Secondary Hyperparthyroidism: Pathogenesis, Diagnosis, Preventive and Therapeutic Strategies

Abstract

Uremic secondary hyperparathyroidism is a multifactorial and complex disease often present in advanced stages of chronic kidney disease. The accumulation of phosphate, the increased FGF23 levels, the reduction in active vitamin D production, and the tendency to hypocalcemia are persistent stimuli for the development and progression of parathyroid hyperplasia with increased secretion of PTH. Parathyroid proliferation may become nodular mainly in cases of advanced hyperparathyroidism. The alterations in the regulation of mineral metabolism, the development of bone disease and extraosseous calcifications are essential components of chronic kidney disease-mineral and bone disorder and have been associated with negative outcomes. The management of hyperparathyroidism includes the correction of vitamin D deficiency and control of serum phosphorus and PTH without inducing hypercalcemia. An update of the leading therapeutic tools available for the prevention and clinical management of secondary hyperparathyroidism, its diagnosis, and the main mechanisms and factors involved in the pathogenesis of the disease will be described in this review.

This is a preview of subscription content, access via your institution.

Fig. 1
Fig. 2

References

  1. 1.

    LeBeoff MS, et al. Regulation of parathyroid hormone release and cytosolic calcium by extracellular calcium in dispersed and cultured bovine and pathological human parathyroid cells. J Clin Invest. 1985;75:49–57.

    Article  Google Scholar 

  2. 2.

    Brown EM, et al. Cloning and characterization of an extracellular Ca(2+)-sensing receptor from bovine parathyroid. Nature. 1993;366:575–80.

    CAS  PubMed  Article  Google Scholar 

  3. 3.

    Shilo V, et al. Parathyroid-specific deletion of dicer-dependent microRNAs abrogates the response of the parathyroid to acute and chronic hypocalcemia and uremia. FASEB J. 2015;29:3964–76.

    CAS  PubMed  Article  Google Scholar 

  4. 4.

    Lavi-Moshayoff V, et al. PTH increases FGF23 gene expression and mediates the high-FGF23 levels of experimental kidney failure: a bone parathyroid feedback loop. Am J Physiol Renal Physiol. 2010;299:F882–9.

    CAS  PubMed  Article  Google Scholar 

  5. 5.

    Rodríguez-Ortiz ME, et al. Calcium deficiency reduces circulating levels of FGF23. J Am Soc Nephrol. 2012;23:1190–7.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  6. 6.

    Kilav R, et al. Parathyroid hormone gene expression in hypophosphatemic rats. J Clin Invest. 1995;96:327–33.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  7. 7.

    Almadén Y, et al. Direct effect of phosphorus on PTH secretion from whole rat parathyroid glands in vitro. J Bone Miner Res. 1996;11:970–6.

    PubMed  Article  Google Scholar 

  8. 8.

    Nielsen PK, et al. A direct effect in vitro of phosphate on PTH release from bovine parathyroid tissue slices but not from dispersed parathyroid cells. Nephrol Dial Transplant. 1996;11:1762–8.

    CAS  PubMed  Article  Google Scholar 

  9. 9.

    Slatopolsky E, et al. Phosphorus restriction prevents parathyroid gland growth. High phosphorus directly stimulates PTH secretion in vitro. J Clin Invest. 1996;97:2534–40.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  10. 10.

    Estepa JC, et al. Effect of phosphate on parathyroid hormone secretion in vivo. J Bone Miner Res. 1999;14:1848–54.

    CAS  PubMed  Article  Google Scholar 

  11. 11.

    De Francisco ALM, et al. Effect of serum phosphate on parathyroid hormone secretion during hemodialysis. Kidney Int. 1998;54:2140–5.

    CAS  PubMed  Article  Google Scholar 

  12. 12.

    Moallem E, et al. RNA-protein binding and post-transcriptional regulation of parathyroid hormone gene expression by calcium and phosphate. J Biol Chem. 1998;273:5253–9.

    CAS  PubMed  Article  Google Scholar 

  13. 13.

    Silver J, et al. Regulation by vitamin D metabolites of parathyroid hormone gene transcription in vivo in the rat. J Clin Invest. 1986;78:1296–301.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  14. 14.

    Fukagawa M, et al. Regulation of parathyroid hormone synthesis in chronic renal failure in rats. Kidney Int. 1991;39:874–81.

    CAS  PubMed  Article  Google Scholar 

  15. 15.

    Shimada T, et al. Cloning and characterization of FGF23 as a causative factor of tumor-induced osteomalacia. Proc Natl Acad Sci U S A. 2001;98:6500–5.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  16. 16.

    Shimada T, et al. Targeted ablation of Fgf23 demonstrates an essential physiological role of FGF23 in phosphate and vitamin D metabolism. J Clin Invest. 2004;113:561–8.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  17. 17.

    Rodríguez M, et al. FGF23 and mineral metabolism, implications in CKD-MBD. Nefrología. 2012;32:275–8.

    PubMed  Google Scholar 

  18. 18.

    Ben-Dov IZ, et al. The parathyroid is a target organ for FGF23 in rats. J Clin Invest. 2007;117:4003–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  19. 19.

    Canalejo R, et al. FGF23 fails to inhibit uremic parathyroid glands. J Am Soc Nephrol. 2010;21:1125–35.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  20. 20.

    Gattineni J, et al. FGF23 decreases renal NaPi-2a and NaPi-2c expression and induces hypophosphatemia in vivo predominantly via FGF receptor 1. Am J Physiol Renal Physiol. 2009;297:F282–91.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  21. 21.

    Fukuda N, et al. Decreased, 1,25-dihydroxyvitamin D3 receptor density is associated with a more severe form of parathyroid hyperplasia in chronic uremic patients. J Clin Invest. 1993;92:1436–43.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  22. 22.

    Tallón S, et al. Relative effects of PTH and dietary phosphorus on calcitriol production in normal and azotemic rats. Kidney Int. 1996;49:1441–6.

    PubMed  Article  Google Scholar 

  23. 23.

    Rodríguez M, et al. Calcemic response to parathyroid hormone in renal failure: role of phosphorus and its effect on calcitriol. Kidney Int. 1991;40:1055–62.

    PubMed  Article  Google Scholar 

  24. 24.

