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The Risk for Chronic Kidney Disease in Patients with Heart Diseases

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The Risk for Chronic Kidney Disease in Patients with Heart Diseases Liu et al. BMC Nephrology 2012, 13:77 http://www.biomedcentral.com/1471-2369/13/77 RESEARCH ARTICLE Open Access The risk for chronic kidney disease in patients with heart diseases: a 7-year follow-up in a cohort study in Taiwan Jiung-Hsiun Liu1,2,3, Shih-Yi Lin1,3, Chung-Yi Hsu4, Hsin-Hung Lin1,3, Chih-Chia Liang1, Fung-Chang Sung2,4* and Chiu-Ching Huang1,3* Abstract Background: The worldwide increasing trend of chronic kidney disease (CKD) is of great concern and the role of heart disease deserves longitudinal studies. This study investigated the risk of developing CKD among patients with heart diseases. Methods: From universal insurance claims data in Taiwan, we retrospectively identified a cohort of 26005 patients with newly diagnosed heart diseases and 52010 people without such disease from the 2000–2001 claims. We observed prospectively both cohorts until the end of 2007 to measure CKD incidence rates in both cohorts and hazard ratios (HR) of CKD. Results: The incidence of CKD in the cohort with heart disease was 4.1 times greater than that in the comparison cohort (39.5 vs. 9.65 per 10,000 person-years). However, the HR changed into 2.37 (95% confidence interval (CI) = 2.05 – 2.74) in the multivariate Cox proportional hazard model after controlling for sociodemographic characteristics and comorbidity. Compared with individuals aged < 40 years, the HRs for CKD ranged from 2.70 to 4.99 in older age groups. Significant estimated relative risks of CKD observed in our patients were also independently associated with hypertension (HR = 2.26, 95% CI = 1.94 - 2.63) and diabetes mellitus (HR = 2.44, 95% CI = 2.13 - 2.80), but not with hyperlipidemia (HR =1.13, 95% CI = 0.99-1.30). Conclusions: This population study provides evidence that patients with heart disease are at an elevated risk of developing CKD. Hypertension and diabetes mellitus are also comorbidity associated with increasing the CKD risk independently. Background represents the concept of primary disorder of either the The cardiac and renal diseases are always coexisting and heart or kidney often results in secondary injury to each may significantly increase mortality, other complications, other. CRS has been well defined and classified but has and the cost of health care [1,2]. Heart diseases and not yet concluded a consensus process [3,4]. Studies have chronic kidney disease (CKD) are thus often diagnosed reported the interaction between chronic cardiac dysfunc- and cared simultaneously in clinical practices. But, the tion and CKD, focusing the attention on the direction of nature of this association has not been well identified primary CKD in the effect on heart disorders [5-10]. despite physicians’ efforts to take the clinical history in Although reports have provided data on CKD preva- detail. The term “cardiorenal syndrome” (CRS) lence in heart diseases [11,12], several issues remain to be clarified. First, these study populations have been based on ethnic Caucasians and African Americans, and * Correspondence: [email protected]; [email protected] 1Division of Nephrology and Kidney Institute, Department of Internal there are scant data on the ethnic Asian populations. Medicine, China University Hospital, 2 Yuh-Der Road, Taichung City 404, Second, the subject number has been limited, cross- Taiwan sectional design; fragmented appreciation of epidemi- 2Department of Pubic Health, China Medical University, 91 Hsueh-Shih Road, Taichung City 404, Taiwan ology, or the follow-up time has been relatively short. Full list of author information is available at the end of the article © 2012 Liu et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Liu et al. BMC Nephrology 2012, 13:77 Page 2 of 8 http://www.biomedcentral.com/1471-2369/13/77 Third, a further challenge in describing the epidemi- requirement for the registry system. Eventually, there ology of CRS is that patients may be also in transition were 26005 heart disease cases and 52010 references in between acute and chronic condition at various time this study. Patients with the baseline comorbidity includ- points. For these reasons, we need more evidence; ing hypertension (ICD-9-CM 401–405 and A-code A260 knowing if this association between primary chronic A269), diabetes mellitus (ICD-9-CM 250 and A-code heart dysfunction and subsequent development of CKD A181), and hyperlipidemia (ICD-9-CM 272 and A-code is real. A182) were also identified. The Bureau of National This study, a retrospective cohort study on ethnic Health Insurance conducted periodic review of claims