THE RELATIONSHIP BETWEEN CHRONIC OBSTRUCTIVE LUNG DISEASE AND CHRONIC RENAL FAILURE

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1 THE RELATIONSHIP BETWEEN CHRONIC OBSTRUCTIVE LUNG DISEASE AND CHRONIC RENAL FAILURE Magda M. Sherif 1, Eman O. Arram 2, Walid M Afifi 1, and Doaa A. Shahin 3 1 Department of Internal Medicine Nephrology Unit, Faculty of Medicine, Zagazig University. 2 Department of Chest, Faculty of Medicine, Mansoura University, 3 Department of clinical pathology, Faculty of Medicine, Mansoura University. ABSTRACT: Background: Chronic obstructive pulmonary disease (COPD) is recognized as source of systemic inflammation and is associated with development of cardiovascular disease. However little is known about association between COPD and chronic Kidney disease (CKD). Objective: the aim of this study was to investigate the relationship between COPD and CRF and correlates chronic renal failure either concealed or overt renal failure with severity of COPD patients. Patients and methods: This study included 100 outpatients with COPD and 50 agematched outpatients free from COPD the diagnosis of COPD was made according the standards provided by the American Thoracic Society. The patients were divided into three categories according to severity of COPD. The GFR was estimated using the Modification of Diet in Renal Disease Study Group equation. Patients having normal renal function (GFR 60 ml/min/1.73 m 2 ), concealed CRF (normal serum creatinine and reduced GFR<60 ml/min/1.73 m 2 ), or overt CRF (increased serum creatinine and reduced GFR<60 ml/min/1.73m 2 ). Results: there is a strong association between chronic renal failure and COPD. Concealed renal failure was present in 20 %in patients COPD and overt renal failure was present in 30% of COPD patients.corresponding figures in control were 14%and 26% respectively, and this association is related to severity of COPD. The mean serum level of serum creatinine and estimated GFR in this populations were ( mg/dl, ml/min/1.73 m 2, mg/dl and ml/min/1,73m 2 ), respectively. Conclusion: CRF is highly prevelant in patents with COPD even with normal serum creatinine, and this prevalence is related to degree of severity of COPD. Abbreviation: COPD= chronic obstructive pulmonary disease; CRF=chronic renal failure, GFR= glomerular filteration Rate. INTRODUCTION: Chronic renal failure is a major health care problem worldwide and affects a large number of individuals, (13% of US adult population) [1]. This is mainly due to the increased prevalence of cardiovascular risk factor such as diabetes, hypertension, and obesity [1,2]. In addition, the presence of cardiovascular disease is also important in development and deterioration of kidney disease [3]. Chronic obstructive lung disease is the sevens most frequent chronic disease and is expected to rank fourth by 2020 [4]. It is associated with several co morbidities [5] however, little is known about the association between COPD and chronic kidney disease. (COPD) is characterized by an abnormal inflammatory response of the lung to the noxious particles and gases [4] and is associated with cardiovascular diseases. However the inflammation is not restricted to the lung but also extend s systemically previous studies showed that systemic inflammation (99)

