Husain-Syed Faeq, Mallawaarachchi Indika V, Axelsson Gísli Thor, Ma Jennie Z, Debban Catherine L, Hoffman Eric A, McGroder Claire, Anderson Michaela R, Raghu Ganesh, Kawut Steven M, Podolanczuk Anna J, Manichaikul Ani, Rich Stephen S, Hunninghake Gary Matthew, Hatabu Hiroto, Hida Tomoyuki, Launer Lenore J, Scialla Julia J, Guðnason Vilmundur, Guðmundsson Gunnar, Garcia Christine Kim, Oelsner Elizabeth C, Barr R Graham, Kim John S
Department of Medicine, University of Virginia School of Medicine, Charlottesville, VA, USA.
Department of Internal Medicine II, University Hospital Giessen and Marburg, Justus-Liebig-University Giessen, Giessen, Germany.
ERJ Open Res. 2025 Jun 23;11(3). doi: 10.1183/23120541.01221-2024. eCollection 2025 May.
Pulmonary microvascular dysfunction has been suggested to be an early feature of interstitial lung changes, which may precede interstitial lung disease. The prospective association of albuminuria, a marker of endothelial dysfunction, with interstitial lung abnormalities (ILA) and high-attenuation areas (HAA) remains unexplored.
The study included participants with available spot urinary albumin-creatinine ratio (UACR) and computed tomography data for ILA and HAA enrolled in two independent cohorts, Multi-Ethnic Study of Atherosclerosis (MESA; n=2248) and Age Gene/Environment Susceptibility (AGES)-Reykjavik (n=3509). HAA were defined as the percentage of imaged lungs with attenuation between -600 and -250 HU (MESA only). Regression modelling was performed to assess the associations of UACR with ILA and HAA, adjusted for anthropometric and demographic variables and kidney function. Cox proportional-hazard models were used to examine whether ILA modified the association between albuminuria and all-cause mortality.
Log-transformed UACR was significantly associated with ILA, with an OR 1.21 (95% CI 1.12-1.30) in MESA and OR 1.13 (95% CI 1.06-1.21) in AGES-Reykjavik. In multivariable-adjusted models incorporating age, albuminuria was no longer associated with ILA, nor with ILA progression in AGES-Reykjavik. In MESA, higher levels of albuminuria were associated with greater HAA (mean increase of 1.01% per 1-unit increment in log-transformed UACR, 95% CI 1.01-1.02%), even after adjusting for covariates including age. Albuminuria was more strongly associated with death among those with ILA in MESA, but not in AGES-Reykjavik.
Albuminuria was not associated with ILA after accounting for chronological age. Our findings suggest that there may be a common systemic pathology of ageing that underlies albuminuria and interstitial lung changes.
肺微血管功能障碍被认为是间质性肺改变的早期特征,可能先于间质性肺病出现。内皮功能障碍标志物蛋白尿与间质性肺异常(ILA)和高衰减区(HAA)之间的前瞻性关联尚待探索。
该研究纳入了两个独立队列——动脉粥样硬化多族裔研究(MESA;n = 2248)和年龄基因/环境易感性(AGES)-雷克雅未克研究(n = 3509)中可获取即时尿白蛋白肌酐比值(UACR)以及ILA和HAA的计算机断层扫描数据的参与者。HAA定义为影像中衰减值在-600至-250 HU之间的肺组织百分比(仅适用于MESA)。进行回归建模以评估UACR与ILA和HAA之间的关联,并对人体测量和人口统计学变量以及肾功能进行了调整。采用Cox比例风险模型来检验ILA是否改变了蛋白尿与全因死亡率之间的关联。
对数转换后的UACR与ILA显著相关,在MESA中比值比(OR)为1.21(95%置信区间[CI] 1.12 - 1.30),在AGES-雷克雅未克中OR为1.13(95% CI 1.06 - 1.21)。在纳入年龄的多变量调整模型中,蛋白尿在AGES-雷克雅未克中不再与ILA相关,也与ILA进展无关。在MESA中,即使在调整包括年龄在内的协变量后,较高水平的蛋白尿仍与更大的HAA相关(对数转换后的UACR每增加1个单位,平均增加1.01%,95% CI 1.01 - 1.02%)。在MESA中,ILA患者中蛋白尿与死亡的关联更强,但在AGES-雷克雅未克中并非如此。
在考虑年龄因素后,蛋白尿与ILA无关。我们的研究结果表明,可能存在一种共同的衰老系统性病理机制,它是蛋白尿和间质性肺改变的基础。