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Relation Between PTH and the Risk of Mortality in CKD

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Parathyroid Glands in Chronic Kidney Disease

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Abstract

Serum parathyroid hormone (PTH) is a well-recognized marker of parathyroid function and bone remodelling in chronic kidney disease (CKD) patients, both high and low levels being associated with poor outcomes. This may be due not only to the effect on CKD mineral and bone disorders (CKD-MBD) but also to the major ‘off-target’ effects in the cardiovascular system. As a matter of fact, an increasing number of observational cohort studies reported significant and independent associations between serum PTH levels and adverse outcomes including mortality in general population as in CKD, although the proof of a causal role for PTH in cardiovascular disease is still lacking. Therefore, normalization of PTH levels using either vitamin D, phosphate binders, calcimimetics or even parathyroidectomy might be an attractive option for the clinicians. However, studies trying to demonstrate a positive effect of PTH lowering therapies on cardiovascular or all-cause mortality revealed inconsistent results. Therefore, it has been proposed that PTH lowering medication should be used to improve the achievement of biochemical control of CKD-MBD and not with the purpose of reducing cardiovascular outcomes and/or improving survival. In addition to calcimimetics or vitamin D, moderate evidence data suggests a positive role of surgical parathyroidectomy in improving survival in dialyzed patients with severe hyperparathyroidism refractory to medical treatment. All in all, even if PTH remains one of the main target when it comes to treat CKD-MBD, there is still an opened debate if this translates into improved outcomes.

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References

  1. Hill NR, Fatoba ST, Oke JL, Hirst JA, O’Callaghan CA, Lasserson DS, et al. Global prevalence of chronic kidney disease−a systematic review and meta-analysis. PLoS One. 2016;11(7):e0158765.

    Article  Google Scholar 

  2. Iwasaki Y, Yamato H, Nii-Kono T, Fujieda A, Uchida M, Hosokawa A, et al. Insufficiency of PTH action on bone in uremia. Kidney Int Suppl. 2006;102:S34–6.

    Article  CAS  Google Scholar 

  3. Nii-Kono T, Iwasaki Y, Uchida M, Fujieda A, Hosokawa A, Motojima M, et al. Indoxyl sulfate induces skeletal resistance to parathyroid hormone in cultured osteoblastic cells. Kidney Int. 2007;71(8):738–43.

    Article  CAS  Google Scholar 

  4. Slatopolsky E, Finch J, Clay P, Martin D, Sicard G, Singer G, et al. A novel mechanism for skeletal resistance in uremia. Kidney Int. 2000;58(2):753–61.

    Article  CAS  Google Scholar 

  5. Andress DL. Adynamic bone in patients with chronic kidney disease. Kidney Int. 2008;73(12):1345–54.

    Article  CAS  Google Scholar 

  6. Kalla A, Krishnamoorthy P, Gopalakrishnan A, Garg J, Patel NC, Figueredo VM. Primary hyperparathyroidism predicts hypertension: Results from the national inpatient sample. Int J Cardiol. 2017;227:335–7.

    Article  CAS  Google Scholar 

  7. Sofronie AC, Kooij I, Bursot C, Santagati G, Coindre JP, Piccoli GB. Full normalization of severe hypertension after parathryoidectomy—a case report and systematic review. BMC Nephrol. 2018;19(1):112.

    Article  Google Scholar 

  8. Saleh FN, Schirmer H, Sundsfjord J, Jorde R. Parathyroid hormone and left ventricular hypertrophy. Eur Heart J. 2003;24(22):2054–60.

    Article  CAS  Google Scholar 

  9. Kestenbaum B, Katz R, de Boer I, Hoofnagle A, Sarnak MJ, Shlipak MG, et al. Vitamin D, parathyroid hormone, and cardiovascular events among older adults. J Am Coll Cardiol. 2011;58(14):1433–41.

    Article  CAS  Google Scholar 

  10. Vaidya A, Brown JM, Williams JS. The renin-angiotensin-aldosterone system and calcium-regulatory hormones. J Hum Hypertens. 2015;29(9):515–21.