2 might be the missing link between COPD and development and progression of atherosclerosis and cardiovascular disease [6]. Consequently, given that a number of investigator [7,8] have shown that COPD is associated with cardiovascular disease in people with normal kidney function, it seems reasonable to propose that COPD in patient with vascular disease may also be associated with CKD independent of other covariates that might influence kidney function loss. Therefore, we investigated the relationship between COPD and CKD either concealed or overt renal failure. MATERIALS AND METHODS: Study population This study was conducted on 100 patients with clinically definite COPD and 50 non COPD control group. Subjects were considered to have a clinical diagnosis of COPD as recurrent history of cough, dyspnea, sputum production and their pulmonary medications use, this diagnosis was based on a post-bronchodilator pulmonary function tests which was performed by 80% of patients with clinical diagnosis. The severity of COPD was categorized according to Global Initiative for chronic obstructive lung disease (COLD) criteria using forced expiratory volume in 1s (FEV1)/ forced vital capacity (FVC)ratio and the percentage of the predicted FEV1 [13].This approach is suggested by American Thoracic Society (ATS) [13] and European Respiratory Society (ERS) [9]. Outcomes The primary outcomes variable was CRF. Serum creatinine was assessed in all patients (n=150) who were included in this analysis CRF was defined as estimated GFR <60ml/min/1.73m2 using the equation of the Modification of Diet in Renal Disease (MDRD) Study Group equation [12]): 170 x [serum creatinine] x [age] x [blood urea] x [serum albumin] x (0.762 for women) x (1.180 for African-American subjects). The MDRD formula was preferred over other formulas, such as the Cockroft- Gault, because it seems to be more accurate in older people [10], Serum createnine was measured in mg/dl, age in years and estimated GFR was expressed as ml/min/1.73m 2 this cut off was chosen on the basis of the National Kidney foundations (NKF) Kidney Disease Outcomes Quality Initiative (KDOQ) guidelines [11]. Other variables In all patients we records the following age, sex, body mass index, serum albumin, serum haemoglobin. C reactive protein. ESR, Blood gases as PO2 and C02 and current smoking status. Exclusion criteria; COPD Patients were excluded if they were <18years diabetics, uncontrolled hypertension, cardiac and other lung disease than COPD. and the most common main diseases in the control group were hypertension, cardiovascular disease and diabetes Statistical analysis The data collected were statistically analyzed using statistical package for social sciences (SPSS/version 16) software (Inc., Chicago, USA). Parametric data was expressed as mean and SD, Student's test for quantitative independent variables was done for analysis of difference correlation between quantitative variables is done using pearson's bivariate test chi-square test of significance was used in order to compare two categorical variables. In all tests p-value <0.01 is significant, and p- value <0.001 is considered as highly significant. RESULTS: The demographic and laboratory data of 100 patients are presented in Table 1 based on degree of severity of COPD.The mean age of enrolled patients was 65.5 years (SD 4.5) 89.6% of them were males.the mean serum creatinine (100)

3 concentration and estimated GFR in this patients were ( , , ) and ( , , ) respectively. There were highly significant relation ship between COPD and renal function tests as regard serum creatinin and GFR (P<0.001), and this significant are more prevalent in moderate and sever degree of COPD. Table 2 shows the percentages of chronic renal failure either concealed or overt among studied group. Concealed CRF was found in 20% of COPD patients and overt CRF was found in 30%of COPD in comparison to control group. There was highly significant difference (p 0.001) in the prevalanve of CRF in patients with COPD and this prevalance was related to severity of COPD. Correlation between severity of COPD and multiple variables are summarized in table (3). There was highly significant correlation between severity of COPD and chronic renal failure (p <0.000) and no significant relationship was observed for mild COPD as shown in fig (1). Low serum albumin was present at 40% of the patients with COPD, and highly significant correlation among patients with chronic renal failure either concealed and overt renal failure as shown in fig (2). In addition low hemoglobin level was prevalence in 20% moderate severity COPD and 30% OF sever degree of COPD and the prevalence of anaemia increased in both concealed and overt renal failure as shown in fig (3). In addition there were highly significant correlations p<.000 between severity of COPD and po2, co2, FEV1, and pack year smoking Index as shown in table (4) Table (1): Demographic and laboratory Data of patients according to severity of COPD. Mild COPD Moderate COPD Sever COP P-value N=30 N=40 N=30 Sex Bodywt Hight Haemoglobin Albumin CRP ESR Pack year index of smoking Po Co FEV S. creat mg/dl GFR ml/min/1.73m Data are number of cases or mean SD (101)

Table (2): Association of chronic renal failure among studied groups JESN, 12(1) Dec., 2011 COPD N= % NO COPD N= % No CRF 5o 50% 30 60% Concealed CRF 20 20% 7 14% Overt CRF 30 30% 13 26% P value 0.

73m 2 Albumin COPD severity Pearson Correlation 1.000.812 ** -.341 * -.775 ** -.649 ** S. creat mg/dl Pearson Correlation.812 ** 1.000 -.560 ** -.562 ** -.602 ** GFR ml/minl Pearson Correlation -.

