RESUMO
Patients affected by chronic kidney disease (CKD) have an increased risk of developing cognitive impairment. The cause of mental health disorders in CKD and in chronic hemodialysis patients is multifactorial, due to the interaction of classical cardiovascular disease risk factors, kidney- and dialysis-related risk factors with depression, and multiple drugs overuse. A large number of compounds, defined as uremic toxins that normally are excreted by healthy kidneys, accumulate in the circulations, in the tissues, and in the organs of CKD patients. Among the candidate uremic toxins are several guanidino compounds, such as Guanidine. Uremic toxins may also accumulate in the brain and may have detrimental effects on cerebral resident cells (neurons, astrocytes, microglia) and microcirculation. The present study aims to analyze the effect of Guanidine on hippocampal excitatory postsynaptic field potentials (fEPSPs) and in CA1 pyramidal neurons recorded intracellularly. Moreover, we compared these effects with the alterations induced in vitro by CKD patients derived serum samples. Our results show an increased, dose-dependent, synaptic activity in the CA1 area in response to both synthetic Guanidine and patient's serum, through a mechanism involving glutamatergic transmission. In particular, the concomitant increase of both NMDA and AMPA component of the excitatory postsynaptic currents (EPSCs) suggests a presynaptic mechanism. Interestingly, in presence of the lower dose of guanidine, we measure a significant reduction of EPSCs, in fact the compound does not inhibit GABA receptors allowing their inhibitory effect of glutamate release. These findings suggest that cognitive symptoms induced by the increase of uremic compounds in the serum of CKD patients are caused, at least in part, by an increased glutamatergic transmission in the hippocampus.
RESUMO
Fatigue is still present in up to 40-50% of kidney transplant recipients (KTR), the results of studies comparing the prevalence among patients on hemodialysis (HD) and KTR led to conflicting results. Fatigue correlates include inflammation, symptoms of depression, sleep disorders and obesity. Fatigue in KTR leads to significant functional impairment, it is common among KTR poorly adherent to immunosuppressive therapy and is associated with a serious deterioration of quality of life. The following databases were searched for relevant studies up to November 2020: Medline, PubMed, Web of Science and the Cochrane Library. Several studies have compared the prevalence and severity of fatigue between KTR and hemodialysis or healthy patients. They have shown that fatigue determines a significant functional deterioration with less chance of having a paid job and a significant change in quality of life. The aim of the review is to report methods to assess fatigue and its prevalence in KTR patients, compared to HD subjects and define the effects of fatigue on health status and daily life. There is no evidence of studies on the treatment of this symptom in KTR. Efforts to identify and treat fatigue should be a priority to improve the quality of life of KTR.
