Brain function and metabolism in patients with long-term tacrolimus therapy after kidney transplantation in comparison to patients after liver transplantation

Abstract

Background About 50% of the patients 5-7 years after kidney transplantation show impairment of memory, attention and executive function. Tacrolimus frequently induces neurological complications in the first few weeks after transplantation. Furthermore, tacrolimus treatment is associated with impaired cognitive function in the long-term in patients after liver transplantation. We hypothesize that long-term tacrolimus therapy is associated with cognitive dysfunction and alterations of brain structure and metabolism in patients after kidney transplantation. Methods Twenty-one patients 10 years after kidney transplantation underwent cognitive testing, magnetic resonance imaging and whole brain 31-phosphor magnetic resonance spectroscopy for the assessment of brain function, structure and energy metabolism. Using a cross-sectional study design the results were compared to those of patients 1 (n = 11) and 5 years (n = 10) after kidney transplantation, and healthy controls (n = 17). To further analyze the share of transplantation, tacrolimus therapy and kidney dysfunction on the results patients after liver transplantation (n = 9) were selected as a patient control group.

Tacrolimus-Induced Leukoencephalopathy in a Renal Transplantation Patient

“…However, severe complications in the form of confusion, seizures, psychosis, cortical blindness, and coma are rare, affecting 1–6% of transplant recipients. Neurotoxicity is more common early after initiation of the drug, but can happen months or years later [8].…”

Cognitive Impairment and Kidney Transplantation: Underestimated, Underrecognized but Clinically Relevant Problem

“…Otherwise, traditional risk factors such as ageing, comorbid disease, i.e., hypertension, diabetes mellitus, hypercholesterolemia, and nontraditional risk factors, i.e., chronic inflammation, oxidative stress, hypercoagulable state should also be taken into consideration [1,8,12]. Additionally, many studies reported that magnetic resonance imaging (MRI) of the brain in CKD patients, also young patients, show subclinical brain lesions like white matter hyperintensities, silent lacunar infarcts, microbleeds, and cerebral atrophy [13][14][15]. The prevalence of cognitive impairment in endstage renal disease patients has been estimated at 50%-80% [16,17].…”

“…There have been far fewer studies assessing the long-term effects of kidney transplantation on cognition. Recently, Pflugrad et al [15] investigated cognitive function, brain structure, and metabolism in patients treated by standard-dose tacrolimus therapy 10 years after kidney transplantation. The control group consisted of kidney recipients 1 and 5 years after successful surgery, tacrolimus treated patients after liver transplantation and healthy controls.…”

“…Additionally, researchers found significantly reduced brain adenosine triphosphate concentrations and, in consequence, reduced brain metabolism in patients after kidney but not liver transplantation (patients also received tacrolimus) as compared to healthy controls. These results indicate that many years after kidney transplantation cognitive problems may reoccur in recipients and tacrolimus therapy alone is not sufficient to lead to cognitive decline and altered brain energy metabolism in kidney recipients [15]. Two other studies investigated cognitive function outcomes approximately 5 and 7 years after successful kidney transplantation [36, 37].…”

“…Thus, depressive symptoms might affect attention, memory, and executive function or weaken the final result in cognitive testing. Only in some studies, the results were adjusted for symptoms of depression [15, 33, 35]. In addition, there is a notable lack of specific treatments available.…”