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      The Risk of Peripheral Arterial Disease after Parathyroidectomy in Patients with End-Stage Renal Disease

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          Abstract

          Purpose

          The changes of the risk of peripheral arterial disease (PAD) in patients with end-stage renal disease after parathyroidectomy are scant.

          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.

          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 non-PTX 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.

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          Most cited references40

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          Prevalence of and risk factors for peripheral arterial disease in the United States: results from the National Health and Nutrition Examination Survey, 1999-2000.

          Peripheral arterial disease (PAD) is associated with significant morbidity and mortality and is an important marker of subclinical coronary heart disease. However, estimates of PAD prevalence in the general US population have varied widely. We analyzed data from 2174 participants aged 40 years and older from the 1999-2000 National Health and Nutrition Examination Survey. PAD was defined as an ankle-brachial index <0.90 in either leg. The prevalence of PAD among adults aged 40 years and over in the United States was 4.3% (95% CI 3.1% to 5.5%), which corresponds to approximately 5 million individuals (95% CI 4 to 7 million). Among those aged 70 years or over, the prevalence was 14.5% (95% CI 10.8% to 18.2%). In age- and gender-adjusted logistic regression analyses, black race/ethnicity (OR 2.83, 95% CI 1.48 to 5.42) current smoking (OR 4.46, 95% CI 2.25 to 8.84), diabetes (OR 2.71, 95% CI 1.03 to 7.12), hypertension (OR 1.75, 95% CI 0.97 to 3.13), hypercholesterolemia (OR 1.68, 95% CI 1.09 to 2.57), and low kidney function (OR 2.00, 95% CI 1.08 to 3.70) were positively associated with prevalent PAD. More than 95% of persons with PAD had 1 or more cardiovascular disease risk factors. Elevated fibrinogen and C-reactive protein levels were also associated with PAD. This study provides nationally representative prevalence estimates of PAD in the United States, revealing that PAD affects more than 5 million adults. PAD prevalence increases dramatically with age and disproportionately affects blacks. The vast majority of individuals with PAD have 1 or more cardiovascular disease risk factors that should be targeted for therapy.
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            Parathyroidectomy and survival among Japanese hemodialysis patients with secondary hyperparathyroidism.

            Parathyroidectomy (PTx) drastically improves biochemical parameters and clinical symptoms related to severe secondary hyperparathyroidism (SHPT) but the effect of PTx on survival has not been adequately investigated. Here we analyzed data on 114,064 maintenance hemodialysis patients from a nationwide registry of the Japanese Society for Dialysis Therapy to evaluate the associations of severity of SHPT and history of PTx with 1-year all-cause and cardiovascular mortality. We then compared the mortality rate between 4428 patients who had undergone PTx and 4428 propensity score-matched patients who had not despite severe SHPT. During a 1-year follow-up, 7926 patients of the entire study population died, of whom 3607 died from cardiovascular disease. Among patients without a history of PTx, severe SHPT was associated with an increased risk for all-cause and cardiovascular mortality. However, such an increased risk of mortality was not observed among patients with a history of PTx. In the propensity score-matched analysis, patients who had undergone PTx had a 34% and 41% lower risk for all-cause and cardiovascular mortality, respectively, compared to the matched controls. The survival benefit associated with PTx was robust in several sensitivity analyses and consistent across subgroups, except for those who had persistent postoperative SHPT. Thus, successful PTx may reduce the risk for all-cause and cardiovascular mortality in hemodialysis patients with severe, uncontrolled SHPT.
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              Vascular calcification: contribution of parathyroid hormone in renal failure.

              Hyperphosphatemia is a driving force in the pathogenesis of vascular calcification (VC) and secondary hyperparathyroidism associated with renal failure. To test for the possible contribution of parathyroid hormone (PTH) to cardiovascular calcification, we removed the parathyroid glands from rats but infused synthetic hormone at a supraphysiologic rate. All rats were pair-fed low, normal, or high phosphorus diets and subjected to a sham or 5/6 nephrectomy (remnant kidney). Control rats were given a normal diet and underwent both sham parathyroidectomy and 5/6 nephrectomy. Heart weight/body weight ratios and serum creatinine levels were higher in remnant kidney rats than in the sham-operated rats. Remnant kidney rats on the high phosphorus diet and PTH replacement developed hyperphosphatemia and hypocalcemia along with low bone trabecular volume. Remnant kidney rats on the low phosphorus diet or intact kidney rats on a normal phosphorus diet, each with hormone replacement, developed hypercalcemia. All rats on PTH replacement developed intense aortic medial calcification, and some animals presented coronary calcification. We suggest that high PTH levels induce high bone turnover and medial calcification resembling Mömckeberg's sclerosis independent of uremia. This model may be useful in defining mechanisms underlying VC.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                10 June 2016
                2016
                : 11
                : 6
                : e0156863
                Affiliations
                [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
                Emory University, UNITED STATES
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Conceived and designed the experiments: Y-HH C-HK. Analyzed the data: Y-HH H-YY H-JC T-CL C-HK. Contributed reagents/materials/analysis tools: C-HK. Wrote the paper: Y-HH H-YY H-JC T-CL C-CH C-HK. Final approval of the manuscript: Y-HH H-YY H-JC T-CL C-CH C-HK.

                Article
                PONE-D-16-03579
                10.1371/journal.pone.0156863
                4902219
                27284924
                edb47c75-81f8-459d-9057-1f74995f2e60
                © 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.

                History
                : 26 January 2016
                : 17 May 2016
                Page count
                Figures: 2, Tables: 3, Pages: 12
                Funding
                Funded by: funder-id http://dx.doi.org/10.13039/100008903, Ministry of Health and Welfare;
                Award ID: MOHW105-TDU-B-212-133019
                Award Recipient :
                This study is supported in part by Taiwan Ministry of Health and Welfare Clinical Trial and Research Center of Excellence (MOHW105-TDU-B-212-133019), 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.
                Categories
                Research Article
                Medicine and Health Sciences
                Surgical and Invasive Medical Procedures
                Endocrine System Procedures
                Parathyroidectomy
                Medicine and Health Sciences
                Nephrology
                Chronic Kidney Disease
                Medicine and Health Sciences
                Endocrinology
                Endocrine Disorders
                Diabetes Mellitus
                Medicine and Health Sciences
                Metabolic Disorders
                Diabetes Mellitus
                Medicine and Health Sciences
                Cardiology
                Arrhythmia
                Atrial Fibrillation
                Medicine and Health Sciences
                Pulmonology
                Chronic Obstructive Pulmonary Disease
                Medicine and Health Sciences
                Vascular Medicine
                Vascular Diseases
                Peripheral Vascular Disease
                Medicine and Health Sciences
                Health Care
                Health Statistics
                Morbidity
                Medicine and Health Sciences
                Nephrology
                Medical Dialysis
                Custom metadata
                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 agreement must be signed by the applicant and his/her supervisor upon application submission. All applications are reviewed for approval of data release.

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