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Incidence and Risk Factors of Persistent Hyperparathyroidism After Kidney Transplantation
Incidence and Risk Factors of Persistent Hyperparathyroidism After Kidney Transplantation K. Nakaia,b, H. Fujiia, T. Ishimurac, M. Fujisawac, and S. Nishia,* a Division of Nephrology and Kidney Center, Kobe University Graduate School of Medicine, Kobe, Japan; bDepartment of Nephrology and Kidney Center, Kakogawa East City Hospital, Kakogawa, Japan; and cDepartment of Organs Therapeutics, Division of Urology, Kobe University Graduate School of Medicine, Kobe, Japan
ABSTRACT Persistent hyperparathyroidism after kidney transplantation is related to graft function, but pre-transplantation risk factors of persistent hyperparathyroidism have not been evaluated in detail. We enrolled 86 patients who had undergone kidney transplantation between 2008 and 2014. Nine patients showed persistent hyperparathyroidism characterized by the following: 1) serum parathyroid hormone levels >65 pg/mL and serum calcium levels >10.5 mg/dL at 1 year after kidney transplantation; 2) parathyroidectomy after kidney transplantation; and 3) reintroduction of cinacalcet after kidney transplantation. Compared with other patients, these 9 patients had significantly longer duration of dialysis therapy (186 74 mo vs 57 78 mo) and more frequent treatment with cinacalcet during dialysis (89% vs 12%). Multivariate analysis showed that dialysis vintage, calcium phosphate products, and cinacalcet use before kidney transplantation were independent risk factors of persistent hyperparathyroidism after kidney transplantation. A receiver operating characteristic curve showed 72 months as the cutoff value of dialysis vintage and 55 as the cutoff value of calcium phosphate products. In conclusion, dialysis vintage >6 years, calcium phosphate products >55 (mg/dL)2, and cinacalcet use before kidney transplantation are strong predictors of persistent hyperparathyroidism. High-risk patients should be evaluated for parathyroid enlargement, and parathyroidectomy must be considered before kidney transplantation.
C
HRONIC kidney disease mineral and bone disorder often persists after kidney transplantation and is related to graft function. Although high pre-transplantation levels of parathyroid hormone and phosphate are well known risk factors of persistent hyperparathyroidism [1,2], calcimimetics that modulate the calcium-sensing receptor have dramatically improved control of hyperparathyroidism during dialysis therapy [3]. In the cinacalcet era, it was difficult to predict the persistence of hyperparathyroidism only by checking serum levels of parathyroid hormone and phosphate before kidney transplantation [4]. The present study aimed to evaluate the risk factors of persistent hyperparathyroidism after kidney transplantation. METHODS All study patients had undergone kidney transplantation from 2008 to 2014. Patients with the following characteristics were excluded ª 2016 Elsevier Inc. All rights reserved. 230 Park Avenue, New York, NY 10169
Transplantation Proceedings, 49, 53e56 (2017)
from the present study: 1) pediatric patients; 2) patients undergoing simultaneous pancreas and kidney transplantation; and 3) patients with primary nonfunction of the graft. In total, 86 patients (60 men and 26 women; overall age, 47 13 years) were included in this study. We evaluated the relationship of persistent hyperparathyroidism with the use of clinical characteristics and laboratory parameters. Persistent hyperparathyroidism was defined as follows:
Funding: Grants-in-Aid for Intractable Renal Diseases Research, Research on Rare and Intractable Diseases, Research on Ideal Treatment Methods for the Prevention of Progression of Chronic Kidney Disease, and Practical Research for Kidney Diseases and Health and Labor Sciences Research Grants from the Ministry of Health, Labor, and Welfare of Japan. *Address correspondence to Shinichi Nishi, MD, PhD, Division of Nephrology and Kidney Center, Kobe University Graduate School of Medicine, 7-5-2, Kusunoki-cho, Chuo-ku, Kobe, Hyogo 650-0017, Japan. E-mail: [email protected] 0041-1345/16 http://dx.doi.org/10.1016/j.transproceed.2016.10.011
53
54 1) serum parathyroid hormone levels >65 pg/mL and serum calcium levels >10.5 mg/dL at 1 year after kidney transplantation; 2) parathyroidectomy after kidney transplantation; and 3) reintroduction of cinacalcet after kidney transplantation. The study was conducted in accordance with the Helsinki Declaration of 1975 as revised in 1983. All statistical tests were 2 sided, and P < .05 was considered to be statistically significant. Statistical analyses were performed with the use of JMP version 7.0 (SAS Institute, Cary, North Carolina).