    Article  CAS  Google Scholar 

  11. Donald J. McMahon, Angela Carrelli, Nick Palmeri, Chiyuan Zhang, Marco DiTullio, Shonni J. Silverberg, Marcella D. Walker, (2015) Effect of Parathyroidectomy Upon Left Ventricular Mass in Primary Hyperparathyroidism: A Meta-Analysis. The Journal of Clinical Endocrinology & Metabolism 100 (12):4399-4407

    Google Scholar 

  12. Hagstrom E, Hellman P, Larsson TE, Ingelsson E, Berglund L, Sundstrom J, et al. Plasma parathyroid hormone and the risk of cardiovascular mortality in the community. Circulation. 2009;119(21):2765–71.

    Article  Google Scholar 

  13. Reid LJ, Muthukrishnan B, Patel D, Seckl JR, Gibb FW. Predictors of nephrolithiasis, osteoporosis and mortality in primary hyperparathyroidism. J Clin Endocrinol Metab. 2019.

    Google Scholar 

  14. Mazhar AR, Johnson RJ, Gillen D, Stivelman JC, Ryan MJ, Davis CL, et al. Risk factors and mortality associated with calciphylaxis in end-stage renal disease. Kidney Int. 2001;60(1):324–32.

    Article  CAS  Google Scholar 

  15. Lau WL, Kalantar-Zadeh K, Kovesdy CP, Mehrotra R. Alkaline phosphatase: better than PTH as a marker of cardiovascular and bone disease? Hemodial Int Int Sympos Home Hemodial. 2014;18(4):720–4.

    Article  Google Scholar 

  16. Kalantar-Zadeh K, Kuwae N, Regidor DL, Kovesdy CP, Kilpatrick RD, Shinaberger CS, et al. Survival predictability of time-varying indicators of bone disease in maintenance hemodialysis patients. Kidney Int. 2006;70(4):771–80.

    Article  CAS  Google Scholar 

  17. Ginsberg C, Craven TE, Chonchol MB, Cheung AK, Sarnak MJ, Ambrosius WT, et al. PTH, FGF23, and intensive blood pressure lowering in chronic kidney disease participants in SPRINT. Clin J Am Soc Nephrol. 2018;13(12):1816–24.

    Article  Google Scholar 

  18. Slinin Y, Foley RN, Collins AJ. Calcium, phosphorus, parathyroid hormone, and cardiovascular disease in hemodialysis patients: the USRDS waves 1, 3, and 4 study. J Am Soc Nephrol. 2005;16(6):1788–93.

    Article  CAS  Google Scholar 

  19. Young EW, Albert JM, Satayathum S, Goodkin DA, Pisoni RL, Akiba T, et al. Predictors and consequences of altered mineral metabolism: the dialysis outcomes and practice patterns study. Kidney Int. 2005;67(3):1179–87.

    Article  CAS  Google Scholar 

  20. Floege J, Kim J, Ireland E, Chazot C, Drueke T, de Francisco A, et al. Serum iPTH, calcium and phosphate, and the risk of mortality in a European haemodialysis population. Nephrol Dial Transplant. 2011;26(6):1948–55.

    Article  CAS  Google Scholar 

  21. Liu CT, Lin YC, Lin YC, Kao CC, Chen HH, Hsu CC, et al. Roles of serum Calcium, Phosphorus, PTH and ALP on mortality in peritoneal dialysis patients: A nationwide, population-based longitudinal study using TWRDS 2005–2012. Sci Rep. 2017;7(1):33.

    Article  Google Scholar 

  22. Wang M, Obi Y, Streja E, Rhee CM, Lau WL, Chen J, et al. Association of parameters of mineral bone disorder with mortality in patients on hemodialysis according to level of residual kidney function. Clin J Am Soc Nephrol. 2017;12(7):1118–27.

    Article  CAS  Google Scholar 

  23. Kovesdy CP, Ahmadzadeh S, Anderson JE, Kalantar-Zadeh K. Secondary hyperparathyroidism is associated with higher mortality in men with moderate to severe chronic kidney disease. Kidney Int. 2008;73(11):1296–302.

    Article  CAS  Google Scholar 

  24. Palmer SC, Teixeira-Pinto A, Saglimbene V, Craig JC, Macaskill P, Tonelli M, et al. Association of drug effects on serum parathyroid Hormone, Phosphorus, and Calcium levels with mortality in CKD: A meta-analysis. Am J Kidney Dis. 2015;66(6):962–71.

