Nephrologisches Zentrum, Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, Munich, Germany.
Kidney Int. 2013 Jun;83(6):1010-6. doi: 10.1038/ki.2012.440. Epub 2013 Jan 16.
Chronic kidney disease (CKD) and end-stage renal disease (ESRD) are associated with systemic inflammation and acquired immunodeficiency, which promote cardiovascular disease, body wasting, and infections as leading causes of death. This phenomenon persists despite dialysis-related triggers of immune deregulation having been largely eliminated. Here we propose a potential immunoregulatory role of the intestinal microbiota in CKD/ESRD. We discuss how the metabolic alterations of uremia favor pathogen overgrowth (dysbiosis) in the gut and an increased translocation of living bacteria and bacterial components. This process has the potential to activate innate immunity and systemic inflammation. Persistent innate immune activation involves the induction of immunoregulatory mediators that suppress innate and adaptive immunity, similar to the concept of 'endotoxin tolerance' or 'immune paralysis' in advanced sepsis or chronic infections. Renal science has largely neglected the gut as a source of triggers for CKD/ESRD-related immune derangements and complications and lags behind on the evolving microbiota research. Interdisciplinary research activities at all levels are needed to unravel the pathogenic role of the intestinal microbiota in kidney disease and to evaluate if therapeutic interventions that manipulate the microbiota, such as pre- or probiotics, have a therapeutic potential to correct CKD/ESRD-related immune deregulation and to prevent the associated complications.
慢性肾脏病 (CKD) 和终末期肾病 (ESRD) 与全身炎症和获得性免疫缺陷有关，这些会导致心血管疾病、身体消瘦和感染，成为主要的死亡原因。尽管透析相关的免疫失调触发因素已基本消除，但这种现象仍然存在。在这里，我们提出肠道微生物群在 CKD/ESRD 中的潜在免疫调节作用。我们讨论了尿毒症的代谢改变如何有利于肠道中病原体的过度生长（失调）和活细菌及其成分的增加易位。这个过程有可能激活先天免疫和全身炎症。持续的先天免疫激活涉及诱导抑制先天和适应性免疫的免疫调节介质，类似于晚期脓毒症或慢性感染中“内毒素耐受”或“免疫麻痹”的概念。肾脏科学在很大程度上忽视了肠道作为 CKD/ESRD 相关免疫紊乱和并发症的触发因素的来源，并且在不断发展的微生物组研究方面落后了。需要在各个层面开展跨学科研究活动，以揭示肠道微生物群在肾脏疾病中的致病作用，并评估是否可以通过操纵微生物群的治疗干预措施（如益生菌或益生元）来纠正 CKD/ESRD 相关的免疫失调并预防相关并发症。