    Kifor O, et al. Reduced immunostaining for the extracellular Ca2+−sensing receptor in primary and uremic secondary hyperparathyroidism. J Clin Endocrinol Metab. 1996;81:1598–606.

    CAS  PubMed  Google Scholar 

  25. 25.

    Gogusev J, et al. Depressed expression of calcium receptor in parathyroid gland tissue of patients with hyperparathyroidism. Kidney Int. 1997;51:328–36.

    CAS  PubMed  Article  Google Scholar 

  26. 26.

    Mathias RS, et al. Reduced expression of the renal calcium-sensing receptor in rats with experimental chronic renal insufficiency. J Am Soc Nephrol. 1998;9:2067–74.

    CAS  PubMed  Google Scholar 

  27. 27.

    Brown AJ, et al. Decreased calcium-sensing receptor expression in hyperplastic parathyroid glands of uremic rats: role of dietary phosphate. Kidney Int. 1999;55:1284–92.

    CAS  PubMed  Article  Google Scholar 

  28. 28.

    Ritter CS, et al. Parathyroid hyperplasia in uremic rats precedes down-regulation of the calcium receptor. Kidney Int. 2001;60:1737–44.

    CAS  PubMed  Article  Google Scholar 

  29. 29.

    Bellorin-Font E, et al. Altered adenylate cyclase kinetics in hyperfunctioning human parathyroid glands. J Clin Endocrinol Metab. 1981;52:499–507.

    CAS  PubMed  Article  Google Scholar 

  30. 30.

    Canaff, et al. Human calcium-sensing receptor gene. Vitamin D response elements in promoters P1 and P2 confer transcriptional responsiveness to 1,25-dihydroxyvitamin. D. J Biol Chem. 2002;277:30337–50.

    CAS  PubMed  Article  Google Scholar 

  31. 31.

    Naveh-Many T, et al. Parathyroid cell proliferation in normal and chronic renal failure rats. The effect of calcium, phosphate, and vitamin D. J Clin Invest. 1995;96:1786–93.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  32. 32.

    Garfia B, et al. Regulation of parathyroid vitamin D receptor expression by extracellular calcium. J Am Soc Nephrol. 2000;13:2945–52.

    Article  Google Scholar 

  33. 33.

    Cañadillas S, et al. Upregulation of parathyroid VDR expression by extracellular calcium is mediated by ERK1/2-MAPK signaling pathway. Am J Physiol Renal Physiol. 2010;298:F1197–204.

    PubMed  Article  CAS  Google Scholar 

  34. 34.

    Zhang MY, et al. Dietary phosphorus transcriptionally regulates 25-hydroxyvitamin D-1alpha-hydroxylase gene expression in the proximal renal tubule. Endocrinology. 2002;143:587–95.

    CAS  Google Scholar 

  35. 35.

    Yi H, et al. Prevention of enhanced parathyroid hormone secretion, synthesis and hyperplasia by mild dietary phosphorus restriction in early chronic renal failure in rats: possible role of phosphorus. Nephron. 1995;70:242–8.

    CAS  PubMed  Article  Google Scholar 

  36. 36.

    Denda M, et al. Phosphorus accelerates the development of parathyroid hyperplasia and secondary hyperparathyroidism in rats with renal failure. Am J Kidney Dis. 1996;28:596–602.

    CAS  PubMed  Article  Google Scholar 

  37. 37.

    Wang Q, et al. Parathyroid cell proliferation in the rat: effect of age and of phosphate administration and recovery. Endocrinology. 1996;137:4558–62.

    CAS  PubMed  Article  Google Scholar 

  38. 38.

    Canalejo A, et al. The effect of a high phosphorus diet on the parathyroid cell cycle. Nephrol Dial Transplant. 1998;13(Suppl 3):19–22.

    CAS  PubMed  Article  Google Scholar 

  39. 39.

    Almadén Y, et al. Proliferation in hyperplastic human and normal rat parathyroid glands: role of phosphate, calcitriol, and gender. Kidney Int. 2003;64:2311–7.

    PubMed  Article  Google Scholar 

  40. 40.

    Dusso AS, et al. p21 (WAF1) and transforming growth factor-alpha mediate dietary phosphate regulation of parathyroid cell growth. Kidney Int. 2001;59:855–65.

    CAS  PubMed  Article  Google Scholar 

  41. 41.

    Szabo A, et al. 1,25(OH)2 vitamin D3 inhibits parathyroid cell proliferation in experimental uremia. Kidney Int. 1989;35:1049–56.

    CAS  PubMed  Article  Google Scholar 

  42. 42.

    Kremer R, et al. Influence of calcium and 1,25-dihyddroxycholecalciferol on proliferation and proto-oncogene expression in primary cultures of bovine parathyroid cells. Endocrinology. 1989;125:935–41.

    CAS  PubMed  Article  Google Scholar 

  43. 43.

    Russell J, et al. Interaction between calcium and 1,25-dihydroxyvitamin D3 in the regulation of preproparathyroid hormone and vitamin D receptor messenger ribonucleic acid in avian parathyroids. Endocrinology. 1993;132:2639–44.

    CAS  PubMed  Google Scholar 

  44. 44.

    Arcidiacono MV, et al. Parathyroid-specific epidermal growth factor-receptor inactivation prevents uremia-induced parathyroid hyperplasia in mice. Nephrol Dial Transplant. 2015;30:434–40.

    PubMed  Article  Google Scholar 

  45. 45.

    Patel SR, et al. Inhibition of calcitriol receptor binding to vitamin D response elements by uremic toxins. J Clin Invest. 1995;96:50–9.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  46. 46.

    Sawaya BP, et al. Secondary hyperparathyroidism and vitamin D receptor binding to vitamin D response elements in rats with incipient renal failure. J Am Soc Nephrol. 1997;8:271–8.

    CAS  PubMed  Google Scholar 

  47. 47.

    Fernández E, et al. Association between vitamin D receptor gene polymorphism and relative hypoparathyroidism in patients with chronic renal failure. J Am Soc Nephrol. 1997;8:1546–52.

    PubMed  Google Scholar 

  48. 48.

    Larsson T, et al. Circulating concentration of FGF-23 increases as renal function declines in patients with chronic kidney disease, but does not change in response to variation in phosphate intake in healthy volunteers. Kidney Int. 2003;64:2272–9.

    CAS  PubMed  Article  Google Scholar 

  49. 49.

