Assessing Fibrosis Progression and Endothelial Dysfunction in SSc-ILD and COPD: An Integrated Biomarker and CT Densitometry Approach

<i>Background and Objectives:</i> Chronic lung diseases act as multi-organ conditions in which systemic inflammation, vascular dysfunction, and fibrosis intersect. The pulmo-renal continuum-functional crosstalk between lungs and kidneys-remains poorly characterized. We compared year-long changes in endothelin-1 (ET-1), galectin-3 (Gal-3), renal indices (eGFR, ACR), and quantitative CT densitometry in COPD and systemic sclerosis-associated ILD (SSc-ILD). <i>Materials and Methods</i>: In this prospective observational study (January 2023-December 2024), 112 patients were consecutively enrolled (COPD, n = 58; SSc-ILD, n = 54). Assessments were performed at baseline and 12 months. ET-1 (ELISA) and Gal-3 (chemiluminescence) were measured in serum; eGFR was calculated by the creatinine-based CKD-EPI (2021) equation; ACR was photometric. High-resolution chest CT provided lung volume and parenchymal density (Hounsfield units) at six predefined axial levels per lung. Non-parametric statistics were applied: Wilcoxon signed-rank (within-group), Mann-Whitney U (between-group), and Spearman rank correlations for associations; results are reported with <i>p</i>-values (and 95% CIs). <i>Results:</i> Baseline eGFR was normal (COPD 90.37; SSc-ILD 92.4 mL/min/1.73 m²). eGFR declined by 6.76% in COPD (<i>p</i> = 0.001) and 3.16% in SSc-ILD (<i>p</i> = 0.029). ET-1 increased in both cohorts but more in COPD (+83.78%, <i>p</i> = 0.0002) than in SSc-ILD (+23.83%, <i>p</i> = 0.0001). Gal-3 rose significantly only in SSc-ILD (+10.2%, <i>p</i> = 0.043). FVC decreased in COPD (-4.01%, <i>p</i> = 0.01) and was unchanged in SSc-ILD. Total lung volume declined in SSc-ILD (-6.08%, <i>p</i> = 0.02) but not in COPD. CT density shifts were small: several slices in COPD and one slice (L6) in SSc-ILD reached statistical but not biological relevance. <i>Conclusions:</i> COPD exhibited larger vascular and renal biomarker shifts (ET-1 up, eGFR down, ACR up), suggesting systemic inflammation and early renal involvement. In SSc-ILD, biomarker and CT changes predominantly reflected pulmonary fibrosis progression with limited renal impact. Integrating biomarkers with quantitative CT may help delineate organ-specific trajectories along the pulmo-renal continuum; longer, larger studies are warranted. Limitations: This was a single-center cohort with a modest sample (58 COPD and 54 SSc-ILD) and a 12-month, two-time-point follow-up, which may not capture long-term trajectories and may limit it generalizability; larger multicenter studies with an extended follow-up are warranted.