Treatment of Hyperparathyroidism (SHPT)

Patients with CKD G3-5

Optimal PTH levels are not established for patients with CKD G3-5 (Evidence)

1.1 If serum PTH levels are progressively increasing or persistently above the reference value for the method, serum levels of calcium (Ca), phosphorus (P), urinary fractional excretion of P (if available), alkaline phosphatase (AP) and 25-hydroxyvitamin D (25-vit D) should be evaluated (Evidence).

1.2 The changes found should be corrected: Ca salts for hypocalcemia, dietary guidance and/or use of P binders for hyperphosphatemia and use of ergocalciferol (vitamin D2) or cholecalciferol (vitamin D3) for hypovitaminosis D (Evidence).

1.3 For patients with persistently elevated PTH levels, despite correction of the parameters mentioned in sub-item 1.2, treatment with calcitriol, at an initial dose of 0.25-0.5 mcg/day, should be considered (Evidence).

Patients with CKD G5D

PTH levels for patients with CKD G5D should be maintained within the target level of 2 to 9 times the upper value of the method.

2.1 For patients with PTH progressively elevated, even if within the target level, or above 9 times the reference value for the method, Ca and P control measures and the use of vitamin D analogues (such as paricalcitol) and/or calcimimetics (such as cinacalcet) should be implemented (Evidence).

When choosing the drug to start treatment of SHPT, serum levels of Ca and P should be considered.

3.1 In the presence of hypercalcemia and/or hyperphosphatemia, the use of paricalcitol should be avoided. In this case, it is recommended to start treatment with cinacalcet (Evidence).

3.2 In case of hypocalcemia, the use of cinacalcet should be avoided until hypocalcemia is corrected. It is recommended to start treatment with paricalcitol (Evidence).

3.3 The use of oral calcitriol as pulse therapy is reserved for patients on conservative treatment, on peritoneal dialysis, and those with persistent post-Tx SHPT with graft dysfunction (Opinion).

Patients treated with paricalcitol who develop hypercalcemia and/or hyperphosphatemia should have the medication dose reduced or suspended and, if necessary, cinacalcet added to the therapeutic regimen (Evidence).

Patients treated with cinacalcet, who develop hypocalcemia, should have their dose reduced or suspended and, if necessary, paricalcitol added to the therapeutic scheme (Evidence).

The association of paricalcitol and cinacalcet is recommended to optimize control of serum PTH levels (Evidence).

Titration of paricalcitol and cinacalcet doses could be done every 2-4 weeks, with monitoring of serum Ca, P, and PTH levels, in order to keep them within their target levels (Opinion).

Patients with serum PTH levels below 150 pg/mL should have the use of paricalcitol and/or cinacalcet suspended (Evidence).

Patients who do not respond to pharmacological treatment of SHPT, with paricalcitol and/or cinacalcet, should be referred for parathyroidectomy (Evidence).

Rational

SHPT is a progressive disease, associated with increased morbidity and mortality. Despite the restrictions, only biochemical changes guide therapeutic intervention. In addition, therapies for the control of SHPT have several limitations, making it difficult to achieve the current goals set by KDIGO1.

The optimal serum PTH levels for patients with CKD G3-5D have not yet been established. In the early stages of CKD, in response to the loss of kidney function, PTH elevation occurs, aiming to maintain Ca and P levels within normal ranges. It is not always possible to distinguish when this change in PTH becomes abnormal, so when there is a progressive elevation, a more frequent dosing of this hormone should be performed. Serum AP levels, analyzed in conjunction with PTH, are important for following the progression and treatment of SHPT, at all stages of CKD2.

For patients on conservative treatment, Ca supplementation should be done only in those with hypocalcemia, to avoid the risk of vascular calcification3. In the presence of hyperphosphatemia, it is recommended starting a low P diet and Ca-based binders, monitoring fractional excretion of P4.

Hypovitaminosis D is associated with the progression and severity of SHPT, and its treatment with vitamin D supplementation is recommended5^-7. It is important to remember that calcitriol should not be used in this situation, just as presentations of vitamin D, associated with Ca or other vitamins, are not recommended.

The use of vitamin D analogue, oral calcitriol, in patients with CKD 3-5D has been discussed. KDIGO 2009 suggests that moderate elevations in PTH are likely to correspond to an adaptive response to loss of kidney function, as previously discussed, with the use of calcitriol reserved for patients with progressive elevation of PTH8^,9.