    Shigematsu T, et al. Possible involvement of circulating fibroblast growth factor 23 in the development of secondary hyperparathyroidism associated with renal insufficiency. Am J Kidney Dis. 2004;44:250–6.

    CAS  PubMed  Article  Google Scholar 

  50. 50.

    Hassan A, et al. The fibroblast growth factor receptor mediates the increased FGF23 expression in acute and chronic uremia. Am J Physiol Renal Physiol. 2016;310:F217–21.

    CAS  PubMed  Article  Google Scholar 

  51. 51.

    Koh N, et al. Severely reduced production of klotho in human chronic renal failure kidney. Biochem Biophys Res Commun. 2001;280:1015–20.

    CAS  PubMed  Article  Google Scholar 

  52. 52.

    Galitzer H, et al. Parathyroid cell resistance to fibroblast growth factor 23 in secondary hyperparathyroidism of chronic kidney disease. Kidney Int. 2010;77:211–8.

    CAS  PubMed  Article  Google Scholar 

  53. 53.

    Komaba H, et al. Depressed expression of klotho and FGF receptor 1 in hyperplastic parathyroid glands from uremic patients. Kidney Int. 2010;77:232–8.

    CAS  PubMed  Article  Google Scholar 

  54. 54.

    Krajisnik T, et al. Parathyroid klotho and FGF-receptor 1 expression decline with renal function in hyperparathyroid patients with chronic kidney disease and kidney transplant recipients. Kidney Int. 2010;78:1024–32.

    CAS  PubMed  Article  Google Scholar 

  55. 55.

    Isakova T, et al. Fibroblast growth factor 23 is elevated before parathyroid hormone and phosphate in chronic kidney disease. Kidney Int. 2011;79:1370–8.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  56. 56.

    Herencia C, et al. Procaine inhibits osteo/Odontogenesis through Wnt/β-catenin inactivation. PLoS One. 2016;11:e0156788.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  57. 57.

    Ling L, et al. Wnt signaling controls the fate of mesenchymal stem cells. Gene. 2009;433:1–7.

    CAS  PubMed  Article  Google Scholar 

  58. 58.

    Monroe DG, et al. Update on Wnt signaling in bone cell biology and bone disease. Gene. 2012;492:1–18.

    CAS  PubMed  Article  Google Scholar 

  59. 59.

    Carrillo-López N, et al. Direct inhibition of osteoblastic Wnt pathway by fibroblast growth factor 23 contributes to bone loss in chronic kidney disease. Kidney Int. 2016;90:77–89.

    PubMed  Article  CAS  Google Scholar 

  60. 60.

    Björklund P, et al. Accumulation of nonphosphorilated beta-catenin and c-myc in primary and uremic secondary hyperparathyroid tumors. J Clin Endocrinol Metab. 2007;92:338–44.

    PubMed  Article  CAS  Google Scholar 

  61. 61.

    Björklund P, et al. An LRP5 receptor with internal deletion in hyperparathyroid tumors with implications for deregulated WNT/β-catening signaling. PLoS Med. 2007;4:e328.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  62. 62.

    Vieira JG. PTH assays: understanding what we have and forecasting what we will have. J Osteopor. 2012;2012:523246.

    Article  CAS  Google Scholar 

  63. 63.

    Arnaud CD, et al. Radioimmunoassay of human parathyroid hormone in serum. J Clin Invest. 1971;50:21–34.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  64. 64.

    Brossard JH, et al. Accumulation of a non-(1-84) molecular form of parathyroid hormone (PTH) detected by intact PTH assay in renal failure: importance in the interpretation of PTH values. J Clin Endocrinol Metab. 1996;81:3923–9.

    CAS  PubMed  Google Scholar 

  65. 65.

    Lepage R, et al. A non-(1-84) circulating parathyroid hormone (PTH) fragment interferes significantly with intact PTH commercial assay measurements in uremic samples. Clin Chem. 1998;44:805–9.

    CAS  PubMed  Google Scholar 

  66. 66.

    Huan J, et al. Parathyroid hormone 7-84 induces hypocalcemia and inhibits the parathyroid hormone 1-84 secretory response to hypocalcemia in rats with intact parathyroid glands. J Am Soc Nephrol. 2006;17:1923–30.

    CAS  PubMed  Article  Google Scholar 

  67. 67.

    Gao P, et al. Development of a novel immunoradiometric assay exclusively for biologically active whole parathyroid hormone 1-84: implications for improvement of accurate assessment of parathyroid function. J Bone Miner Res. 2001;16:605–14.

    CAS  PubMed  Article  Google Scholar 

  68. 68.

    Taniguchi M, et al. Comparison between whole and intact parathyroid hormone assays. Ther Apher Dial. 2011;15(Suppl 1):42–9.

    CAS  PubMed  Article  Google Scholar 

  69. 69.

    Gannagé-Yared MH, et al. Comparison between a second and a third generation parathyroid hormone assay in hemodialysis patients. Metabolism. 2013;62:1416–22.

    PubMed  Article  CAS  Google Scholar 

  70. 70.

    Monier-Faugere, et al. Improved assessment of bone turnover by the PTH-(1–84)/large C-PTH fragments ratio in ESRD patients. Kidney Int. 2001;60:1460–8.

    CAS  PubMed  Article  Google Scholar 

  71. 71.

    Coen G, et al. PTH 1-84 and PTH “7-84” in the noninvasive diagnosis of renal bone disease. Am J Kidney Dis. 2002;40:348–54.

    CAS  PubMed  Article  Google Scholar 

  72. 72.

    Lehmann G, et al. Specific measurement of PTH (1-84) in various forms of renal osteodistrophy (ROD) as assessed by bone histomorphometry. Kidney Int. 2005;68:1206–14.

    CAS  PubMed  Article  Google Scholar 

  73. 73.

    Souberbielle JC, et al. Inter-method variabilidy in PTH measurement: implication for the care of CKD patients. Kidney Int. 2006;70:345–50.

    CAS  PubMed  Article  Google Scholar 

  74. 74.

    Almond A, et al. Current parathyroid hormone immunoassays do not adequately meet the needs of patients with chronic kidney disease. Ann Clin Biochem. 2012;49:63–7.

    CAS  PubMed  Article  Google Scholar 

  75. 75.

