Reassessing parathyroidectomy outcomes in kidney transplant recipients with hyperparathyroidism: A fragility-index...

The optimal timing of parathyroidectomy (PTX) for secondary hyperparathyroidism (SHPT) in kidney transplant recipients remains controversial. Existing studies report conflicting effects of pre- and post-transplant PTX on graft outcomes, yet the statistical robustness of these findings has not been systematically evaluated. The fragility index (FI) offers a complementary method to assess the stability of statistically significant results and can offer insight into improved treatment guidelines METHODS: We conducted a structured literature review using systematic search methods to identify studies evaluating PTX timing, management strategies, and outcomes in adult kidney transplant recipients with SHPT. Studies reporting dichotomous or continuous outcomes permitting FI calculation were included. Data were synthesized narratively without meta-analysis. FI was calculated for statistically significant outcomes to assess robustness, with FI values categorized as non-significant (FI = 0), weak robustness (FI = 1-3), or higher robustness (FI ≥ 8). Risk of bias was assessed using ROBINS-I and the Newcastle-Ottawa Scale.

Nineteen observational studies and one randomized control trial met inclusion criteria. Twelve studies (60%) reported graft survival or graft loss outcomes, and nine (45%) evaluated graft function. Persistent hyperparathyroidism after transplantation was associated with higher graft loss in 8 of 12 studies (66.7%), with reported hazard ratios ranging from 1.94 to 2.42. Studies comparing PTX timing demonstrated inconsistent findings, with 3 of 6 studies (50.0%) reporting worse short-term graft outcomes following early post-transplant PTX and 3 reporting no difference. Across studies, graft loss rates ranged from 11.4 to 17.1% in patients with persistent hyperparathyroidism versus 0-8.5% in those without persistent disease or after PTX. A total of 26 statistically significant outcomes were eligible for FI analysis. Of these, 18 (69.2%) had an FI of 0, and an additional 5 (19.2%) had FI values of 1-3. Only 3 outcomes (11.5%) demonstrated FI ≥ 8, all derived from studies evaluating persistent hyperparathyroidism rather than PTX timing. Overall, 88.5% of statistically significant findings were dependent on three or fewer outcome events.

The current literature evaluating parathyroidectomy timing in kidney transplant recipients is dominated by statistically fragile findings. While persistent hyperparathyroidism is consistently associated with adverse graft outcomes, evidence guiding the optimal timing of PTX is limited by low statistical robustness. These findings highlight the need for cautious interpretation of existing data while also emphasizing the need for proactive management of hyperparathyroidism which may include parathyroidectomy for patients whom medical management alone would not lead to durable control.