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 Table of Contents  
ORIGINAL ARTICLE
Year : 2017  |  Volume : 10  |  Issue : 1  |  Page : 19-24

Clinical significance of microalbuminuria and hypoxemia in patients with chronic obstructive pulmonary disease


Department of Pulmonary Medicine, J. N. Medical College, Belagavi, Karnataka, India

Date of Web Publication18-Jan-2017

Correspondence Address:
Dr. J Sujay
Department of Pulmonary Medicine, J. N. Medical College, Belagavi - 590 010, Karnataka
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/2349-5006.198577

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  Abstract 

Background: Cardiovascular disease is a major cause of mortality in chronic obstructive pulmonary disease (COPD), particularly in patients with mild to moderate severity. Microalbuminuria (MAB) has a strong association with cardiovascular events and death, and it reflects generalized endothelial dysfunction. There is evidence of vascular dysfunction in patients with COPD.
Objectives: (a) To study the prevalence of MAB in stable COPD patients. (b) To determine the relationship of MAB with clinical and physiological descriptors of COPD severity and cardiovascular risk factors.
Materials and Methods: A cross-sectional study in 150 COPD patients over a period of 1 year. Lung function, 6-min walk distance, smoking history, arterial blood pressure (BP), BODE index, and arterial blood gases were measured. Screening for MAB was done by measuring urinary albumin-to-creatinine ratio in a random spot urine collection. Stepwise logistic regression was performed using MAB as the dependent variable. P < 0.05 was taken as statistically significant.
Results: Forty-six patients (30.0%) had MAB. There was negative association between hypoxemia and MAB. Stepwise logistic regression analysis with MAB as the dependent variable showed smoking (odds ratio [OR]: 2.29; 95% confidence interval [CI]: 1.54-3.41), lower forced expiratory volume in 1 s % (OR: 1.04; 95% CI: 0.98-1.10), and PaO2 (OR: 0.68; 95% CI: 0.57-0.83) as independent predictors of MAB.
Conclusions: MAB in severe COPD patients should be examined in regular periods for risk of cardiovascular morbidity or mortality.

Keywords: 6-min walk distance, BODE index, chronic obstructive pulmonary disease, forced expiratory volume in 1 s%, hypercapnia, hypoxemia, microalbuminuria, modified Medical Research Council, pack-years


How to cite this article:
Sujay J, Gajanan GS. Clinical significance of microalbuminuria and hypoxemia in patients with chronic obstructive pulmonary disease. Indian J Health Sci Biomed Res 2017;10:19-24

How to cite this URL:
Sujay J, Gajanan GS. Clinical significance of microalbuminuria and hypoxemia in patients with chronic obstructive pulmonary disease. Indian J Health Sci Biomed Res [serial online] 2017 [cited 2019 Jul 17];10:19-24. Available from: http://www.ijournalhs.org/text.asp?2017/10/1/19/198577


  Introduction Top


Chronic obstructive pulmonary disease (COPD) is a cause for major chronic morbidity and mortality in countries at all levels of development. COPD affects more than 400 million people worldwide.[1] The global burden of disease study projects that by 2030, COPD will become the third leading cause of death worldwide.[2]

COPD is associated with an abnormal inflammatory response in the lungs, with extra-pulmonary manifestations. Cardiovascular disease is one of the major causes of mortality in COPD, particularly in patients with mild to moderate severity.[3],[4] The likelihood of identifying cardiovascular subclinical abnormalities in patients with COPD during daily clinical practice strongly depends on the diagnostic techniques used.

The discovery of novel biomarkers helps identify cardiovascular risk in patients with COPD. Ideally, the biomarker should be inexpensive, noninvasive, and easily assessable.[5] C-reactive protein (CRP) has been proposed as one such biomarker, but it does not provide additional prognostic information beyond traditional risk factors in the general population.[6]

Microalbuminuria (MAB) is a sensitive marker of cardiovascular risk.[7] MAB is believed to reflect a state of generalized endothelial dysfunction. The presence of MAB is consistently associated with worse cardiovascular outcomes in patients with diabetes and hypertension but most importantly in the general population.[8] It has a stronger association with cardiovascular events and death than CRP.[6]

A limited number of studies have evaluated the presence of MAB in patients with COPD, mostly during exacerbations.[9],[10]

The aim of this study is to determine the prevalence of MAB in a group of stable COPD patients and evaluate the relationship of MAB levels with clinical and physiological descriptors of COPD severity.


