Abstract
The purpose of our study was to investigate the relationship between pulmonary function and serum levels of C-reactive protein (CRP), ferritin, albumin, and erythrocyte sedimentation rate, as inflammatory biomarkers, in hemodialysis patients. Ninety-eight patients, who were dialyzed at least for 3 months, were included in this study. Patients’ blood samples were collected and pulmonary function tests, forced vital capacity (FVC), forced expiratory volume in the first second (FEV1), and peak expiratory flow (PEF) were measured and expressed as the %predicted using appropriate normal values for the patients’ sex, age, and height (%FVC, %FEV1, and %PEF), at the same time. The patients with CRP ≥ 10 μg/mL were significantly older and had lower values of %FEV1, %FVC and %PEF (p = 0.006, p = 0.001, and p = 0.016, respectively); whereas just %FEV1 (p = 0.025) and %FVC (p = 0.009) had significant differences between the patients with ferritin ≥ 100 μg/L and other patients. However, no other significant differences were found between inflammatory biomarkers and the pulmonary function tests. We concluded that inflammation has a close relation with pulmonary dysfunction in hemodialysis patients.
INTRODUCTION
The high mortality rate of hemodialysis patients is a clinical problem. Different studies have tried to reveal risk factors in these patients to improve patients’ condition.Citation1 Recently, chronic inflammation has been identified as a nonclassic risk factor of cardiovascular disease in end-stage renal disease (ESRD) patients.Citation2 Approximately 30–50% of patients with ESRD have elevated serum level of C-reactive protein (CRP), a marker of systemic inflammation.Citation3,4 Investigators found that mortality caused by cardiovascular diseases in hemodialysis patients has a direct relation with high levels of CRP.Citation5
Furthermore, inflammation is also an important risk factor for complications in patients with pulmonary disease as well as in patient with ESRD.Citation6,7 Pulmonary function is significantly and inversely associated with plasma levels of inflammatory biomarkers.Citation3,8,9 The serum level of CRP is a significant predictor of future risk of death in patients with mild to moderate chronic obstructive pulmonary disease (COPD).Citation8 Also, acute inflammatory cytokines are increased in ESRD patients. These cytokines induce proteolysis in muscle, protein-energy malnutrition, muscle wasting, and so on,Citation10 which can decrease pulmonary function due to reduced respiratory muscle power in dialysis patients.
Although numerous studies reported strong associations between inflammation and cardiovascular disease in ESRD patients, the role of pulmonary dysfunction in these patients has not yet been thoroughly investigated. Two previous researches found significant negative correlation between CRP level and pulmonary function in ESRD patients.Citation11,12
The aim of this study was to investigate the relationship between pulmonary function and CRP, as hallmark of inflammation, and other biomarkers including ferritin, albumin, and erythrocyte sedimentation rate (ESR) that to some extent predict inflammation, in hemodialysis patients.
MATERIALS AND METHODS
Our study was carried out on 98 patients, suffering from chronic renal failure, who were dialyzed at least for 3 months in two dialysis centers, Tehran. All agreed to participate in this study and signed their informed consent. Based on examination and history, patients with age older than 70, pulmonary diseases, inflammatory diseases, rheumatologic diseases, active infectious diseases, cancer, cardiac diseases, hepatic disorders, and thyroid dysfunctions in recent 3 months were excluded from the study.
Demographic information was collected via a questionnaire. The spirometric assessments: forced vital capacity (FVC), forced expiratory volume in the first second (FEV1), and peak expiratory flow (PEF), were obtained on a non-hemodialysis day and calculated as %predicted using appropriate normal values for the patients’ sex, age and height (%FVC, %FEV1, and %PEF).Citation13 At the same time, patients’ blood samples were collected and serum levels of CRP, ferritin, albumin, and ESR were measured in a reliable laboratory. CRP, ferritin, ESR, and albumin were assessed by highly sensitive ELISA, electrochemiluminescence, Western Green, and colorimetric methods, respectively. All patients were hemodialyzed by the same apparatus.
%FVC, %FEV1, and %PEF relations with inflammation condition (CRP ≥ 10 μg/mL, ferritin ≥ 100 μg/L, albumin < 3.5 g/dL, and ESR ≥ 10 mm/h) were analyzed. For statistical analysis, we used SPSS 16 software (IBM, NY, USA). ANOVA was used to analyze the laboratory indexes in different etiologies. Bonferroni test was performed for post-hoc analysis. Correlation between pulmonary function tests and inflammatory biomarkers was assessed by Pearson’s correlation coefficients. The Student’s t-test is used to evaluate parametric data. p-Value < 0.05 is assumed as a significance indicator. The study is accepted by the ethics committee of Tehran University, Iran.
