Tacrolimus-induced encephalopathy and polyneuropathy in a renal transplant recipient

Abstract

Tacrolimus is an immunosuppressant frequently used following solid organ transplantation, including renal transplantation. Peripheral neuropathy is an uncommon neurological side effect of tacrolimus and has rarely been reported in renal transplantation. We report a patient who received a living-related donor kidney transplant and presented with altered mental status and new-onset bilateral foot drop. Laboratory tests including cerebrospinal fluid tests excluded infection, and MRI of the brain showed chronic microvascular ischaemic changes. Electromyography and nerve conduction study confirmed bilateral common peroneal nerve demyelination. He was also found to have inadvertently overdosed on tacrolimus at home. After switching from tacrolimus to cyclosporine, the patient's symptoms improved within 5 months. His renal function was maintained with an immunosuppressant regimen of cyclosporine, prednisone and mycophenolic acid. The prompt recognition of tacrolimus as a potential neurotoxic drug in a patient with renal transplant and substituting tacrolimus with a different immunosuppressant may prevent permanent neurological damage.

Neurological Complications after Renal Transplantation: A Retrospective Clinical Study

“…Posterior leukoencephalopathy syndrome (PLES) is a reversible encephalopathy, which partially affects the cerebral cortex, and the sym-metric involvement of posterior regions has been commonly reported. PLES is clinically characterized by altered mental status, seizures, and frequent visual disturbances, and it is generally reported in patients who receive immunosuppressive drugs after transplantation (10,11,12,13,14). In our study, the sudden onset of drowsiness, diffuse delta and theta waves in EEG, and a suicide attempt in one patient suggested diffuse encephalopathy.…”

“…One patient with both CNS and neuropathy was reported in the literature; however, the involvement of both systems was observed while the patient was taking tacrolimus and inadvertently had an overdose of the drug (11).…”

Influence of Germline Genetics on Tacrolimus Pharmacokinetics and Pharmacodynamics in Allogeneic Hematopoietic Stem Cell Transplant Patients

“…However, we are unable to confirm the effects of phenoconversion on tacrolimus PK/PD because the approach to tacrolimus dose adjustments due to potential drug-drug interactions with strong and moderate CYP3A4/5 and P-gp inhibitors was inconsistent among our prescribers. Second, there was a lack of standardized documentation to fully evaluate tacrolimus-induced neurotoxicity, which often manifests as tremor [67][68][69]. Therefore, in our ongoing prospective CYP3A4/5-guided study, we have included tacrolimus-induced toxicities, including both neurotoxicity and nephrotoxicity, using the Common Terminology Criteria for Adverse Events v5.0 criteria [70] and comprehensive medication reconciliation to monitor for new prescriptions, over-the-counter medications, and herbal supplements, as well as relevant dose changes to those medications and products.…”

Neurologic complications in kidney transplant recipients

“…The treatment of immunosuppressive neurotoxicity consists of correction of electrolyte imbalance and hypertension, immunosuppressant dose reduction and switching from cyclosporine to tacrolimus or vice versa, if necessary [109,196,233]. Use of combinations, such as CNI plus mycophenolate or mTOR inhibitor, enables lower doses of cyclosporine or tacrolimus to be used without weakening the immunosuppressive effect [124].…”