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This is a repository copy of Effect on mortality of elective parathyroid surgery in one hundred and three patients with chronic kidney disease : our experience. White Rose Research Online URL for this paper: http://eprints.whiterose.ac.uk/117463/ Version: Accepted Version Article: Sylvester, D, Srivastava, R, Lamplugh, A et al. (4 more authors) (2016) Effect on mortality of elective parathyroid surgery in one hundred and three patients with chronic kidney disease : our experience. Clinical otolaryngology : official journal of ENT-UK ; official journal of Netherlands Society for Oto-Rhino-Laryngology & Cervico-Facial Surgery. ISSN 1749-4486 https://doi.org/10.1111/coa.12768 Reuse Items deposited in White Rose Research Online are protected by copyright, with all rights reserved unless indicated otherwise. They may be downloaded and/or printed for private study, or other acts as permitted by national copyright laws. The publisher or other rights holders may allow further reproduction and re-use of the full text version. This is indicated by the licence information on the White Rose Research Online record for the item. Takedown If you consider content in White Rose Research Online to be in breach of UK law, please notify us by emailing eprints@whiterose.ac.uk including the URL of the record and the reason for the withdrawal request. eprints@whiterose.ac.uk https://eprints.whiterose.ac.uk/

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Page 1 of 23 ELECTIVE PARATHYROID SURGERY IN DIALYSIS PATIENTS WITH CHRONIC KIDNEY DISEASE (CKD) AND MORTALITY AUTHORS AND INSTITUTIONS Deborah Sylvester FRCS 1 Rishi Srivastava MRCS 1 Archie Lamplugh 2 Victoria Allgar PhD 3 Chris Snowden FRCS 4 Sunil Bhandari PhD 2 James England FRCS 1 Corresponding Author: Deborah Sylvester, dsylvester@doctors.net.uk, +447970025727 1 Department of Otolaryngology, Castle Hill Hospital, Castle Road, Cottingham, HU16 5JQ 2 Department of Renal Medicine, Hull Royal Infirmary, Anlaby Road, Hull, HU3 2JZ 3 Department of Health Sciences The University of York, Seebohm Rowntree Building, Heslington, York, YO10 5DD 4 Department of Anaesthesia, Castle Hill Hospital, Castle Road, Cottingham, HU16 5JQ

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Page 14 of 23-1. De Francisco ALM. (2004) Secondary hyperparathyroidism: review of the disease and its treatment. Clin Ther. 12, 1976 93. 2. Gogusev J, Duchambon P, Hory B, et al. (1997) Depressed expression of calcium receptor in parathyroid gland tissue of patients with hyperparathyroidism. Kidney Int. 51, 328 36. 3. Hruska KA, Teitelbaum SL. (1995) Renal osteodystrophy. N Engl J Med. 20, 166 74. 4. Goodman WG. (2004) The consequences of uncontrolled secondary hyperparathyroidism and its treatment in chronic kidney disease. Semin Dial. 17, 209 16. 5. Razzaque MS. (2009)The FGF23 Klotho axis: endocrine regulation of phosphate homeostasis. Nat Rev Endocrin. 5, 611-9. 6. www.nice.org.uk/guidance/ta117 7. Cheung CK, England J, Bhandari S. (2011) The Utility of intra-operative PTH measurement in surgical parathyroidectomy after renal transplantation. Clinical Nephrol. 76, 104-9. 8. Kestenbaum B, Seliger SL, Gillen DL et al. (2009) Parathyroidectomy rates among United States dialysis patients: 1990-1999. Kidney Int. 65, 282 8. 9. Foley RN, Li S, Liu J et al. (2005) The fall and rise of parathyroidectomy in U.S. hemodialysis patients, 1992 to 2002. J Am Soc Nephrol 16, 210 8. 10.Brown OT, Allgar V. Bhandari S. (2014) Analysis of factors predicting mortality of new patients commencing renal replacement therapy 10 years of follow-up. BMC Nephrol. 15, 20.

