Capasso Giovambattista, Franssen Casper F M, Perna Alessandra F, Massy Ziad A, Menzies Robert I, Zoccali Carmine, Tessitore Alessandro, Nedergaard Maiken, Okusa Mark D, Ortiz Alberto, Wagner Carsten A, Unwin Robert J
Biogem, Institute of Molecular Biology and Genetics, Ariano Irpino, Italy.
Department of Translational Medical Science, University of Campania Luigi Vanvitelli, Naples, Italy.
Nat Rev Nephrol. 2025 Apr 25. doi: 10.1038/s41581-025-00963-0.
Cognitive impairment is highly prevalent among individuals with chronic kidney disease (CKD). Despite its high prevalence, the contributing factors and mechanisms underlying brain-kidney dysfunction in CKD remain poorly understood. However, advances in neuroscience, including novel imaging techniques and cognitive assessment methods, have begun to clarify this complex relationship. Several factors contribute directly to cognitive decline in people with CKD, including accumulation of uraemic toxins, microvascular damage, malnutrition, chronic inflammation and disruptions in key neuroprotective pathways, such as those involving Klotho and the glymphatic system. These factors are also linked to the accelerated ageing observed in people with CKD, a key contributor to cognitive decline. However, most studies on cognition in people with CKD have been cross-sectional and associative, offering limited insight into causation. Research advances, such as studies on the effect of uraemic toxins on the blood-brain barrier and the role of the endothelial glycocalyx in vascular damage, offer promising new directions. Emerging data from longitudinal cohort studies are also enhancing our understanding of these processes, with potential implications for both the treatment of CKD-related cognitive decline and the broader issue of cognitive dysfunction in ageing populations. Here, we examine key mechanisms linking CKD to cognitive decline and consider potential therapeutic interventions.
认知障碍在慢性肾脏病（CKD）患者中极为普遍。尽管其患病率很高，但CKD患者脑-肾功能障碍的促成因素和潜在机制仍知之甚少。然而，神经科学的进展，包括新型成像技术和认知评估方法，已开始阐明这种复杂的关系。有几个因素直接导致CKD患者的认知能力下降，包括尿毒症毒素的蓄积、微血管损伤、营养不良、慢性炎症以及关键神经保护途径的破坏，如涉及Klotho和类淋巴系统的途径。这些因素还与CKD患者中观察到的加速衰老有关，而加速衰老是认知能力下降的一个关键因素。然而，大多数关于CKD患者认知的研究都是横断面研究且为关联性研究，对因果关系的洞察有限。研究进展，如关于尿毒症毒素对血脑屏障的影响以及内皮糖萼在血管损伤中的作用的研究，提供了有前景的新方向。纵向队列研究的新数据也在增进我们对这些过程的理解，对治疗CKD相关的认知能力下降以及老年人群中更广泛的认知功能障碍问题都有潜在影响。在此，我们研究将CKD与认知能力下降联系起来的关键机制，并考虑潜在的治疗干预措施。
