Cystatin C, E-Selectin, and Pulmonary Function as Markers of Renal Dysfunction in Chronic Obstructive Pulmonary Disease with Stable Ischemic Heart Disease

Abstract

Background: Chronic obstructive pulmonary disease (COPD) frequently coexists with ischemic heart disease (IHD), and this combination may amplify systemic inflammation, endothelial injury, and renal dysfunction. Sensitive markers capable of detecting early renal involvement in this multimorbid phenotype remain incompletely characterized.

Objective: To evaluate cystatin C, cystatin C-based estimated glomerular filtration rate (eGFR), E-selectin, and forced expiratory volume in 1 second (FEV₁) as markers of renal dysfunction in patients with COPD with stable IHD, and to examine their relationships with inflammatory and cardiac biomarkers.

Methods: This comparative observational study included 135 patients with GOLD II-IV COPD: 90 with stable IHD and 45 without IHD. Within each GOLD stage, 30 patients had COPD plus IHD and 15 had COPD alone. Spirometry, serum cystatin C, creatinine, E-selectin, tumor necrosis factor-alpha (TNF-α), and N-terminal pro-B-type natriuretic peptide (NT-proBNP) were assessed. eGFR was calculated from cystatin C. Pearson correlation and receiver operating characteristic (ROC) analyses were performed.

Results: Cystatin C increased progressively from GOLD II to IV and was higher in COPD plus IHD than COPD alone at each stage (1.39±0.02 vs 1.20±0.03 mg/L; 1.72±0.04 vs 1.54±0.04 mg/L; and 2.00±0.04 vs 1.90±0.03 mg/L, respectively; P<0.01 for each comparison). Corresponding eGFR values were lower in the comorbid group at GOLD II (70.1±1.5 vs 81.8±1.7 mL/min/1.73 m²; P<0.001) and GOLD III (61.4±1.2 vs 67.1±1.8; P<0.05), while both groups showed marked filtration impairment at GOLD IV (44.6±1.2 vs 46.6±1.4; P>0.05). E-selectin, TNF-α, and NT-proBNP were also higher in COPD plus IHD. FEV₁ was inversely correlated with NT-proBNP in the comorbid group, with stronger associations as COPD severity increased (r=-0.524, -0.578, and -0.724 for GOLD II, III, and IV, respectively). For identifying renal dysfunction, ROC AUCs were 0.86 (95% CI 0.79-0.92) for cystatin C, 0.78 (0.70-0.85) for E-selectin, and 0.71 (0.63-0.79) for FEV₁.

Conclusion: Renal filtration impairment in COPD worsened in parallel with airflow limitation and was accentuated by coexisting stable IHD, particularly at moderate and severe stages. Cystatin C showed the strongest discriminatory performance, while E-selectin and FEV₁ provided complementary information reflecting endothelial and pulmonary contributions to the pulmonary-cardiac-renal continuum.