The Risk of Peripheral Arterial Disease after Parathyroidectomy in Patients with EndStage Renal Disease Yueh-Han Hsu1,2,3☯, Hui-Yi Yu4,5☯, Hsuan-Ju Chen6,7, Tsai-Chung Li8,9, ChihCheng Hsu1,10, Chia-Hung Kao11,12*
OPEN ACCESS Citation: Hsu Y-H, Yu H-Y, Chen H-J, Li T-C, Hsu CC, Kao C-H (2016) The Risk of Peripheral Arterial Disease after Parathyroidectomy in Patients with End-Stage Renal Disease. PLoS ONE 11(6): e0156863. doi:10.1371/journal.pone.0156863 Editor: Jeff M Sands, Emory University, UNITED STATES
1 Department of Health Services Administration, China Medical University, Taichung, Taiwan, 2 Division of Nephrology, Department of Internal Medicine, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chia-Yi, Taiwan, 3 Department of Nursing, Min-Hwei Junior College of Health Care Management, Tainan, Taiwan, 4 Division of Endocrinology and Metabolism, Department of Internal Medicine, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chia-Yiy, Taiwan, 5 Department of Sports Management, Chia Nan University of Pharmacy and Science, Tainan, Taiwan, 6 Management Office for Health Data, China Medical University Hospital, Taichung, Taiwan, 7 College of Medicine, China Medical University, Taichung, Taiwan, 8 Graduate Institute of Biostatistics, College of Public Health, China Medical University, Taichung, Taiwan, 9 Department of Healthcare Administration, College of Health Science, Asia University, Taichung, Taiwan, 10 Institute of Population Health Sciences, National Health Research Institutes, Zhunan, Miaoli, Taiwan, 11 Graduate Institute of Clinical Medical Science and School of Medicine, College of Medicine, China Medical University, Taichung, Taiwan, 12 Department of Nuclear Medicine and PET Center, China Medical University Hospital, Taichung, Taiwan ☯ These authors contributed equally to this work. * [email protected]
Received: January 26, 2016 Accepted: May 17, 2016
Published: June 10, 2016
The changes of the risk of peripheral arterial disease (PAD) in patients with end-stage renal disease after parathyroidectomy are scant.
Copyright: © 2016 Hsu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Data Availability Statement: The data on the study population that were obtained from the NHIRD (http:// nhird.nhri.org.tw/en/index.html) are maintained in the NHIRD (http://nhird.nhri.org.tw/). The NHRI is a nonprofit foundation established by the government. Only citizens of the Republic of China who fulfill the requirements of conducting research projects are eligible to apply for the NHIRD. The use of NHIRD is limited to research purposes only. Applicants must follow the Computer-Processed Personal Data Protection Law (http://www.winklerpartners.com/?p= 987) and related regulations of National Health Insurance Administration and NHRI, and an
Methods We used a nationwide health insurance claims database to select all dialysis-dependent patients with end-stage renal disease aged 18 years and older for the study population in 2000 to 2006. Of the patients with end-stage renal disease, we selected 947 patients who had undergone parathyroidectomy as the parathyroidectomy group and frequency matched 3746 patients with end-stage renal disease by sex, age, years since the disease diagnosis, and the year of index date as the non-parathyroidectomy group. We used a multivariate Cox proportional hazards regression analysis with the use of a robust sandwich covariance matrix estimate, accounting for the intra-cluster dependence of hospitals or clinics, to measure the risk of peripheral arterial disease for the parathyroidectomy group compared with the non-parathyroidectomy group after adjusting for sex, age, premium-based income, urbanization, and comorbidity.
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agreement must be signed by the applicant and his/ her supervisor upon application submission. All applications are reviewed for approval of data release. Funding: This study is supported in part by Taiwan Ministry of Health and Welfare Clinical Trial and Research Center of Excellence (MOHW105-TDU-B212-133019), China Medical University Hospital, Academia Sinica Taiwan Biobank Stroke Biosignature Project (BM10501010037), NRPB Stroke Clinical Trial Consortium (MOST 104-2325-B-039 -005), Tseng-Lien Lin Foundation, Taichung, Taiwan, Taiwan Brain Disease Foundation, Taipei, Taiwan, and Katsuzo and Kiyo Aoshima Memorial Funds, Japan; and CMU under the Aim for Top University Plan of the Ministry of Education, Taiwan. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. No additional external funding was received for this study. Competing Interests: The authors have declared that no competing interests exist. Abbreviations: aHR, adjusted hazard ratio; CI, confidence interval; CKD, chronic kidney disease; DM, diabetes mellitus; ESRD, end-stage renal disease; ICD-9-CM, International Classification of Diseases, Ninth Revision, Clinical Modification; NHIRD, National Health Insurance Research Database; LHID 2000, Longitudinal Health Insurance Database 2000; PAD, peripheral arterial disease; PTX, Parathyroidectomy.