  Materials and Methods Top


This was a cross-sectional study conducted on 150 patients who were diagnosed with COPD as per GOLD guidelines in the Outpatient Department of Pulmonary Medicine during January 2015-December 2015.

Inclusion criteria

All patients who came to outpatient clinic aged diagnosed as a case of COPD, based on GOLD guidelines (history of smoking >10 pack-years and a postbronchodilator forced expiratory volume in 1 s [FEV1]/forced vital capacity <0.70),[11] who are stable for 6 weeks and received optimal therapy.

Exclusion criteria

  1. History of renal disease or presence of macroalbuminuria (urinary albumin-to-creatinine ratio >300 mg/g)
  2. Previously diagnosed diabetes mellitus
  3. Cardiovascular disease
  4. Comorbidities such as malignancy, fever, urinary tract infections
  5. Asthma
  6. Hypertension.


Procedure

The study was approved by the Ethical and Research Committee. The selected patients were briefed about the study and written informed consent was obtained.

The enrolled patients were given a questionnaire concerning age, gender, height, weight, presenting symptoms, history and duration of COPD, history of smoking.

Lung function tests were done and COPD was classified as per GOLD guidelines.[11] Arterial blood gases, body mass index (BMI), and BP were measured. The 6-min walk distance (6MWD) was measured according to the American Thoracic Society guidelines.[12] Dyspnea was evaluated by the modified Medical Research Council (mMRC) scale.[13] The FEV1 %, BMI, 6MWD, and mMRC values were integrated into the BODE index.[14] According to the American Diabetes Association, screening for MAB was done by measuring the urinary albumin-to-creatinine ratio in a random spot urine collection.[15] MAB was defined when the urinary albumin-to-creatinine ratio was between 20 mg/g in men and 30 mg/g in women and the upper threshold of 299 mg/g for both sexes.[16]

Statistical analysis

Statistical analysis was performed using the IBM's Statistical Package for Social Sciences (SPSS) software version 19 (IBM SPSS, Inc. Chicago, Illinois). The results are expressed as percentages or mean ± standard deviation as specified. Pearson's Chi-square method was used for comparing proportions and percentages, whereas Student's t-test was used for comparison of continuous variables. Stepwise logistic regression was performed using MAB as the dependent variable. P < 0.05 was taken as statistically significant.


  Results Top


A total of 150 patients diagnosed with COPD were enrolled in the study. There were 145 male patients and five female patients. Their mean age was 59.67 years, mean smoking pack-years was 28.91, and mean BMI was 24.94. There were 38 (25%) GOLD Stage I, 32 (21%) Stage II, 30 (20%) Stage III, and 50 (34%) Stage IV COPD cases. The mean predicted FEV1% was 51.32 ± 23.63. The mean PaO2 was 77.48 ± 9.18 mmHg and PaCO2 was 42.09 ± 4.97 mmHg. The mean 6MWD was 453.02 ± 107.18 m, BODE index score 3.58 ± 2.47, systolic BP 115.77 ± 11.32 mm Hg, and diastolic BP 69.66 ± 6.45 mm Hg. MAB was present in 46 (30%) patients out of 150 [Table 1].
Table 1: Baseline characteristics of the patients in the study


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COPD patients having MAB were significantly higher in mean age compared to COPD patients without MAB (65.39 ± 5.21 vs. 57.14 ± 3.54 years; P = 0.0001). Patients with COPD having MAB had low FEV1% (mean 37.24 ± 18.99 vs. 57.52 ± 22.85) and higher BODE index (mean 5.13 ± 2.07 vs. 2.89 ± 2.35) compared to COPD patients without MAB and was statistically significant [Table 2].
Table 2: Baseline characteristics in patients with and without microalbuminuria


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It was observed that as the pack-years increased, the risk of MAB had also increased. Application of Chi-square test showed a significant association of pack-years with MAB (P < 0.0001) [Table 2].

