Long-term effects of hypercalcemia in kidney transplant recipients with persistent hyperparathyroidism

Juan Carlos Ramirez-Sandoval; Lluvia Marino; Gabriel Cojuc-Konigsberg; Estefania Reul-Linares; Nathalie Desire Pichardo-Cabrera; Cristino Cruz; Elisa Naomi Hernández-Paredes; Nathan Berman-Parks; Vanessa Vidal-Ruíz; Jonathan Mauricio Estrada-Linares; Alfredo Adolfo Reza-Albarrán; Ricardo Correa-Rotter; Luis Eduardo Morales-Buenrostro

doi:10.1007/s40620-023-01815-5

Long-term effects of hypercalcemia in kidney transplant recipients with persistent hyperparathyroidism

J Nephrol. 2023 Nov 30. doi: 10.1007/s40620-023-01815-5. Online ahead of print.

Authors

Affiliations

¹ Department of Nephrology and Mineral Metabolism, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Vasco de Quiroga 15, colonia Sección XVI, 14080, Mexico City, CDMX, Mexico. carlos.ramirezs@incmnsz.mx.
² Department of Nephrology and Mineral Metabolism, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Vasco de Quiroga 15, colonia Sección XVI, 14080, Mexico City, CDMX, Mexico.
³ Department of Endocrinology and Metabolism, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico.

PMID: 38032457
DOI: 10.1007/s40620-023-01815-5

Abstract

Background: Hypercalcemia is highly prevalent in kidney transplant recipients with hyperparathyroidism. However, its long-term impact on graft function is uncertain.

Methods: We conducted a prospective cohort study investigating adverse graft outcomes associated with persistent hypercalcemia (free calcium > 5.2 mg/dL in ≥ 80% of measures) and inappropriately elevated intact parathyroid hormone (> 30 pg/mL) in kidney transplant recipients. Asymptomatic mild hypercalcemia was monitored unless complications developed.

Results: We included 385 kidney transplant recipients. During a 4-year (range 1-9) median follow-up time, 62% of kidney transplant recipients presented persistent hypercalcemia. Compared to kidney transplant recipients without hypercalcemia, there were no significant differences in graft dysfunction (10% vs. 12%, p = 0.61), symptomatic urolithiasis (5% vs. 3%, p = 0.43), biopsy-proven calcium deposits (6% vs. 5%, p = 1.0), fractures (6% vs. 4%, p = 0.64), and a composite outcome of urolithiasis, calcium deposits, fractures, and parathyroidectomy indication (16% vs. 13%, p = 0.55). In a subset of 76 kidney transplant recipients, subjects with persistent hypercalcemia had higher urinary calcium (median 84 [43-170] vs. 38 [24-64] mg/day, p = 0.03) and intact fibroblast growth factor 23 (median 36 [24-54] vs. 27 [19-40] pg/mL, p = 0.04), and lower 25-hydroxyvitamin D levels (11.3 ± 1.2 vs. 16.3 ± 1.4 ng/mL, p < 0.001). In multivariate analysis, pretransplant intact parathyroid hormone < 300 pg/mL was associated with a reduced risk of post-transplant hypercalcemia (OR 0.51, 95% CI 0.32-0.80).

Conclusions: Long-term persistent mild hypercalcemia (tertiary hyperparathyroidism) was frequent in kidney transplant recipients in our series. This condition presented with lower phosphate and 25-hydroxyvitamin D, and higher urinary calcium and intact fibroblast growth factor 23 levels compared to kidney transplant recipients without hypercalcemia, resembling a mild form of primary hyperparathyroidism. Despite these metabolic derangements, the risk of adverse graft outcomes was low.

Keywords: Calcium; Mineral bone disease; Post-transplant hyperparathyroidism; Tertiary hyperparathyroidism; Transplant.