Parathyroidectomy After Kidney Transplantation

Официальное название

Subtotal Parathyroidectomy for the Treatment of Persistent Hyperparathyroidism After Kidney Transplantation

Обзор

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.

Подробное описание

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.

Secondary objectives include evaluation of changes in mineral metabolism parameters, bone turnover markers, bone microarchitecture, physical function and muscle strength, quality of life and symptom burden, kidney graft function, and safety outcomes.

Вмешательства

• Процедура Subtotal Parathyroidectomy
  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 are used to guide the extent of resection. Standard perioperative care and postoperative follow-up are provided.
• Другое Conservative Management
  Conservative management according to standard clinical practice, including 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 based on clinical judgment.

Первичные конечные точки

• Change in bone mineral density (BMD) at the total hip [Срок оценки: From baseline to end of study at 12 months]

Вторичные конечные точки (12)

• Changes in cortical and trabecular bone microarchitecture [Срок оценки: From baseline to end of study at 12 months]
• Mineral metabolism: Change in plasma parathyroid hormone (PTH) [Срок оценки: From baseline to end of study at 12 months]
• Mineral metabolism: Changes in serum ionized calcium and phosphate [Срок оценки: From baseline to end of study at 12 months]
• Mineral metabolism: Change in plasma fibroblast growth factor 23 (FGF23) [Срок оценки: From baseline to end of study at 12 months]
• Bone turnover marker: Change in bone-specific alkaline phosphatase (BALP) [Срок оценки: From baseline to end of study at 12 months]
• Bone turnover marker: Change in plasma C-terminal crosslinks (CTX) [Срок оценки: 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) [Срок оценки: From baseline to end of study at 12 months]
• Bone turnover marker: Change in plasma tartrate-resistant acid phosphatase isoform 5b (TRAP5b). [Срок оценки: From baseline to end of study at 12 months]
• Kidney function: Stability of kidney graft function based on estimated glomerular filtration rate (GFR) slope [Срок оценки: 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 [Срок оценки: From baseline to end of study at 12 months.]
• Change in isometric lower extremity muscle strength [Срок оценки: From baseline to end of study at 12 months]
• Change in mobility measured by the Timed Up and Go (TUG) test [Срок оценки: From baseline to end of study at 12 months.]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Дания · 1 центр

• Departement of Nephrology, Aarhus University hospital — Aarhus

Публикации

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• Jorgensen HS, Claes K, Smout D, Naesens M, Kuypers D, D'Haese P, Cavalier E, Evenepoel P. Associations of Changes in Bone Turnover Markers with Change in Bone Mineral Density in Kidney Transplant Patients. Clin J Am Soc Nephrol. 2024 Apr 1;19(4):483-493. doi: 10.2215/CJN.0000000000000368. Epub 2023 Nov 29. PMID 38030558
• Jorgensen HS, Behets G, Bammens B, Claes K, Meijers B, Naesens M, Sprangers B, Kuypers DRJ, Cavalier E, D'Haese P, Evenepoel P. Natural History of Bone Disease following Kidney Transplantation. J Am Soc Nephrol. 2022 Mar;33(3):638-652. doi: 10.1681/ASN.2021081081. Epub 2022 Jan 19. PMID 35046132
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• Tong A, Budde K, Gill J, Josephson MA, Marson L, Pruett TL, Reese PP, Rosenbloom D, Rostaing L, Warrens AN, Wong G, Craig JC, Crowe S, Harris T, Hemmelgarn B, Manns B, Tugwell P, Van Biesen W, Wheeler DC, Winkelmayer WC, Evangelidis N, Sautenet B, Howell M, Chapman JR. Standardized Outcomes in Nephrology-Transplantation: A Global Initiative to Develop a Core Outcome Set for Trials in Kidney Transp PMID 27500269
• Cheng SP, Lee JJ, Liu TP, Yang TL, Chen HH, Wu CJ, Liu CL. Parathyroidectomy improves symptomatology and quality of life in patients with secondary hyperparathyroidism. Surgery. 2014 Feb;155(2):320-8. doi: 10.1016/j.surg.2013.08.013. Epub 2013 Sep 11. PMID 24035616
• Pasieka JL, Parsons LL. A prospective surgical outcome study assessing the impact of parathyroidectomy on symptoms in patients with secondary and tertiary hyperparathyroidism. Surgery. 2000 Oct;128(4):531-9. doi: 10.1067/msy.2000.108117. PMID 11015085

Идентификаторы

NCT: NCT07415421 · 1-10-72-137-25 · NNF22SA0079901

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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