Department III of Internal Medicine, Heart Center, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany.
Center for Molecular Medicine Cologne, University of Cologne, Cologne, Germany.
Basic Res Cardiol. 2022 Jul 27;117(1):38. doi: 10.1007/s00395-022-00945-4.
Chronic kidney disease's prevalence rises globally. Whereas dialysis treatment replaces the kidney's filtering function and prolongs life, dreaded consequences in remote organs develop inevitably over time. Even milder reductions in kidney function not requiring replacement therapy associate with bacterial infections, cardiovascular and heart valve disease, which markedly limit prognosis in these patients. The array of complications is diverse and engages a wide gamut of cellular and molecular mechanisms. The innate immune system is profoundly and systemically altered in chronic kidney disease and, as a unifying element, partakes in many of the disease's complications. As such, a derailed immune system fuels cardiovascular disease progression but also elevates the propensity for serious bacterial infections. Recent data further point towards a role in developing calcific aortic valve stenosis. Here, we delineate the current state of knowledge on how chronic kidney disease affects innate immunity in cardiovascular organs and on a systemic level. We review the role of circulating myeloid cells, monocytes and neutrophils, resident macrophages, dendritic cells, ligands, and cellular pathways that are activated or suppressed when renal function is chronically impaired. Finally, we discuss myeloid cells' varying responses to uremia from a systems immunology perspective.
慢性肾脏病的发病率在全球范围内呈上升趋势。透析治疗虽然可以替代肾脏的过滤功能并延长生命，但随着时间的推移，远程器官不可避免地会出现可怕的后果。即使是不需要替代治疗的轻度肾功能下降，也与细菌感染、心血管和心脏瓣膜疾病相关，这显著限制了这些患者的预后。并发症的种类繁多，涉及广泛的细胞和分子机制。慢性肾脏病会导致固有免疫系统发生深刻而系统性的改变，并且作为一个统一的元素，参与了许多疾病的并发症。因此，失调的免疫系统会促进心血管疾病的进展，但也会增加严重细菌感染的倾向。最近的数据进一步指出了其在发展钙化性主动脉瓣狭窄中的作用。在这里，我们阐述了慢性肾脏病如何影响心血管器官和全身固有免疫的现有知识状态。我们回顾了循环髓样细胞、单核细胞和中性粒细胞、固有巨噬细胞、树突状细胞、配体以及当肾功能慢性受损时被激活或抑制的细胞途径的作用。最后，我们从系统免疫学的角度讨论了髓样细胞对尿毒症的不同反应。