As with conservative treatment, the optimal serum PTH levels for dialysis patients are not established. Factors related to the methodology employed in PTH measurement, the lack of correlation between bone histology and intermediate PTH values, make it difficult to determine optimal levels of this hormone10^,11. It is known that the extremes of PTH values should be avoided, since there are studies showing increased mortality associated with excessively low or increased levels of PTH12^,13. Thus, KDIGO suggested values between 2 and 9 times the upper value of the method, and if there is a trend of increasing PTH serum levels, a therapeutic scheme should be proposed, aiming at returning to the suggested levels1.

With the progression of SHPT, there is a histological modification of the parathyroid glands. Diffuse hyperplasia becomes nodular, with decreased expression of vitamin D receptors (VDR) and Ca-sensing receptor (CaR), which may result in resistance to pharmacological treatment. Thus, besides controlling serum levels of Ca, P, and vitamin D, drugs that act on the modulation and/or expression of these receptors are more effective in the treatment of SHPT, such as vitamin D analogues (paricalcitol) and calcimimetics (cinacalcet)14^,15. All of these are equally considered first-line drugs to start the treatment of SHPT. Thus, the criterion for drug choice should be based on serum levels of Ca and P. If their serum levels are within the normal range, either medication, i.e. paricalcitol or cinacalcet, could be started at the discretion of the nephrologist. In the presence of hyperphosphatemia and/or hypercalcemia, treatment should be initiated with cinacalcet. On the other hand, if the patient has hypocalcemia, treatment should be with paricalcitol.

Calcitriol, a nonselective VDR activator, was the first therapeutic agent introduced for the treatment of SHPT. Oral calcitriol could be administered as intermittent high dose (pulse therapy) in patients on conservative treatment, on peritoneal dialysis and in those with persistent post-Tx HPT with graft dysfunction. Treatment with calcitriol may lead to unwanted side effects, such as hypercalcemia and/or hyperphosphatemia due to greater intestinal absorption of Ca and P, increasing the risk of vascular calcification and mortality14. Another complication of the use of calcitriol is excessive suppression of PTH, which favors the development of adynamic bone disease, reiterating the need to monitor treatment with PTH and AP measurements16.

Paricalcitol, a selective VDR activator, is a drug with a mechanism of action that differs from calcitriol in that it has a greater affinity for the parathyroid gland than for the intestine. Thus, it promotes PTH suppression with a lower incidence of side effects, such as hyperphosphatemia and/or hypercalcemia. Its efficacy and tolerance are well described17, although in our context only presentation IV is available. Comparative studies between calcitriol and paricalcitol have shown that paricalcitol suppresses PTH faster and with lower occurrence of hypercalcemia18, and that patients in use of paricalcitol seem to have longer survival19. Another study demonstrated conflicting results, for example, not evidencing the superiority of paricalcitol over calcitriol in reducing serum PTH levels or in the onset of hypercalcemia and/or hyperphosphatemia20.

Several factors are associated with the lack of response to the treatment with calcitriol/paricalcitol, including the development of monoclonal hyperplasia of the (autonomous) parathyroid glands, which have reduced number of VDR and CaR, in addition to the development of hypercalcemia and/or hyperphosphatemia, which requires dose reduction or drug discontinuation14^,21.

Cinacalcet, an oral calcimimetic, allosterically modulates CaR, increasing the sensitivity of parathyroid cells to extracellular Ca, decreasing PTH production and secretion and the concentration of serum Ca and P22^,23. It is indicated in the treatment of SHPT as the drug of first choice, even with serum levels of calcium and phosphorus within normal ranges, or in the absence of patient's response to the treatment with calcitriol/paricalcitol, due to hyperphosphatemia and/or hypercalcemia1. The choice between cinacalcet and paricalcitol as monotherapy is not always easy, due to the particularities of each drug, even when Ca and P levels allow it24. Studies report that both drugs are equally effective in controlling mild or moderate SHPT in conjunction with the other standard measures25^,26. Besides its classical actions, studies have shown other beneficial effects of cinacalcet, such as reduced progression of vascular calcification, reduction in cardiovascular events27^-29 and incidence of clinical fractures30.

