2 型糖尿病患者的肾脏生物标志物与 eGFR 下降。
Kidney Biomarkers and Decline in eGFR in Patients with Type 2 Diabetes.
机构信息
Division of Cardiometabolic Trials, Baim Institute for Clinical Research, Boston, Massachusetts.
Department of Medicine, Renal Division, Brigham and Women's Hospital, Boston, Massachusetts.
出版信息
Clin J Am Soc Nephrol. 2018 Mar 7;13(3):398-405. doi: 10.2215/CJN.05280517. Epub 2018 Jan 16.
BACKGROUND AND OBJECTIVES
Biomarkers may improve identification of individuals at risk of eGFR decline who may benefit from intervention or dialysis planning. However, available biomarkers remain incompletely validated for risk stratification and prediction modeling.
DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We examined serum cystatin C, urinary kidney injury molecule-1 (uKIM-1), and urinary neutrophil gelatinase-associated lipocalin (UNGAL) in 5367 individuals with type 2 diabetes mellitus and recent acute coronary syndromes enrolled in the Examination of Cardiovascular Outcomes with Alogliptin versus Standard of Care (EXAMINE) trial. Baseline concentrations and 6-month changes in biomarkers were also evaluated. Cox proportional regression was used to assess associations with a 50% decrease in eGFR, stage 5 CKD (eGFR<15 ml/min per 1.73 m), or dialysis.
RESULTS
eGFR decline occurred in 98 patients (1.8%) over a median of 1.5 years. All biomarkers individually were associated with higher risk of eGFR decline (<0.001). However, when adjusting for baseline eGFR, proteinuria, and clinical factors, only baseline cystatin C (adjusted hazard ratio per 1 SD change, 1.66; 95% confidence interval, 1.41 to 1.96; <0.001) and 6-month change in urinary neutrophil gelatinase-associated lipocalin (adjusted hazard ratio per 1 SD change, 1.07; 95% confidence interval, 1.02 to 1.12; =0.004) independently associated with CKD progression. A base model for predicting kidney function decline with nine standard risk factors had strong discriminative ability (C-statistic 0.93). The addition of baseline cystatin C improved discrimination (C-statistic 0.94), but it failed to reclassify risk categories of individuals with and without eGFR decline.
CONCLUSIONS
The addition of cystatin C or biomarkers of tubular injury did not meaningfully improve the prediction of eGFR decline beyond common clinical factors and routine laboratory data in a large cohort of patients with type 2 diabetes and recent acute coronary syndrome.
PODCAST
This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2018_01_16_CJASNPodcast_18_3_G.mp3.
背景与目的
生物标志物可能有助于识别 eGFR 下降风险较高的个体，并为其提供干预或透析计划。然而，目前可用的生物标志物在风险分层和预测模型方面仍未得到充分验证。
方法、设置、参与者和测量：我们在参加评估阿格列汀与标准治疗对心血管结局影响的试验（EXAMINE）的 5367 例 2 型糖尿病合并近期急性冠脉综合征患者中，检测了血清胱抑素 C、尿肾损伤分子-1（uKIM-1）和尿中性粒细胞明胶酶相关脂质运载蛋白（UNGAL）。还评估了生物标志物的基线浓度和 6 个月变化。Cox 比例风险回归用于评估与 eGFR 下降 50%（eGFR<15 ml/min/1.73 m）、CKD 5 期（eGFR<15 ml/min/1.73 m）或透析相关的关联。
结果
中位随访 1.5 年期间，98 例患者（1.8%）发生 eGFR 下降。所有生物标志物单独与较高的 eGFR 下降风险相关（<0.001）。然而，在调整基线 eGFR、蛋白尿和临床因素后，仅基线胱抑素 C（每 SD 变化的调整 HR，1.66；95%置信区间，1.41 至 1.96；<0.001）和尿中性粒细胞明胶酶相关脂质运载蛋白的 6 个月变化（每 SD 变化的调整 HR，1.07；95%置信区间，1.02 至 1.12；=0.004）与 CKD 进展独立相关。基于 9 个标准风险因素的预测肾功能下降的基础模型具有较强的判别能力（C 统计量为 0.93）。添加基线胱抑素 C 可提高判别能力（C 统计量为 0.94），但无法重新分类有和无 eGFR 下降患者的风险类别。
结论
在 2 型糖尿病合并近期急性冠脉综合征的大型患者队列中，除了常见的临床因素和常规实验室数据外，胱抑素 C 或肾小管损伤的生物标志物并不能显著改善 eGFR 下降的预测。
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