Department of Paediatrics, University of Cambridge, Cambridge, UK.
Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, UK.
Pediatr Diabetes. 2020 Nov;21(7):1322-1332. doi: 10.1111/pedi.13095. Epub 2020 Aug 17.
To identify biomarkers of renal disease in adolescents with type 1 diabetes (T1D) and to compare findings in adults with T1D.
Twenty-five serum biomarkers were measured, using a Luminex platform, in 553 adolescents (median [interquartile range] age: 13.9 [12.6, 15.2] years), recruited to the Adolescent Type 1 Diabetes Cardio-Renal Intervention Trial. Associations with baseline and final estimated glomerular filtration rate (eGFR), rapid decliner and rapid increaser phenotypes (eGFR slopes <-3 and > 3 mL/min/1.73m /year, respectively), and albumin-creatinine ratio (ACR) were assessed. Results were also compared with those obtained in 859 adults (age: 55.5 [46.1, 64.4) years) from the Scottish Diabetes Research Network Type 1 Bioresource.
In the adolescent cohort, baseline eGFR was negatively associated with trefoil factor-3, cystatin C, and beta-2 microglobulin (B2M) (B coefficient[95%CI]: -0.19 [-0.27, -0.12], P = 7.0 × 10 ; -0.18 [-0.26, -0.11], P = 5.1 × 10 ; -0.12 [-0.20, -0.05], P = 1.6 × 10 ), in addition to clinical covariates. Final eGFR was negatively associated with osteopontin (-0.21 [-0.28, -0.14], P = 2.3 × 10 ) and cystatin C (-0.16 [-0.22, -0.09], P = 1.6 × 10 ). Rapid decliner phenotype was associated with osteopontin (OR: 1.83 [1.42, 2.41], P = 7.3 × 10 ), whereas rapid increaser phenotype was associated with fibroblast growth factor-23 (FGF-23) (1.59 [1.23, 2.04], P = 2.6 × 10 ). ACR was not associated with any of the biomarkers. In the adult cohort similar associations with eGFR were found; however, several additional biomarkers were associated with eGFR and ACR.
In this young population with T1D and high rates of hyperfiltration, osteopontin was the most consistent biomarker associated with prospective changes in eGFR. FGF-23 was associated with eGFR increases, whereas trefoil factor-3, cystatin C, and B2M were associated with baseline eGFR.
鉴定青少年 1 型糖尿病患者肾脏疾病的生物标志物，并与成人 1 型糖尿病患者的发现进行比较。
对 553 名青少年（中位[四分位距]年龄：13.9[12.6，15.2]岁）进行了 25 种血清生物标志物的测量，使用 Luminex 平台进行检测。这些青少年均参与了青少年 1 型糖尿病心脏肾脏干预试验。评估了与基线和最终估算肾小球滤过率（eGFR）、快速下降和快速增加表型（eGFR 斜率分别为<-3 和>3 mL/min/1.73m 2 /年）以及白蛋白-肌酐比值（ACR）的相关性。结果还与来自苏格兰糖尿病研究网络 1 型生物资源的 859 名成人（年龄：55.5[46.1，64.4]岁）的结果进行了比较。
在青少年队列中，基线 eGFR 与三叶因子-3、胱抑素 C 和β2 微球蛋白（B2M）呈负相关（B 系数[95%CI]：-0.19[-0.27，-0.12]，P=7.0×10 -3 ；-0.18[-0.26，-0.11]，P=5.1×10 -3 ；-0.12[-0.20，-0.05]，P=1.6×10 -2 ），此外还与临床协变量相关。最终 eGFR 与骨桥蛋白呈负相关（-0.21[-0.28，-0.14]，P=2.3×10 -3 ）和胱抑素 C（-0.16[-0.22，-0.09]，P=1.6×10 -3 ）。快速下降表型与骨桥蛋白相关（OR：1.83[1.42，2.41]，P=7.3×10 -3 ），而快速增加表型与成纤维细胞生长因子-23（FGF-23）相关（1.59[1.23，2.04]，P=2.6×10 -3 ）。ACR 与任何生物标志物均无相关性。在成人队列中也发现了与 eGFR 相似的相关性，但还有其他几种生物标志物与 eGFR 和 ACR 相关。
在这个青少年 1 型糖尿病患者中，骨桥蛋白是与 eGFR 前瞻性变化最相关的生物标志物，该人群中存在高滤过率。FGF-23 与 eGFR 升高相关，而三叶因子-3、胱抑素 C 和 B2M 与基线 eGFR 相关。
