Hyperparathyroidism, Kidney Transplantation Recipients
Conditions
Keywords
Persistent hyperparathyroidism, Kidney transplant recipients, Parathyroidectomy, Bone mineral density, Muscle function, Quality of life, Randomized controlled trial
Brief summary
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.
Detailed description
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.
Interventions
PROCEDURESubtotal 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.
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.
Sponsors
Aarhus University Hospital
University of Aarhus
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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 two consecutive biochemical measurements: PTH ≥1.5 times normal limit of assay and ionized calcium ≥1.35 mmol/L or albumin-corrected calcium ≥2.70 mmol/L or phosphate ≤0.50 mmol/L
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in bone mineral density (BMD) at the total hip | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Changes in cortical and trabecular bone microarchitecture | From baseline to end of study at 12 months | Bone microarchitecture will be assessed using high-resolution peripheral quantitative computed tomography (HR-pQCT) at baseline and after 12 months. Parameters will include measures of trabecular and cortical bone structure. The outcome is the change in these parameters from baseline to 12 months. |
| Mineral metabolism: Change in plasma parathyroid hormone (PTH) | From baseline to end of study at 12 months | Plasma plasma parathyroid hormone PTH \[pmol/L\] will be measured at baseline and 12 months. Outcome is change from baseline to 12 months. |
| Mineral metabolism: Changes in serum ionized calcium and phosphate | From baseline to end of study at 12 months | Serum ionized calcium \[mmol/L\] and phosphate \[mmol/L\] will be measured at baseline and 12 months. Outcome is change from baseline to 12 months. |
| Mineral metabolism: Change in plasma fibroblast growth factor 23 (FGF23) | From baseline to end of study at 12 months | Plasma fibroblast growth factor 23 FGF23 \[ng/L\] will be measured at baseline and 12 months. Outcome is change from baseline to 12 months |
| Bone turnover marker: Change in bone-specific alkaline phosphatase (BALP) | From baseline to end of study at 12 months | Bone-specific alkaline phosphataseBALP \[µg/l\] will be measured at baseline and 12 months. Outcome is change from baseline to 12 months. |
| Bone turnover marker: Change in plasma C-terminal crosslinks (CTX) | From baseline to end of study at 12 months | CTX \[µg/L\] will be measured at baseline and 12 months. Outcome is change from baseline to 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 | Plasma procollagen type I N-terminal propeptide (PINP, intact and total forms) \[µg/L\] will be measured at baseline and 12 months. Outcome is change from baseline to 12 months. |
| Bone turnover marker: Change in plasma tartrate-resistant acid phosphatase isoform 5b (TRAP5b). | From baseline to end of study at 12 months | Plasma TRAP5b \[U/L\] will be measured at baseline and 12 months. Outcome is change from baseline to 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. | Lower extremity function will be assessed using the 30-second Chair Stand Test at baseline and after 12 months. The outcome is the change in the number of repetitions from baseline to 12 months, where a higher number of repetitions indicates better performance. |
| Change in isometric lower extremity muscle strength | From baseline to end of study at 12 months | Isometric lower extremity muscle strength will be assessed using a dynamometer chair at baseline and after 12 months. The outcome is the change in maximal isometric strength from baseline to 12 months, where higher values indicate greater muscle strength. |
| Change in mobility measured by the Timed Up and Go (TUG) test | From baseline to end of study at 12 months. | Mobility will be assessed using the Timed Up and Go (TUG) test at baseline and after 12 months. The outcome is the change in time (seconds) from baseline to 12 months, where a shorter time indicates better performance. |
| Change in handgrip strength | From baseline to end of study at 12 months. | Handgrip strength (HGS) test will be performed using a hand dynamometer at baseline and after 12 months. Handgrip strength will be measured in kilograms. The outcome is the change in handgrip strength from baseline to 12 months, where higher values indicate greater muscle strength. |
| Change in quality of life measured by the Primary Hyperparathyroidism Quality of Life questionnaire (PHPQoL) | From baseline to end of study at 12 months. | Quality of life will be assessed using the Primary Hyperparathyroidism Quality of Life questionnaire (PHPQoL) at baseline and after 12 months. The PHPQoL consists of 16 items assessing health-related quality of life in patients with hyperparathyroidism. Items are scored from 0 to 4 and summed to a total score of 0-64, which is subsequently normalized to a 0-100 scale, where higher scores indicate better quality of life. The outcome is the change in normalized PHPQoL total score from baseline to 12 months. |
| Change in symptom burden measured by the Parathyroidectomy Assessment of Symptoms (PAS) score | From baseline to end of study at 12 months. | Symptom burden will be assessed using the Parathyroidectomy Assessment of Symptoms (PAS) score at baseline and after 12 months. The PAS score consists of 13 symptom items, each scored from 0 (no symptoms) to 100 (maximum symptom severity), where higher scores indicate greater symptom burden. The outcome is the change in PAS total score from baseline to 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. | Post-transplant quality of life will be assessed using a questionnaire developed for the post-transplant setting in collaboration with patient representatives (SONG initiative) at baseline and after 12 months. Items are scored using a five-point Likert scale with the response options: Never, Rarely, Sometimes, Usually, Always, with an additional Not applicable option. The outcome is the change in questionnaire score from baseline to 12 months. |
Countries
Denmark
Contacts
CONTACTHanne S Jørgensen, MD, PhD
CONTACTAmal Derai, MD
PRINCIPAL_INVESTIGATORHanne S Jørgensen, MD, PhD
Department of Nephrology, Aarhus University Hospital
Outcome results
None listed