Majority of COPD patients with MAB had FEV1% 30-49 (33.3%) and FEV1 %≤30 (56.0%), when compared to FEV1 % 50-80 and FEV1 % ≥81 (10.53% and 12.5% respectively). Also it was observed, that as the FEV1 % decreases, the risk of MAB had also increased (P < 0.0001) [Table 3].
Table 3: Association between forced expiratory volume in 1 s % and microalbuminuria


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MAB was significantly more in COPD patients having PaO2 below 70 mm Hg as compared to COPD patients having PaO2 above 70 mm Hg (100% vs. 7.14%, respectively, P < 0.0001), which indicates COPD patients with MAB were more hypoxemic [Table 4].
Table 4: Association between hypoxemic status and microalbuminuria


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MAB was significantly more in COPD patients having PaCO2 ≥45 mm Hg as compared to COPD patients having PaCO2 <45 mm Hg (67.86% vs. 8.51%, respectively, P < 0.0001), which indicates COPD patients with MAB were more hypercapnic [Table 5].
Table 5: Association between hypercapnia and microalbuminuria


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The BODE index was compared with the prevalence of MAB. 47.62% of COPD patients with BODE index ≥3 had MAB when compared to 9.09% COPD patients with BODE index <3, and it was statistically significant P = 0.0001.

Stepwise logistic regression analysis with MAB as the dependent variable showed that smoking pack-years (odds ratio [OR]: 2.29; 95% CI: 1.54-3.41), lower FEV1 % (OR: 1.04; 95% CI: 0.98-1.10), and PaO2 (OR: 0.68; 95% CI: 0.57-0.83) were independent and significant predictors of MAB. There was a negative association of the PaO2 and MAB in patients with COPD.


  Discussion Top


Cardiovascular disease is one of the major causes of mortality in COPD, particularly in patients with mild to moderate severity.[3],[4] MAB is a sensitive marker of cardiovascular risk.[7] Moreover, it reflects a state of generalized endothelial dysfunction. It is consistently associated with worse cardiovascular outcomes in patients with diabetes and hypertension but most importantly in the general population also.[8],[17]

In the present study, a total of 46 patients (30%) out of 150 stable COPD patients had MAB. A recent publication by Casanova et al.[18] observed the prevalence of MAB to be 24% in stable COPD patients. In a study by Bulcun et al.,[19] it was found that the prevalence of MAB to be 39%. In a study by Mehmood and Sofi,[20] it was found that MAB was more frequent in COPD patients compared to smokers without obstruction (20.6% vs. 7.4%, respectively).

In the present study, majority of COPD patients with MAB had GOLD stage of III (33.3%) and Stage IV (56.0%), and this association was statistically significant; P = 0.0001. In a study by Casanova et al.,[18] any association between MAB and spirometric severity of COPD was not observed. Mehmood and Sofi[20] found that COPD patients with MAB had significantly lower levels of FEV1 .

In this study, it was observed that as the smoking pack-years increased, the risk of MAB had also increased. In a study by Casanova et al.,[18] the number of pack-years smoked was not associated with the levels of MAB. In another study by Mehmood and Sofi,[20] MAB was significantly associated with higher pack-years of smoking exposure possibly because of endothelial cells could be directly affected by the cigarette smoke products.

In the present study, majority of COPD patients with MAB had mMRC dyspnea Grade IV (39.13%) and Grade III (36.95%) indicating that COPD patients with MAB were more dyspneic and were statistically significant. In another study by Mehmood and Sofi,[20] majority of COPD patients with MAB had mMRC dyspnea Grade III-IV (32.5%).