The prescription of cinacalcet should always start at the lowest dose (30 mg) and, if necessary, be increased every 2-4 weeks, with new controls of Ca, P and PTH. It is worth noting that, for better absorption of the drug, cinacalcet should always be administered immediately after the major meals of the day. The most common side effects of cinacalcet are hypocalcemia and gastrointestinal intolerance14. The management in case of hypocalcemia depends on the severity, but it generally requires lowering the dose of cinacalcet, association of vitamin D analogues and, if necessary, Ca supplementation31, which, if recommended, may also be done with Ca-based P binders. In cases of severe hypocalcemia, suspension of cinacalcet is recommended until Ca values are within normal range. With respect to gastric intolerance, which generally occurs after doses equal to or greater than 60 mg, we recommend, before discontinuing cinacalcet, fractioning the doses according to the patient's preference. The association of proton pump inhibitors and/or antiemetics often improves gastric intolerance to cinacalcet32.

Treatment failure with cinacalcet is mainly related to its side effects and to the presence of severe SHPT33. Thus, considering also the factors that lead to calcitriol/paricalcitol inefficiency, a strategy to be considered is the association of the two drugs, especially for patients with severe SHPT. It is worth noting that these drugs, besides presenting different mechanisms of action, have complementary action, since cinacalcet, by activating CaR, also increases the expression of VDR34. Another advantage of this association is that cinacalcet minimizes the side effects of calcitriol/paricalcitol and vice versa. The study by Moe et al. showed that the addition of cinacalcet to the treatment of a group of patients who were already using calcitriol, its analogues or selective VDR activators, allowed a greater proportion of patients to achieve adequate levels of Ca, P and PTH35.

The use of cinacalcet in conservative treatment is off label and controversial among nephrologists36^,37, but it has been considered in cases of patients who, despite the use of 25 vitamin D and calcitriol, persist with elevated PTH. However, in these cases, the association of cinacalcet is performed in low doses, 30 mg, and may be used daily, on alternate days or 3 times a week, according to the patient's needs. The use of cinacalcet in these conditions requires more frequent monitoring of Ca, P, and PTH38^,39.

SHPT is a disease with complex pathophysiology, and an effective treatment is likely to include several drugs. And for patients who do not respond to clinical therapy, that is, who develop refractory SHPT, parathyroidectomy is indicated40^,41.