Results The mean post-op follow-up periods were 5.08 and 4.52 years for the parathyroidectomy and non-parathyroidectomy groups, respectively; the incidence density rate of PAD in the PTX group was 12.26 per 1000 person-years, significantly lower than the data in the nonPTX group (24.09 per 1000 person-years, adjusted HR = 0.66, 95% CI = 0.46–0.94).
Conclusion Parathyroidectomy is associated with reduced risk of peripheral arterial disease in patients with end-stage renal disease complicated with severe secondary hyperparathyroidism.
Introduction The risk of peripheral arterial disease (PAD) in patients with end-stage renal disease (ESRD) is 10 times higher than non-ESRD patients In the United States . The prevalence of PAD in ESRD patients is 17–48% [2, 3]. PAD, as reviewed by O’Hare et al, confers substantial risks for morbidity and mortality in the ESRD population . From previous studies, risk factors of PAD in general population and ESRD might be different. Reported risk factors for PAD in general population including age, male, smoking, diabetes mellitus (DM), chronic kidney disease (CKD), albuminuria and hepatitis C [4–9]. DM is still an important risk factor of PAD in ESRD ; while secondary hyperparathyroidism (SHPT) was reported to be a critical risk factor of PAD in ESRD . SHPT was traditionally considered as an important factor for cardiovascular morbidity and mortality of ESRD patients . Though certain previous studies reported negative associations between PTH levels and CV morbidity [12, 13], it was considered that low PTH levels represented residual confounding by nutritional status . Parathyroidectomy (PTX) is the main treatment for severe SHP refractory to medical treatment. We previously reported PTX to be associated with 43% lower risk of stroke . Several studies reported reduced overall mortality and cardiovascular mortality in SHPT patients who received PTX [16–19]. However, research addressing CV morbidity statuses in these patients is few. In the report by Conzo et al, PTX did not modify CV morbidity and mortality rates in hemodialysis (HD) patients with SHPT . Ishani et al reported PTX to be associated with significant morbidity in the 30 days after hospital discharge and in the year after the procedure, emphasizing evidence-based determinations for the indication for PTX . The relationship between PTX and incident PAD in dialysis-dependent ESRD patients was seldom approached. The aim of this research was to investigate this relationship in a retrospective cohort by using a nationwide health insurance database. We hypothesized that receiving PTX might be associated with a reduced risk of incident PAD in ESRD patient
Methods Data source The Taiwan National Health Insurance (NHI) program has offered comprehensive, universal health insurance to all residents of Taiwan since 1995 and covers more than 99% of the residents. The National Health Insurance Research Database (NHIRD) is a research database developed and managed by National Health Research Institute (NHRI), and confidentiality is maintained according to the directives of the Bureau of NHI. In this study, we used the Registry
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of Catastrophic Illnesses Patient Database (RCIPD), which is part of the NHIRD. The RCIPD contains health claims data for the treatment of catastrophic illness and includes 30 categories of diseases requiring long-term care. For privacy protection, all insured subjects had been scrambled cryptographically to attain anonymity. The diagnoses and procedures are coded in the International Classification of Disease, Ninth Revision, Clinical Modification (ICD-9-CM) format.
Study population Fig 1 shows the study framework. From 2000 to 2006, we selected ESRD patients (aged 18 years) defined as those who had catastrophic illness registration cards for ESRD (ICD-9-CM 585) and who underwent long-term renal replacement therapy. From the ESRD population, we conducted a population-based retrospective cohort study among patients who newly received PTX (ICD-9 codes for procedure 06.8) but without a history of PAD (ICD-9-CM 440.2, 440.3, 440.8, 440.9, 443, 444.22, 444.8, 447.8, and 447.9), renal transplantation (ICD9-CM V42.0), parathyroid tumor (ICD-9-CM 194.1 and 227.1), or other parathyroid disorder (ICD-9-CM 252.8) during 2000–2007. The diagnosis of PAD was made clinically. The date of first-time PTX was defined as the index date. For each ESRD patient who received PTX, we selected 4 patients randomly from the remaining ESRD patients without receiving PTX and matched on sex, 5-year age interval, dialysis vintage (years since ESRD diagnosis and receiving regular dialysis), and year of index date, using the inclusion criteria similar to the PTX group. The demographic factors included sex, age (in age group of 18–34 years, 35–49 years, 50–64 years, and 65 years and above), insured amount, and urbanization. Amount of insurance premium was categorized into three levels: