From the Guidelines
Tacrolimus does not typically cause hyponatremia as a primary side effect. The medication is more commonly associated with other electrolyte abnormalities, such as hyperkalemia and hypomagnesemia, due to its mechanism of action as a calcineurin inhibitor, which can lead to decreased potassium excretion and subsequent hyperkalemia 1. When monitoring patients on tacrolimus, clinicians should focus on regular blood work, including CBC count, renal function, glucose level, lipid profile, and potassium and magnesium levels, as well as frequent blood pressure measurements, but hyponatremia is not a characteristic adverse effect that needs to be specifically monitored or managed as a result of tacrolimus therapy. Some key points to consider when evaluating electrolyte abnormalities in patients taking tacrolimus include:
- Monitoring for drug/drug interactions that may affect tacrolimus levels or increase the risk of other electrolyte imbalances 1
- Prophylaxis against infections, such as Pneumocystis jiroveci, which may be relevant in the context of immunosuppression but not directly related to hyponatremia 1
- Investigating other potential causes of hyponatremia, such as diuretic use, syndrome of inappropriate antidiuretic hormone secretion (SIADH), heart failure, liver disease, or kidney dysfunction, if the condition occurs in a patient taking tacrolimus. Adjusting tacrolimus dosing specifically to address hyponatremia would not be an appropriate management strategy, as the primary approach should be to evaluate and manage the underlying cause of the electrolyte abnormality.
From the Research
Tacrolimus and Hyponatremia
- Tacrolimus has been associated with hyponatremia in several studies 2, 3, 4, 5.
- A case report published in the Indian Journal of Nephrology described a kidney transplant recipient who developed recurrent hyponatremia and graft dysfunction due to tacrolimus-induced salt-wasting nephropathy 2.
- A retrospective chart review of lung transplant recipients found that 5 patients developed severe hyponatremia after transplantation, which resolved or improved after switching from a tacrolimus-based to a cyclosporine-based immunosuppressive regimen 3.
- Another study reported a case of severe symptomatic hyponatremia in a renal transplant recipient on tacrolimus, despite a normal tacrolimus trough level 4.
- A retrospective study of 125 renal transplant recipients found that hyponatremia and hyperkalemia were more frequent in patients treated with tacrolimus than with cyclosporin 5.
Mechanism and Risk Factors
- The exact mechanism of tacrolimus-induced hyponatremia is not fully understood, but it may be related to the drug's nephrotoxic effects 5.
- A study found that the tacrolimus metabolism rate, expressed as the blood concentration normalized by the dose (C/D ratio), influences renal function after kidney transplantation 6.
- Fast metabolizers of tacrolimus were found to have lower estimated glomerular filtration rate (eGFR) values and a higher incidence of CNI nephrotoxicity and BK nephropathy compared to slow metabolizers 6.