REFERENCES

• 1. Ketteler M, Block GA, Evenepoel P, Fukagawa M, Herzog CA, McCann L, et al. Executive summary of the 2017 KDIGO Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD) Guideline Update: what's changed and why it matters. Kidney Int. 2017 Jul 1;92(1):P26-36. https://doi.org/10.1016/j.kint.2017.04.006
  » https://doi.org/10.1016/j.kint.2017.04.006
• 2. Bover J, Ureña P, Aguilar A, Mazzaferro S, Benito S, López-Báez V, et al. Alkaline Phosphatases in the Complex Chronic Kidney Disease-Mineral and Bone Disorders. Calcif Tissue Int. 2018 Aug;103(2):111-24. https://doi.org/10.1007/s00223-018-0399-z
  » https://doi.org/10.1007/s00223-018-0399-z
• 3. Russo D, Miranda I, Ruocco C, Battaglia Y, Buonanno E, Manzi S, et al. The progression of coronary artery calcification in predialysis patients on calcium carbonate or sevelamer. Kidney Int. 2007 Nov 2;72(10):P1255-61. https://doi.org/10.1038/sj.ki.5002518
  » https://doi.org/10.1038/sj.ki.5002518
• 4. Oliveira RB, Cancela ALE, Graciolli FG, Dos Reis LM, Draibe SA, Cuppari L, et al. Early control of PTH and FGF23 in normophosphatemic CKD patients: a new target in CKD-MBD therapy? Clin J Am Soc Nephrol. 2010 Feb;5(2):286-91. https://doi.org/10.2215/CJN.05420709
  » https://doi.org/10.2215/CJN.05420709
• 5. National Kidney Foundation. K/DOQI clinical practice guidelines for bone metabolism and disease in chronic kidney disease. Am J Kidney Dis. 2003 Oct;42(4 Suppl 3):S1-201.
• 6. Zisman AL, Hristova M, Ho LT, Sprague SM. Impact of ergocalciferol treatment of vitamin D deficiency on serum parathyroid hormone concentrations in chronic kidney disease. Am J Nephrol. 2007;27(1):36-43. https://doi.org/10.1159/000098561
  » https://doi.org/10.1159/000098561
• 7. Cuppari L, Garcia-Lopes MG. Hypovitaminosis D in chronic kidney disease patients: prevalence and treatment. J Ren Nutr. 2009 Jan 1;19(1):P38-43. https://doi.org/10.1053/j.jrn.2008.10.005
  » https://doi.org/10.1053/j.jrn.2008.10.005
• 8. Mazzaferro S, Goldsmith D, Larsson TE, Massy ZA, Cozzolino M. Vitamin D metabolites and/or analogs: which D for which patient? Curr Vasc Pharmacol. 2014 Mar;12(2):339-49. https://doi.org/10.2174/15701611113119990024
  » https://doi.org/10.2174/15701611113119990024
• 9. 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 Aug:(113):S1-130. https://doi.org/10.1038/ki.2009.188
  » https://doi.org/10.1038/ki.2009.188
• 10. Souberbielle J-C, Boutten A, Carlier M-C, Chevenne D, Coumaros G, Lawson-Body E, et al. Inter-method variability in PTH measurement: implication for the care of CKD patients. Kidney Int. 2006 Jul 2;70(2):P345-50. https://doi.org/10.1038/sj.ki.5001606
  » https://doi.org/10.1038/sj.ki.5001606
• 11. Barreto FC, Barreto DV, Moysés RMA, Neves KR, Canziani MEF, Draibe SA, et al. K/DOQI-recommended intact PTH levels do not prevent low-turnover bone disease in hemodialysis patients. Kidney Int. 2008 Mar 2;73(6):P771-7. https://doi.org/10.1038/sj.ki.5002769
  » https://doi.org/10.1038/sj.ki.5002769
• 12. Frazão JM, Martins P. Adynamic bone disease: clinical and therapeutic implications. Curr Opin Nephrol Hypertens. 2009 Jul;18(4):303-7. https://doi.org/10.1097/MNH.0b013e32832c4df0
  » https://doi.org/10.1097/MNH.0b013e32832c4df0
• 13. Tentori F, Blayney MJ, Albert JM, Gillespie BW, Kerr PG, Bommer J, et al. Mortality risk for dialysis patients with different levels of serum calcium, phosphorus, and PTH: the Dialysis Outcomes and Practice Patterns Study (DOPPS). Am J Kidney Dis. 2008 Sep 1;52(3):P519-30. https://doi.org/10.1053/j.ajkd.2008.03.020
  » https://doi.org/10.1053/j.ajkd.2008.03.020
• 14. Cunningham J, Locatelli F, Rodriguez M. Secondary hyperparathyroidism: pathogenesis, disease progression, and therapeutic options. Clin J Am Soc Nephrol. 2011 Apr;6(4):913-21. https://doi.org/10.2215/CJN.06040710
  » https://doi.org/10.2215/CJN.06040710
• 15. Malluche HH, Mawad H, Koszewski NJ. Update on vitamin D and its newer analogues: actions and rationale for treatment in chronic renal failure. Kidney Int. 2002 Aug 1;62(2):P367-74. https://doi.org/10.1046/j.1523-1755.2002.00450.x
