Official reprint from UpToDate®
www.uptodate.com ©2017 UpToDate, Inc. and/or its affiliates. All Rights Reserved.

Persistent hyperparathyroidism after renal transplantation

Sri G Yarlagadda, MD
Thomas Nickolas, MD, MS
L Darryl Quarles, MD
Section Editor
Daniel C Brennan, MD, FACP
Deputy Editor
Albert Q Lam, MD


Renal transplant recipients are vulnerable to persistent hyperparathyroidism and other disorders of mineral and bone metabolism associated with chronic kidney disease (CKD).

This topic reviews recommendations regarding monitoring and treatment of hyperparathyroidism, hypercalcemia, and hypophosphatemia among renal transplant candidates and recipients.

Other bone disorders that affect renal transplant recipients, including osteoporosis and osteonecrosis, are discussed elsewhere. (See "Bone disease after renal transplantation".)

The pathogenesis of metabolic bone disease and the treatment of hyperparathyroidism in nontransplant CKD patients are discussed elsewhere. (See "Overview of chronic kidney disease-mineral and bone disorder (CKD-MBD)" and "Management of secondary hyperparathyroidism in adult nondialysis patients with chronic kidney disease" and "Management of secondary hyperparathyroidism in dialysis patients".)


Most patients with chronic kidney disease (CKD) develop some degree of secondary hyperparathyroidism by the time they initiate renal replacement therapy (RRT). Secondary hyperparathyroidism occurs in response to multiple abnormalities that initially stem from decreased glomerular filtration rate (GFR) [1]. The pathophysiology of secondary hyperparathyroidism in CKD patients is discussed at length elsewhere. (See "Overview of chronic kidney disease-mineral and bone disorder (CKD-MBD)", section on 'Overview'.)

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:

Subscribers log in here

Literature review current through: Nov 2017. | This topic last updated: Dec 06, 2017.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2017 UpToDate, Inc.
  1. Cunningham J, Locatelli F, Rodriguez M. Secondary hyperparathyroidism: pathogenesis, disease progression, and therapeutic options. Clin J Am Soc Nephrol 2011; 6:913.
  2. Heaf JG. Bone disease after renal transplantation. Transplantation 2003; 75:315.
  3. Julian BA, Benfield M, Quarles LD. Bone loss after organ transplantation. Transplant Rev 1993; 7:82.
  4. Julian BA, Quarles LD, Niemann KM. Musculoskeletal complications after renal transplantation: pathogenesis and treatment. Am J Kidney Dis 1992; 19:99.
  5. Cundy T, Kanis JA, Heynen G, et al. Calcium metabolism and hyperparathyroidism after renal transplantation. Q J Med 1983; 52:67.
  6. Bonarek H, Merville P, Bonarek M, et al. Reduced parathyroid functional mass after successful kidney transplantation. Kidney Int 1999; 56:642.
  7. Evenepoel P, Claes K, Kuypers D, et al. Natural history of parathyroid function and calcium metabolism after kidney transplantation: a single-centre study. Nephrol Dial Transplant 2004; 19:1281.
  8. Sprague SM, Belozeroff V, Danese MD, et al. Abnormal bone and mineral metabolism in kidney transplant patients--a review. Am J Nephrol 2008; 28:246.
  9. D'Alessandro AM, Melzer JS, Pirsch JD, et al. Tertiary hyperparathyroidism after renal transplantation: operative indications. Surgery 1989; 106:1049.
  10. David DS, Sakai S, Brennan BL, et al. Hypercalcemia after renal transplantation. Long-term follow-up data. N Engl J Med 1973; 289:398.
  11. Garvin PJ, Castaneda M, Linderer R, Dickhans M. Management of hypercalcemic hyperparathyroidism after renal transplantation. Arch Surg 1985; 120:578.
  12. Parfitt AM. Hypercalcemic hyperparathyroidism following renal transplantation: differential diagnosis, management, and implications for cell population control in the parathyroid gland. Miner Electrolyte Metab 1982; 8:92.
  13. Messa P, Sindici C, Cannella G, et al. Persistent secondary hyperparathyroidism after renal transplantation. Kidney Int 1998; 54:1704.
  14. Torres A, Lorenzo V, Salido E. Calcium metabolism and skeletal problems after transplantation. J Am Soc Nephrol 2002; 13:551.
  15. Borchhardt K, Sulzbacher I, Benesch T, et al. Low-turnover bone disease in hypercalcemic hyperparathyroidism after kidney transplantation. Am J Transplant 2007; 7:2515.
  16. Sirilak S, Chatsrisak K, Ingsathit A, et al. Renal phosphate loss in long-term kidney transplantation. Clin J Am Soc Nephrol 2012; 7:323.
  17. Reinhardt W, Bartelworth H, Jockenhövel F, et al. Sequential changes of biochemical bone parameters after kidney transplantation. Nephrol Dial Transplant 1998; 13:436.
  18. Heaf J, Tvedegaard E, Kanstrup IL, Fogh-Andersen N. Hyperparathyroidism and long-term bone loss after renal transplantation. Clin Transplant 2003; 17:268.
  19. Wolf M, Weir MR, Kopyt N, et al. A Prospective Cohort Study of Mineral Metabolism After Kidney Transplantation. Transplantation 2016; 100:184.
  20. Fukuda N, Tanaka H, Tominaga Y, 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.
  21. Arnold A, Brown MF, Ureña P, et al. Monoclonality of parathyroid tumors in chronic renal failure and in primary parathyroid hyperplasia. J Clin Invest 1995; 95:2047.
  22. Drüeke TB. The pathogenesis of parathyroid gland hyperplasia in chronic renal failure. Kidney Int 1995; 48:259.
  23. Tillmann FP, Wächtler C, Hansen A, et al. Vitamin D and cinacalcet administration pre-transplantation predict hypercalcaemic hyperparathyroidism post-transplantation: a case-control study of 355 deceased-donor renal transplant recipients over 3 years. Transplant Res 2014; 3:21.
  24. Bonnin MR, González MT, Huguet J, et al. 1,25-Dihydroxycholecalciferol as measured by a radioreceptor assay in normal subjects and patients after kidney transplantation. Clin Chem 1990; 36:389.
  25. Bhan I, Shah A, Holmes J, et al. Post-transplant hypophosphatemia: Tertiary 'Hyper-Phosphatoninism'? Kidney Int 2006; 70:1486.
  26. Pande S, Ritter CS, Rothstein M, et al. FGF-23 and sFRP-4 in chronic kidney disease and post-renal transplantation. Nephron Physiol 2006; 104:p23.
  27. Ghanekar H, Welch BJ, Moe OW, Sakhaee K. Post-renal transplantation hypophosphatemia: a review and novel insights. Curr Opin Nephrol Hypertens 2006; 15:97.
  28. Evenepoel P, Naesens M, Claes K, et al. Tertiary 'hyperphosphatoninism' accentuates hypophosphatemia and suppresses calcitriol levels in renal transplant recipients. Am J Transplant 2007; 7:1193.
  29. Liu S, Quarles LD. How fibroblast growth factor 23 works. J Am Soc Nephrol 2007; 18:1637.
  30. Lavi-Moshayoff V, Wasserman G, Meir T, 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.
  31. López I, Rodríguez-Ortiz ME, Almadén Y, et al. Direct and indirect effects of parathyroid hormone on circulating levels of fibroblast growth factor 23 in vivo. Kidney Int 2011; 80:475.
  32. Quinn SJ, Thomsen AR, Pang JL, et al. Interactions between calcium and phosphorus in the regulation of the production of fibroblast growth factor 23 in vivo. Am J Physiol Endocrinol Metab 2013; 304:E310.
  33. Gutierrez O, Isakova T, Rhee E, et al. Fibroblast growth factor-23 mitigates hyperphosphatemia but accentuates calcitriol deficiency in chronic kidney disease. J Am Soc Nephrol 2005; 16:2205.
  34. Imanishi Y, Inaba M, Nakatsuka K, et al. FGF-23 in patients with end-stage renal disease on hemodialysis. Kidney Int 2004; 65:1943.
  35. Larsson T, Nisbeth U, Ljunggren O, 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.