RESULTS
Our study was carried out on 98 patients (60 men and 38 women). The mean age of the patients was 55 ± 13. Mean of dialysis period in patients was 72 month. Etiologies of renal failure were hypertension (n = 28, 28.6%), diabetes (n = 22, 22.4%), hypertension and diabetes (n = 10, 10.2%), unknown (n = 28, 28.6%), and others (n = 10, 10.2%).
Pulmonary function tests and serum levels of inflammatory biomarkers showed no significant correlation with the duration within which the patients were dialyzed (p > 0.05). Serum levels of inflammatory biomarkers and pulmonary function tests were compared in patients with different etiology of ESRD in and there was no significant correlation (p > 0.05).
Table 1. Serum inflammatory biomarkers levels and pulmonary function tests in hemodialysis patients in function of the etiology of the disease.
Mean serum levels of inflammatory biomarkers were CRP, 13.6 ± 18 μg/mL (normal: <10 μg/mL); ferritin, 828 ± 1255 μg/L (normal: 50–100 μg/L); albumin, 3.7 ± 0.4 g/dL (normal: 3.5–5 g/dL); and ESR, 60.5 ± 34 mm/h (normal: <10 mm/h). The percent of patients who had serum levels of CRP, ferritin, and ESR higher than normal were 38.8%, 83.7%, and 89.8%, respectively; while 18.4% of patients had lower albumin levels. There were significant correlations between CRP and ferritin levels (R = 0.517 and p = 0.001), and between albumin and ferritin levels (R = −0.317 and p = 0.026) in these patients and no other correlations were found (p > 0.05).
Mean of %FVC, %FEV1, and %PEF was 69.1 ± 11, 72.5 ± 8, and 68.8 ± 7, respectively. There were significant negative correlations between CRP level and all pulmonary function tests (%FVC: R = −0.465; %FEV1: R = −0.505; and %PEF: R = −0.396). Also, significant negative correlation was found between ferritin level and %FVC (R = −0.313) and %FEV1 (R = −0.291). ESR and albumin’s serum levels showed no significant correlation with pulmonary function tests (p > 0.05).
The patients with CRP ≥ 10 μg/mL were significantly older (59 ± 7 vs. 52 ± 9, p = 0.026) and had lower values of %FEV1, %FVC, and %PEF, whereas just %FEV1 and %FVC were significantly different between the patients with ferritin ≥ 100 μg/L and other patients. However, no other significant differences were found ().
Table 2. Differences in pulmonary function tests with inflammatory biomarkers levels in serum.
DISCUSSION
In this study, we found significant relation between pulmonary dysfunction with CRP and ferritin level, as inflammatory biomarkers. The serum level of CRP in 38.8% of hemodialysis patients was higher than normal (≥10 μg/mL). The mean of all pulmonary function tests in these patients were significantly lower than other patients. These data were similar to the two previous investigationsCitation11,12; the mean of %PEF in Yoon et al.Citation12 study was not significant, though. There is a possibility that the lower average level of inflammation in their research is the cause of this different result.
To the best of our knowledge, the relation between pulmonary function and ferritin, albumin, and ESR level has previously not been reported in hemodialysis patients. Our data indicated that the hemodialysis patients with the ferritin level higher than normal had significantly lower %FVC and %FEV1. This correlation was reported in some previous studies on nonrenal disease patients, too.Citation14,15 Also, ferritin level was significantly correlated with two other inflammatory biomarkers, CRP, and albumin.
Level of ESR in most of our patients was higher than normal. Confirming two separate studies on non-ESRD patients,Citation16,17 we could not find any significant correlation between ESR and pulmonary function tests in hemodialysis patients. This correlation was not significant for albumin, too. However, Gonlugur et al. showed a good relation between serum albumin and pulmonary function in COPD patients.Citation18 Also, contrary to Panichi’s results,Citation19 no significant relation between CRP and albumin concentrations was found. This contradiction may result from the delay in changes of serum albumin in comparison with CRP. In addition, other factors besides inflammation may influence serum albumin level.
It was documented that inflammatory response and accumulation of proinflammatory cytokines contribute to muscle wasting by stimulating protein catabolism via the ubiquitin–proteasome pathway.Citation20 This may also affect respiratory muscles, potentially contributing to impaired pulmonary function in hemodialysis patients. Furthermore, development of pulmonary dysfunction in these patients may be due to cardiovascular disorders, which are the main cause of morbidity and mortality in ESRD patients.
Based on our findings, inflammatory biomarkers had a close relation with impaired pulmonary function in hemodialysis patients. So, further investigations on preventions and treatments are essential to prevent the morbidity and mortality rate of respiratory disorders.
Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.
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