    KDIGO. Clinical practice guideline update on diagnosis, evaluation. Prevention and Treatment of CKD-MBD: Public Review Draft; 2016.

    Google Scholar 

  76. 76.

    Iimori S, et al. Diagnostic usefulness of bone mineral density and biochemical markers of bone turnover in predicting fracture in CKD stage 5D patients - a single center cohort study. Nephrol Dial Transplant. 2012;27:345–51.

    CAS  PubMed  Article  Google Scholar 

  77. 77.

    Yenchek RH, et al. Bone mineral density and fracture risk in older individuals with CKD. Clin J Am Soc Nephrol. 2012;7:1130–6.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  78. 78.

    Naylor KL, et al. Comparison of fracture risk prediction among individuals with reduced and normal kidney function. Clin J Am Soc Nephrol. 2015;10:646–53.

    PubMed  PubMed Central  Article  Google Scholar 

  79. 79.

    West SL, et al. Bone mineral density predicts fractures in chronic kidney disease. J Bone Miner Res. 2015;30:913–9.

    PubMed  Article  Google Scholar 

  80. 80.

    Sprague SM, et al. Diagnostic accuracy of bone turnover markers and bone histology in patients with CKD treated by dialysis. Am J Kidney Dis. 2016;67:559–66.

    PubMed  Article  Google Scholar 

  81. 81.

    Shigematsu T, et al. Preventive strategies for vascular calcification in patients with chronic kidney disease. Contrib Nephrol. 2017;189:169–77.

    PubMed  Article  Google Scholar 

  82. 82.

    Block GA, et al. Mineral metabolism, mortality, and morbidity in maintenance hemodialysis. J Am Soc Nephrol. 2004;15:2208–18.

    CAS  PubMed  Article  Google Scholar 

  83. 83.

    Fernández-Martín JL, et al. Improvement of mineral and bone metabolism markers is associated with better survival in haemodialysis patients: the COSMOS study. Nephrol Dial Transplant. 2015;30:1542–51.

    PubMed  Article  Google Scholar 

  84. 84.

    Kidney Disease. Improving Global Outcomes (KDIGO) CKD-MBD Work Group. KDIGO clinical practice guideline for the diagnosis, evaluation, prevention, and treatment of Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD). Kidney Int Suppl. 2009;113:S1–130.

    Google Scholar 

  85. 85.

    Moe SM, et al. Vegetarian compared with meat dietary protein source and phosphorus homeostasis in chronic kidney disease. Clin J Am Soc Nephrol. 2011;6:257–64.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  86. 86.

    Ando S, et al. The effect of various boiling conditions on reduction of phosphorus and protein in meat. J Ren Nutr. 2015;25:504–9.

    CAS  PubMed  Article  Google Scholar 

  87. 87.

    Bohnert BN, et al. Impact of phosphorus restriction and vitamin D-substitution on secondary hyperparathyroidism in a proteinuric mouse model. Kidney Blood Press Res. 2015;40:153–65.

    CAS  PubMed  Article  Google Scholar 

  88. 88.

    López I, et al. The calcimimetic AMG 641 accelerates regression of extraosseous calcification in uremic rats. Am J Physiol Renal Physiol. 2009;296:F1376–85.

    PubMed  Article  CAS  Google Scholar 

  89. 89.

    Alfrey AC, et al. The dialysis encephalopathy syndrome. Possible aluminum intoxication. N Engl J Med. 1976;294:184–8.

    CAS  PubMed  Article  Google Scholar 

  90. 90.

    Swartz R, et al. Microcytic anemia in dialysis patients: reversible marker of aluminum toxicity. Am J Kidney Dis. 1987;9:217–23.

    CAS  PubMed  Article  Google Scholar 

  91. 91.

    Malluche HH. Aluminium and bone disease in chronic renal failure. Nephrol Dial Transplant. 2002;17:21–4.

    CAS  PubMed  Article  Google Scholar 

  92. 92.

    Fournier A, et al. Calcium carbonate, an aluminum-free agent for control of hyperphosphatemia, hypocalcemia, and hyperparathyroidism in uremia. Kidney Int Suppl. 1986;18:S114–9.

    CAS  PubMed  Google Scholar 

  93. 93.

    Hercz G, et al. Use of calcium carbonate as a phosphate binder in dialysis patients. Miner Electrolyte Metab. 1986;12:314–9.

    CAS  PubMed  Google Scholar 

  94. 94.

    Emmett M, et al. Calcium acetate control of serum phosphorus in hemodialysis patients. Am J Kidney Dis. 1991;17:544–50.

    CAS  PubMed  Article  Google Scholar 

  95. 95.

    Pflanz S, et al. Calcium acetate versus calcium carbonate as phosphate-binding agents in chronic haemodialysis. Nephrol Dial Transplant. 1994;9:1121–4.

    CAS  PubMed  Article  Google Scholar 

  96. 96.

    Delmez JA, et al. Calcium acetate as a phosphorus binder in hemodialysis patients. J Am Soc Nephrol. 1992;3:96–102.

    CAS  PubMed  Google Scholar 

  97. 97.

    Goodman WG, et al. Coronary-artery calcification in young adult with end-stage renal disease who are undergoing dialysis. N Engl J Med. 2000;342:1478–83.

    CAS  PubMed  Article  Google Scholar 

  98. 98.

    Guerin AP, et al. Arterial stiffening and vascular calcifications in end-stage renal disease. Nephrol Dial Transplant. 2000;15:1014–21.

    CAS  PubMed  Article  Google Scholar 

  99. 99.

    Chertow GM, et al. Determinants of progressive vascular calcification in haemodialysis patients. Nephrol Dial Transplant. 2004;19:1489–96.

    PubMed  Article  CAS  Google Scholar 

  100. 100.

    London GM, et al. Association of bone activity, calcium load, aortic stiffness, and calcifications in ESRD. J Am Soc Nephrol. 2008;19:1837–5.

    Article  CAS  Google Scholar 

  101. 101.

    Jamal SA, et al. Effect of calcium-based versus non-calcium-based phosphate binders on mortality in patients with chronic kidney disease: an updated systematic review and meta-analysis. Lancet. 2013;382:1268–77.

    CAS  PubMed  Article  Google Scholar 

  102. 102.

    Delmez JA, et al. Magnesium carbonate as a phosphorus binder: a prospective, controlled, crossover study. Kidney Int. 1996;49:163–7.

