Therapy for persistent hypercalcemic hyperparathyroidism post-renal transplant: cinacalcet versus parathyroidectomy

Rivelli, Gabriel Giollo; Lima, Marcelo Lopes de; Mazzali, Marilda

doi:10.1590/2175-8239-JBN-2019-0207

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Brazilian Journal of Nephrology

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Original Article • J. Bras. Nefrol. 42 (3) • Jul-Sep 2020 • https://doi.org/10.1590/2175-8239-JBN-2019-0207 copy

Therapy for persistent hypercalcemic hyperparathyroidism post-renal transplant: cinacalcet versus parathyroidectomy

Authorship SCIMAGO INSTITUTIONS RANKINGS

ABSTRACT

Background:

Persistent hyperparathyroidism post-transplant is associated with increases in the incidence of cardiovascular events, fractures, and deaths. The aim of this study was to compare both therapeutic options available: parathyroidectomy (PTX) and the calcimimetic agent cinacalcet.

Methods:

A single center retrospective study including adult renal transplant recipients who developed hypercalcemia due to persistent hyperparathyroidism. Inclusion criteria: PTH > 65 pg/mL with serum calcium > 11.5 mg/dL at any time after transplant or serum calcium persistently higher than 10.2 mg/dL one year after transplant. Patients treated with cinacalcet (n=46) were compared to patients treated with parathyroidectomy (n=30). Follow-up period was one year. Clinical and laboratory data were analyzed to compare efficacy and safety of both therapeutic modalities.

Results:

PTX controlled calcemia faster (month 1 x month 6) and reached significantly lower levels at month 12 (9.1±1.2 vs 9.7±0.8 mg/dL, p < 0.05); PTX patients showed significantly higher levels of serum phosphate (3.8±1.0 vs 2.9±0.5 mg/dL, p < 0.05) and returned PTH to normal levels (45±51 pg/mL). Cinacalcet, despite controlling calcium and phosphate in the long term, decreased but did not correct PTH (197±97 pg/mL). The proportion of patients that remained with PTH above normal range was 95% in the cinacalcet group and 22% in the PTX group. Patients treated with cinacalcet had better renal function (creatinine 1.2±0.3 vs 1.7±0.7 mg/dL, p < 0.05).

Conclusions:

Surgical treatment was superior to cinacalcet to correct the metabolic disorders of hyperparathyroidism despite being associated with worse renal function in the long term. Cinacalcet proved to be a safe and well tolerated drug.

Keywords:
Hyperparathyroidism; Hypercalcemia; Hypophosphatemia; Parathyroidectomy; Cinacalcet; Kidney Transplantation

	Cinacalcet	Parathyroidectomy	p
Number of patients	46	30
Age (years old)	50 ±11	47 ± 9	0.32
Race (% white)	60%	70%	0.18
Gender (% male)	58%	50%	0.32
Length on dialysis (months)	67 ± 34	78 ± 35	0.37
Donor source (% deceased)	100%	86%	< 0.001
Interval from transplant to intervention (months)	37 ± 40	38 ± 31	0.18
Etiology of chronic kidney disease
✓ Chronic glomerulonephritis	32%	30%	0.87
✓ Systemic Hypertension	28%	23%	0.50
✓ Others	40%	47%	0.39
Blood pressure (mmHg)
✓ Systolic	133	136	0.13
✓ Diastolic	77	80	0.33
Comorbidities (%)
✓ Hypertension	90%	92%	0.47
✓ Dyslipidemia	41%	45%	0.38
✓ Diabetes	22%	25%	0.34
✓ Coronary artery disease	34%	30%	0.35
✓ Smoking	19%	15%	0.42
Laboratory data at transplant
✓ Serum calcium (mg/dL)	9.2 ± 0,8	9.3 ± 1,0	0.79
✓ Serum phosphate (mg/dL)	5.5 ± 1,8	5.6 ± 1,7	0.45
✓ PTH (pg/mL)	1271 ± 765	1298 ± 846	0.84
Imunossupression
✓ Basiliximab induction	39%	86%
✓ Thymoglobulin induction	61%	0%
✓ No induction therapy	0%	14%
✓ Tacrolimus / Cyclosporine	100% / 0%	55% / 45%
✓ Mycophenolate / Azathioprine	86% / 14%	49% / 51%
✓ Prednisone	100%	100%

