Tacrolimus Toxicity Presenting As Acute Peroneal Neuropathy in a Kidney Transplant Recipient: A Case Report

Introduction

Peripheral neuropathy, especially isolated mononeuropathy, although recognized, is considered a rare manifestation of tacrolimus neurotoxicity and is often underdiagnosed due to its variable presentation and the confounding influence of comorbidities common in transplant recipients.^1,2 In this context, we report a kidney transplant recipient who developed acute unilateral foot drop associated with tacrolimus toxicity.

Case Report

A 55-year-old male with known chronic kidney disease of unexplained cause (CKDx) for the last 4 years underwent deceased-donor kidney transplantation in May 2024. Induction immunosuppression included rabbit antithymocyte globulin, followed by maintenance therapy with tacrolimus, mycophenolate mofetil, and prednisolone. Two months post-transplantation, he developed acute left foot drop with numbness over the dorsum of the foot for 3 days. There was no history of trauma, prolonged squatting, recent infection, vaccination, back pain, radicular symptoms, or sphincter disturbances. He also did not have a history of diabetes mellitus, alcohol abuse, neuropathic symptoms, foot drop, or other neurological deficits before transplantation. Notably, he had switched his tacrolimus brand one week prior to the onset of symptoms.

Examination revealed a left high-stepping gait. Motor testing revealed complete loss of dorsiflexion and eversion (0/5), with preserved plantar flexion and inversion. Sensory examination showed reduced pinprick and light touch over the dorsum of the left foot in the superficial peroneal nerve distribution. Reflexes were intact with no upper motor neuron or cranial nerve abnormalities.

Nerve conduction studies demonstrated markedly reduced compound muscle action potential amplitudes in both peroneal nerves, with normal distal latency and conduction velocity, indicating bilateral axonal motor neuropathy despite unilateral symptoms. Sensory studies and tibial nerve conduction were normal. Magnetic resonance imaging of the brain and lumbosacral spine showed no abnormalities. Laboratory evaluation revealed negative anti-neutrophil cytoplasmic antibodies serology, undetectable hepatitis C virus ribonucleic acid and normal blood glucose and thyroid function tests... Serum creatinine had increased from 1.57–1.99 mg/dL. Tacrolimus trough level was markedly elevated at 23.9 ng/mL.

Tacrolimus-induced neuropathy was diagnosed based on elevated drug levels, temporal association with brand change, and exclusion of alternative causes. The tacrolimus dose was reduced. Physiotherapy and ankle-foot orthosis were initiated. The patient improved steadily. Within 2 weeks, tacrolimus levels declined to 8.8 ng/mL and kidney function stabilized. Dorsiflexion improved to 3/5 by week 3, with near-complete neurological recovery by week 4. A repeat nerve conduction study was not available after recovery; therefore, complete electrophysiological reversibility of the asymptomatic contralateral abnormality could not be confirmed. At 1 year, he remained asymptomatic with stable graft function (creatinine 1.0 mg/dL).

Discussion

Tacrolimus-related peripheral neuropathy is rare. Reported cases typically describe symmetrical sensorimotor axonal polyneuropathy.^3,4 Isolated mononeuropathy, such as peroneal nerve palsy, is uncommon and presents a diagnostic challenge due to broad differentials including compressive, metabolic, infectious, and autoimmune causes.^1,2,5

According to the World Health Organization – Uppsala Monitoring Centre causality assessment system, tacrolimus was classified as a probable/likely cause of neuropathy in our case because of the clear temporal relationship between supratherapeutic tacrolimus exposure and symptom onset, exclusion of alternative etiologies, and significant clinical improvement following dose reduction and normalization of tacrolimus levels.⁵ Although approved tacrolimus formulations meet regulatory bioequivalence criteria, tacrolimus possesses a narrow therapeutic index and substantial pharmacokinetic variability. Consequently, formulation substitution may occasionally result in clinically relevant changes in drug exposure, necessitating close therapeutic drug monitoring.⁶

This case highlights three important clinical lessons: a) Tacrolimus toxicity may present as an isolated mononeuropathy; b) Drug levels should be promptly checked in transplant recipients with new neurological deficits; and c) Early recognition and dose adjustment may permit complete neurological recovery and preserve graft function.