  » https://doi.org/10.1046/j.1523-1755.2002.00450.x
• 16. Ho LT, Sprague SM. Renal osteodystrophy in chronic renal failure. Semin Nephrol. 2002 Nov 1;22(6):P488-93. https://doi.org/10.1053/snep.2002.35965
  » https://doi.org/10.1053/snep.2002.35965
• 17. Dyer CA. Safety and tolerability of paricalcitol in patients with chronic kidney disease. Expert Opin Drug Saf. 2013 Sep;12(5):717-28. https://doi.org/10.1517/14740338.2013.791675
  » https://doi.org/10.1517/14740338.2013.791675
• 18. Sprague SM, Llach F, Amdahl M, Taccetta C, Batlle D. Paricalcitol versus calcitriol in the treatment of secondary hyperparathyroidism. Kidney Int. 2003 Apr 1;63(4):P1483-90. https://doi.org/10.1046/j.1523-1755.2003.00878.x
  » https://doi.org/10.1046/j.1523-1755.2003.00878.x
• 19. Teng M, Wolf M, Lowrie E, Ofsthun N, Lazarus JM, Thadhani R. Survival of patients undergoing hemodialysis with paricalcitol or calcitriol therapy. N Engl J Med. 2003 Jul 31;349(5):446-56. ttps://doi.org/10.1056/NEJMoa022536
  » ttps://doi.org/10.1056/NEJMoa022536
• 20. Cai P, Tang X, Qin W, Ji L, Li Z. 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 Apr;48(4):571-84. https://doi.org/10.1007/s11255-015-1195-6
  » https://doi.org/10.1007/s11255-015-1195-6
• 21. Cozzolino M, Brancaccio D. Emerging role for the vitamin D receptor activator (VDRA), paricalcitol, in the treatment of secondary hyperparathyroidism. Expert Opin Pharmacother. 2008 Apr;9(6):947-54. https://doi.org/10.1517/14656566.9.6.947
  » https://doi.org/10.1517/14656566.9.6.947
• 22. Cannata-Andía JB, Rodriguez-García M, Román-García P, Poultel DT, López-Hernández F, Rodríguez-Puyol D. New therapies: calcimimetics, phosphate binders and vitamin D receptor activators. Pediatr Nephrol. 2010 Apr;25(4):609-16. https://doi.org/10.1007/s00467-010-1462-9
  » https://doi.org/10.1007/s00467-010-1462-9
• 23. Goodman WG. Calcimimetic agents and secondary hyperparathyroidism: rationale for use and results from clinical trials. Pediatr Nephrol. 2003 Dec;18(12):1206-10. https://doi.org/10.1007/s00467-003-1290-2
  » https://doi.org/10.1007/s00467-003-1290-2
• 24. Sprague SM, Wetmore JB, Gurevich K, Da Roza G, Buerkert J, Reiner M, et al. Effect of cinacalcet and vitamin D analogs on fibroblast growth factor-23 during the treatment of secondary hyperparathyroidism. Clin J Am Soc Nephrol. 2015 Jun;10(6):1021-30. https://doi.org/10.2215/CJN.03270314
  » https://doi.org/10.2215/CJN.03270314
• 25. Wetmore JB, Gurevich K, Sprague S, Da Roza G, Buerkert J, Reiner M, et al. A randomized trial of cinacalcet versus vitamin D analogs as monotherapy in secondary hyperparathyroidism (PARADIGM). Clin J Am Soc Nephrol. 2015 Jun 5;10(6):1031-40. https://doi.org/10.2215/CJN.07050714
  » https://doi.org/10.2215/CJN.07050714
• 26. Xu J, Yang Y, Ma L, Fu P, Peng H. Cinacalcet plus vitamin D versus vitamin D alone for the treatment of secondary hyperparathyroidism in patients undergoing dialysis: a meta-analysis of randomized controlled trials. Int Urol Nephrol. 2019 Nov;51(11):2027-36. https://doi.org/10.1007/s11255-019-02271-6
  » https://doi.org/10.1007/s11255-019-02271-6
• 27. Torres PAU, De Broe M. Calcium-sensing receptor, calcimimetics, and cardiovascular calcifications in chronic kidney disease. Kidney Int. 2012 Jul 1;82(1):P19-25. https://doi.org/10.1038/ki.2012.69
  » https://doi.org/10.1038/ki.2012.69
• 28. Caudrillier A, Mentaverri R, Brazier M, Kamel S, Massy ZA. Calcium-sensing receptor as a potential modulator of vascular calcification in chronic kidney disease. J Nephrol. 2010 Jan-Feb;23(1):17-22.
• 29. Chertow GM, Pupim LB, Block GA, Correa-Rotter R, Drueke TB, Floege J, et al. Evaluation of cinacalcet therapy to lower cardiovascular events (EVOLVE): rationale and design overview. Clin J Am Soc Nephrol. 2007 Sep;2(5):898-905. https://doi.org/10.2215/CJN.04381206
  » https://doi.org/10.2215/CJN.04381206