Page 15 of 23 11.Kovesdy CP, Ahmadzadeh S, Anderson JE, et al. (2008). Secondary hyperparathyroidism is associated with higher mortality in men with moderate to severe chronic kidney disease. Kidney Int. 73, 1296-302. 12.Kestenbaum B, Andress DL, Schwartz SM, et al. (2004) Survival following parathyroidectomy among United States dialysis patients. Kidney Int. 66, 2010 6. 13.Trombetti A, Stoermann C, Robert JH, et al. (2007) Survival after parathyroidectomy in patients with end-stage renal disease and severe hyperparathyroidism. World J Surg. 31, 1014 21. 14.Sharma J, Raggi P, Kutner N, et al. (2012) Improved long-term survival of dialysis patients after near-total parathyroidectomy. J Am Coll Surg. 214, 400 7. 15.Komaba H, Taniguchi M, Wada A, et al. (2015) Parathyroidectomy and survival among Japanese hemodialysis patients with secondary hyperparathyroidism. Kidney Int 88, 350 9. 16.Latus J, Roesel M, Fritz P, et al. Incidence of and risk factors for hungry bone syndrome in 84 patients with secondary hyperparathyroidism. Int J Nephrol Renov Dis. 6, 131 7. 17.Zhang YB, Smogorzewski M, Ni Z, et al. (1994) Massry SG. Altered cytosolic calcium homeostasis in rat cardiac myocytes in CRF. Kidney Int. 45:1113 9. 18.Amann K, Ritz E, Wiest G, Klaus G, Mall G. A role of parathyroid hormone for the activation of cardiac fibroblasts in uremia. J Am Soc Nephrol. 1994; 4, 1814 19.

Page 16 of 23 19.Melamed ML, Eustace JA, Plantinga L, et al. (2006) Changes in serum calcium, phosphate, and PTH and the risk of death in incident dialysis patients: a longitudinal study. Kidney Int. 70, 351 7. 20.Coen G, Manni M, Mantella D, et al. (2007) Are PTH serum levels predictive of coronary calcifications in haemodialysis patients? Nephrol Dial Transplant. 22, 3262-7. 21.Block G, Port FK. (2003) Calcium phosphate metabolism and cardiovascular disease in patients with chronic kidney disease. Semin Dial. 16, 140 7. 22.Goodman WG, Goldin J, Kuizon BD, et al. (2000) Coronary-artery calcification in young adults with end-stage renal disease who are undergoing dialysis. N Engl J Med. 342, 1478 83. 23.Goldsmith DJ, Covic AA, Venning MC, et al. (1996) Blood pressure reduction after parathyroidectomy for secondary hyperparathyroidism: further evidence implicating calcium homeostasis in blood pressure regulation. Am J Kidney Dis.; 27, 819 25. 24.Coen G, Calabria S, Bellinghieri G, et al. (2001) Parathyroidectomy in chronic renal failure: short- and long-term results on parathyroid function, blood pressure and anemia. Nephron. 88, 149 55.

Page 17 of 23 Table 1: Descriptive characteristics of parathyroidectomy compared with the nonoperative group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

Page 18 of 23 Table 2. A table to show the breakdown of the causes of chronic renal failure in both cohorts 2(,((;9< - * %! $#! 54 -$" $ %$ $ % '(( %! $!# 2(,-( # $! -,-,=-5!! >,(5?-( #! %% * /(- $% # @(A'( '" $#! 64(,(- $ # >B(- $% % # +4((- $% #,4 %! $ 6( # $$$%

Page 19 of 23 Table 3: Descriptive characteristics of propensity matched parathyroidectomy compared with the non-operative group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

Page 20 of 23 Legends for Figures Figure 1: Kaplan Meier estimates of cumulative survival among patients undergoing parathyroidectomy compared with the non-operative group Figure 2: Kaplan Meier estimates of cumulative survival among propensity matched patients undergoing parathyroidectomy compared with the non-operative group

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