NAKAI, FUJII, ISHIMURA ET AL
phosphate, and calcium between the 2 groups (Table 1). Serum calcium phosphate products were higher, but not significantly, in the HPT group than in the control group. Moreover, multivariate analysis indicated that dialysis vintage, calcium phosphate products, and cinacalcet use before kidney transplantation were independent risk factors of persistent hyperparathyroidism (Table 2). A receiver operating characteristic curve showed 72 months as the cutoff value of dialysis vintage and 55 (mg/dL)2 as the cutoff value of calcium phosphate products.
RESULTS
Six of the 86 patients underwent parathyroidectomy or received cinacalcet prescription within 1 year after kidney transplantation; in addition, 3 patients exhibited high serum levels of calcium and parathyroid hormone at 1 year after kidney transplantation. Compared with other patients, these 9 patients with persistent hyperparathyroidism (HPT group) had significantly longer duration of dialysis therapy (186 74 mo vs 57 78 mo) and more frequent treatment with cinacalcet during dialysis (89% vs 12%; Fig 1). Although ultrasonography was performed in only 46% of patients, the prevalence of parathyroid enlargement was significantly higher in the HPT group. No significant differences were observed regarding age at transplantation, sex, diabetes, and serum levels of parathyroid hormone, alkaline phosphatase,
DISCUSSION
The results of our study suggested that dialysis vintage >6 years, calcium phosphate products >55 (mg/dL)2, and cinacalcet use before kidney transplantation were strong predictors of persistent hyperparathyroidism. Although parathyroid enlargement may be a reliable predictor, it can not be relied on, because ultrasonography was underperformed before kidney transplantation. Persistent hyperparathyroidism was associated with poor prognosis and graft loss [5]. In multivariate analyses, patients with parathyroid hormone levels above the normal limit (65 pg/mL) exhibited a significantly higher risk than those with normal/low levels of all-cause death
Fig 1. Clinical and biochemical characteristics of patients from both study groups. (A) Duration of dialysis vintage was significantly longer (186 74 mo vs 57 78 mo) in patients with persistent hyperparathyroidism (HPT group) than in the other patients (control group). (B) Serum calcium phosphate products were higher, but not significantly higher, in the HPT group than in the control group (P ¼ .12). (C) Cinacalcet treatment during dialysis was more frequent (89% vs 12%) in the HPT group than in the control group. (D) Although ultrasonography was performed in only 46% patients, the prevalence of parathyroid enlargement was significantly higher in the HPT group.
PERSISTENT HYPERPARATHYROIDISM AFTER KT
55
Table 1. Comparison of Clinical Characteristics at Transplantation HPT Group (n ¼ 9)
Male 7 (78) Age at 50 15 transplantation (y) Diabetes mellitus 0 (0) PEKT 0 (0) Laboratory data before transplantation Intact PTH (pg/mL) 197.3 88.7 ALP (U/L) 194.0 63.4 Corrected calcium 9.4 0.7 (cCa, mg/dL) Phosphate 6.3 1.4 (P, mg/dL) cCa P product 59.0 10.5 ([mg/dL]2)
Control Group (n ¼ 77)
P Value
53 (69) 47 13
.58 .57
13 (16) 9 (12)
.18 .28
192.6 144.8 220.6 88.5 9.2 0.8
.92 .41 .48
5.6 1.4
.17
51.5 13.3
.11
Note. Values are presented as n (%) or mean SD. Abbreviations: HPT, persistent hyperparathyroidism; PEKT, pre-emptive kidney transplantation; PTH, parathyroid hormone; ALP, alkaline phosphatase.
