#1286 Utility of cinacalcet treatment in kidney transplant recipients with persistent hyperparathyroidism
Authors: Akcay Omer Faruk , Yeter Hasan Hacı , Guz Galip 
Published: May 2024

Abstract

Background and Aims
Secondary hyperparathyroidism occurs in the majority of patients with chronic kidney disease (CKD). It may persist in up to 50-66% of patients despite the initial decrease in PTH levels after successful kidney transplantation (KT). Maintaining parathyroid hormone (PTH) levels within the normal range during the post-transplant period is crucial because it is related to hypercalcemia, hypophosphatemia, and reduced bone mass in KT recipients. Studies have already demonstrated that persistent hyperparathyroidism is associated with graft loss and all-cause mortality. Vitamin D, vitamin D analogs, and calcimimetics are most commonly used to manage hyperparathyroidism. However, studies about the long-term effect of calcimimetic therapy on the allograft are still limited. In this study, we aim to investigate the long-term allograft results of patients who received cinacalcet treatment for hyperparathyroidism.

Method
This study was conducted in Gazi University nephrology dialysis and transplantation unit with 312 patients who were transplanted between 1996 and 2019 and continued routine follow-up visits. Persistent hyperparathyroidism is defined as elevated PTH levels after the first year of KT (serum PTH&gt;88 pg/mL). All patients without concurrent hypercalcemia were treated with vitamin D or analogs according to their vitamin D levels. Patients with non-functional allograft and parathyroidectomy after KT were excluded from this study. In addition, patients with rejection episodes, which could be confounding factor for allograft survival, were excluded to evaluate the isolated effect of cinacalcet on the allograft function. We identified 115 patients with persistent hyperparathyroidism, of whom were treated with cinacalcet (n = 21) or not (n = 94). We analyzed the baseline characteristics, comorbidities, and immunosuppressive treatments of the groups. Additionally, annual eGFR changes (Δ eGFR) calculated based on baseline (post-transplantation 6th month) eGFR after KT was also examined to evaluate the effect of cinacalcet on the graft.

Results
The mean age of the patients was 44.3 ± 12.6 years, and 47 (41%) were women. The median follow-up time of the patients was 87 (49-117) months. Twenty-nine patients (25%) underwent cadaveric transplantation, and 47 (41%) patients received anti-thymoglobulin (ATG) in induction therapy. While all patients were given glucocorticoids as maintenance immunosuppressive therapy, 93 (81%) of the patients received tacrolimus and, 9 (8%) cyclosporin as CNI, 78 (68%) received anti-metabolite therapy. Fifty-eight patients (19%) were used mTORi. A total of 21 patients with persistent hyperparathyroidism (21%) were treated with cinacalcet. Dialysis time is longer in the cinacalcet-treated group than in the patients not treated with cinacalcet (p &lt; 0.001). The preemptive transplantation rate was lower (p = 0.03), and the delayed graft function was higher in the cinacalcet-treated group (p = 0.04). In the first year after KT, serum median PTH levels were 227 (167-341) pg/ml in the cinacalcet group and 110 (86-160) pg/ml in the other group, respectively (&lt;0.001). Also, serum phosphate level is lower in the treatment group (2.7 ± 0.4 mg/dl vs. 3.1 ± 0.7 mg/dl, p = 0.03). At the last visit of patients, we observed similar median PTH levels between groups [141 (100-222) vs. 108 (73-159), p = 0.08]. During the follow-up, CMV episodes and BKV nephropathy diagnosis rates were similar between the groups (Table 1). Δ eGFRs in the first year (p = 0.7), second year (p = 0.2), third year (p = 0.4), and fifth year (p = 0.6) after KT were similar between both groups.

Conclusion
Our study suggests that cinacalcet treatment could be a safe and effective treatment for patients with persistent hyperparathyroidism. In long-term follow-up, there is no evidence of a reduction of kidney function. However, more trials are still required for other clinical outcomes such as fracture risk and cardiovascular morbidity and mortality.