    CAS  PubMed  Article  Google Scholar 

  103. 103.

    Spiegel DM, et al. Magnesium carbonate is an effective phosphate binder for chronic hemodialysis patients: a pilot study. J Ren Nutr. 2007;17:416–22.

    PubMed  Article  Google Scholar 

  104. 104.

    Rodríguez-Ortiz ME, et al. Magnesium modulates parathyroid hormone secretion and upregulates parathyroid receptor expression at moderately low calcium concentration. Nephrol Dial Transplant. 2014;29:282–9.

    PubMed  Article  CAS  Google Scholar 

  105. 105.

    João Matias P, et al. Lower serum magnesium is associated with cardiovascular risk factors and mortality in haemodialysis patients. Blood Purif. 2014;38:244–52.

    PubMed  Article  CAS  Google Scholar 

  106. 106.

    Silva AP, et al. Low magnesium levels and FGF-23 dysregulation predict mitral valve calcification as well as intima media thickness in predialysis diabetic patients. Int J Endocrinol. 2015;2015:308190.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  107. 107.

    Chertow GM, et al. Poly[allylamine hydrochloride] (RenaGel): a noncalcemic phosphate binder for the treatmentof hyperphosphatemia in chronic renal failure. Am J Kidney Dis. 1997;29:66–71.

    CAS  PubMed  Article  Google Scholar 

  108. 108.

    Chertow GM, et al. Long-term effects of sevelamer hydrochloride on the calcium x phosphate product and lipid profile of haemodialysis patients. Nephrol Dial Transplant. 1999;14:2907–14.

    CAS  PubMed  Article  Google Scholar 

  109. 109.

    Di Iorio B, et al. Mortality in kidney disease patients treated with phosphate binders: a randomized study. Clin J Am Soc Nephrol. 2012;7:487–93.

    CAS  PubMed  Article  Google Scholar 

  110. 110.

    Russo D, et al. Effects of phosphorus-restricted diet and phosphate-binding therapy on outcomes in patients with chronic kidney disease. J Nephrol. 2015;28:73–80.

    CAS  PubMed  Article  Google Scholar 

  111. 111.

    Di Iorio B, et al. Sevelamer versus calcium carbonate in incident hemodialysis patients: results of an open-label 24-month randomized clinical trial. Am J Kidney Dis. 2013;62:771–8.

    CAS  PubMed  Article  Google Scholar 

  112. 112.

    Patel L et al. Sevelamer versus calcium-based binders for treatment of hyperphosphatemia in CKD: A meta-analysis of randomized controlled trials. Clin J Am Soc Nephrol. 2016;11:232–244. Ojo, cambiado de orden con el siguiente trabajo!

  113. 113.

    Sekercioglu N, et al. Comparative effectiveness of phosphate binders in patients with chronic kidney disease: a systematic review and network meta-analysis. PLoS One. 2016;11:e0156891.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  114. 114.

    Habbous S, et al. The efficacy and safety of sevelamer and lanthanum versus calcium-containing and iron-based binders in treating hyperphosphatemia in patients with chronic kidney disease: a systematic review and meta-analysis. Nephrol Dial Transplant. 2016; (in press)

  115. 115.

    Chertow GM, et al. Sevelamer attenuates the progression of coronary and aortic calcification in hemodialysis patients. Kidney Int. 2002;62:245–52.

    CAS  PubMed  Article  Google Scholar 

  116. 116.

    Caglar K, et al. Short-term treatment with sevelamer increases serum fetuin-a concentration and improves endothelial dysfunction in chronic kidney disease stage 4 patients. Clin J Am Soc Nephrol. 2008;3:61–8.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  117. 117.

    Westenfeld R, et al. Fetuin-a protects agains atherosclerotic calcification in CKD. J Am Soc Nephrol. 2009;20:1264–74.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  118. 118.

    Evenepoel P, et al. Efficacy and safety of sevelamer hydrochloride and calcium acetate in patients on peritoneal dialysis. Nephrol Dial Transplant. 2009;24:278–85.

    CAS  PubMed  Article  Google Scholar 

  119. 119.

    Ohno I, et al. Sevelamer decreases serum uric acid concentration through adsorption of uric acid in maintenance hemodialysis patients. Intern Med. 2009;48:415–20.

    PubMed  Article  Google Scholar 

  120. 120.

    Ramos R, et al. Sevelamer hydrochloride in peritoneal dialysis patients: results of a multicenter cross-sectional study. Perit Dial. 2007;27:697–701.

    CAS  Google Scholar 

  121. 121.

    Iimori S, et al. Effects of sevelamer hydrochloride on mortality, lipid abnormality and arterial stiffness in hemodialylzed patients: a propensity-matched observational study. Clin Exp Nephrol. 2012;16:930–7.

    CAS  PubMed  Article  Google Scholar 

  122. 122.

    Hutchison AJ, et al. Efficacy, tolerability, and safety of lanthanum carbonate in hyperphosphatemia: a 6-month, randomized, comparative trial versus calcium carbonate. Nephron Clin Pract. 2005;100:c8–19.

    CAS  PubMed  Article  Google Scholar 

  123. 123.

    Hutchison AJ, et al. Long-term efficacy and tolerability of lanthanum carbonate: results from a 3-year study. Nephron Clin Pract. 2006;102:c61–71.

    CAS  PubMed  Article  Google Scholar 

  124. 124.

    Shigematsu T, et al. Lanthanum carbonate effectively controls serum phosphate without affecting serum calcium levels in patients undergoing dialysis. Ther Apher Dial. 2008;12:55–61.

    CAS  PubMed  Article  Google Scholar 

  125. 125.

    Uhling K, et al. KDOQI US commentary on the 2009 KDIGO clinical practice guideline for the diagnosis, evaluation, and treatment of CKD-mineral and bone disorder (CKD-MBD). Am J Kidney Dis. 2010;55:773–99.

    Article  Google Scholar 

  126. 126.

    Inaba M, et al. Restoration of parathyroid function after change of phosphate binder from calcium carbonate to lanthanum carbonate in hemodialysis patients with suppressed serum parathyroid hormone. J Ren Nutr. 2015;25:242–6.

    CAS  PubMed  Article  Google Scholar 

  127. 127.

