Incidence, risk factors and survival outcomes of post-transplant tertiary hyperparathyroidism in kidney recipients

Abstract

BACKGROUND

Post-transplant tertiary hyperparathyroidism (PT-tHPT) is a well-recognized complication following kidney transplantation, characterized by persistent excessive secretion of parathyroid hormone (PTH) despite improved renal function. It is potentially associated with an increased risk of cardiovascular events, renal osteodystrophy, pathologic fractures, graft loss, and mortality.

AIM

To evaluate the incidence, risk factors, and outcomes of PT-tHPT amongst kidney transplant recipients.

METHODS

A total of 887 transplant recipients who underwent transplantation between 2000 and 2020 were evaluated. Univariable and multivariable logistic regression was performed to determine the predictors of tertiary hyperparathyroidism. Graft and recipient outcomes were assessed using multivariable Cox regression. A separate multivariable Cox regression was performed to determine the effect of treatment strategies on outcomes.

RESULTS

PT-tHPT, defined as elevated PTH (> 65 ng/L) and persistent hypercalcemia (> 2.60 mmol/L), was diagnosed in 14% of recipients. Risk factors for PT-tHPT included older age [odds ratio (OR) = 1.36, P < 0.001], Asian ethnicity (OR = 0.33, P = 0.006), total ischemia time (OR = 1.03, P = 0.048 per hour), pre-transplant serum calcium (OR = 1.38, P < 0.001) per decile increase, pre-transplant PTH level (OR = 1.31, P < 0.001) per decile increase, longer dialysis duration (OR = 1.12, P = 0.002) per year, history of acute rejection (OR = 2.37, P = 0.012), and slope of estimated glomerular filtration rate change (OR = 0.91, P = 0.001). There were a 3.4-fold higher risk of death-censored graft loss and a 1.9-fold greater risk of recipient death with PT-tHPT. The three treatment strategies of conservative management, calcimimetic and parathyroidectomy did not significantly change the graft or patient outcome.

CONCLUSION

Pretransplant elevated calcium and PTH levels, older age and dialysis duration are associated with PT-tHPT. While PT-tHPT significantly affects graft and recipient survival, the treatment strategies did not affect survival.

Keywords: Post-transplant tertiary hyperparathyroidism; Kidney transplantation; Parathyroid hormone; Parathyroidectomy; Calcimimetics; Graft survival; Risk factors; Mineral bone disorder; Fibroblast growth factor 23; Treatment outcomes

Core Tip: This study explores post-transplant tertiary hyperparathyroidism (PT-tHPT) in kidney transplant recipients, identifying elevated pre-transplant calcium and parathyroid hormone levels, prolonged dialysis duration, and acute rejection as key risk factors. PT-tHPT significantly increases the risks of graft loss and patient mortality. However, survival outcomes were comparable across treatment strategies: (1) Conservative management; (2) Calcimimetics; and (3) Parathyroidectomy. These findings highlight the need for optimized pre-transplant care and vigilant post-transplant monitoring to reduce PT-tHPT-related complications. Further research is essential to determine the most effective treatment strategy to improve outcomes and minimize morbidity and mortality associated with PT-tHPT.