Rejnmark Lars, Ayodele Olulade, Lax Angela, Mu Fan, Swallow Elyse, Gosmanova Elvira O
Department of Endocrinology and Internal Medicine, Aarhus University and Aarhus University Hospital, Aarhus, Denmark.
Takeda Pharmaceuticals USA, Inc., Lexington, Massachusetts, USA.
Clin Endocrinol (Oxf). 2023 Apr;98(4):496-504. doi: 10.1111/cen.14813. Epub 2022 Aug 28.
This study assessed the risk of developing chronic kidney disease (CKD) and decline in estimated glomerular filtration rate (eGFR) over a period of up to 5 years in adult patients with chronic hypoparathyroidism treated with recombinant human parathyroid hormone (1-84) (rhPTH[1-84]) compared with a historical control cohort of patients not treated with rhPTH(1-84).
Retrospective cohort study of patients with chronic hypoparathyroidism treated with rhPTH(1-84) derived from the REPLACE (NCT00732615), RELAY (NCT01268098), RACE (NCT01297309) and HEXT (NCT01199614, and its continuation study NCT02910466) clinical trials and a historical control cohort who did not receive PTH selected from an electronic medical record database.
One hundred and eighteen patients treated with rhPTH(1-84) and 497 patient controls.
Incident CKD was defined as ≥2 eGFR measurements <60 ml/min/1.73 m ≥3 months apart during the study and a sustained eGFR decline of ≥30% from baseline.
Over the 5-year period, Kaplan-Meier analyses showed that rhPTH(1-84)-treated patients had a significantly lower risk of developing CKD (log-rank p = .002) and a lower risk for a sustained eGFR decline ≥30% from baseline (log-rank p < .001) compared with patients in the control cohort. In adjusted analyses, patients in the rhPTH(1-84)-treated cohort had a 53% lower risk of developing CKD (hazard ratio [HR], 0.47; 95% confidence interval [CI], 0.25-0.87) and a 65% lower risk for sustained eGFR decline ≥30% from baseline (HR, 0.35; 95% CI, 0.13-0.89) compared with controls.
Patients with chronic hypoparathyroidism treated with rhPTH(1-84) in long-term clinical trials had a significantly lower risk of developing CKD compared with patients in a historical control cohort not treated with rhPTH(1-84).
本研究评估了与未接受重组人甲状旁腺激素（1-84）（rhPTH[1-84]）治疗的历史对照队列相比，接受rhPTH(1-84)治疗的成年慢性甲状旁腺功能减退患者在长达5年的时间里发生慢性肾脏病（CKD）的风险以及估计肾小球滤过率（eGFR）的下降情况。
对来自REPLACE（NCT00732615）、RELAY（NCT01268098）、RACE（NCT01297309）和HEXT（NCT01199614及其延续研究NCT02910466）临床试验中接受rhPTH(1-84)治疗的慢性甲状旁腺功能减退患者以及从电子病历数据库中选取的未接受甲状旁腺激素治疗的历史对照队列进行回顾性队列研究。
118例接受rhPTH(1-84)治疗的患者和497例患者对照。
在研究期间，新发CKD定义为≥2次eGFR测量值<60 ml/min/1.73 m²且间隔≥3个月，以及eGFR从基线持续下降≥30%。
在5年期间，Kaplan-Meier分析显示，与对照队列中的患者相比，接受rhPTH(1-84)治疗的患者发生CKD的风险显著更低（对数秩检验p = 0.002），且eGFR从基线持续下降≥30%的风险更低（对数秩检验p < 0.001）。在调整分析中，与对照组相比，接受rhPTH(1-84)治疗的队列中的患者发生CKD的风险降低53%（风险比[HR]，0.47；95%置信区间[CI]，0.25 - 0.87），且eGFR从基线持续下降≥30%的风险降低65%（HR，0.35；95% CI，0.13 - 0.89）。
在长期临床试验中，接受rhPTH(1-84)治疗的慢性甲状旁腺功能减退患者与未接受rhPTH(1-84)治疗的历史对照队列中的患者相比，发生CKD的风险显著更低。