    Komaba H, et al. Survival advantage of lanthanum carbonate for hemodialysis patients with uncontrolled hyperphosphatemia. Nephrol Dial Transplant. 2015;30:107–14.

    PubMed  Article  Google Scholar 

  128. 128.

    Tsuchida K, et al. Impact of lanthanum carbonate on prognosis of chronic hemodialysis patients: a retrospective cohort study (Kawashima study). Ther Apher Dial. 2016;20:142–8.

    CAS  PubMed  Article  Google Scholar 

  129. 129.

    Block GA, et al. A 12-week, double-blind, placebo-controlled trial of ferric citrate for the treatment of iron deficiency anemia and reduction of serum phosphate in patients with CKD stages 3-5. Am J Kidney Dis. 2015;65:728–36.

    CAS  PubMed  Article  Google Scholar 

  130. 130.

    Lewis JB, et al. Ferric citrate controls phosphorus and delivers iron in patients on dialysis. J Am Soc Nephrol. 2015;26:493–503.

    PubMed  Article  CAS  Google Scholar 

  131. 131.

    Floege J, et al. A phase III study of the efficacy and safety of a novel iron-based phosphate binder in dialysis patients. Kidney Int. 2014;86:638–47.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  132. 132.

    Locatelli F, et al. Evaluation of colestilan in chronic kidney disease dialysis patients with hyperphosphatemia and dyslipidaemia: a randomized, placebo-controlled, multiple fixed-dose trial. Nephrol Dial Transplant. 2013;28:1874–88.

    CAS  PubMed  Article  Google Scholar 

  133. 133.

    Locatelli F, et al. Long-term evaluation of colestilan in chronic kidney disease stage 5 dialysis patients with hyperphosphatemia. Blood Purif. 2016;41:247–53.

    CAS  PubMed  Article  Google Scholar 

  134. 134.

    Lenglet A et al. Efficacy and safety of nicotinamide in haemodialysis patients: the NICOREN study. Nephrol Dial Transplant 2016.

  135. 135.

    Metzger M, et al. Relation between circulating levels of 25(OH) vitamin D and parathyroid hormone in chronic kidney disease: quest for a threshold. J Clin Endocrinol Metab. 2013;98:2922–8.

    CAS  PubMed  Article  Google Scholar 

  136. 136.

    Melamed ML, et al. 25-hydroxyvitamin D levels, race, and the progression of kidney disease. J Am Soc Nephrol. 2009;20:2631–9.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  137. 137.

    García-Cantón C, et al. Vascular calcification and 25-hydroxyvitamin D levels in non-dialysis patients with chronic kidney disease stages 4 and 5. Nephrol Dial Transplant. 2011;26:2250–6.

    PubMed  Article  CAS  Google Scholar 

  138. 138.

    Pilz S, et al. Vitamin D status and mortality in chronic kidney disease. Nephrol Dial Transplant. 2011;26:3603–9.

    CAS  PubMed  Article  Google Scholar 

  139. 139.

    Nordal KP, et al. Low dose calcitriol versus placebo in patients with predialysis chronic renal failure. J Clin Endocrinol Metab. 1988;67:929–36.

    CAS  PubMed  Article  Google Scholar 

  140. 140.

    Andress DL, et al. Intravenous calcitriol in the treatment of refractory osteitis fibrosa of chronic renal failure. N Engl J Med. 1989;321:274–9.

    CAS  PubMed  Article  Google Scholar 

  141. 141.

    Dunlay R, et al. Direct inhibitory effect of calcitriol on parathyroid function (sigmoidal curve) in dialysis. Kidney Int. 1989;36:1093–8.

    CAS  PubMed  Article  Google Scholar 

  142. 142.

    Liang XX, et al. The significance of ultrasound in determining whether SHPT patients are sensitive to calcitriol treatment. Biomed Res Int. 2016;2016:6193751.

    PubMed  PubMed Central  Google Scholar 

  143. 143.

    Tonbul HZ, et al. Efficacy and tolerability of intravenous paricalcitol in calcitriol-resistant hemodialysis patients with secondary hyperparathyroidism: 12-month prospective study. Ren Fail. 2012;34:297–303.

    CAS  PubMed  Article  Google Scholar 

  144. 144.

    Coyne DW, et al. Effects of paricalcitol on calcium and phosphate metabolism and markers of bone health in patients with diabetic nephropathy: results of the VITAl study. Nephrol Dial Transplant. 2013;28:2260–8.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  145. 145.

    Sprague SM, et al. Suppression of parathyroid hormone secretion in hemodialysis patients: comparison of paricalcitol with calcitriol. Am J Kidney Dis. 2001;38:S51–6.

    CAS  PubMed  Article  Google Scholar 

  146. 146.

    Sprague SM, et al. Paricalcitol versus calcitriol in the treatment of secondary hyperparathyroidism. Kidney Int. 2003;63:1483–90.

    CAS  PubMed  Article  Google Scholar 

  147. 147.

    Večerić-Haler Ž, et al. Comparison of the pharmacological effects of paricalcitol versus calcitriol on secondary hyperparathyroidism in the dialysis population. Ther Apher Dial. 2016;20:261–6.

    PubMed  Article  CAS  Google Scholar 

  148. 148.

    Ketteler M, et al. Paricalcitol versus cinacalcet plus low-dose vitamin D therapy for the treatment of secondary hyperparathyroidism in patients receiving haemodialysis: results of the IMPACT SHPT study. Nephrol Dial Transplant. 2012;27:3270–8.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  149. 149.

    Borrego Utiel FJ, et al. Effect of paricalcitol on mineral bone metabolism in kidney transplant recipients with secondary hyperparathyroidism. Nefrologia. 2015;35:363–73.

    PubMed  Article  Google Scholar 

  150. 150.

    Amer H, et al. Oral paricalcitol reduces the prevalence of posttransplant hyperparathyroidism: results of an open label randomized trial. Am J Transplant. 2013;13:1576–85.

    CAS  PubMed  Article  Google Scholar 

  151. 151.

    Donate-Correa J, et al. Effect of paricalcitol on FGF-23 and klotho in kidney transplant recipients. Transplantation. 2016;100:2432–8.

    CAS  PubMed  Article  Google Scholar 

  152. 152.

    Cai P, et al. Comparison between paricalcitol and active non-selective vitamin D receptor activator for secondary hyperparathyroidism in chronic kidney disease: a systematic review and meta-analysis of randomized controlled trials. Int Urol Nephrol. 2016;48:571–84.

