Associations of albuminuria with interstitial lung abnormalities in older community-dwelling adults confounded by age

Faeq Husain-Syed; Indika V Mallawaarachchi; Gísli Thor Axelsson; Jennie Z Ma; Catherine L Debban; Eric A Hoffman; Claire McGroder; Michaela R Anderson; Ganesh Raghu; Steven M Kawut; Anna J Podolanczuk; Ani Manichaikul; Stephen S Rich; Gary Matthew Hunninghake; Hiroto Hatabu; Tomoyuki Hida; Lenore J Launer; Julia J Scialla; Vilmundur Guðnason; Gunnar Guðmundsson; Christine Kim Garcia; Elizabeth C Oelsner; R Graham Barr; John S Kim

Associations of albuminuria with interstitial lung abnormalities in older community-dwelling adults confounded by age

Faeq Husain-Syed, Indika V Mallawaarachchi, Gísli Thor Axelsson, Jennie Z Ma, Catherine L Debban, Eric A Hoffman, Claire McGroder, Michaela R Anderson, Ganesh Raghu, Steven M Kawut, Anna J Podolanczuk, Ani Manichaikul, Stephen S Rich, Gary Matthew Hunninghake, Hiroto Hatabu, Tomoyuki Hida, Lenore J Launer, Julia J Scialla, Vilmundur Guðnason, Gunnar GuðmundssonChristine Kim Garcia, Elizabeth C Oelsner, R Graham Barr, John S Kim

Faculty of Medicine

Research output: Contribution to journal › Article › peer-review

Útdráttur/Abstract

BACKGROUND: 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.

METHODS: 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.

RESULTS: 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.

CONCLUSIONS: 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.

Original language	English / enska
Article number	01221-2024
Journal	ERJ Open Research
Volume	11
Issue number	3
Publication status	Published - May 2025

Bibliographical note

Fingrafar/Fingerprint

Efnisorð tengjast rannsóknaefni og saman mynda þau svokallað fingrafar --- Dive into the research topics of 'Associations of albuminuria with interstitial lung abnormalities in older community-dwelling adults confounded by age'. Together they form a unique fingerprint.

Cite this

Husain-Syed, F., Mallawaarachchi, I. V., Axelsson, G. T., Ma, J. Z., Debban, C. L., Hoffman, E. A., McGroder, C., Anderson, M. R., Raghu, G., Kawut, S. M., Podolanczuk, A. J., Manichaikul, A., Rich, S. S., Hunninghake, G. M., Hatabu, H., Hida, T., Launer, L. J., Scialla, J. J., Guðnason, V., ... Kim, J. S. (2025). Associations of albuminuria with interstitial lung abnormalities in older community-dwelling adults confounded by age. ERJ Open Research, 11(3), Article 01221-2024.

@article{4ac8760396864e1caa69ee8595fb9f33,

title = "Associations of albuminuria with interstitial lung abnormalities in older community-dwelling adults confounded by age",

abstract = "BACKGROUND: 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.METHODS: 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.RESULTS: 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.CONCLUSIONS: 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.",

author = "Faeq Husain-Syed and Mallawaarachchi, \{Indika V\} and Axelsson, \{G{\'i}sli Thor\} and Ma, \{Jennie Z\} and Debban, \{Catherine L\} and Hoffman, \{Eric A\} and Claire McGroder and Anderson, \{Michaela R\} and Ganesh Raghu and Kawut, \{Steven M\} and Podolanczuk, \{Anna J\} and Ani Manichaikul and Rich, \{Stephen S\} and Hunninghake, \{Gary Matthew\} and Hiroto Hatabu and Tomoyuki Hida and Launer, \{Lenore J\} and Scialla, \{Julia J\} and Vilmundur Gu{\dh}nason and Gunnar Gu{\dh}mundsson and Garcia, \{Christine Kim\} and Oelsner, \{Elizabeth C\} and Barr, \{R Graham\} and Kim, \{John S\}",

note = "Copyright {\textcopyright}The authors 2025.",

year = "2025",

month = may,

language = "English / enska",

volume = "11",

journal = "ERJ Open Research",

issn = "2312-0541",

publisher = "European Respiratory Society",

number = "3",

}

Husain-Syed, F, Mallawaarachchi, IV, Axelsson, GT, Ma, JZ, Debban, CL, Hoffman, EA, McGroder, C, Anderson, MR, Raghu, G, Kawut, SM, Podolanczuk, AJ, Manichaikul, A, Rich, SS, Hunninghake, GM, Hatabu, H, Hida, T, Launer, LJ, Scialla, JJ, Guðnason, V , Guðmundsson, G, Garcia, CK, Oelsner, EC, Barr, RG & Kim, JS 2025, 'Associations of albuminuria with interstitial lung abnormalities in older community-dwelling adults confounded by age', ERJ Open Research, vol. 11, no. 3, 01221-2024.

TY - JOUR

T1 - Associations of albuminuria with interstitial lung abnormalities in older community-dwelling adults confounded by age

AU - Husain-Syed, Faeq

AU - Mallawaarachchi, Indika V

AU - Axelsson, Gísli Thor

AU - Ma, Jennie Z

AU - Debban, Catherine L

AU - Hoffman, Eric A

AU - McGroder, Claire

AU - Anderson, Michaela R

AU - Raghu, Ganesh

AU - Kawut, Steven M

AU - Podolanczuk, Anna J

AU - Manichaikul, Ani

AU - Rich, Stephen S

AU - Hunninghake, Gary Matthew

AU - Hatabu, Hiroto

AU - Hida, Tomoyuki

AU - Launer, Lenore J

AU - Scialla, Julia J

AU - Guðnason, Vilmundur

AU - Guðmundsson, Gunnar

AU - Garcia, Christine Kim

AU - Oelsner, Elizabeth C

AU - Barr, R Graham

AU - Kim, John S

PY - 2025/5

Y1 - 2025/5

N2 - BACKGROUND: 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.METHODS: 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.RESULTS: 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.CONCLUSIONS: 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.

AB - BACKGROUND: 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.METHODS: 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.RESULTS: 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.CONCLUSIONS: 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.

UR - https://www.scopus.com/pages/publications/105009134919

M3 - Article

C2 - 40551804

SN - 2312-0541

VL - 11

JO - ERJ Open Research

JF - ERJ Open Research

IS - 3

M1 - 01221-2024

ER -