Subtotal Parathyroidectomy for the Treatment of Persistent Hyperparathyroidism After Kidney Transplantation
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 85
- 试验地点
- 1
- 主要终点
- Change in bone mineral density (BMD) at the total hip
研究概览
简要总结
This study aims to clarify whether surgical treatment of persistent hyperparathyroidism after kidney transplantation offers clinically meaningful benefits compared with a conservative treatment strategy.
Kidney transplant recipients (>6 mo after transplantation) with persistent hyperparathyroidism (elevated PTH and either hypercalcemia or hypophosphatemia) will be randomized in a 1:1 ratio to either subtotal parathyroidectomy or conservative management according to standard clinical practice. The study is conducted as an open-label, randomized controlled pilot trial with a 12-month follow-up period.
Outcomes include bone density, physical function, quality of life and symptom burden.
详细描述
Persistent hyperparathyroidism is a frequent complication after kidney transplantation. Despite improved kidney function, many transplant recipients continue to have elevated parathyroid hormone (PTH) levels, often accompanied by hypercalcemia and/or hypophosphatemia. These disturbances are associated with adverse effects on skeletal health and have been linked to increased risk of fractures, graft dysfunction, and mortality.
Currently, there are no evidence-based guidelines for the optimal management of persistent hyperparathyroidism after kidney transplantation. Conservative management with biochemical monitoring and supportive medical therapy is commonly used, while surgical parathyroidectomy is typically reserved for patients with severe biochemical abnormalities. Although parathyroidectomy is effective in normalizing PTH, calcium, and phosphate levels, and observational data suggest beneficial effects on bone mineral density, randomized controlled trials comparing surgical and conservative management strategies in this population are lacking.
The purpose of this study is to evaluate the safety and efficacy of subtotal parathyroidectomy compared with conservative management in kidney transplant recipients with persistent hyperparathyroidism.
The study is conducted as an open-label, randomized controlled pilot trial with a 12-month follow-up period. Kidney transplant recipients (>6 mo after transplantation, no upper limit) with persistent hyperparathyroidism (elevated PTH and either hypercalcemia or hypophosphatemia) will be randomized in a 1:1 ratio to either subtotal parathyroidectomy or conservative management according to standard clinical practice. Controls will be treated with calcium, vitamin D and phosphate supplements as needed. Calcimimetic use is not mandated for controls, but can be utilized at the discretion of the treating physician.
The primary objective is to assess the change in bone mineral density at the total hip after 12 months.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age > 18 years and legally competent and able to understand spoken and written Danish
- •Kidney transplantation ≥6 months prior (no upper limit of time after transplantation)
- •Stable kidney graft function, defined as estimated GFR ≥ 30 ml/min/1.73m3
- •On minimum two separate biochemical measurements:
- •PTH > upper normal limit of assay and
- •serum ionized calcium ≥1.33 mmol/L or
- •serum total calcium ≥2.60 mmol/L or
- •serum phosphate ≤0.60 mmol/L despite sufficient dietary intake
- •with measurements obtained within
- •3 months in patients 6-12 months post-transplant
- •6 months in patients >12 months post-transplant
- •and not attributable to calcium supplementation or treatment with thiazide diuretics or lithium.
排除标准
- •Inability to provide written, informed consent
- •Current anti-resorptive therapy (bisphosphonate, denosumab)
- •Current bone anabolic therapy (teriparatide, romosozumab)
- •Previous surgical parathyroidectomy
- •Not considered fit for surgery (including pregnancy)
- •Ionized calcium ≥1.50 mmol/L or albumin-corrected calcium ≥3.00 mmol/L despite discontinuation of calcium supplements.
研究组 & 干预措施
Surgery group
Participants assigned to this arm will undergo subtotal parathyroidectomy performed according to standard surgical practice. The procedure involves removal of the majority of parathyroid tissue with preservation of a small remnant. Intraoperative parathyroid hormone (PTH) measurements will be used to guide the extent of resection, in accordance with standard surgical principles. Surgery will be performed by experienced ear, nose and throat (ENT) surgeons. Participants will receive standard perioperative care and postoperative follow-up.
干预措施: Subtotal Parathyroidectomy (Procedure)
Control group
Participants assigned to this arm will receive conservative management according to standard clinical practice. This includes regular clinical follow-up and biochemical monitoring of calcium, phosphate, and parathyroid hormone levels. Medical treatment, such as calcium or vitamin D supplementation and/or calcimimetic therapy, may be initiated or adjusted at the discretion of the treating physician. No parathyroid surgery will be performed during the 12-month study period.
干预措施: Conservative Management (Other)
结局指标
主要结局
Change in bone mineral density (BMD) at the total hip
时间窗: From baseline to end of study at 12 months
Bone mineral density (BMD) at the total hip will be measured using dual-energy X-ray absorptiometry (DXA) according to standardized procedures. Measurements will be performed at baseline and after 12 months. The primary outcome is the change in bone mineral density from baseline to 12 months.
次要结局
- Changes in cortical and trabecular bone microarchitecture(From baseline to end of study at 12 months)
- Mineral metabolism: Change in plasma parathyroid hormone (PTH)(From baseline to end of study at 12 months)
- Mineral metabolism: Changes in serum ionized calcium and phosphate(From baseline to end of study at 12 months)
- Mineral metabolism: Change in plasma fibroblast growth factor 23 (FGF23)(From baseline to end of study at 12 months)
- Bone turnover marker: Change in bone-specific alkaline phosphatase (BALP)(From baseline to end of study at 12 months)
- Bone turnover marker: Change in plasma C-terminal crosslinks (CTX)(From baseline to end of study at 12 months)
- Bone turnover marker: Change in plasma procollagen type I N-terminal propeptide (PINP, intact and total forms)(From baseline to end of study at 12 months)
- Bone turnover marker: Change in plasma tartrate-resistant acid phosphatase isoform 5b (TRAP5b).(From baseline to end of study at 12 months)
- Kidney function: Stability of kidney graft function based on estimated glomerular filtration rate (GFR) slope(From baseline to end of study at 12 months)
- Change in lower extremity function measured by the 30-second Chair Stand Test at 12 months(From baseline to end of study at 12 months.)
- Change in isometric lower extremity muscle strength(From baseline to end of study at 12 months)
- Change in mobility measured by the Timed Up and Go (TUG) test(From baseline to end of study at 12 months.)
- Change in handgrip strength(From baseline to end of study at 12 months.)
- Change in quality of life measured by the Primary Hyperparathyroidism Quality of Life questionnaire (PHPQoL)(From baseline to end of study at 12 months.)
- Change in symptom burden measured by the Parathyroidectomy Assessment of Symptoms (PAS) score(From baseline to end of study at 12 months.)
- Change in post-transplant quality of life measured by a SONG (Standardised Outcomes in Nephrology) -based questionnaire(From baseline to end of study at 12 months.)