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.

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.

Inclusion criteria

• 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.

Exclusion criteria

• 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.

De-identified individual participant data that underlie the results reported in publications will be shared. This includes demographic data, baseline characteristics, outcome measures, and relevant laboratory and imaging data used for primary and secondary analyses. Data will be shared in an anonymized format to protect participant confidentiality. Only data necessary to reproduce the reported results will be made available. Additional data not included in publications will not be routinely shared. Data sharing will be conducted in accordance with applicable data protection regulations and national legislation.

Beginning after publication of the primary study results and available until December 2035.

De-identified (pseudo-anonymized) individual participant data and supporting documents will be made available to qualified researchers upon reasonable request. Requests must include a methodologically sound research proposal. Access will be subject to approval by the principal investigator and relevant institutional authorities. Data sharing will require a data transfer agreement in accordance with the Danish Data Protection Act and the General Data Protection Regulation (GDPR), including Chapter V concerning transfers to third countries. Data will be shared in a secure manner and solely for research purposes.