    Article  CAS  Google Scholar 

  25. Chertow GM, Block GA, Correa-Rotter R, Drueke TB, Floege J, Goodman WG, et al. Effect of cinacalcet on cardiovascular disease in patients undergoing dialysis. N Engl J Med. 2012;367(26):2482–94.

    Article  CAS  Google Scholar 

  26. Palmer SC, Nistor I, Craig JC, Pellegrini F, Messa P, Tonelli M, et al. Cinacalcet in patients with chronic kidney disease: a cumulative meta-analysis of randomized controlled trials. PLoS Med. 2013;10(4):e1001436.

    Article  Google Scholar 

  27. Goldsmith D, Covic A, Vervloet M, Cozzolino M, Nistor I. Should patients with CKD stage 5D and biochemical evidence of secondary hyperparathyroidism be prescribed calcimimetic therapy? An ERA-EDTA position statement. Nephrol Dial Transplant. 2015;30(5):698–700.

    Article  CAS  Google Scholar 

  28. Phrommintikul A, Haas SJ, Elsik M, Krum H. Mortality and target haemoglobin concentrations in anaemic patients with chronic kidney disease treated with erythropoietin: a meta-analysis. Lancet. 2007;369(9559):381–8.

    Article  CAS  Google Scholar 

  29. Fellstrom BC, Jardine AG, Schmieder RE, Holdaas H, Bannister K, Beutler J, et al. Rosuvastatin and cardiovascular events in patients undergoing hemodialysis. N Engl J Med. 2009;360(14):1395–407.

    Article  CAS  Google Scholar 

  30. Apetrii M, Goldsmith D, Nistor I, Siriopol D, Voroneanu L, Scripcariu D, et al. Impact of surgical parathyroidectomy on chronic kidney disease-mineral and bone disorder (CKD-MBD)—a systematic review and meta-analysis. PLoS One. 2017;12(11):e0187025.

    Article  Google Scholar 

  31. Goldsmith DJ, Covic AA, Venning MC, Ackrill P. Blood pressure reduction after parathyroidectomy for secondary hyperparathyroidism: further evidence implicating calcium homeostasis in blood pressure regulation. Am J Kidney Dis. 1996;27(6):819–25.

    Article  CAS  Google Scholar 

  32. Takahashi H, Komaba H, Takahashi Y, Sawada K, Tatsumi R, Kanai G, et al. Impact of parathyroidectomy on serum FGF23 and soluble Klotho in hemodialysis patients with severe secondary hyperparathyroidism. J Clin Endocrinol Metab. 2014;99(4):E652–8.

    Article  CAS  Google Scholar 

  33. Bleyer AJ, Burkart J, Piazza M, Russell G, Rohr M, Carr JJ. Changes in cardiovascular calcification after parathyroidectomy in patients with ESRD. Am J Kidney Dis. 2005;46(3):464–9.

    Article  Google Scholar 

  34. Wang CC, Hsu YJ, Wu CC, Yang SS, Chen GS, Lin SH, et al. Serum fetuin-A levels increased following parathyroidectomy in uremic hyperparathyroidism. Clin Nephrol. 2012;77(2):89–96.

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. University of Medicine and Pharmacy “Grigore T. Popa”, Iași, Romania

    Mugurel Apetrii & Adrian Covic

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  1. Mugurel Apetrii
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  2. Adrian Covic
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Correspondence to Mugurel Apetrii .

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Editors and Affiliations

  1. Internal Medicine - Nephrology, Grigore T. Popa University of Medicine and Pharmacy, Iași, Romania

    Adrian Covic

  2. Renal Unit, Guy's and St Thomas' NHS Foundation Hospital, London, UK

    David Goldsmith

  3. Nephrology-Dialysis Service, AURA Nord Saint Ouen, Saint Ouen, France

    Pablo A. Ureña Torres

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Apetrii, M., Covic, A. (2020). Relation Between PTH and the Risk of Mortality in CKD. In: Covic, A., Goldsmith, D., Ureña Torres, P. (eds) Parathyroid Glands in Chronic Kidney Disease. Springer, Cham. https://doi.org/10.1007/978-3-030-43769-5_13

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  • DOI: https://doi.org/10.1007/978-3-030-43769-5_13

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  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-030-43768-8

  • Online ISBN: 978-3-030-43769-5

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