The association of cognition with protein energy wasting and synaptic transmission in chronic kidney disease

Abstract

AbstractIntroduction: In recent years, consciousness impairment in patients with end‐stage renal disease (ESRD) has been paid more and more attention, but the cause and mechanism of consciousness state change is not clear. Methods: As the hippocampus played a crucial role in consciousness, we explored the pathological and electrophysiological changes in chronic kidney disease (CKD) mouse hippocampus. Results: Whole‐cell recordings in hippocampal neurons showed that miniature excitatory postsynaptic current (mEPSC) frequency decreased, but the amplitude was unaltered in CKD_8w mice. In addition, α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazole‐propionic acid receptor‐mediated EPSCs (AMPAR‐EPSCs) and N‐methyl‐D‐aspartic acid receptor‐mediated EPSCs (NMDAR‐EPSCs) in hippocampal Schaffer collateral‐CA1 synapses displayed a significant decline in CKD_8w mice. Although the ratio of AMPAR‐/NMDAR‐EPSCs did not change, the paired‐pulse ratio (PPR) in CKD_8w mice increased. Intriguingly, the mEPSC frequency and AMPAR‐/NMDAR‐EPSCs amplitudes were positively associated with body weight, and the mEPSC frequency was negatively correlated with serum creatinine in CKD_8w mice, indicating a potential correlation between cognition and nutritional status in patients with CKD. To confirm the above hypothesis, we collected the clinical data from multiple hemodialysis centers to analyze the correlation between cognition and nutritional status. Conclusion: Our analysis indicated that protein energy wasting (PEW) was a possible independent risk factor for consciousness dysfunction in maintenance hemodialysis (MHD) patients. Our results provided a more detailed mechanism underlying the cognitive impairment (CI) in ESRD patients at the synaptic level. Last but not least, our results showed that PEW was a probable new independent risk factor for CI in cases with ESRD.