Nephrology Section, Veterans Affairs San Diego Healthcare System, La Jolla, CA.
Department of Obstetrics & Gynecology, University of Washington, Seattle, WA.
Am J Kidney Dis. 2021 Sep;78(3):361-368.e1. doi: 10.1053/j.ajkd.2021.01.021. Epub 2021 Apr 20.
RATIONALE & OBJECTIVE: The Systolic Blood Pressure Intervention Trial (SPRINT) compared the effect of intensive versus standard systolic blood pressure targets on cardiovascular morbidity and mortality. In this ancillary study, we evaluated the use of exploratory factor analysis (EFA) to combine biomarkers of kidney tubule health in urine and plasma and then study their role in longitudinal estimated glomerular filtration rate (eGFR) change and risk of acute kidney injury (AKI).
Observational cohort nested in a clinical trial.
SETTING & PARTICIPANTS: 2,351 SPRINT participants with eGFR < 60 mL/min/1.73 m at baseline.
Levels of neutrophil gelatinase-associated lipocalin (NGAL), interleukin 18 (IL-18), chitinase-3-like protein (YKL-40), kidney injury molecule 1 (KIM-1), monocyte chemoattractant protein 1 (MCP-1), α-microglobulin (A1M) and β-microglobulin (B2M), uromodulin (UMOD), fibroblast growth factor 23 (FGF-23), and intact parathyroid hormone (PTH).
Longitudinal changes in eGFR and risk of AKI.
We performed EFA to capture different tubule pathophysiologic processes. We used linear mixed effects models to evaluate the association of each factor with longitudinal changes in eGFR. We evaluated the association of the tubular factors scores with AKI using Cox proportional hazards regression.
From 10 biomarkers, EFA generated 4 factors reflecting tubule injury/repair (NGAL, IL-18, and YKL-40), tubule injury/fibrosis (KIM-1 and MCP-1), tubule reabsorption (A1M and B2M), and tubule reserve/mineral metabolism (UMOD, FGF-23, and PTH). Each 1-SD higher tubule reserve/mineral metabolism factor score was associated with a 0.58% (95% CI, 0.39%-0.67%) faster eGFR decline independent of baseline eGFR and albuminuria. Both the tubule injury/repair and tubule injury/fibrosis factors were independently associated with future risk of AKI (per 1 SD higher, HRs of 1.18 [95% CI, 1.10-1.37] and 1.23 [95% CI, 1.02-1.48], respectively).
The factors require validation in other settings.
EFA allows parsimonious subgrouping of biomarkers into factors that are differentially associated with progressive eGFR decline and AKI. These subgroups may provide insights into the pathological processes driving adverse kidney outcomes.
收缩压干预试验（SPRINT）比较了强化与标准收缩压目标对心血管发病率和死亡率的影响。在这项辅助研究中，我们评估了探索性因子分析（EFA）在结合尿液和血浆中肾小管健康生物标志物方面的应用，然后研究其在纵向估算肾小球滤过率（eGFR）变化和急性肾损伤（AKI）风险中的作用。
临床试验中的观察性队列嵌套。
2351 名基线时 eGFR<60 mL/min/1.73 m 的 SPRINT 参与者。
中性粒细胞明胶酶相关脂质运载蛋白（NGAL）、白细胞介素 18（IL-18）、壳聚糖酶-3 样蛋白（YKL-40）、肾损伤分子 1（KIM-1）、单核细胞趋化蛋白 1（MCP-1）、α-微球蛋白（A1M）和β-微球蛋白（B2M）、尿调蛋白（UMOD）、成纤维细胞生长因子 23（FGF-23）和完整甲状旁腺激素（PTH）的水平。
eGFR 的纵向变化和 AKI 风险。
我们进行了 EFA 以捕获不同的肾小管病理生理过程。我们使用线性混合效应模型来评估每个因子与 eGFR 纵向变化的相关性。我们使用 Cox 比例风险回归评估肾小管因子评分与 AKI 的相关性。
从 10 种生物标志物中，EFA 产生了 4 个因子，反映了肾小管损伤/修复（NGAL、IL-18 和 YKL-40）、肾小管损伤/纤维化（KIM-1 和 MCP-1）、肾小管重吸收（A1M 和 B2M）和肾小管储备/矿物质代谢（UMOD、FGF-23 和 PTH）。每个 1-SD 更高的肾小管储备/矿物质代谢因子评分与 eGFR 下降速度加快 0.58%（95%CI，0.39%-0.67%）相关，独立于基线 eGFR 和白蛋白尿。肾小管损伤/修复和肾小管损伤/纤维化因子均与未来 AKI 风险独立相关（每增加 1SD，HR 分别为 1.18（95%CI，1.10-1.37）和 1.23（95%CI，1.02-1.48））。
这些因子需要在其他环境中进行验证。
EFA 允许将生物标志物分组为因子，这些因子与进行性 eGFR 下降和 AKI 相关，这在分组上更加简洁。这些亚组可能为驱动不良肾脏结局的病理过程提供见解。