4 Table (2): Association of chronic renal failure among studied groups JESN, 12(1) Dec., 2011 COPD N= % NO COPD N= % No CRF 5o 50% 30 60% Concealed CRF 20 20% 7 14% Overt CRF 30 30% 13 26% P value total Table (3): Correlation between COPD severity and other variables. COPD severity S. creat mg/dl GFR ml/min/ Haemoglobin 1.73m 2 Albumin COPD severity Pearson Correlation ** * ** ** S. creat mg/dl Pearson Correlation.812 ** ** ** ** GFR ml/minl Pearson Correlation * ** m 2 Sig. (2-tailed) Haemoglobin Pearson Correlation ** ** * Sig. (2-tailed) Albumin Pearson Correlation ** ** * Sig. (2-tailed) **. Correlation is significant at the 0.01 level (2-tailed). *. Correlation is significant at the 0.05 level (2-tailed). Fig. (1): Shows the corellation between severity of COPD And serum creatinine Fig. (2): Shown the corellation between COPD and serum albumin (102)

Fig. (3): shows correlation between COPD severity and hemoglobin Table (4): Correlation of COPD severity regarding FEV1 and blood gases and pack year smoking index COPD severity po 2 Co 2 FEV1 pack

5 Fig. (3): shows correlation between COPD severity and hemoglobin Table (4): Correlation of COPD severity regarding FEV1 and blood gases and pack year smoking index COPD severity po 2 Co 2 FEV1 pack year index of smoking COPD severity Pearson Correlation **.837 ** **.941 ** po2 Pearson Correlation ** **.938 ** ** Co2 Pearson Correlation.837 ** ** **.870 ** FEV1 Pearson Correlation **.938 ** ** ** pack year index of smoking Pearson Correlation.941 ** **.870 ** ** **. Correlation is significant at the 0.01 level (2-tailed). DISCUSSION: Several risk factors have been identified for development and progression of CKD e.g. hypertension, diabetes, and cigarette smoking [14]. However in this study we asses the relationship between COPD and CRF.we demonstrate that the presence of COPD is highly associated with CRF tobacco smoking plays an important role in both development of and progression of COPD and chronic renal failure [15]. COPD is generally recognized as a cause of systemic inflammation [16]. Proinflammatory cytokines, especially the disease process [17,18]. In addition systemic inflammatory state in patients with COPD is associated with atherosclerosis [17, 18]. A recent study by Iwamoto and colleagues found airflow limitation to be associated (103)

6 with increased mean carotid intema media thickness in smokers compared to control smokers and never smokers [19]. This suggests that airflow limitation instead of smoking status is independently related to subclinical atherosclerosis. Subsequently, atherosclerosis might affect the vasculature in the kidneys leading to renal failure. So the systemic inflammation seen in patient with COPD might explain the association observed in our study. Moreover, it has been previously demonstrated that increased inflammation levels are present in patients with chronic renal disease. The Cardiovascular Health Study found kidney dysfunction to be independently associated with elevated levels of high levels of high sensitivity C-reactive protien, fibrinogen and interleukin-6 In participant of 65 years and older [20].This might suggested that the inflammatory response observed in patients with kidney disease might be exacerbated by concomitant COPD. Another possible explanation of our result might be pulmonary hypertension secondary to COPD, which has been associated with progression of kidney disease patients with COPD have sever salt and water retension, reduction in renal blood flow and glomerula filteration and neurohormonal activation [21]. In our study we found highly association between COPD and chronic renal failure and this association is related to degree of severity of COPD.in contrast to our result Raffaele et al. [22] found that sever COPD patients is not associated chronic renal failure. And they explain that patients with sever COPD died because of their respiratory failure before they could develop kidney disease [23]. Moderate severity of COPD is associated with concealed renal failure and sever degree or COPD is associated with overt renal failure. The positive association between severity of COPD and both po 2 and Co 2 explain that hypoxemia and high CO 2 might depress GFR by increasing renal peripheral vascular resistance [24]). Also in our study we found high correlation between hemoglobin level and severity of COPD. So CRF might explain the link between COPD and anemia. the prevalence of anemia in COPD depending COPD severity and chronic inflammation has been considered its main causal factor with iron and folate deficits playing a minor role [25]. In summary, mainly moderate and sever COPD was found to be associated chronic renal failure either concealed and overt renal failure. So CRF should be considered a common co morbidity of COPD. CRF should not be ignored or underestimated simply because it frequently cannot be diagnosed on the bases of serum creatinine. REFERENCES: 1) Coresh J, Selvin E, Stevens LA, et al. Prevealance of chronic renal failure in the United States. Jama 2007; 298: ) Schieppati A, Remuzzi G, Renal diseases as a puplic health problem: epidemology, social and economic implications. Kidney Int Supp 2005; S7-S10 3) Elsayed EF, Tighiouart H,Griffith J et al. Cardiovascular disease and subsequent kidney disease. Arch Intern Med 2007; 167: ) Rabe KF, Hurd S, Anzueto A, et al; Global Initiative for Chronic Obstructive Lung Disease. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD executive summary. Am J Respir Crit Care Med. 2007; 176 (6 ): :1130 5) Fabbri LM, Luppi F, Beghé B, Rabe KF. Complex chronic comorbidities of COPD. Eur Respir J. 2008; 31 (1): ) Sin DD, Man SF. Why are patients with chronic obstructive pulmonary disease at increased risk of cardiovascular disease? The potential role of systemic inflammation in chronic obstructive pulmonary disease: GOLD executive summary. Am J Respir Crit Care Med ; 176 ( 6 ): : ) Engstrom G, Lind P, Hedblad B et al. Lung function and cardiovascular risk: relationship with inflammation-sensitive plasma protein.circulation 2002; 106: ) Jousilahti P, Vartianen E, Tuomilehto J et al. (104)