MAB was significantly more in COPD patients having PaO2 below 70 mm Hg as compared to COPD patients having PaO2 above 70 mm Hg (100% vs. 7.14%, respectively, P < 0.0001), which indicates COPD patients with MAB were more hypoxemic. In a study by Casanova et al.[18] and Mehmood and Sofi,[20] patients with COPD and MAB were more hypoxemic than those without MAB, and it was inversely related to PaO2 .

MAB was significantly more in COPD patients having PaCO2 ≥45 mm Hg as compared to COPD patients having PaCO2 <45 mm Hg (67.86% vs. 8.51%, respectively, P < 0.0001), which indicates COPD patients with MAB were more hypercapneic. In a study by Casanova et al.[18] and Mehmood and Sofi,[20] the MAB levels were positively related with the PaCO2 level.

In 6MWD test, it was observed as exercise capacity decreases, the prevalence of MAB increases. Kumar[21] also obtained an inverse relationship of 6MWD with MAB levels in their study.

The BODE index was compared with the prevalence of MAB. 47.62% of COPD patients with BODE index ≥3 had MAB when compared to 9.09% of COPD patients with BODE index <3 and it was statistically significant.

Celli et al.[14] showed that BODE index is a better predictor of mortality for COPD patients than the classical FEV1 values alone. Increased BODE index values are observed in patients with more severe disease. Similarly, in our study, MAB which is predictive for cardiovascular disease risk was related with BODE index and hypoxemia and also related with pulmonary function parameters such as FEV1 %.

Stepwise logistic regression analysis with MAB as the dependent variable showed that smoking pack-years (OR: 2.29; 95% CI: 1.54-3.41), low FEV1 % (OR: 1.04; 95% CI: 0.98-1.10), and PaO2 (OR: 0.68; 95% CI: 0.57-0.83) were independent and significant predictors of MAB. There was a negative association of the PaO2 and MAB in patients with COPD.

The study has some limitations:

  1. The less number of women included in study made impossible any evaluation of possible sex differences in MAB, possibly due to less prevalence of female smokers in this region
  2. We had no follow-up MAB levels in COPD patients to look for stability of MAB levels over a period
  3. We did not compare the MAB with other biomarkers, such as CRP. However, CRP is not a biomarker that has proven useful in COPD, and therefore, is not a comparator gold standard
  4. There was no control group to compare the variation in MAB in patients who are smokers without COPD.



  Conclusions Top


The determination of MAB is simple, inexpensive, and noninvasive. Thus, MAB in patients with severe COPD, with hypoxemia or higher BODE index (≥3) should be examined in regular periods to determine whether there is a risk of cardiovascular morbidity and mortality.

Longitudinal studies in different settings with larger populations are needed to evaluate the practical role of MAB in patients with COPD.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
  References Top

1.
Gupta D, Agarwal R, Aggarwal AN, Maturu VN, Dhooria S, Prasad KT, et al. Guidelines for diagnosis and management of chronic obstructive pulmonary disease: Joint ICS/NCCP (I) recommendations. Lung India 2013;30:228-67.  Back to cited text no. 1
[PUBMED]  Medknow Journal  
2.
World Health Organisation. Burden of COPD; 2016. Available from: http://www.who.int/respiratory/copd/burden/en/. [Last accessed on 2016 Sep 10; Last updated on 2016 Jan; Last cited on 2013 Sep 05].  Back to cited text no. 2
    
3.
Calverley PM, Anderson JA, Celli B, Ferguson GT, Jenkins C, Jones PW, et al. TORCH investigators. Salmeterol and fluticasone propionate and survival in chronic obstructive pulmonary disease. N Engl J Med 2007;356:775-89.  Back to cited text no. 3
    
4.
Sin DD, Anthonisen NR, Soriano JB, Agusti AG. Mortality in COPD: Role of comorbidities. Eur Respir J 2006;28:1245-57.  Back to cited text no. 4
    
5.
Rabe KF, Hurd S, Anzueto A, Barnes PJ, Buist AS, Calverley P, et al. Global strategy for the diagnosis, management and prevention of chronic obstructive pulmonary disease. NHLBI/WHO Global Initiative for chronic obstructive pulmonary disease (GOLD). Workshop summary. Am J Respir Crit Care Med 2007;176:532-55. [Update 2009].  Back to cited text no. 5
    
