Clinical Research Unit, Khoo Teck Puat Hospital, Singapore 768828, Singapore.
Diabetes Centre, Khoo Teck Puat Hospital, Singapore 768828, Singapore.
J Clin Endocrinol Metab. 2017 Oct 1;102(10):3683-3691. doi: 10.1210/jc.2017-00930.
Abnormal angiogenesis plays an important role in pathogenesis of diabetic kidney disease (DKD). Leucine-rich α-2 glycoprotein 1 (LRG1) is a newly identified angiogenic factor.
To study whether plasma LRG1 may independently predict progression of DKD in individuals with type 2 diabetes mellitus (T2DM).
Prospective cohort study in a regional hospital.
In total, 1226 T2DM participants were followed for a mean ± standard deviation (SD) of 3.1 ± 0.4 years.
Albuminuria progression was defined as elevation in albuminuria level to a higher category. Chronic kidney disease (CKD) progression [rapid estimated glomerular filtration rate (eGFR) decline] was defined as a 40% or greater deterioration in eGFR in 3 years.
Both participants with albuminuria progression and those with CKD progression had higher plasma LRG1 levels at baseline. LRG1 independently predicted albuminuria progression above traditional risk factors, including baseline eGFR and urine albumin to creatinine ratio. A 1-SD increment in LRG1 was associated with a 1.26-fold [95% confidence interval (CI), 1.04 to 1.53, P = 0.018] higher adjusted risk for albuminuria progression. The association of LRG1 with microalbuminuria to macroalbuminuria progression was stronger than its association with normoalbuminuria to microalbuminuria progression [odds ratio (OR), 1.51; 95% CI, 1.04 to 2.18, P = 0.029 vs OR, 1.09; 95% CI, 0.86 to 1.37, P = 0.486, per 1-SD LRG1 increment]. Also, LRG1 independently predicted CKD progression above traditional risk factors. A 1-SD increment in LRG1 was associated with a 1.48-fold (95% CI, 1.04 to 2.11, P = 0.032) higher adjusted risk for CKD progression.
Plasma LRG1 predicts both albuminuria and CKD progression beyond traditional risk factors. It may play a role in the pathologic pathway leading to progression of DKD in T2DM.
异常血管生成在糖尿病肾病（DKD）发病机制中起重要作用。富含亮氨酸的α-2 糖蛋白 1（LRG1）是一种新发现的血管生成因子。
研究血浆 LRG1 是否可独立预测 2 型糖尿病（T2DM）个体 DKD 的进展。
地区医院的前瞻性队列研究。
共纳入 1226 例 T2DM 患者，平均随访 3.1 ± 0.4 年。
白蛋白尿进展定义为白蛋白尿水平升高至更高类别。慢性肾脏病（CKD）进展[估算肾小球滤过率（eGFR）快速下降]定义为 eGFR 在 3 年内恶化 40%或更多。
白蛋白尿进展患者和 CKD 进展患者的基线血浆 LRG1 水平均较高。LRG1 独立于传统危险因素预测白蛋白尿进展，包括基线 eGFR 和尿白蛋白/肌酐比值。LRG1 增加 1 个标准差（SD）与白蛋白尿进展的调整后风险增加 1.26 倍[95%置信区间（CI），1.04 至 1.53，P = 0.018]相关。LRG1 与微量白蛋白尿至大量白蛋白尿进展的相关性强于其与正常白蛋白尿至微量白蛋白尿进展的相关性[比值比（OR），1.51；95%CI，1.04 至 2.18，P = 0.029 与 OR，1.09；95%CI，0.86 至 1.37，P = 0.486，每增加 1 个 SD LRG1，P 值]。此外，LRG1 独立于传统危险因素预测 CKD 进展。LRG1 增加 1 个 SD 与 CKD 进展的调整后风险增加 1.48 倍[95%CI，1.04 至 2.11，P = 0.032]相关。
血浆 LRG1 预测 T2DM 患者的白蛋白尿和 CKD 进展均超出传统危险因素。它可能在导致 DKD 进展的病理途径中发挥作用。