7 symptoms of chronic bronchitis and risk of coronary disease. Lancet 1996; 348: ) Celli BR, MacNee W. Standards for diagnosis and treatment of patients with COPD: a summary of the ATS/ERS position paper. Eur Respir J 2004;23: ) Stevens LA, Coresh J, Greene T, Levey AS. Assessing kidney function-measured and estimated glomerular filtration rate.n Engl J Med. 2006; 354 (23): ) Levey AS, Coresh J, Bal E, et al. National Kidney foundation practice guidlines for kidney disease: evaluation, classification, and stratification. Ann Intern Med 2003; 139: ) Levey AS, Bosch JP, Lewis JB, Greenec T, Rogers N, Roth D; Modifi cation of Diet in Renal Disease Study Group. A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Ann Intern Med. 1999; 130 (6): ) American Thoracic Socity: Standards for diagnosis and care of patients whith chronic obstructive pulmonary disease. Am J Respir Crit Care Med 1995; 152:S77-S ) Fox CS, Larson MG, Leip et al. Predictor of new onset kidney disease in acommunity based population. JAMA 2004; 291: ) Orth SR, Ritz E. Schrier RW. The renal risks of smoking.kidney Int 1997; 51: ) Gan WQ, MAN SF, Senthilselvan A et al. Association between chronic obstructive pulmonary disease and systemic inflammation: a systemic review and meta analysis. Thorax 2004; 59: ) Sevenoaks MJ, Stockley RA. Chronic Obstructive pulmonary Disease, Inflammation and co-morbidity- a common inflammatory phenotype? Respir Res2006; 7:70. 18) VanEden SF, Sin DD. Chronic Obstructive pulmonary Disease: a chronic systemic inflammatory disease. Respiration 2008; 75: ) Iwamoto H, Yokoyama A Kitahara Y et al. Airflow limitation in smokers is associated with atherosclerosis. Am J Respir Crit Care Med 2009; 179: ) Shlipak MG, Fried LF, Crump C etal. Elevations of inflammatory and procoagulant biomarkers in eledery persons with renal insufficiency. Circulation 2003; 107: ) Anad IS, Chandrashekhar Y, Ferrari R et al. Pathogenesis of congestive state in chronic obstructive pulmonary disease. Studies of body water and sodium, renal fuction, hemodynamics. And plasma hormones during odema and after recovery. Circulation1992; 86; ) Raffaele A,Andrea C, Claudio P, et al. Extrapulmonary Consequence of COPD in The Eledery Study of the Invstigator. Chest 2010; 137: ) Sin DD, Anthonisen NR, Soriano JB et al. Mortality in COPD: role of co morbidities. Eur Respir J 2006'; 28: ) Sharkey RA, Mulloy EM, O Neill SJ. The acute effects of oxygen and carbon dioxide on renal vascular resistance in patients with an acute exacerbation of COPD. Chest. 1999; 115 ( 6 ): ) John M, Hoernig S, Doehner W, Okonko DD, Witt C, Anker SD. Anemia and inflammation in COPD. Chest. 2005; 127 (3): (105)

Prevalence of anemia in patients with chronic obstructive pulmonary disease

Prevalence of anemia in patients with chronic obstructive pulmonary disease Original Article 1. Marzieh Nojomi, MD, MPH. Professor of Community Medicine, Fellow, Clinical Epidemiology, Department of Community Medicine, School of Medicine, 2. Arash Ehteshami Afshar, MD, 3. Amin