■肾小管间质损害是早期慢性肾脏病(CKD)的特征,但是目前的临床试验很难捕捉到它。肾小管间质健康的尿液生物标志物可以确定CKD的风险。
■前瞻性队列(社区动脉粥样硬化风险[ARIC])和病例队列(多种族动脉粥样硬化研究[MESA]和卒中地理和种族差异原因[REGARDS])。
■估计肾小球滤过率(eGFR)≥60mL/min/1.73m2且在ARIC中没有糖尿病的成年人,关于,MESA研究。
■基线尿单核细胞趋化蛋白-1(MCP-1),α-1-微球蛋白(α1m),肾损伤分子-1,表皮生长因子,和几丁质酶-3-样蛋白1.
■CKD或终末期肾病。
■每个队列的多变量Cox比例风险回归;所有3个队列结果的荟萃分析。
■872名ARIC参与者(444例CKD事件),636名MESA参与者(158例),对924名REGARDS参与者(488例)进行了抽样。跨队列,平均年龄60±10至63±8岁,基线eGFR范围为88±13至91±14mL/min/1.73m2。在ARIC,较高浓度的尿液MCP-1,α1m,肾损伤分子-1与CKD相关。在MESA,尿液MCP-1浓度较高和表皮生长因子浓度较低均与CKD相关.Inregards,这些生物标志物均未与CKD相关.在所有3个队列的荟萃分析中,α1m浓度每增加2倍与CKD相关(HR,1.19;95%CI,1.08-1.31)。
■观察性设计容易混淆;长期随访期间的竞争风险;荟萃分析仅限于3个队列。
■在3个没有普遍CKD或糖尿病的成人组合队列中,尿α1m浓度升高与CKD发病独立相关.当单独分析时,4种生物标志物与至少1个队列中的事件CKD相关。肾小管健康标志物可能独立于eGFR和蛋白尿告知CKD风险。
本研究分析了3个队列(ARIC,MESA,和REGARDS)无糖尿病或慢性肾病(CKD)的成年人,以确定肾小管间质健康的5种尿液生物标志物与CKD事件的关联,独立于传统的肾脏健康措施。对所有3个队列结果的荟萃分析表明,较高的尿α-1-微球蛋白基线水平与随访时的CKD事件相关。单个队列的结果表明,除了α-1-微球蛋白,单核细胞趋化蛋白-1、肾损伤分子-1和表皮生长因子也可能与CKD的发生发展有关。这些发现强调了肾小管间质健康在确定与肌酐和尿白蛋白无关的CKD风险中的重要性。
UNASSIGNED: Tubulointerstitial damage is a feature of early chronic kidney disease (CKD), but current clinical tests capture it poorly. Urine biomarkers of tubulointerstitial health may identify risk of CKD.
UNASSIGNED: Prospective cohort (Atherosclerosis Risk in Communities [ARIC]) and case-cohort (Multi-Ethnic Study of Atherosclerosis [MESA] and Reasons for Geographic and Racial Differences in Stroke [REGARDS]).
UNASSIGNED: Adults with estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m2 and without diabetes in the ARIC, REGARDS, and MESA studies.
UNASSIGNED: Baseline urine monocyte chemoattractant protein-1 (MCP-1), alpha-1-microglobulin (α1m), kidney injury molecule-1, epidermal growth factor, and chitinase-3-like protein 1.
UNASSIGNED: Incident CKD or end-stage kidney disease.
UNASSIGNED: Multivariable Cox proportional hazards regression for each cohort; meta-analysis of results from all 3 cohorts.
UNASSIGNED: 872 ARIC participants (444 cases of incident CKD), 636 MESA participants (158 cases), and 924 REGARDS participants (488 cases) were sampled. Across cohorts, mean age ranged from 60 ± 10 to 63 ± 8 years, and baseline eGFR ranged from 88 ± 13 to 91 ± 14 mL/min/1.73 m2. In ARIC, higher concentrations of urine MCP-1, α1m, and kidney injury molecule-1 were associated with incident CKD. In MESA, higher concentration of urine MCP-1 and lower concentration of epidermal growth factor were each associated with incident CKD. In REGARDS, none of the biomarkers were associated with incident CKD. In meta-analysis of all 3 cohorts, each 2-fold increase α1m concentration was associated with incident CKD (HR, 1.19; 95% CI, 1.08-1.31).
UNASSIGNED: Observational design susceptible to confounding; competing risks during long follow-up period; meta-analysis limited to 3 cohorts.
UNASSIGNED: In 3 combined cohorts of adults without prevalent CKD or diabetes, higher urine α1m concentration was independently associated with incident CKD. 4 biomarkers were associated with incident CKD in at least 1 of the cohorts when analyzed individually. Kidney tubule health markers might inform CKD risk independent of eGFR and albuminuria.
This study analyzed 3 cohorts (ARIC, MESA, and REGARDS) of adults without diabetes or prevalent chronic kidney disease (CKD) to determine the associations of 5 urinary biomarkers of kidney tubulointerstitial health with incident CKD, independent of traditional measures of kidney health. Meta-analysis of results from all 3 cohorts suggested that higher baseline levels of urine alpha-1-microglobulin were associated with incident CKD at follow-up. Results from individual cohorts suggested that in addition to alpha-1-microglobulin, monocyte chemoattractant protein-1, kidney injury molecule-1, and epidermal growth factor may also be associated with the development of CKD. These findings underscore the importance of kidney tubule interstitial health in defining risk of CKD independent of creatinine and urine albumin.