Novel Risk Factors for Progression of Diabetic and Nondiabetic CKD: Findings From the Chronic Renal Insufficiency Cohort (CRIC) Study.
Novel Risk Factors for Progression of Diabetic and Nondiabetic CKD: Findings From the Chronic Renal Insufficiency Cohort (CRIC) Study.
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DOI：
10.1053/j.ajkd.2020.07.011
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发表时间：
2021-01
期刊：
影响因子：
--
通讯作者：
CRIC Study Investigators
中科院分区：
文献类型：
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作者：
Anderson AH;Xie D;Wang X;Baudier RL;Orlandi P;Appel LJ;Dember LM;He J;Kusek JW;Lash JP;Navaneethan SD;Ojo A;Rahman M;Roy J;Scialla JJ;Sondheimer JH;Steigerwalt SP;Wilson FP;Wolf M;Feldman HI;CRIC Study Investigators
确定慢性肾脏病（CKD）进展的新风险因素可能会为机制研究提供信息，并改善高风险亚组的识别。目前的研究旨在描述多种风险因素水平下的CKD进展，并确定糖尿病患者和非糖尿病患者中CKD进展的独立风险因素。慢性肾功能不全队列（CRIC）研究是一项在7家美国临床中心进行的成人CKD前瞻性队列研究。参与者（N=3379）接受了长达12.3年的随访; 47%患有糖尿病。在基线时，在社会人口统计学、行为学、临床和生化领域中存在30个CKD进展的风险因素。研究结局为估计的肾小球滤过率（eGFR）斜率和eGFR减半或开始肾脏替代治疗（KRT）的复合终点。采用线性混合效应和考克斯比例风险模型，按糖尿病状态分层，逐步选择独立风险因素。在无糖尿病和有糖尿病的患者中，平均（SD）eGFR斜率分别为-1.4（3.3）和-2.7（4.7）mL/min/1.73m2/year。在糖尿病受试者中，炎症趋化因子CXCL 12、心脏标志物N末端B型利钠肽前体（NTproBNP）和肾损伤标志物尿中性粒细胞明胶酶相关脂质运载蛋白（NGAL）水平较高时，复合结局的多变量校正风险约为2倍或更高。在无糖尿病的患者中，低血清碳酸氢盐以及较高的高敏肌钙蛋白T、NTproBNP和尿NGAL均与1.5倍或更高的复合结局发生率显著相关。观察性研究设计排除了因果推断。心脏标志物、血浆CXCL 12和尿NGAL的强相关性超过了收缩压≥140 mmHg，这是CKD进展的一个公认风险因素。这需要进一步研究这些标志物指示的潜在机制以及使用它们来改善风险分层的机会。 NCT00304148 与CKD进展风险增加相关的几种新型生物标志物本研究的主要目标是在一项前瞻性CKD队列研究（N=3379）中，在有糖尿病和无糖尿病的参与者中确定CKD进展的独立风险因素。在糖尿病患者中，随着炎症趋化因子CXCL 12、心脏标志物NTproBNP和肾损伤标志物尿NGAL水平的升高，CKD进展率大约增加一倍。在无糖尿病的患者中，随着高敏肌钙蛋白T、NTproBNP和尿NGAL水平的升高，患病率增加了1.5倍以上。这些相关性的强度超过了收缩压≥140 mmHg，这是肾脏疾病进展的一个明确风险因素。这些发现为CKD进展的潜在机制提供了见解，并将指导未来的研究，以定义CKD进展最高风险的亚组。
Identification of novel risk factors for chronic kidney disease (CKD) progression may inform mechanistic investigations and improve identification of high-risk subgroups. The current study aimed to characterize CKD progression across levels of numerous risk factors and to identify independent risk factors for CKD progression among those with and without diabetes. The Chronic Renal Insufficiency Cohort (CRIC) Study is a prospective cohort study of adults with CKD conducted at seven US clinical centers. Participants (N=3379) had up to 12.3 years of follow-up; 47% had diabetes. Thirty risk factors for CKD progression across sociodemographic, behavioral, clinical and biochemical domains at baseline. Study outcomes were estimated glomerular filtration rate (eGFR) slope and the composite of halving of eGFR or initiation of kidney replacement therapy (KRT). Stepwise selection of independent risk factors was performed stratified by diabetes status using linear mixed effects and Cox proportional hazards models. Among those without and with diabetes, respectively, the mean (SD) eGFR slope was −1.4 (3.3) and −2.7 (4.7) mL/min/1.73m2/year. Among participants with diabetes, multivariable-adjusted hazard of the composite outcome was approximately twofold or greater with higher levels of the inflammatory chemokine CXCL12, the cardiac marker N-terminal pro-B-type natriuretic peptide (NTproBNP) and the kidney injury marker urine neutrophil gelatinase-associated lipocalin (NGAL). Among those without diabetes, low serum bicarbonate as well as higher high-sensitivity troponin T, NTproBNP and urine NGAL were all significantly associated with a 1.5-fold or greater rate of the composite outcome. The observational study design precludes causal inference. Strong associations for cardiac markers, plasma CXCL12 and urine NGAL exceeded that of systolic blood pressure ≥140 mmHg, a well-established risk factor for CKD progression. This warrants further investigation into the potential mechanisms these markers indicate and opportunities to use them to improve risk stratification. NCT00304148 Several novel biomarkers associated with increased risk of CKD progression The primary goal of this study was to identify independent risk factors of CKD progression among participants with and without diabetes in a prospective CKD cohort study (N=3379). Among those with diabetes, CKD progression rates approximately doubled with higher levels of the inflammatory chemokine CXCL12, the cardiac marker NTproBNP and the kidney injury marker urine NGAL. Among those without diabetes, rates increased over 1.5-fold with higher levels of high-sensitivity troponin T, NTproBNP and urine NGAL. The strength of these associations exceeded that of systolic blood pressure ≥140 mmHg, a well-established risk factor for kidney disease progression. These findings provide insights into potential mechanisms of CKD progression and will guide future research in defining subgroups at highest risk for CKD progression.
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DOI：
10.2215/cjn.10331011
发表时间：
2012-05-01
影响因子：
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