Poesen Ruben, Meijers Björn, Evenepoel Pieter
Division of Nephrology, Department of Microbiology and Immunology, University Hospitals Leuven, Leuven, Belgium.
Semin Dial. 2013 May-Jun;26(3):323-32. doi: 10.1111/sdi.12082. Epub 2013 Mar 4.
Morbidity and mortality related to chronic kidney disease remain unacceptably high, despite tremendous progress in its prevention and treatment. In an ongoing quest to improve outcome in chronic kidney disease patients, the colon might be an appealing, but largely underexplored, therapeutic target. A clear bi-directional functional relationship exists between the colon and kidney, also referred as to the colo-renal axis. Uremia has an important impact on the colonic microbiome. The microbiome, in turn, is an important source of uremic toxins, with p-cresyl sulfate and indoxyl sulfate as important prototypes. These co-metabolites accumulate in the face of a falling kidney function, and may accelerate the progression of renal and cardiovascular disease. Several therapeutic interventions, including prebiotics and adsorbants, specifically target these colon-derived uremic toxins originating from bacterial metabolism. As kidney function declines, the colon also gains importance in the homeostasis and disposal of potassium and oxalate. Their colonic secretion may be increased by drugs increasing the expression of cAMP and by probiotics (e.g., Oxalobacter formigenes).
尽管在慢性肾脏病的预防和治疗方面取得了巨大进展，但其相关的发病率和死亡率仍然高得令人难以接受。在不断寻求改善慢性肾脏病患者预后的过程中，结肠可能是一个有吸引力但在很大程度上未被充分探索的治疗靶点。结肠和肾脏之间存在明确的双向功能关系，也被称为结肠-肾轴。尿毒症对结肠微生物群有重要影响。反过来，微生物群是尿毒症毒素的重要来源，对甲酚硫酸盐和硫酸吲哚酚是重要的典型代表。随着肾功能下降，这些共代谢产物会蓄积，并可能加速肾脏和心血管疾病的进展。包括益生元和吸附剂在内的几种治疗干预措施专门针对这些源自细菌代谢的结肠源性尿毒症毒素。随着肾功能下降，结肠在钾和草酸盐的稳态及排泄中也变得更加重要。增加环磷酸腺苷表达的药物和益生菌（如产甲酸草酸杆菌）可能会增加它们的结肠分泌。