(hazard ratio [HR], 1.46; 95% confidence interval [CI], 1.12e1.92; P ¼ .006) and graft loss (HR, 1.85; 95% CI, 1.41e2.42; P < .001). Therefore, patients at high risk of persistent hyperparathyroidism must undergo parathyroidectomy before kidney transplantation to save graft function and improve graft survival. A retrospective multicenter study evaluated the influence of parathyroidectomy before and after kidney transplantation [6]. Kidney function during 5 years after transplantation was significantly lower in patients who underwent parathyroidectomy at <1 year after transplantation than in those who underwent parathyroidectomy before transplantation (P ¼ .032). Moreover, reintroduction of cinacalcet after kidney transplantation was assessed in a prospective, multicenter, open-label, randomized study that evaluated whether subtotal parathyroidectomy was more effective than cinacalcet for managing persistent hyperparathyroidism after kidney transplant [7]. That study showed that subtotal parathyroidectomy was superior to cinacalcet in correcting high serum levels of calcium and parathyroid hormone. During 1 year after transplant, bone density of the femoral neck improved by subtotal Table 2. Logistic Regression Analyses for Risk Factors of Persistent Hyperparathyroidism 95% CI Risk Factor
Univariate Dialysis vintage (mo) Ca P product Cinacalcet use Multivariate Dialysis vintage (mo) Ca P product Cinacalcet use
OR
Low
High
P Value
1.01 1.04 69.0
1.01 0.99 7.6
1.02 1.09 625.2
<.01 .12 <.01
1.02 1.15 120.0
1.01 1.01 4.49
1.04 1.32 3,209.5
<.01 .04 <.01
Fig 2. Risk factors may predict the persistent hyperparathyroidism after kidney transplantation. Three risk factorsddialysis vintage >6 years, calcium phosphate product >55 (mg/dL)2, and cinacalcet use before kidney transplantationdwere strong predictors of persistent hyperparathyroidism. If these factors are detected, ultrasonography should be performed, and parathyroidectomy is recommended before kidney transplantation.
parathyroidectomy alone, and the decline in kidney function was greater in the cinacalcet group than in the parathyroidectomy group. Because both parathyroidectomy and cinacalcet treatments after kidney transplantation pose a risk of graft loss, parathyroidectomy before transplantation should be considered for patients with severe hyperparathyroidism who require parathyroidectomy after transplantation. Previous studies have reported that discontinuation of cinacalcet at kidney transplantation can cause hyperparathyroidism after transplantation [4,8,9]. Apparently, serum levels of parathyroid hormone and phosphate were well controlled during dialysis therapy, but it was exposed as deceptive after discontinuation of cinacalcet in kidney transplant patients with parathyroid enlargement [4]. In conclusion, as presented in Fig 2, the present study demonstrated that high-risk patients with the 3 risk factors of persistent hyperparathyroidism (dialysis vintage >6 years, calcium phosphate product >55 (mg/dL)2, and cinacalcet use before kidney transplantation) should be evaluated for parathyroid enlargement, and parathyroidectomy must be considered before kidney transplantation in such patients. REFERENCES [1] Roodnat JI, van Gurp EA, Mulder PG, van Gelder T, de Rijke YB, de Herder WW, et al. High pretransplant parathyroid hormone levels increase the risk for graft failure after renal transplantation. Transplantation 2006;82:362e7. [2] Sampaio MS, Molnar MZ, Kovesdy CP, Mehrotra R, Mucsi I, Sim JJ, et al. Association of pretransplant serum phosphorus with posttransplant outcomes. Clin J Am Soc Nephrol 2011;6:2712e21. [3] Fukagawa M, Fukuma S, Onishi Y, Yamaguchi T, Hasegawa T, Akizawa T, et al. Prescription patterns and mineral metabolism abnormalities in the cinacalcet era: results from the MBD-5D study. Clin J Am Soc Nephrol 2012;7:1473e80.
56 [4] Nakai K, Fujii H, Yoshikawa M, Kono K, Yonekura Y, Goto S, et al. Effect of cinacalcet cessation on hyperparathyroidism in kidney transcaplant patients after long-term dialysis therapy. Clin Exp Nephrol 2015;19:1184e8. [5] Pihlstrøm H, Dahle DO, Mjøen G, Pilz S, März W, Abedini S, et al. Increased risk of all-cause mortality and renal graft loss in stable renal transplant recipients with hyperparathyroidism. Transplantation 2015;99:351e9. [6] Jeon HJ, Kim YJ, Kwon HY, Koo TY, Baek SH, Kim HJ, et al. Impact of parathyroidectomy on allograft outcomes in kidney transplantation. Transpl Int 2012;25:1248e56. [7] Cruzado JM, Moreno P, Torregrosa JV, Taco O, Mast R, Gómez-Vaquero C, et al. A randomized study comparing
NAKAI, FUJII, ISHIMURA ET AL parathyroidectomy with cinacalcet for treating hypercalcemia in kidney allograft recipients with hyperparathyroidism. J Am Soc Nephrol 2016;27:2487e94. [8] Evenepoel P, Cooper K, Holdaas H, Messa P, Mourad G, Olgaard K, et al. A randomized study evaluating cinacalcet to treat hypercalcemia in renal transplant recipients with persistent hyperparathyroidism. Am J Transplant 2014;14: 2545e55. [9] Evenepoel P, Sprangers B, Lerut E, Bammens B, Claes K, Kuypers D, et al. Mineral metabolism in renal transplant recipients discontinuing cinacalcet at the time of transplantation: a prospective observational study. Clin Transplant 2012;26: 393e402.
