Electrolyte disturbances after allogeneic hematopoietic cell transplantation in patients receiving calcineurin inhibitors: incidence and severity

Background Electrolyte disorders are highly prevalent in critically ill patients and have been associated with severe clinical manifestations, including cardiac arrhythmia and increased mortality. In the context of allogeneic hematopoietic cell transplantation (HCT), graft-versus-host disease (GVHD), acute kidney injury (AKI), and the use of emetogenic conditioning regimens, calcineurin inhibitors, amphotericin B, foscarnet, diuretics, among other drugs, may contribute to the development of complex and interrelated electrolyte disturbances. However, studies addressing the incidence, severity, and clinical relevance of these electrolyte imbalances in allogeneic HCT recipients remain scarce. In addition, interindividual variability in calcineurin inhibitor exposure, partially influenced by pharmacogenetic factors such as CYP3A5 polymorphisms, may contribute to differences in susceptibility to these disturbances. Objectives To determine the frequency and severity of electrolyte disturbances in allogeneic HCT recipients and to evaluate potential pharmacogenetic-related factors associated with these alterations. Methods This retrospective, single-center study included 374 patients who underwent allogeneic HCT and received tacrolimus or cyclosporine for graft-versus-host disease prophylaxis. Electrolyte disturbances involving potassium, sodium, magnesium, and calcium were defined according to laboratory reference values and graded using the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Clinical and transplant characteristics were obtained from electronic medical records. Results Electrolyte disturbances were highly prevalent, particularly those characterized by low serum concentrations, including hypocalcemia (86.6%), hypomagnesemia (85.6%), hyponatremia (75.7%), and hypokalemia (62.6%), whereas hypercalcemia was rare. Most disturbances were mild to moderate, although hypocalcemia, hyperkalemia, and hypokalemia accounted for a substantial proportion of severe cases. Electrolyte abnormalities frequently occurred concomitantly, demonstrating strong interdependence, especially among potassium, sodium and calcium. Acute kidney injury, total body irradiation, age, and concomitant electrolyte disturbances were identified as significant factors associated with these outcomes. No significant differences in the incidence or severity of disturbances were observed between tacrolimus and cyclosporine. Conclusion Electrolyte disturbances after allogeneic HCT are common, often multifactorial, interdependent, and clinically relevant. These findings highlight the need for integrated monitoring and early management of electrolyte abnormalities in the post-transplant period.