CHRONIC KIDNEY DISEASE IN COPD: ROLE OF INTESTINAL DYSBIOSIS AND INFLAMMATION

Chronic kidney disease (CKD) is a prevalent complication in patients with chronic obstructive pulmonary disease (COPD), affecting up to 40% of this population and significantly increasing mortality risk. Emerging evidence highlights the critical role of the gut-lung-kidney axis in COPD pathophysiology, where intestinal microbiota serves as a central modulator of systemic inflammation and metabolic dysregulation. Gut dysbiosis in COPD patients may contribute to accumulation of uremic toxins, endotoxemia, and chronic inflammation, potentially accelerating CKD progression through enhanced production of inflammatory mediators and oxidative stress. The bidirectional crosstalk between pulmonary disease, gut microbiome alterations, and kidney dysfunction represents a novel paradigm in understanding multi-organ complications in COPD. However, the specific alterations in gut microbiota composition associated with CKD in COPD patients remain poorly characterized, particularly regarding changes at phylum and genus levels. This study aimed to investigate intestinal microbiome composition in COPD patients with and without CKD and explore potential mechanistic links between gut dysbiosis and chronic kidney disease progression.

This cross-sectional study enrolled 180 patients with COPD from Republican Specialized Scientific and Practical Medical Center of Therapy and Medical Rehabilitation  between January 2024 and December 2025. Patients were stratified into two groups: 102 patients without renal dysfunction (control group, estimated glomerular filtration rate [eGFR] ≥60 mL/min/1.73m²) and 98 patients with renal dysfunction (eGFR <60 mL/min/1.73m²). COPD diagnosis was confirmed by spirometry according to GOLD criteria. Gut microbiota composition was assessed using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). Fresh fecal samples were collected using standardized protocols and processed within 2 hours. Microbial identification was performed at phylum, family, and genus levels. Laboratory parameters included serum creatinine measured by enzymatic method, eGFR calculated using the CKD-EPI equation, C-reactive protein (CRP), and tumor necrosis factor-alpha (TNF-α) measured by enzyme-linked immunosorbent assay. Lung function was assessed by spirometry measuring forced expiratory volume in one second (FEV1), forced vital capacity (FVC), and FEV1/FVC ratio. Statistical analysis included Mann-Whitney U test for between-group comparisons, chi-square test for categorical variables, and Spearman correlation for associations between microbiota composition and clinical parameters. Significance was set at p<0.05. The study was approved by the institutional ethics committee, and all participants provided written informed consent.

The mean age of the 180 participants was 58.3±7.4 years (range 38-73 years). Mean FEV1 was 54.7±6.7% of predicted value, indicating moderate to severe COPD. In the 102 patients without renal dysfunction (mean eGFR 78.5±12.4 mL/min/1.73m², mean serum creatinine 0.95±0.18 mg/dL), gut microbiota analysis revealed relatively low abundance of Bacteroidetes and higher proportion of Firmicutes. At the family level, the microbiome was characterized by significant representation of Fusobacteriaceae, Prevotellaceae, and Bacteroidaceae. The Firmicutes/Bacteroidetes ratio in this group was 2.8±0.9. In contrast, the 98 patients with renal dysfunction demonstrated markedly different gut microbiome composition. Mean eGFR was 41.5±18.3 mL/min/1.73m² and mean serum creatinine was 1.85±0.52 mg/dL (p<0.001 compared to control group). This group showed significantly higher prevalence of potentially pathogenic genera including Tannerella, Fusobacterium, Capnocytophaga, and Solobacterium (all p<0.001 compared to control group). The Firmicutes/Bacteroidetes ratio was markedly elevated at 4.2±1.3 (p<0.001 versus control). Patients with renal dysfunction also exhibited higher serum levels of inflammatory markers: CRP 12.8±4.2 mg/L versus 6.5±2.1 mg/L in controls (p<0.001), and TNF-α 18.5±5.3 pg/mL versus 10.2±3.1 pg/mL in controls (p<0.001). Correlation analysis revealed that abundance of Fusobacterium positively correlated with serum creatinine (r=0.58, p<0.001), CRP (r=0.52, p<0.001), and TNF-α (r=0.49, p<0.001), while negatively correlating with eGFR (r=-0.61, p<0.001). Similarly, higher abundance of Tannerella and Solobacterium was associated with worse renal function (r=-0.48 and r=-0.44 with eGFR, respectively, both p<0.001) and lower FEV1 (r=-0.39 and r=-0.36, respectively, both p<0.01). The Firmicutes/Bacteroidetes ratio also showed significant positive correlation with serum creatinine (r=0.55, p<0.001) and inflammatory markers.

This study demonstrates significant alterations in gut microbiota composition in COPD patients with renal dysfunction, characterized by decreased Bacteroidetes abundance, increased Firmicutes proportion, and marked enrichment of potentially pathogenic genera including Tannerella, Fusobacterium, Capnocytophaga, and Solobacterium.  The strong correlations between specific microbial taxa, serum creatinine, inflammatory markers, and both renal and pulmonary function parameters underscore the interconnected nature of the gut-lung-kidney axis in COPD.    Future interventional studies investigating microbiota-targeted therapies are warranted to determine whether restoring gut microbiome balance can improve renal outcomes and reduce systemic inflammation in this high-risk population.