  36. Evenepoel P, Meijers BK, de Jonge H, et al. Recovery of hyperphosphatoninism and renal phosphorus wasting one year after successful renal transplantation. Clin J Am Soc Nephrol 2008; 3:1829.
  37. Tataranni T, Biondi G, Cariello M, et al. Rapamycin-induced hypophosphatemia and insulin resistance are associated with mTORC2 activation and Klotho expression. Am J Transplant 2011; 11:1656.
  38. Wesseling-Perry K, Tsai EW, Ettenger RB, et al. Mineral abnormalities and long-term graft function in pediatric renal transplant recipients: a role for FGF-23? Nephrol Dial Transplant 2011; 26:3779.
  39. Muirhead N, Zaltman JS, Gill JS, et al. Hypercalcemia in renal transplant patients: prevalence and management in Canadian transplant practice. Clin Transplant 2014; 28:161.
  40. Perrin P, Caillard S, Javier RM, et al. Persistent hyperparathyroidism is a major risk factor for fractures in the five years after kidney transplantation. Am J Transplant 2013; 13:2653.
  41. Pihlstrøm H, Dahle DO, Mjøen G, et al. Increased risk of all-cause mortality and renal graft loss in stable renal transplant recipients with hyperparathyroidism. Transplantation 2015; 99:351.
  42. Wolf M, Molnar MZ, Amaral AP, et al. Elevated fibroblast growth factor 23 is a risk factor for kidney transplant loss and mortality. J Am Soc Nephrol 2011; 22:956.
  43. Baia LC, Humalda JK, Vervloet MG, et al. Fibroblast growth factor 23 and cardiovascular mortality after kidney transplantation. Clin J Am Soc Nephrol 2013; 8:1968.
  44. Hernández D, Rufino M, Bartolomei S, et al. Clinical impact of preexisting vascular calcifications on mortality after renal transplantation. Kidney Int 2005; 67:2015.
  45. Roodnat JI, van Gurp EA, Mulder PG, et al. High pretransplant parathyroid hormone levels increase the risk for graft failure after renal transplantation. Transplantation 2006; 82:362.
  46. Slatopolsky E, Delmez JA. Pathogenesis of secondary hyperparathyroidism. Am J Kidney Dis 1994; 23:229.
  47. Schmid T, Müller P, Spelsberg F. Parathyroidectomy after renal transplantation: a retrospective analysis of long-term outcome. Nephrol Dial Transplant 1997; 12:2393.
  48. Ferreira GF, Montenegro FL, Machado DJ, et al. Parathyroidectomy after kidney transplantation: short-and long-term impact on renal function. Clinics (Sao Paulo) 2011; 66:431.
  49. Rostaing L, Moreau-Gaudry X, Baron E, et al. Changes in blood pressure and renal function following subtotal parathyroidectomy in renal transplant patients presenting with persistent hypercalcemic hyperparathyroidism. Clin Nephrol 1997; 47:248.
  50. Evenepoel P, Claes K, Kuypers D, et al. Impact of parathyroidectomy on renal graft function, blood pressure and serum lipids in kidney transplant recipients: a single centre study. Nephrol Dial Transplant 2005; 20:1714.
  51. Evenepoel P, Sprangers B, Lerut E, et al. Mineral metabolism in renal transplant recipients discontinuing cinacalcet at the time of transplantation: a prospective observational study. Clin Transplant 2012; 26:393.
  52. Barros X, Fuster D, Paschoalin R, et al. Changes in bone mineral metabolism parameters, including FGF23, after discontinuing cinacalcet at kidney transplantation. Endocrine 2015; 49:267.
  53. Sharma AK, Masterson R, Holt SG, et al. Impact of cinacalcet pre-transplantation on mineral metabolism in renal transplant recipients. Nephrology (Carlton) 2016; 21:46.
  54. Cruzado JM, Moreno P, Torregrosa JV, et al. A Randomized Study Comparing Parathyroidectomy with Cinacalcet for Treating Hypercalcemia in Kidney Allograft Recipients with Hyperparathyroidism. J Am Soc Nephrol 2016; 27:2487.
  55. Kruse AE, Eisenberger U, Frey FJ, Mohaupt MG. The calcimimetic cinacalcet normalizes serum calcium in renal transplant patients with persistent hyperparathyroidism. Nephrol Dial Transplant 2005; 20:1311.
  56. Serra AL, Schwarz AA, Wick FH, et al. Successful treatment of hypercalcemia with cinacalcet in renal transplant recipients with persistent hyperparathyroidism. Nephrol Dial Transplant 2005; 20:1315.
  57. Srinivas TR, Schold JD, Womer KL, et al. Improvement in hypercalcemia with cinacalcet after kidney transplantation. Clin J Am Soc Nephrol 2006; 1:323.
  58. Szwarc I, Argilés A, Garrigue V, et al. Cinacalcet chloride is efficient and safe in renal transplant recipients with posttransplant hyperparathyroidism. Transplantation 2006; 82:675.
  59. Leca N, Laftavi M, Gundroo A, et al. Early and severe hyperparathyroidism associated with hypercalcemia after renal transplant treated with cinacalcet. Am J Transplant 2006; 6:2391.
  60. El-Amm JM, Doshi MD, Singh A, et al. Preliminary experience with cinacalcet use in persistent secondary hyperparathyroidism after kidney transplantation. Transplantation 2007; 83:546.
  61. Evenepoel P, Cooper K, Holdaas H, et al. A randomized study evaluating cinacalcet to treat hypercalcemia in renal transplant recipients with persistent hyperparathyroidism. Am J Transplant 2014; 14:2545.
  62. Falck P, Vethe NT, Asberg A, et al. Cinacalcet's effect on the pharmacokinetics of tacrolimus, cyclosporine and mycophenolate in renal transplant recipients. Nephrol Dial Transplant 2008; 23:1048.
  63. Ambühl PM, Meier D, Wolf B, et al. Metabolic aspects of phosphate replacement therapy for hypophosphatemia after renal transplantation: impact on muscular phosphate content, mineral metabolism, and acid/base homeostasis. Am J Kidney Dis 1999; 34:875.
  64. Balal M, Paydas S, Seyrek N, et al. Dipyridamole for renal phosphate leak in successfully renal transplanted hypophosphatemic patients. Clin Nephrol 2005; 63:87.