• 30. Moe SM, Abdalla S, Chertow GM, Parfrey PS, Block GA, Correa-Rotter R, et al. Effects of cinacalcet on fracture events in patients receiving hemodialysis: the EVOLVE trial. J Am Soc Nephrol. 2015 Jun;26(6):1466-75. https://doi.org/10.1681/ASN.2014040414
  » https://doi.org/10.1681/ASN.2014040414
• 31. Block GA, Zeig S, Sugihara J, Chertow GM, Chi EM, Turner SA, et al. Combined therapy with cinacalcet and low doses of vitamin D sterols in patients with moderate to severe secondary hyperparathyroidism. Nephrol Dial Transplant. 2008 Jul;23(7):2311-8. https://doi.org/10.1093/ndt/gfn026
  » https://doi.org/10.1093/ndt/gfn026
• 32. Bover J, Ureña P, Ruiz-García C, da Silva I, Lescano P, del Carpio, et al. Clinical and practical use of calcimimetics in dialysis patients with secondary hyperparathyroidism. Clin J Am Soc Nephrol. 2016 Jan 7;11(1):161-74. https://doi.org/10.2215/CJN.01760215
  » https://doi.org/10.2215/CJN.01760215
• 33. Rottembourg J, Ureña-Torres P, Toledano D, Gueutin V, Hamani A, Coldefy O, et al. Factors associated with parathyroid hormone control in haemodialysis patients with secondary hyperparathyroidism treated with cinacalcet in real-world clinical practice: Mimosa study. Clin Kidney J. 2019 Mar 18;12(6):871-9. https://doi.org/10.1093/ckj/sfz021
  » https://doi.org/10.1093/ckj/sfz021
• 34. Rodriguez ME, Almaden Y, Cañadillas S, Canalejo A, Siendones E, Lopez I, et al. The calcimimetic R-568 increases vitamin D receptor expression in rat parathyroid glands. Am J Physiol Renal Physiol. 2007 May 1;292(5):F1390-5. https://doi.org/10.1152/ajprenal.00262.2006
  » https://doi.org/10.1152/ajprenal.00262.2006
• 35. Moe SM, Chertow GM, Coburn JW, Quarles LD, Goodman WG, Block GA, et al. Achieving NKF-K/DOQI bone metabolism and disease treatment goals with cinacalcet HCl. Kidney Int. 2005 Feb 1;67(2):P760-71. https://doi.org/10.1111/j.1523-1755.2005.67139.x
  » https://doi.org/10.1111/j.1523-1755.2005.67139.x
• 36. Chonchol M, Locatelli F, Abboud HE, Charytan C, de Francisco ALM, Jolly S, et al. A randomized, double-blind, placebo-controlled study to assess the efficacy and safety of cinacalcet HCl in participants with CKD not receiving dialysis. Am J Kidney Dis. 2009 Feb 1;53(2):P197-207. https://doi.org/10.1053/j.ajkd.2008.09.021
  » https://doi.org/10.1053/j.ajkd.2008.09.021
• 37. Andress DL, Coyne DW, Kalantar-Zadeh K, Molitch ME, Zangeneh F, Sprague SM. Management of secondary hyperparathyroidism in stages 3 and 4 chronic kidney disease. Endocr Pract. 2008 Jan-Feb;14(1):P18-27. https://doi.org/10.4158/EP.14.1.18
  » https://doi.org/10.4158/EP.14.1.18
• 38. Pérez-Ricart A, Galicia-Basart M, Comas-Sugrañes D, Cruzado-Garrit J-M, Segarra-Medrano A, Montoro-Ronsano J-B. Long-term effectiveness of cinacalcet in non-dialysis patients with chronic kidney disease and secondary hyperparathyroidism. Kidney Res Clin Pract. 2019 Jun 30;38(2):229-38. https://doi.org/10.23876/j.krcp.18.0088
  » https://doi.org/10.23876/j.krcp.18.0088
• 39. Orellana JM, Esteban RJ, Castilla YA, Fernández-Castillo R, Nozal-Fernández G, Esteban MA, et al. Use of cinacalcet for the management of hyperparathyroidism in patients with different degrees of renal failure. Nefrologia. 2016 Mar-Apr;36(2):121-5. https://doi.org/10.1016/j.nefro.2015.10.017
  » https://doi.org/10.1016/j.nefro.2015.10.017
• 40. Lau WL, Obi Y, Kalantar-Zadeh K. Parathyroidectomy in the Management of Secondary Hyperparathyroidism. Clin J Am Soc Nephrol. 2018 Jun 7;13(6):952-61. https://doi.org/10.2215/CJN.10390917
  » https://doi.org/10.2215/CJN.10390917
• 41. de Oliveira RB, da Silva EN, Charpinel DMF, Gueiros JEB, Neves CL, Sampaio E de A, et al. Secondary hyperparathyroidism status in Brazil: Brazilian census of parathyroidectomy. J Bras Nefrol. 2011 Dec;33(4):457-62. https://doi.org/10.1590/S0101-28002011000400011
  » https://doi.org/10.1590/S0101-28002011000400011

Publication Dates

• Publication in this collection
  03 Dec 2021
• Date of issue
  2021

History

• Received
  24 June 2021
• Accepted
  01 July 2021