Parameters	Cinacalcet				Parathyroidectomy
Parameters	Baseline	Month 1	Month 6	Month 12	Basal	Month 1	Month 6	Month 12
Serum calcium (mg/dL)	11.3 ± 0.7	10.4 ± 0.9^* * p < 0.05 versus baseline; + p < 0.05 between groups, for the same time point +	10.1 ± 0.8^* * p < 0.05 versus baseline; + p < 0.05 between groups, for the same time point +	9.7 ± 0.8^* * p < 0.05 versus baseline; + p < 0.05 between groups, for the same time point +	11.1 ± 1.1	9.3 ± 1.4^* * p < 0.05 versus baseline; + p < 0.05 between groups, for the same time point	9.3 ± 1.7^* * p < 0.05 versus baseline; + p < 0.05 between groups, for the same time point	9.1 ± 1.2^* * p < 0.05 versus baseline; + p < 0.05 between groups, for the same time point
Serum phosphate (mg/dL)	2.4 ± 0.6	2.7 ± 0.5^* * p < 0.05 versus baseline; + p < 0.05 between groups, for the same time point +	2.8 ± 0.5^* * p < 0.05 versus baseline; + p < 0.05 between groups, for the same time point +	2.9 ± 0.5^* * p < 0.05 versus baseline; + p < 0.05 between groups, for the same time point +	2.8 ± 0.7	3.5 ± 1.1^* * p < 0.05 versus baseline; + p < 0.05 between groups, for the same time point	3.7 ± 0.9^* * p < 0.05 versus baseline; + p < 0.05 between groups, for the same time point	3.8 ± 1.0^* * p < 0.05 versus baseline; + p < 0.05 between groups, for the same time point
PTH (pg/mL)	287 ± 160+	244 ± 115+	228 ± 133^* * p < 0.05 versus baseline; + p < 0.05 between groups, for the same time point +	197 ± 97^* * p < 0.05 versus baseline; + p < 0.05 between groups, for the same time point +	366 ± 144	34 ± 51^* * p < 0.05 versus baseline; + p < 0.05 between groups, for the same time point	47 ± 52^* * p < 0.05 versus baseline; + p < 0.05 between groups, for the same time point	45 ± 51^* * p < 0.05 versus baseline; + p < 0.05 between groups, for the same time point
Alkaline phosphatase (U/L)	108 ± 52	102 ± 52	97 ± 49^* * p < 0.05 versus baseline; + p < 0.05 between groups, for the same time point +	91 ± 39^* * p < 0.05 versus baseline; + p < 0.05 between groups, for the same time point	237 ± 375	182 ± 267	132± 246^* * p < 0.05 versus baseline; + p < 0.05 between groups, for the same time point	115 ± 188^* * p < 0.05 versus baseline; + p < 0.05 between groups, for the same time point
Creatinine (mg/dL)	1.2 ± 0.3	1.2 ± 0.3+	1.3 ± 0.3+	1.2 ± 0.3+	1.5 ± 0.5	1.6 ± 0.6	1.6 ± 0.6	1.7 ± 0.7^* * p < 0.05 versus baseline; + p < 0.05 between groups, for the same time point
CKD-Epi (mL/min/1.73m²)	64 ± 19			63 ± 18+	52 ± 17			46 ± 17^* * p < 0.05 versus baseline; + p < 0.05 between groups, for the same time point

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[1] Correspondence to: Gabriel Giollo Rivelli. E-mail: gabrielgiollo@yahoo.com.br