    CAS  PubMed  Article  Google Scholar 

  153. 153.

    Zella JB, et al. Novel, selective vitamin D analog suppresses parathyroid hormone in uremic animals and postmenopausal women. Am J Nephrol. 2014;39:476–83.

    CAS  PubMed  Article  Google Scholar 

  154. 154.

    Pandey R, et al. Use of 2MD, a novel oral calcitriol analog, in hemodialysis patients with secondary hyperparathyroidism. Am J Nephrol. 2016;43:213–20.

    CAS  PubMed  Article  Google Scholar 

  155. 155.

    Al-Hilali N, et al. Intravenous alfacalcidol once weekly suppresses parathyroid hormone in hemodialysis patients. Ther Apher Dial. 2008;12:137–42.

    CAS  PubMed  Article  Google Scholar 

  156. 156.

    Michaud J, et al. Effects of serum from patients with chronic renal failure on rat hepatic cytochrome P450. Br J Pharmacol. 2005;144:1067–77.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  157. 157.

    Bezzaoucha S, et al. Efficacy of calcitriol compared to alfacalcidol for the treatment of secondary hyperparathyroidism in peritoneal dialysis patients. Int J Clin Pharmacol Ther. 2015;53:895–6.

    CAS  PubMed  Article  Google Scholar 

  158. 158.

    Messa P, et al. Effect of VDRA on survival in incident hemodialysis patients: results of the FARO-2 observational study. BMC Nephrol. 2015;16:11.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  159. 159.

    Duranton F, et al. Vitamin D treatment and mortality in chronic kidney disease: a systematic review and meta-analysis. Am J Nephrol. 2013;37:239–48.

    CAS  PubMed  Article  Google Scholar 

  160. 160.

    Cupisti A, et al. Vitamin D status and cholecalciferol supplementation in chronic kidney disease: an Italian cohort report. Int J Nephrol Renovasc Dis. 2015;8:151–7.

    PubMed  PubMed Central  Article  Google Scholar 

  161. 161.

    Merino JL, et al. Effects of a single, high oral dose of 15-hydroxycholecalciferol on the mineral metabolism markers in hemodialysis patients. Ther Apher Dial. 2015;19:212–9.

    CAS  PubMed  Article  Google Scholar 

  162. 162.

    Zitt E, et al. Efficacy and safety of body weight-adapted oral cholecalciferol substitution in dialysis patients with vitamin D deficiency. BMC Nephrol. 2015;16:128.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  163. 163.

    Hryszko T, et al. Cholecalciferol supplementation reduces soluble klotho concentration in hemodialysis patients. Pol Arch Med Wewn. 2013;123:277–81.

    CAS  PubMed  Google Scholar 

  164. 164.

    Meireles MS, et al. Effect of cholecalciferol on vitamin D-regulatory proteins in monocytes and on inflammatory markers in dialysis patients: a randomized controlled trial. Clin Nutr. 2016;35:1251–8.

    CAS  PubMed  Article  Google Scholar 

  165. 165.

    Miskulin DC, et al. Ergocalciferol supplementation in hemodialysis patients with vitamin D deficiency: a randomized clinical trial. J Am Soc Nephrol. 2016;27:1801–10.

    PubMed  Article  Google Scholar 

  166. 166.

    Mangoo-Karim R, et al. Ergocalciferol versus cholecalciferol for nutritional vitamin D replacement in CKD. Nephron. 2015;130:99–104.

    CAS  PubMed  Article  Google Scholar 

  167. 167.

    Valle C, et al. Cinacalcet reduces the set point of the PTH-calcium curve. J Am Soc Nephrol. 2008;19:2430–6.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  168. 168.

    Frazao J, et al. Secondary hyperparathyroidism disease stabilization following calcimimetic therapy. NDT Plus. 2008;1:i12–7.

    CAS  PubMed  PubMed Central  Google Scholar 

  169. 169.

    Rodríguez M, et al. The use of calcimimetics for the treatment of secondary hyperparathyroidism: a 10 year evidence review. Semin Dial. 2015;28:497–507.

    PubMed  Article  Google Scholar 

  170. 170.

    Block GA, et al. Cinacalcet for secondary hyperparathyroidism in patients receiving hemodialysis. N Engl J Med. 2004;350:1516–25.

    CAS  PubMed  Article  Google Scholar 

  171. 171.

    Lindberg JS, et al. Cinacalcet HCl, an oral calcimimetic agent for the treatment of secondary hyperparathyroidism in hemodialysis and peritoneal dialysis: a randomized, double-blind, multicenter study. J Am Soc Nephrol. 2005;16:800–7.

    CAS  PubMed  Article  Google Scholar 

  172. 172.

    Palmer SC, et al. Cinacalcet in patients with chronic kidney disease: a cumulative meta-analysis of randomized controlled trials. PLoS Med. 2013;10:e1001436.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  173. 173.

    EVOLVE Trial Investigators. Effect of cinacalcet on cardiovascular disease in patients undergoing dialysis. N Engl J Med. 2012;367:2482–94.

    Article  Google Scholar 

  174. 174.

    Raggi P, et al. The ADVANCE study: a randomized study to evaluate the effects of cinacalcet plus low-dose vitamin D on vascular calcification in patients on hemodialysis. Nephrol Dial Transplant. 2011;26:1327–39.

    CAS  PubMed  Article  Google Scholar 

  175. 175.

    Chertow GM, et al. Evaluation of Cinacalcet therapy to lower cardiovascular events (EVOLVE): rationale and design overview. Clin J Am Soc Nephrol. 2007;2:898–905.

    CAS  PubMed  Article  Google Scholar 

  176. 176.

    Chertow GM, et al. Baseline characteristics of subjects enrolled in the evaluation of Cinacalcet HCl therapy to lower cardiovascular (EVOLVE) trial. Nephrol Dial Transplant. 2012;27:2872–9.

    CAS  PubMed  Article  Google Scholar 

  177. 177.

    Parfrey PS, et al. The effects of cinacalcet in older and younger patients on hemodialysis: the evaluation of cinacalcet HCl therapy to lower cardiovascular events (EVOLVE) trial. Clin J Am Soc Nephrol. 2015;10:791–9.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  178. 178.

