Wagner Carsten A, Massy Ziad A, Capasso Giovambattista, Mattace-Raso Francesco, Pepin Marion, Bobot Mickaël, Zoccali Carmine, Ferreira Ana C, Hoorn Ewout J, Imenez Silva Pedro H, Unwin Robert J, Pesic Vesna
Department of Physiology and Zurich Kidney Center (ZKC), University of Zurich, Zurich, Switzerland.
Clinical Epidemiology, Inserm Unit 1018, CESP, Hôpital Paul Brousse, Paris-Sud University (UPS) Villejuif, France.
Nephrol Dial Transplant. 2025 Apr 1;40(4):621-631. doi: 10.1093/ndt/gfae229.
Cognitive decline is common in patients with acute or chronic kidney disease. Several areas of brain function can be affected, including short- and long-term memory, attention and inhibitory control, sleep, mood, eating control and motor function. Cognitive decline in kidney disease shares risk factors with cognitive dysfunction in people without kidney disease, such as diabetes, high blood pressure, sedentary lifestyle and unhealthy diet. However, additional kidney-specific risk factors may contribute, such as uremic toxins, electrolyte imbalances, chronic inflammation, acid-base disorders or endocrine dysregulation. Traditional and kidney-specific risk factors may interact to cause damage to the blood-brain barrier, induce vascular damage in the brain and cause neurotoxicity or neuroinflammation. Here, we discuss recent insights into the pathomechanisms of cognitive decline from animal models and novel avenues for prevention and therapy. We focus on a several areas that influence cognition: blood-brain barrier disruption, the role of skeletal muscle, physical activity and the endocrine factor irisin, and the emerging therapeutic role of sodium-glucose cotransporter 2 (SGLT2) inhibitors and glucagon-like peptide 1 (GLP-1) receptor agonists. Taken together, these studies demonstrate the importance of animal models in providing a mechanistic understanding of this complex condition and their potential to explain the mechanisms of novel therapies.
认知功能下降在急慢性肾病患者中很常见。大脑功能的几个方面可能会受到影响，包括短期和长期记忆、注意力和抑制控制、睡眠、情绪、饮食控制和运动功能。肾病中的认知功能下降与非肾病患者的认知功能障碍有共同的危险因素，如糖尿病、高血压、久坐不动的生活方式和不健康的饮食。然而，其他肾脏特异性危险因素也可能起作用，如尿毒症毒素、电解质失衡、慢性炎症、酸碱紊乱或内分泌失调。传统危险因素和肾脏特异性危险因素可能相互作用，导致血脑屏障受损、诱发脑部血管损伤并引起神经毒性或神经炎症。在此，我们讨论了从动物模型中获得的关于认知功能下降发病机制的最新见解以及预防和治疗的新途径。我们重点关注几个影响认知的领域：血脑屏障破坏、骨骼肌的作用、身体活动和内分泌因子鸢尾素，以及钠-葡萄糖协同转运蛋白2（SGLT2）抑制剂和胰高血糖素样肽1（GLP-1）受体激动剂新出现的治疗作用。综上所述，这些研究证明了动物模型在提供对这种复杂病症的机制理解及其解释新疗法机制的潜力方面的重要性。