ABSTRACT Persistent hyperparathyroidism after kidney transplantation is related to graft function, but pre-transplantation risk factors of persistent hyperparathyroidism have not been evaluated in detail. We enrolled 86 patients who had undergone kidney transplantation between 2008 and 2014. Nine patients showed persistent hyperparathyroidism characterized by the following: 1) serum parathyroid hormone levels >65 pg/mL and serum calcium levels >10.5 mg/dL at 1 year after kidney transplantation; 2) parathyroidectomy after kidney transplantation; and 3) reintroduction of cinacalcet after kidney transplantation. Compared with other patients, these 9 patients had significantly longer duration of dialysis therapy (186 74 mo vs 57 78 mo) and more frequent treatment with cinacalcet during dialysis (89% vs 12%). Multivariate analysis showed that dialysis vintage, calcium phosphate products, and cinacalcet use before kidney transplantation were independent risk factors of persistent hyperparathyroidism after kidney transplantation. A receiver operating characteristic curve showed 72 months as the cutoff value of dialysis vintage and 55 as the cutoff value of calcium phosphate products. In conclusion, dialysis vintage >6 years, calcium phosphate products >55 (mg/dL)2, and cinacalcet use before kidney transplantation are strong predictors of persistent hyperparathyroidism. High-risk patients should be evaluated for parathyroid enlargement, and parathyroidectomy must be considered before kidney transplantation.
C
HRONIC kidney disease mineral and bone disorder often persists after kidney transplantation and is related to graft function. Although high pre-transplantation levels of parathyroid hormone and phosphate are well known risk factors of persistent hyperparathyroidism [1,2], calcimimetics that modulate the calcium-sensing receptor have dramatically improved control of hyperparathyroidism during dialysis therapy [3]. In the cinacalcet era, it was difficult to predict the persistence of hyperparathyroidism only by checking serum levels of parathyroid hormone and phosphate before kidney transplantation [4]. The present study aimed to evaluate the risk factors of persistent hyperparathyroidism after kidney transplantation. METHODS All study patients had undergone kidney transplantation from 2008 to 2014. Patients with the following characteristics were excluded ª 2016 Elsevier Inc. All rights reserved. 230 Park Avenue, New York, NY 10169
Transplantation Proceedings, 49, 53e56 (2017)
from the present study: 1) pediatric patients; 2) patients undergoing simultaneous pancreas and kidney transplantation; and 3) patients with primary nonfunction of the graft. In total, 86 patients (60 men and 26 women; overall age, 47 13 years) were included in this study. We evaluated the relationship of persistent hyperparathyroidism with the use of clinical characteristics and laboratory parameters. Persistent hyperparathyroidism was defined as follows:
Funding: Grants-in-Aid for Intractable Renal Diseases Research, Research on Rare and Intractable Diseases, Research on Ideal Treatment Methods for the Prevention of Progression of Chronic Kidney Disease, and Practical Research for Kidney Diseases and Health and Labor Sciences Research Grants from the Ministry of Health, Labor, and Welfare of Japan. *Address correspondence to Shinichi Nishi, MD, PhD, Division of Nephrology and Kidney Center, Kobe University Graduate School of Medicine, 7-5-2, Kusunoki-cho, Chuo-ku, Kobe, Hyogo 650-0017, Japan. E-mail: [email protected] 0041-1345/16 http://dx.doi.org/10.1016/j.transproceed.2016.10.011
53
54 1) serum parathyroid hormone levels >65 pg/mL and serum calcium levels >10.5 mg/dL at 1 year after kidney transplantation; 2) parathyroidectomy after kidney transplantation; and 3) reintroduction of cinacalcet after kidney transplantation. The study was conducted in accordance with the Helsinki Declaration of 1975 as revised in 1983. All statistical tests were 2 sided, and P < .05 was considered to be statistically significant. Statistical analyses were performed with the use of JMP version 7.0 (SAS Institute, Cary, North Carolina).
