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

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.