Department of Surgery, University of Alabama at Birmingham Heersink School of Medicine, Birmingham, AL, USA.
School of Medicine, University of Alabama at Birmingham Heersink School of Medicine, Birmingham, AL, USA.
Oncologist. 2024 Apr 4;29(4):e467-e474. doi: 10.1093/oncolo/oyad314.
Hyperparathyroidism (HPT) and malignancy are the most common causes of hypercalcemia. Among kidney transplant (KT) recipients, hypercalcemia is mostly caused by tertiary HPT. Persistent tertiary HPT after KT is associated with allograft failure. Previous studies on managing tHPT were subjected to survivor treatment selection bias; as such, the impact of tertiary HPT treatment on allograft function remained unclear. We aim to assess the association between hypercalcemic tertiary HPT treatment and kidney allograft survival.
We identified 280 KT recipients (2015-2019) with elevated post-KT adjusted serum calcium and parathyroid hormone (PTH). KT recipients were characterized by treatment: cinacalcet, parathyroidectomy, or no treatment. Time-varying Cox regression with delayed entry at the time of first elevated post-KT calcium was conducted, and death-censored and all-cause allograft failure were compared by treatment groups.
Of the 280 recipients with tHPT, 49 underwent PTx, and 98 received cinacalcet. The median time from KT to first elevated calcium was 1 month (IQR: 0-4). The median time from first elevated calcium to receiving cinacalcet and parathyroidectomy was 0(IQR: 0-3) and 13(IQR: 8-23) months, respectively. KT recipients with no treatment had shorter dialysis vintage (P = .017) and lower PTH at KT (P = .002), later onset of hypercalcemia post-KT (P < .001). Treatment with PTx (adjusted hazard ratio (aHR) = 0.18, 95%CI 0.04-0.76, P = .02) or cinacalcet (aHR = 0.14, 95%CI 0.004-0.47, P = .002) was associated with lower risk of death-censored allograft failure. Moreover, receipt of PTx (aHR = 0.28, 95%CI 0.12-0.66, P < .001) or cinacalcet (aHR = 0.38, 95%CI 0.22-0.66, P < .001) was associated with lower risk of all-cause allograft failure.
This study demonstrates that treatment of hypercalcemic tertiary HPT post-KT is associated with improved allograft survival. Although these findings are not specific to hypercalcemia of malignancy, they do demonstrate the negative impact of hypercalcemic tertiary HPT on kidney function. Hypercalcemic HPT should be screened and aggressively treated post-KT.
甲状旁腺功能亢进症(HPT)和恶性肿瘤是引起高钙血症的最常见原因。在肾移植(KT)受者中,高钙血症主要由三发性 HPT 引起。KT 后持续性三发性 HPT 与移植物失功有关。既往关于治疗 tHPT 的研究受到幸存者治疗选择偏倚的影响;因此,三发性 HPT 治疗对移植物功能的影响仍不清楚。我们旨在评估高钙血症性三发性 HPT 治疗与肾移植存活之间的关系。
我们确定了 280 例(2015-2019 年)KT 受者,其术后血清钙和甲状旁腺激素(PTH)升高。根据治疗方法对 KT 受者进行了特征描述:西那卡塞、甲状旁腺切除术或未治疗。采用时间依赖性 Cox 回归,以首次升高的术后血清钙为起始时间点进行延迟入组,并比较各组治疗的死亡风险和全因移植物失功情况。
在 280 例 tHPT 患者中,49 例接受了甲状旁腺切除术,98 例接受了西那卡塞治疗。从 KT 到首次升高血钙的中位时间为 1 个月(IQR:0-4)。从首次升高血钙到接受西那卡塞和甲状旁腺切除术的中位时间分别为 0(IQR:0-3)和 13(IQR:8-23)个月。未治疗的 KT 受者透析时间更短(P=0.017),KT 时 PTH 水平更低(P=0.002),术后高钙血症发生时间更晚(P<0.001)。甲状旁腺切除术(调整后的危险比(aHR)=0.18,95%CI 0.04-0.76,P=0.02)或西那卡塞治疗(aHR=0.14,95%CI 0.004-0.47,P=0.002)与较低的死亡风险和全因移植物失功风险相关。此外,甲状旁腺切除术(aHR=0.28,95%CI 0.12-0.66,P<0.001)或西那卡塞治疗(aHR=0.38,95%CI 0.22-0.66,P<0.001)与较低的全因移植物失功风险相关。
本研究表明,KT 后高钙血症性三发性 HPT 的治疗与移植物存活改善相关。尽管这些发现并非特定于恶性肿瘤引起的高钙血症,但确实表明高钙血症性三发性 HPT 对肾功能有负面影响。应在 KT 后筛查并积极治疗高钙血症性 HPT。