (eGFR) of <60 mL/min/1.73 m from the Chronic Kidney Disease Epidemiology Collaboration.
Adjusted analyses demonstrated significant (p<0.01) associations between higher urine albumin-to-creatinine ratio and peripheral circulating monocytes, independent of other established significant risk factors, including blood pressure, A1C, age and sex. We also identified serum albumin as a potentially important modifying factor of albuminuric kidney disease, which interacts with monocytes in more advanced disease. In contrast, the variable most strongly predictive of eGFR was age.
Circulating monocytes and serum albumin are significantly associated with albuminuria, but not eGFR in DKD. These results support the potential role of the innate immune system in diabetic microvascular end-organ damage and urinary protein loss, and may be readily translatable clinical markers to incorporate into risk-assessment models for prognostication in diabetes.
本研究旨在描述 2 型糖尿病患者外周血免疫细胞与糖尿病肾脏疾病（DKD）的临床相关性。
我们查询了 2018 年至 2019 年期间一个门诊糖尿病初级保健诊所的住院记录，获取临床和实验室数据，包括全血细胞计数（包括分类）、血清白蛋白和球蛋白、糖化血红蛋白（A1C）和尿白蛋白与肌酐比值。198 例患者具有完整的横断面数据，且全血细胞计数和尿白蛋白与肌酐比值具有时间上的相关性。在进行单变量相关评估后，我们使用向前逐步多元线性回归模型来检验以下假设，即循环固有免疫细胞数量较高与 DKD 相关，同时考虑到已知的人口统计学、临床和实验室危险因素。我们将 DKD 定义为白蛋白与肌酐比值>3mg/mmol 或慢性肾脏病流行病学合作组估计的肾小球滤过率（eGFR）<60mL/min/1.73m。
调整后的分析表明，在其他已确定的重要危险因素（包括血压、A1C、年龄和性别）之外，更高的尿白蛋白与肌酐比值与外周循环单核细胞之间存在显著（p<0.01）相关性。我们还发现血清白蛋白是白蛋白尿性肾脏疾病的一个潜在重要调节因素，它与更严重疾病中的单核细胞相互作用。相比之下，最能预测 eGFR 的变量是年龄。
循环单核细胞和血清白蛋白与 DKD 中的白蛋白尿显著相关，但与 eGFR 无关。这些结果支持固有免疫系统在糖尿病微血管终末器官损伤和尿蛋白丢失中的潜在作用，并且可能是可直接转化为临床的标志物，可纳入糖尿病预后风险评估模型。