NAKAI, FUJII, ISHIMURA ET AL
phosphate, and calcium between the 2 groups (Table 1). Serum calcium phosphate products were higher, but not significantly, in the HPT group than in the control group. Moreover, multivariate analysis indicated that dialysis vintage, calcium phosphate products, and cinacalcet use before kidney transplantation were independent risk factors of persistent hyperparathyroidism (Table 2). A receiver operating characteristic curve showed 72 months as the cutoff value of dialysis vintage and 55 (mg/dL)2 as the cutoff value of calcium phosphate products.
RESULTS
Six of the 86 patients underwent parathyroidectomy or received cinacalcet prescription within 1 year after kidney transplantation; in addition, 3 patients exhibited high serum levels of calcium and parathyroid hormone at 1 year after kidney transplantation. Compared with other patients, these 9 patients with persistent hyperparathyroidism (HPT group) had significantly longer duration of dialysis therapy (186 74 mo vs 57 78 mo) and more frequent treatment with cinacalcet during dialysis (89% vs 12%; Fig 1). Although ultrasonography was performed in only 46% of patients, the prevalence of parathyroid enlargement was significantly higher in the HPT group. No significant differences were observed regarding age at transplantation, sex, diabetes, and serum levels of parathyroid hormone, alkaline phosphatase,
DISCUSSION
The results of our study suggested that dialysis vintage >6 years, calcium phosphate products >55 (mg/dL)2, and cinacalcet use before kidney transplantation were strong predictors of persistent hyperparathyroidism. Although parathyroid enlargement may be a reliable predictor, it can not be relied on, because ultrasonography was underperformed before kidney transplantation. Persistent hyperparathyroidism was associated with poor prognosis and graft loss [5]. In multivariate analyses, patients with parathyroid hormone levels above the normal limit (65 pg/mL) exhibited a significantly higher risk than those with normal/low levels of all-cause death
Fig 1. Clinical and biochemical characteristics of patients from both study groups. (A) Duration of dialysis vintage was significantly longer (186 74 mo vs 57 78 mo) in patients with persistent hyperparathyroidism (HPT group) than in the other patients (control group). (B) Serum calcium phosphate products were higher, but not significantly higher, in the HPT group than in the control group (P ¼ .12). (C) Cinacalcet treatment during dialysis was more frequent (89% vs 12%) in the HPT group than in the control group. (D) Although ultrasonography was performed in only 46% patients, the prevalence of parathyroid enlargement was significantly higher in the HPT group.
PERSISTENT HYPERPARATHYROIDISM AFTER KT
55
Table 1. Comparison of Clinical Characteristics at Transplantation HPT Group (n ¼ 9)
Male 7 (78) Age at 50 15 transplantation (y) Diabetes mellitus 0 (0) PEKT 0 (0) Laboratory data before transplantation Intact PTH (pg/mL) 197.3 88.7 ALP (U/L) 194.0 63.4 Corrected calcium 9.4 0.7 (cCa, mg/dL) Phosphate 6.3 1.4 (P, mg/dL) cCa P product 59.0 10.5 ([mg/dL]2)
Control Group (n ¼ 77)
P Value
53 (69) 47 13
.58 .57
13 (16) 9 (12)
.18 .28
192.6 144.8 220.6 88.5 9.2 0.8
.92 .41 .48
5.6 1.4
.17
51.5 13.3
.11
Note. Values are presented as n (%) or mean SD. Abbreviations: HPT, persistent hyperparathyroidism; PEKT, pre-emptive kidney transplantation; PTH, parathyroid hormone; ALP, alkaline phosphatase.
(hazard ratio [HR], 1.46; 95% confidence interval [CI], 1.12e1.92; P ¼ .006) and graft loss (HR, 1.85; 95% CI, 1.41e2.42; P < .001). Therefore, patients at high risk of persistent hyperparathyroidism must undergo parathyroidectomy before kidney transplantation to save graft function and improve graft survival. A retrospective multicenter study evaluated the influence of parathyroidectomy before and after kidney transplantation [6]. Kidney function during 5 years after transplantation was significantly lower in patients who underwent parathyroidectomy at <1 year after transplantation than in those who underwent parathyroidectomy before transplantation (P ¼ .032). Moreover, reintroduction of cinacalcet after kidney transplantation was assessed in a prospective, multicenter, open-label, randomized study that evaluated whether subtotal parathyroidectomy was more effective than cinacalcet for managing persistent hyperparathyroidism after kidney transplant [7]. That study showed that subtotal parathyroidectomy was superior to cinacalcet in correcting high serum levels of calcium and parathyroid hormone. During 1 year after transplant, bone density of the femoral neck improved by subtotal Table 2. Logistic Regression Analyses for Risk Factors of Persistent Hyperparathyroidism 95% CI Risk Factor
Univariate Dialysis vintage (mo) Ca P product Cinacalcet use Multivariate Dialysis vintage (mo) Ca P product Cinacalcet use
OR
Low
High
P Value
1.01 1.04 69.0
1.01 0.99 7.6
1.02 1.09 625.2
<.01 .12 <.01
1.02 1.15 120.0
1.01 1.01 4.49
1.04 1.32 3,209.5
<.01 .04 <.01
Fig 2. Risk factors may predict the persistent hyperparathyroidism after kidney transplantation. Three risk factorsddialysis vintage >6 years, calcium phosphate product >55 (mg/dL)2, and cinacalcet use before kidney transplantationdwere strong predictors of persistent hyperparathyroidism. If these factors are detected, ultrasonography should be performed, and parathyroidectomy is recommended before kidney transplantation.