6.
Kistorp C, Raymond I, Pedersen F, Gustafsson F, Faber J, Hildebrandt P. N-terminal pro-brain natriuretic peptide, C-reactive protein, and urinary albumin levels as predictors of mortality and cardiovascular events in older adults. JAMA 2005;293:1609-16.  Back to cited text no. 6
    
7.
Diercks GF, van Boven AJ, Hillege JL, de Jong PE, Rouleau JL, van Gilst WH. The importance of microalbuminuria as a cardiovascular risk indicator: A review. Can J Cardiol 2002;18:525-35.  Back to cited text no. 7
    
8.
Papaioannou GI, Seip RL, Grey NJ, Katten D, Taylor A, Inzucchi SE, et al. Brachial artery reactivity in asymptomatic patients with type 2 diabetes mellitus and microalbuminuria (from the detection of ischemia in asymptomatic diabetics-brachial artery reactivity study). Am J Cardiol 2004;94:294-9.  Back to cited text no. 8
    
9.
Kömürcüoglu A, Kalenci S, Kalenci D, Kömürcüoglu B, Tibet G. Microalbuminuria in chronic obstructive pulmonary disease. Monaldi Arch Chest Dis 2003;59:269-72.  Back to cited text no. 9
    
10.
Cogo A, Ciaccia A, Legorini C, Grimaldi A, Milani G. Proteinuria in COPD patients with and without respiratory failure. Chest 2003;123:652-3.  Back to cited text no. 10
    
11.
Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global Strategy for the Diagnosis, Management and Prevention of COPD; 2014. Available from: http://www.goldcopd.org/. [Last accessed on 2016 Sep 13].  Back to cited text no. 11
    
12.
ATS Committee on Proficiency Standards for Clinical Pulmonary Function Laboratories. ATS statement: Guidelines for the six-minute walk test. Am J Respir Crit Care Med 2002;166:111-7.  Back to cited text no. 12
    
13.
Bestall JC, Paul EA, Garrod R, Garnham R, Jones PW, Wedzicha JA. Usefulness of the Medical Research Council (MRC) dyspnoea scale as a measure of disability in patients with chronic obstructive pulmonary disease. Thorax 1999;54:581-6.  Back to cited text no. 13
    
14.
Celli BR, Cote CG, Marin JM, Casanova C, Montes de Oca M, Mendez RA, et al. The body-mass index, airflow obstruction, dyspnea, and exercise capacity index in chronic obstructive pulmonary disease. N Engl J Med 2004;350:1005-12.  Back to cited text no. 14
    
15.
American Diabetes Association. Nephropathy in diabetes. Diabetes Care 2004;27:S79-80.  Back to cited text no. 15
    
16.
de Jong PE, Curhan GC. Screening, monitoring, and treatment of albuminuria: Public health perspectives. J Am Soc Nephrol 2006;17:2120-6.  Back to cited text no. 16
    
17.
Mulè G, Cottone S, Vadalà A, Volpe V, Mezzatesta G, Mongiovì R, et al. Relationship between albumin excretion rate and aortic stiffness in untreated essential hypertensive patients. J Intern Med 2004;256:22-9.  Back to cited text no. 17
    
18.
Casanova C, de Torres JP, Navarro J, Aguirre-Jaíme A, Toledo P, Cordoba E, et al. Microalbuminuria and hypoxemia in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2010;182:1004-10.  Back to cited text no. 18
    
19.
Bulcun E, Ekici M, Ekici A, Kisa U. Microalbuminuria in chronic obstructive pulmonary disease. COPD 2013;10:186-92.  Back to cited text no. 19
    
20.
Mehmood K, Sofi FA. Microalbuminuria and hypoxemia in patients with COPD. J Pulm Respir Med 2015;5:280.  Back to cited text no. 20
    
21.
Kumar R. Study of microalbuminuria in patients with stable COPD. Ann Int Med Dent Res 2016;2:95-8.  Back to cited text no. 21
    



 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5]



 

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