Department of Pediatric Endocrinology, Pamukkale University, Denizli, Turkey.
Department of Medical Biochemistry, Pamukkale University, Denizli, Turkey.
Pediatr Nephrol. 2023 Dec;38(12):4043-4049. doi: 10.1007/s00467-023-06019-4. Epub 2023 Jul 4.
Glomerular endothelial dysfunction and neoangiogenesis play a significant role in the pathogenesis of diabetic kidney disease (DKD). Leucine-rich α-2 glycoprotein 1 (LRG1) is a recently discovered protein that participates in the molecular pathway of inflammation and angiogenesis. We aimed to investigate efficacy of LRG1 to predict estimated glomerular filtration rate (eGFR) decrease in children and adolescents with type 1 diabetes mellitus (T1DM).
The study comprised 72 participants with diabetes duration for ≥ 2 years. At study initiation, LRG1, urine albumin, eGFR (cystatin C-based, and Schwartz), HbA1c, and lipid values were evaluated and diabetes-related clinical features and anthropometric measurements were collected. These results were compared with final control values after ≥ 1 year. Patients were divided into subgroups according to presence of albuminuria progression, eGFR decrease, and metabolic control parameters.
There was positive correlation between LRG1 level and Schwartz and cystatin C-based eGFR decline (r = 0.360, p = 0.003; r = 0.447, p = 0.001, respectively), and negative correlation between final cystatin C-based eGFR and LRG1 (p = 0.01, r = -0.345). Patients with cystatin C-based eGFR decrease > 10% had significantly higher LRG1 levels (p = 0.03), however, LRG1 was not different between albuminuria progression subgroups. A 0.282 μg/ml increase in LRG1 correlated with a 1% decrease in eGFR in simple linear regression analysis (β = 0.282, %CI 0.11-0.45, p = 0.001) and LRG1 was an independent predictor of GFR decline even in the presence of covariates.
Our study supports the relationship between plasma LRG1 and eGFR decline and suggests LRG1 may be an early marker of DKD progression in children with T1DM. A higher resolution version of the Graphical abstract is available as Supplementary information.
肾小球内皮功能障碍和新生血管形成在糖尿病肾病（DKD）的发病机制中起重要作用。富含亮氨酸的α-2 糖蛋白 1（LRG1）是一种新发现的蛋白，参与炎症和血管生成的分子途径。我们旨在研究 LRG1 预测 1 型糖尿病（T1DM）儿童和青少年估算肾小球滤过率（eGFR）下降的疗效。
本研究纳入了糖尿病病程≥2 年的 72 名参与者。在研究开始时，评估了 LRG1、尿白蛋白、基于胱抑素 C 的 eGFR（Schwartz）、HbA1c 和血脂值，并收集了糖尿病相关的临床特征和人体测量学指标。这些结果与≥1 年后的最终对照值进行了比较。根据白蛋白尿进展、eGFR 下降和代谢控制参数，将患者分为亚组。
LRG1 水平与 Schwartz 和基于胱抑素 C 的 eGFR 下降呈正相关（r=0.360，p=0.003；r=0.447，p=0.001），与最终基于胱抑素 C 的 eGFR 呈负相关（p=0.01，r=-0.345）。基于胱抑素 C 的 eGFR 下降>10%的患者 LRG1 水平显著升高（p=0.03），但在白蛋白尿进展亚组中，LRG1 无差异。简单线性回归分析显示，LRG1 增加 0.282μg/ml 与 eGFR 下降 1%相关（β=0.282，95%CI 0.11-0.45，p=0.001），LRG1 是 GFR 下降的独立预测因子，即使在存在协变量的情况下也是如此。
本研究支持血浆 LRG1 与 eGFR 下降之间的关系，并表明 LRG1 可能是 T1DM 儿童 DKD 进展的早期标志物。更清晰的图文摘要版本可在补充信息中查看。