parathyroidectomy alone, and the decline in kidney function was greater in the cinacalcet group than in the parathyroidectomy group. Because both parathyroidectomy and cinacalcet treatments after kidney transplantation pose a risk of graft loss, parathyroidectomy before transplantation should be considered for patients with severe hyperparathyroidism who require parathyroidectomy after transplantation. Previous studies have reported that discontinuation of cinacalcet at kidney transplantation can cause hyperparathyroidism after transplantation [4,8,9]. Apparently, serum levels of parathyroid hormone and phosphate were well controlled during dialysis therapy, but it was exposed as deceptive after discontinuation of cinacalcet in kidney transplant patients with parathyroid enlargement [4]. In conclusion, as presented in Fig 2, the present study demonstrated that high-risk patients with the 3 risk factors of persistent hyperparathyroidism (dialysis vintage >6 years, calcium phosphate product >55 (mg/dL)2, and cinacalcet use before kidney transplantation) should be evaluated for parathyroid enlargement, and parathyroidectomy must be considered before kidney transplantation in such patients. REFERENCES [1] Roodnat JI, van Gurp EA, Mulder PG, van Gelder T, de Rijke YB, de Herder WW, et al. High pretransplant parathyroid hormone levels increase the risk for graft failure after renal transplantation. Transplantation 2006;82:362e7. [2] Sampaio MS, Molnar MZ, Kovesdy CP, Mehrotra R, Mucsi I, Sim JJ, et al. Association of pretransplant serum phosphorus with posttransplant outcomes. Clin J Am Soc Nephrol 2011;6:2712e21. [3] Fukagawa M, Fukuma S, Onishi Y, Yamaguchi T, Hasegawa T, Akizawa T, et al. Prescription patterns and mineral metabolism abnormalities in the cinacalcet era: results from the MBD-5D study. Clin J Am Soc Nephrol 2012;7:1473e80.
56 [4] Nakai K, Fujii H, Yoshikawa M, Kono K, Yonekura Y, Goto S, et al. Effect of cinacalcet cessation on hyperparathyroidism in kidney transcaplant patients after long-term dialysis therapy. Clin Exp Nephrol 2015;19:1184e8. [5] Pihlstrøm H, Dahle DO, Mjøen G, Pilz S, März W, Abedini S, et al. Increased risk of all-cause mortality and renal graft loss in stable renal transplant recipients with hyperparathyroidism. Transplantation 2015;99:351e9. [6] Jeon HJ, Kim YJ, Kwon HY, Koo TY, Baek SH, Kim HJ, et al. Impact of parathyroidectomy on allograft outcomes in kidney transplantation. Transpl Int 2012;25:1248e56. [7] Cruzado JM, Moreno P, Torregrosa JV, Taco O, Mast R, Gómez-Vaquero C, et al. A randomized study comparing
NAKAI, FUJII, ISHIMURA ET AL parathyroidectomy with cinacalcet for treating hypercalcemia in kidney allograft recipients with hyperparathyroidism. J Am Soc Nephrol 2016;27:2487e94. [8] Evenepoel P, Cooper K, Holdaas H, Messa P, Mourad G, Olgaard K, et al. A randomized study evaluating cinacalcet to treat hypercalcemia in renal transplant recipients with persistent hyperparathyroidism. Am J Transplant 2014;14: 2545e55. [9] Evenepoel P, Sprangers B, Lerut E, Bammens B, Claes K, Kuypers D, et al. Mineral metabolism in renal transplant recipients discontinuing cinacalcet at the time of transplantation: a prospective observational study. Clin Transplant 2012;26: 393e402.