    Parfrey PS, et al. The clinical course of treated hyperparathyroidism among patients receiving hemodialysis and the effect of cinacalcet: the EVOLVE trial. J Clin Endocrinol Metab. 2013;98:4834–44.

    CAS  PubMed  Article  Google Scholar 

  179. 179.

    Moe SM, et al. Effects of cinacalcet on fracture events in patients receiving hemodialysis: the EVOLVE trial. J Am Soc Nephrol. 2015;26:1466–75.

    CAS  PubMed  Article  Google Scholar 

  180. 180.

    Paschoalin RP, et al. Cinacalcet treatment for stable kidney transplantation patients with hypercalcemia due to persistent secondary hyperparathyroidism: a long-term follow-up. Transplant Proc. 2012;44:2588–9.

    CAS  PubMed  Article  Google Scholar 

  181. 181.

    Torregrosa JV, et al. Cinacalcet for hypercalcaemic secondary hyperparathyroidism after renal transplantation: a multicentre, retrospective, 3-year study. Nephrology. 2014;19:84–93.

    CAS  PubMed  Article  Google Scholar 

  182. 182.

    Thiem U, et al. Long-term clinical practice experience with cinacalcet for treatment of hypercalcemic hyperparathyroidism after kidney transplantation. Biomed Res Int. 2015;2015:292654.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  183. 183.

    Cohen JB, et al. Cinacalcet for the treatment of hyperparathyroidism in kidney transplant recipients: a systematic review and meta-analysis. Transplantation. 2012;94:1041–8.

    CAS  PubMed  Article  Google Scholar 

  184. 184.

    Walter S, et al. Pharmacology of AMG 416 (Velcalcetide), a novel peptide agonist of the calcium-sensing receptor, for the treatment of secondary hyperparathyroidism in hemodialysis patients. J Pharmacol Exp Ther. 2013;346:229–40.

    CAS  PubMed  Article  Google Scholar 

  185. 185.

    Walter S, et al. Comparison of AMG 416 and cinacalcet in rodent models of uremia. BMC Nephrol. 2014;15:81.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  186. 186.

    Martin KJ, et al. Velcalcetide (AMG 416), a novel peptide agonist of the calcium-sensing receptor, reduces serum parathyroid hormone and FGF23 levels in healthy male subjects. Nephrol Dial Transplant. 2014;29:385–92.

    CAS  PubMed  Article  Google Scholar 

  187. 187.

    Martin KJ, et al. AMG 416 (velcalcetide) is a novel peptide for the treatment of secondary hyperparathyroidism in a single-dose study in hemodialysis patients. Kidney Int. 2014;85:191–7.

    CAS  PubMed  Article  Google Scholar 

  188. 188.

    Bell G, et al. A randomized, double-blind-phase 2 study evaluating the safety and efficacy of AMG 416 for the treatment of secondary hyperparathyroidism in hemodialysis patients. Curr Med Res Opin. 2015;31:943–52.

    CAS  PubMed  Article  Google Scholar 

  189. 189.

    Goldsmith D, et al. 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;30:698–700.

    PubMed  Article  Google Scholar 

  190. 190.

    Messa P, et al. The OPTIMA study: assessing a new cinacalcet (Sensipar/Mimpara) treatment algorithm for secondary hyperparathyroidism. Clin J Am Soc Nephrol. 2008;3:36–45.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  191. 191.

    Kim SM, et al. Rates and outcomes of parathyroidectomy for secondary hyperparathyroidism in the United States. Clin J Am Soc Nephrol. 2016;11:1260–7.

    PubMed  Article  Google Scholar 

  192. 192.

    Hsu YH, et al. The risk of peripheral arterial disease after parathyroidectomy in patients with end-stage renal disease. PLoS One. 2016;11:e0156863.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  193. 193.

    Kovacevic B, et al. Parathyroidectomy for the attainment of NKF-K/DOQI™ and KDIGO recommended values for bone and mineral metabolism in dialysis patients with uncontrollable secondary hyperparathyroidism. Langenbeck's Arch Surg. 2012;397:413–20.

    Article  Google Scholar 

  194. 194.

    Chen C, et al. Impacts of parathyroidectomy on renal anemia and nutritional status of hemodialysis patients with secondary hyperparathyroidism. Int J Clin Exp Med. 2015;8:9830–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  195. 195.

    Jiang Y, et al. Association of increased serum leptin with ameliorated anemia and malnutrition in stage 5 chronic kidney disease patients after parathyroidectomy. Sci Rep. 2016;27918

  196. 196.

    Chen L, et al. Long-term mortality after parathyroidectomy among chronic kidney disease patients with secondary hyperparathyroidism: a systematic review and meta-analysis. Ren Fail. 2016;38:1050–8.

    CAS  PubMed  Article  Google Scholar 

  197. 197.

    Konturek K, et al. Subtotal parathyroidectomy for secondary renal hyperparathyroidism: a 20-year surgical outcome study. Langenbeck's Arch Surg. 2016;401:965–74.

    Article  Google Scholar 

  198. 198.

    Yang M, et al. Factors predictive of critical value of hypocalcemia after total parathyroidectomy without autotransplantation in patients with secondary hyperparathyroidism. Ren Fail. 2016;38:1224–7.

    CAS  PubMed  Article  Google Scholar 

  199. 199.

    Zhang L, et al. Diagnostic accuracy study of intraoperative and perioperative serum intact PTH level for successful parathyroidectomy in 501 secondary hyperparathyroidism patients. Sci Rep. 2016;6:26841.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

Download references

Acknowledgements

María E. Rodríguez-Ortiz is recipient of a “Sara Borrell” research contract from the National Institute of Health Carlos III.

Author information

Affiliations

Authors

Corresponding author

Correspondence to Mariano Rodríguez Portillo.

Ethics declarations

Conflict of Interest

The authors declare that they have no conflict of interest.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Portillo, M.R., Rodríguez-Ortiz, M.E. Secondary Hyperparthyroidism: Pathogenesis, Diagnosis, Preventive and Therapeutic Strategies. Rev Endocr Metab Disord 18, 79–95 (2017). https://doi.org/10.1007/s11154-017-9421-4

Download citation

Keywords

  • Secondary hyperparathyroidism
  • Calcium
  • Phosphorus
  • Vitamin D
  • Calcimimetic
  • Parathyroidectomy