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Hyperparathyroidism Is an Independent Risk Factor for Allograft Dysfunction in Pediatric Kidney Transplantation
Agnieszka Prytula1, Rukshana Shroff2, Kai Krupka3
1Department of Pediatric Nephrology and Rheumatology, Ghent University Hospital, Ghent, Belgium.
Insights
In children, high parathyroid hormone levels (hyperparathyroidism) are linked to kidney transplant problems. This study highlights hyperparathyroidism as a key risk factor for graft dysfunction after pediatric kidney transplantation.
Area of Science:
- Pediatric Nephrology
- Transplantation Immunology
- Endocrinology
Background:
- Chronic kidney disease-mineral and bone disorder (CKD-MBD) significantly impacts pediatric kidney transplant recipients.
- The long-term effects of CKD-MBD parameters on kidney allograft function in children remain poorly understood.
Purpose of the Study:
- To investigate the relationship between CKD-MBD parameters and kidney allograft outcomes in pediatric transplant recipients.
- To identify specific CKD-MBD derangements that predict graft dysfunction or loss over time.
Main Methods:
- A registry study involving 1210 children from the Cooperative European Paediatric Renal Transplant Initiative (CERTAIN).
- Data collected at multiple time points up to 5 years post-transplant.
- Survival analysis using conventional Cox proportional hazards and marginal structural models to assess associations of parathyroid hormone (PTH), calcium, phosphate, and 25-hydroxyvitamin D with graft outcomes.
Main Results:
- Hyperparathyroidism (elevated PTH) was independently associated with an increased risk of graft dysfunction (HR, 2.94; 95% CI, 1.82-4.74).
- Hyperphosphatemia showed an initial association but was not significant in marginal structural models, suggesting its effect may be secondary to declining eGFR.
- The composite endpoint of graft loss or significant eGFR decline occurred in 21% of patients.
Conclusions:
- Hyperparathyroidism is identified as a significant independent risk factor for kidney allograft dysfunction in children.
- Monitoring and management of PTH levels are crucial for optimizing long-term graft survival in pediatric kidney transplant recipients.
Introduction:
Little is known about the consequences of deranged chronic kidney disease-mineral and bone disorder (CKD-MBD) parameters on kidney allograft function in children. We examined a relationship between these parameters over time and allograft outcome.
Methods:
This registry study from the Cooperative European Paediatric Renal Transplant Initiative (CERTAIN) collected data at baseline, months 1, 3, 6, 9, and 12 after transplant; and every 6 months thereafter up to 5 years. Survival analysis for a composite end point of graft loss or estimated glomerular filtration rate (eGFR) ≤30 ml/min per 1.73 m2 or a ≥50% decline from eGFR at month 1 posttransplant was performed. Associations of parathyroid hormone (PTH), calcium, phosphate, and 25-hydroxyvitamin D (25(OH)D) with allograft outcome were investigated using conventional stratified Cox proportional hazards models and further verified with marginal structural models with time-varying covariates.
Results:
We report on 1210 patients (61% boys) from 16 European countries. The composite end point was reached in 250 grafts (21%), of which 11 (4%) were allograft losses. In the conventional Cox proportional hazards models adjusted for potential confounders, only hyperparathyroidism (hazard ratio [HR], 2.94; 95% confidence interval [CI], 1.82-4.74) and hyperphosphatemia (HR, 1.94; 95% CI, 1.28-2.92) were associated with the composite end point. Marginal structural models showed similar results for hyperparathyroidism (HR, 2.74; 95% CI, 1.71-4.38), whereas hyperphosphatemia was no longer significant (HR, 1.35; 95% CI, 0.87-2.09), suggesting that its association with graft dysfunction can be ascribed to a decline in eGFR.
Conclusion:
Hyperparathyroidism is a potential independent risk factor for allograft dysfunction in children.
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