The Effect of Maintenance Treatment with Twice-Daily or Prolonged Once-Daily Tacrolimus Formulation on Visual Evoked Potentials in Stable Kidney Transplant Recipients.

Sebastian Sirek,Andrzej Więcek,Tomasz Dwulit,Małgorzata Jurys,Dorota Pojda-Wilczek,Aureliusz Kolonko

doi:10.3390/jcm9061827

Abstract

In kidney transplant recipients (KTRs), uraemia-induced central nervous system damage partly subsides, while the long-lasting exposure to tacrolimus may cause pathologic visual evoked potentials (VEP) findings, which have not been investigated yet. Thus, the aim of the present study was to assess the effect of tacrolimus maintenance treatment on bioelectrical function of optic nerves in stable KTRs. Sixty-five stable KTRs were enrolled, including 30 patients treated with twice-daily (Prograf) and 35 patients treated with prolonged once-daily (Advagraf) tacrolimus formulation. In all patients, pattern and flash VEP measurements were performed. Tacrolimus dosing and exposure were also analyzed. Overall, 129 eyes were analyzed. In pattern VEP, both (1°) and (15′) latencies of P100 waves were significantly longer, whereas (1°) and (15′) amplitudes were lower in the Advagraf group as compared with the Prograf group. Multivariate regression analyses revealed that the use of Advagraf (vs. Prograf) was independently associated with longer (1°) and (15′) P100 latencies and lower corresponding amplitudes, whereas log tacrolimus daily dose was only related to amplitudes in a whole study group. In flash VEP, log tacrolimus trough level was associated with negative changes in P2 wave amplitude irrespective of tacrolimus formulation, whereas its association with P2 latency was observed only in the Prograf group. Both the type of tacrolimus formulation and drug exposure influenced the VEP parameters in stable KTRs.

Highlights

Nowadays, tacrolimus is the main immunosuppressive agent used in kidney transplantation [1]
The main finding and the novelty of the present study is the association between tacrolimus exposure and parameters of both pattern and flash visual evoked potentials (VEP) spectra in stable non-diabetic kidney transplant recipients (KTRs)
The negative effect on the bioelectrical function of the visual pathway seemed to be more intensified in patients treated with once-daily tacrolimus formulation

Summary

Introduction

Tacrolimus is the main immunosuppressive agent used in kidney transplantation [1] The introduction of this potent calcineurin inhibitor into the clinical practice improved early and long-term kidney graft outcomes, mostly as a consequence of the reduction of acute rejection episodes [2]. Mild neurological complications include headache, paresthesia, tremor, sleep disturbances and photophobia, while more severe symptoms, such as confusion, seizures, dysarthria, vision loss and encephalopathy may occur [3,4,5]. Their mechanisms are not fully elucidated, being perhaps intermediated by oligodendrocytes, glia and vascular endothelium injury [6]. There is a need for a diagnostic procedure, which might be useful in the early detection of tacrolimus-induced neurotoxicity

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