Chinese, provides a unique opportunity to investigate data to ensure the accuracy of claims. the incidence of new-onset CKD among patients with pre-existing heart disease. The study subjects were of Statistical analysis homogenous ethnicity. Longitudinal follow-up data Data analysis compared distributions of age, sex, occupa- made causal inference possible. We investigated whether tion, residential area, income, and comobidity between heart disease has effect on subsequent development of the study cohort (subjects with heart disease) and the CKD in this cohort. comparison cohort (subjects without heart disease), which were examined by Chi-square test. We calculated Methods the incidence density rates of CKD by these variables Data source and study population and the corresponding study cohort to comparison co- The Taiwan National Health Insurance (NHI), a univer- hort rate ratios of CKD. For incidence density calcula- sal health program established in 1995, has covered tion, we calculated follow-up person-years for study more than 96% of all 23 million people and has subjects until CKD diagnosed, or until 31 December contracted with 90% of the hospitals and practitioners 2007 for those uncensored, or the censoring date for the since 1996. We obtained the claims data of the Longitu- censored for other reasons, such as death, emigration dinal Health Insurance Database established by the and termination of the insured program. The same pa- National Health Research Institute, Department of Health, tient might have multiple admissions with different CKD Taiwan. This data contained the registry of a randomly stages. Only the first CKD event was used to estimate selected one million insured people as of 2005. The the follow-up person-years. Variables that were categor- claims data covered ambulatory care claims registry (CD), ized included age (< 40, 40–49, 50–59 and ≥ 60 years), inpatient claims (DD) and the updated registry for bene- residential area (north, central, south, and east and off ficiaries (ID) in 1996–2007. We used the scrambled islands) and income [less than New Taiwan Dollar identification number to link data sets to safeguard the (NTD) 15,000, 15,000-29,999, and more than 30,000/ confidentiality of the insured population without ethical per month], urbanization level (population density) of violation. This study was thus exempted from the ethical residential township or district (high, moderate, and review. low) and occupation (white collar, blue collar, and others).We calculated hazard ratios (HRs) and 95% con- Study subjects fidence interval (CI) using Cox hazard proportional The study cohort of heart diseases consisted of new model to assess the hazard ratio of CKD for patients patients with at least 2diagnostic records of the heart with the heart disease. Two multivariate models were disease in 2000–2001 based on The International classi- used by controlling categorical covariates. One model fication of Disease, 9th Revision, Clinical Modification included sociodemographic variables with significant as- (ICD-9-CM) codes. They were rheumatic heart disease sociation. The other model included also baseline (ICD-9-CM 391, 393–398, and A-code 251), hyperten- comorbidity. A plot of the Kaplan-Meier analysis was sive heart disease (ICD 402), ischemic heart disease used to show the probability of persons remaining with- (ICD 410–414, and A270, A279) and others (ICD 420– out CKD, and the log-rank test was used to test the dif- 429 and A281). The comparison cohort consisted of ran- ference between the study cohort and the comparison domly selected people insured in 2000–2001 without cohort. All analyses were performed by SAS statistical heart diseases and frequency matched with age. We also software (version 9.1 for Windows; SAS Institute, Inc., excluded subjects with CKD at baseline (ICD-9-CM Cary, NC, USA). The hazard ratios are presented with code 585), identified before the date subjects were 95 percent CIs, and p-values are two sides. selected for inclusion in the study. CKD is defined based on the glomerular filtration rate and/or abnormal serum Results creatinine concentration by the Taiwan Association of Subjects characteristics Nephrology which had established a registry system for Table 1 compares distributions of sociodemographic CKD. The accuracy of diagnosis is the primary characteristics and baseline comorbidity status between Liu et al. BMC Nephrology 2012, 13:77 Page 3 of 8 http://www.biomedcentral.com/1471-2369/13/77 Table 1 Comparisons in demographic characteristics and baseline comobidities between cohort of patients with heart disease and cohort without heart disease diagnosed in 2000-2001 Variables Heart Disease No Yes† Total N = 52010 N = 26005 N = 78015 n
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