Respiratory tract diseases are among the most common conditions in clinical practice. The lungs are internal organs that are in constant contact with the surrounding environment, ensuring continuous gas exchange, but they are also exposed to the harmful effects of inhaled air. This impact affects the human body as a whole very often. In recent years, increasing evidence has shown that chronic obstructive pulmonary disease (COPD) is a heterogeneous disease. Therefore, the updated definition includes not only functional impairment with airflow limitation but also clinical symptoms, structural changes, and other functional abnormalities that precede the decline in pulmonary function test (PFT) parameters.^[1]

COPD is described as a chronic inflammatory disease of the airways, leading to both bronchial obstruction and destruction of the pulmonary parenchyma.

Increasing attention is being paid to comorbidities as an important factor influencing the severity and progression of COPD.^[2]

And while the respiratory system largely reflects the condition of the surrounding environment and certain harmful habits, the kidneys are the organs that respond most rapidly to changes occurring in the human body. For this reason, renal function is directly related to overall health.

Chronic kidney disease (CKD) is a clinical and laboratory syndrome characterized by a slow and insidious decline in renal function, representing the functional expression of a progressively reduced nephron mass.

The Kidney Disease: Improving Global Outcomes (KDIGO) Foundation defines chronic kidney disease (CKD) using kidney damage markers such as proteinuria, glomerular filtration rate (GFR), and morphological changes in the kidneys. According to the KDIGO Clinical Practice Guidelines, CKD is classified into five stages (G1-G5) based on the estimated glomerular filtration rate (eGFR). Later, the degree of albuminuria was added to these criteria.^[3] In recent decades, scientific reports in the global literature have increasingly sought to identify direct relationships between normal function and pathological conditions of the lungs and the kidneys. Uric acid is the final product of purine nucleotide catabolism. It is mainly eliminated through the kidneys (approximately 70%); therefore, they play a critical role in maintaining uric acid homeostasis and its plasma concentration. Impaired renal excretion leads to hyperuricemia.^[4] On the other hand, a direct association between serum uric acid levels and CKD has been established.^[5]

Recently, data have been published regarding the role of uric acid as a factor in the severity and clinical course of COPD. A lot of evidence suggests elevated uric acid levels during COPD exacerbations. High serum uric acid levels have also been observed in patients with stable COPD, correlating with changes in other proinflammatory markers, supporting the systemic nature of COPD.

To investigate the role of uric acid in the development of chronic kidney disease (CKD) in patients with chronic obstructive pulmonary disease.

The study was descriptive, cross-sectional, and analytical, with elements of both a retrospective and prospective design. A total of 90 unselected, stable outpatients with established COPD were included, of whom 63 were male. The mean age of the patients was 67 years. All patients were included on a voluntary basis after signing an informed consent. The only exclusion criterion was a COPD exacerbation within four weeks prior to each visit. This study was approved by the Research Ethics Committee of the Medical University of Pleven. They were followed over two visits during the period from June 2023 to January 2025 and were recruited from the outpatient practice. At the second visit, 78 patients remained—five had died and seven had withdrawn their informed consent.

The following methods were used in the study: sociological methods, clinical diagnostic and therapeutic methods, and laboratory methods. Laboratory analyses were performed in a certified clinical laboratory using a BioSystems S.A. Costa Brava analyzer (BioSystems S.A., Costa Brava, Spain). The estimated glomerular filtration rate (eGFR) was calculated using the Modification of Diet in Renal Disease (MDRD) formula and was followed for a period exceeding 3 months. Based on eGFR results, COPD patients were divided into two groups: without CKD: eGFR≥60 mL/min/1.73 m²; with CKD: eGFR<60 mL/min/1.73 m².

At the first visit, among the 90 patients examined, 38 (42.2%) had both COPD and CKD, while 52 (57.8%) had COPD without CKD. At the second visit, among 78 patients, 41 (52.6%) were in the COPD with CKD group, and 37 (47.4%) had COPD only.

We identified an inverse correlation between uric acid and eGFR, with a Pearson correlation coefficient of R=−0.269 (p=0.010). We analyzed the percentage distribution by groups (cross-tabulation) as well as differences in mean uric acid levels between the groups with and without CKD. A statistically significant difference was observed with respect to elevated uric acid levels in patients with COPD and low eGFR(Fig. 1).

Using non-parametric tests (chi-squared and Kruskal–Wallis tests), we demonstrated that in the group with eGFR<60 mL/min/1.73 m², 62.5% of patients had elevated uric acid levels and 34% had normal levels (χ²=7.252, df=1, p=0.007; Kruskal–Wallis=7.127, df=1, p=0.007). Conversely, in the group with eGFR≥60 mL/min/1.73 m², 66% of patients had normal uric acid levels and only 37.5% had elevated levels. Elevated uric acid levels were more frequently observed in patients with CKD among those with COPD (OR=3.3052, 95% CI 1.8512–5.9013, p=0.0001).

Comparing the mean uric acid levels between the two groups, with and without CKD, we found a statistically significant difference. Due to the Gaussian distribution of uric acid values, parametric tests were used for statistical analysis. In the group with eGFR≥60 mL/min/1.73 m², the mean uric acid level was 376.4 µmol/L with a standard deviation of 84.95, while in the group with eGFR<60 mL/min/1.73 m², the mean uric acid level was 442.95 µmol/L (Fig. 2) with a standard deviation of 121.45 (ANOVA, p=0.003).

When assessing the association between uric acid levels and eGFR, we identified a cut-off value for CKD of 393.5 µmol/L, with a combined accuracy (AUC) of 67%, a Gini Index of 0.338, sensitivity of 66%, and specificity of 65% (Fig. 3).

