Prevalence and risk factors for tertiary hyperparathyroidism in kidney transplant recipients

Abstract

Background: Tertiary hyperparathyroidism after kidney transplantation has been associated with graft dysfunction, cardiovascular morbidity, and osteopenia; however, its true prevalence is unclear. The objective of our study was to evaluate the prevalence of and risk factors for tertiary hyperparathyroidism.

Methods: A prospective cohort of 849 adult kidney transplantation recipients (December 2008-February 2020) was used to estimate the prevalence of hyperparathyroidism 1-year post-kidney transplant. Tertiary hyperparathyroidism was defined as hypercalcemia (≥10mg/dL) and hyperparathyroidism (parathyroid hormone≥70pg/mL) 1-year post-kidney transplantation. Modified Poisson regression models were used to evaluate risk factors associated with the development of both persistent hyperparathyroidism and tertiary hyperparathyroidism.

Results: Among kidney transplantation recipients, 524 (61.7%) had persistent hyperparathyroidism and 182 (21.5%) had tertiary hyperparathyroidism at 1-year post-kidney transplantation. Calcimimetic use before kidney transplantation was associated with 1.30-fold higher risk of persistent hyperparathyroidism (adjusted prevalence ratio = 1.30, 95% CI: 1.12-1.51) and 1.84-fold higher risk of tertiary hyperparathyroidism (adjusted prevalence ratio = 1.84, 95% CI: 1.25-2.72). Pre-kidney transplantation parathyroid hormone ≥300 pg/mL was associated with 1.49-fold higher risk of persistent hyperparathyroidism (adjusted prevalence ratio = 1.49, 95% CI = 1.19-1.85) and 2.21-fold higher risk of tertiary hyperparathyroidism (adjusted prevalence ratio = 2.21, 95% CI = 1.25-3.90). Pre-kidney transplantation tertiary hyperparathyroidism was associated with an increased risk of post-kidney transplantation tertiary hyperparathyroidism (adjusted prevalence ratio = 1.71, 95% CI = 1.29-2.27), but not persistent hyperparathyroidism. Furthermore, 73.0% of patients with persistent hyperparathyroidism and 61.5% with tertiary hyperparathyroidism did not receive any treatment at 1-year post-kidney transplantation.

Conclusion: Persistent hyperparathyroidism affected 61.7% and tertiary hyperparathyroidism affected 21.5% of kidney transplantation recipients; however, the majority of patients were not treated. Pre-kidney transplantation parathyroid hormone levels ≥300pg/mL and the use of calcimimetics are associated with the development of tertiary hyperparathyroidism. These findings encourage the re-evaluation of recommended pre-kidney transplantation parathyroid hormone thresholds and reconsideration of pre-kidney transplantation secondary hyperparathyroidism treatments to avoid the adverse sequelae of tertiary hyperparathyroidism in kidney transplantation recipients.

Figure 1:. Sample Selection Process of Study Population.

The figure displays the number of kidney transplant (KT) recipients enrolled and included in analysis. KT: kidney transplant; PTH: parathyroid hormone.

Figure 2:. Prevalence of Persistent Hyperparathyroidism (HPT) and Tertiary Hyperparathyroidism (THPT) Among Kidney Transplant Recipients (n=849).

Persistent HPT was defined as parathyroid hormone (PTH) level ≥70 pg/ml at 1-year post-KT. THPT was defined as PTH level ≥70 pg/ml (hyperparathyroidism) and calcium ≥10 mg/dl (hypercalcemia) at 1-year post-KT.

Figure 3:. Post-Transplant Treatments at One Year for Kidney Transplant Recipients with Persistent Hyperparathyroidism (HPT) (n=524) and Recipients with Tertiary Hyperparathyroidism (THPT) (n=182).

Persistent HPT was defined as parathyroid hormone (PTH) level ≥70 pg/ml at 1-year post-KT. THPT was defined as PTH level ≥70 pg/ml (hyperparathyroidism) and calcium ≥10 mg/dl (hypercalcemia) at 1-year post-KT.