We performed an analysis using a general linear model with repeated measures to investigate differences in changes in uric acid levels both between the two visits and between the two groups: eGFR≥60 mL/min/1.73 m² and eGFR<60 mL/min/1.73 m². During dynamic follow-up of uric acid levels in COPD patients across the two visits, we observed a statistically significant difference between the groups with and without CKD (p=0.04). Our results showed that uric acid levels in patients with COPD and CKD tended to decrease between the first and second visits, without reaching a statistically significant difference between the two visits. In the COPD-only group, there was a trend toward increased uric acid levels at the second visit. This change was not associated with the use of uricolytic medication in the first group (Fig. 4).

CKD as a comorbidity in patients with COPD has been increasingly discussed in various reports.^[6] According to some literature data, the prevalence of CKD among COPD patients ranges from 6.9% to 22.2%, but according to C. Kovesdy, 44% of Americans over the age of 70 meet the criteria for CKD.^[7,8] These large differences are due to the mixing of the concepts of chronic renal failure and chronic kidney disease. In our study, we observed a prevalence of CKD in COPD patients of 42.2% at the first visit and 52.6% at the second visit. These figures significantly exceed those reported in the literature. In our study, we investigated the relationship of uric acid as a biomarker for the development of CKD in COPD. Serum uric acid is the end product of purine degradation or purine-containing compounds and is present in high concentrations in the epithelial lining of the respiratory tract and in plasma. Hyperuricemia (defined as serum uric acid levels >420 µmol/L in men and >340 µmol/L in women) is common in CKD. This is because it is frequently observed in type 2 diabetes and arterial hypertension, which are the most common conditions leading to CKD.^[9,10]CKD is associated with reduced renal excretion of uric acid. Consequently, the prevalence of gout increases from 1%–2% among adults with normal renal function to 32% in those with stage 4 CKD.^[11] The prevalence of hyperuricemia also rises from 11% in individuals with normal renal function to 80% in those with stage 4 CKD. Hyperuricemia has been identified as an independent predictor for CKD and metabolic diseases, even among otherwise healthy subjects. A direct relationship has also been observed between serum uric acid levels and the prevalence of hypertension, diabetes, and CKD.^[12] Factors contributing to the development of CKD in COPD include chronic inflammation, oxidative stress, and elevated levels of heavy metals in the blood.^[13,14] Uric acid has a dual nature: it possesses both antioxidant and pro-oxidant and pro-inflammatory properties.^[15] Due to this characteristic, the role of uric acid in lung function and the progression of pulmonary diseases remains controversial. A report by Yang et al. indicated that elevated serum uric acid levels have a negative impact on pulmonary function parameters in patients with COPD, but do not affect healthy individuals.^[16] Wattanachayakul et al. published a meta-analysis in 2020, including eight studies with a total of 1,612 participants. The serum uric acid level in COPD patients was significantly higher than in individuals without COPD, with a pooled mean difference (MD) of 0.91 mg/dL (95% CI: 0.45–1.38; I²=89%; 1 mg/dL=59.48 µmol/L). They concluded that elevated uric acid levels are significantly more common in patients with COPD than in those without COPD.^[17] Herui Li and Yan Chen, in a 2021 meta-analysis, reported significantly higher serum uric acid levels in patients with stable COPD compared to healthy control subjects (MD 1.91, 95% CI 1.55–2.28). Lower uric acid levels were observed in the GOLD 1+2 subgroup compared to GOLD 3+4 (MD −1.39, 95% CI 1.63–1.15).^[18]

A study conducted in Zagreb, Croatia, involving 109 patients with stable COPD and 95 healthy controls, reported that. The mean uric acid level in COPD patients was 333 µmol/L, compared to 292 µmol/L in healthy controls. Higher uric acid levels in COPD patients also corresponded with elevated levels of common inflammatory markers compared to healthy controls.^[19]

In our study, we found mean uric acid levels of 376.4 µmol/L in the COPD group and 442.95 µmol/L in the COPD with CKD group. Our results are consistent with those reported in the global literature, with values even exceeding those reported in previous studies, not only for the COPD with CKD group but also for the COPD-only group.

Some studies have highlighted the importance of uric acid in the development of CKD in COPD. Uric acid as a biomarker for CKD development in COPD has been investigated in Egypt in a study including 100 patients with stable COPD. Although the authors found higher levels of the biomarker in severe forms compared to mild forms, no statistically significant difference was observed between the COPD-only and COPD with CKD groups in terms of biomarker levels.^[20] Palaia et al., in a study conducted in Italy on over 700 patients with mild to moderate COPD and a disease duration of up to 5 years, found that uric acid was associated not only with the development of CKD but also with a rapid decline in eGFR.^[21] We also observed a relationship between elevated uric acid levels and the risk of developing CKD in patients with COPD. Elevated uric acid levels were more frequently found in COPD patients with CKD (p=0.0001).

During dynamic follow-up, we observed an increase in uric acid levels only in patients with COPD and a slight decrease among patients with COPD and CKD. Despite this result, we found a statistically significant difference in uric acid levels between the two groups. Despite the increase in uric acid levels in the group with eGFR≥60 mL/min/1.73 m², the levels in the group with eGFR<60 mL/min/1.73 m² remained higher. The most likely explanation for the observed uric acid results in the COPD-only group is that the second assessment was performed during the autumn-winter season, when there is a higher likelihood of activation of proinflammatory markers, without evidence of exacerbation.

Elevated uric acid levels are a risk factor for the development of CKD in patients with COPD, serving as a biomarker with moderate sensitivity but low specificity.