There are 130 uremic solutes according to the research group, EuTox. Blood urea nitrogen and creatinine are only two of these solutes and are simply used as surrogate markers for the other 128. Of these uremic solutes, two of the most extensively studied are indoxyl sulfate and p-cresyl sulfate. They have been shown to have a variety of deleterious effects on body tissues including tubular cell damage, coagulation disturbances, endothelial dysfunction, leukocyte activation, cardiac fibrosis and hypertrophy, and insulin resistance (Vanholder 2014)).
Interestingly, these two solids are derived from the metabolism of the gut microbiome. In an interesting study (Aronov 2011), metabolomic profiles of dialysis patients with colons and without colons or compared. These two compounds are virtually absent in dialysis patients without colons indicating that they are derived from the gut microbiome. There are multiple other colon-derived uremic solids, but these two in particular are important because they are actually shown to have harmful effects on the body and they are tightly albumin-bound meaning that they have poor clearance with hemodialysis.
In addition to producing uremic solutes, the gut microbiome has a variety of beneficial effects on the body, including vitamin synthesis, immune system development, and production of short-chain fatty acids which our colon enterocytes use for energy, thus helping maintain the integrity of the gut epithelial barrier (Barrows 2015, Hooper 2002, Kasubuchi 2015). Unfortunately, chronic kidney disease and some of the medications used in it’s treatment cause dysbiosis, reducing some beneficial effects of the gut microbiome. The field of gut microbiome research is a hot topic right now and it will be an important one to watch in the coming years. It is important for us not only because some uremic solutes are made by the colon, but also because CKD and other treatments for renal disease affect the gut microbiome.
References:
Aronov, P. A., Luo, F. J. G., Plummer, N. S., Quan, Z., Holmes, S., Hostetter, T. H., & Meyer, T. W. (2011). Colonic contribution to uremic solutes. Journal of the American Society of Nephrology, 22(9), 1769-1776.
Barrows, I. R., Ramezani, A., & Raj, D. S. (2015). Gut Feeling in AKI: The Long Arm of Short–Chain Fatty Acids.
Hooper, L. V., Midtvedt, T., & Gordon, J. I. (2002). How host-microbial interactions shape the nutrient environment of the mammalian intestine. Annual review of nutrition, 22(1), 283-307.
Kasubuchi, M., Hasegawa, S., Hiramatsu, T., Ichimura, A., & Kimura, I. (2015). Dietary gut microbial metabolites, short-chain fatty acids, and host metabolic regulation. Nutrients, 7(4), 2839-2849.
Vanholder, R., Schepers, E., Pletinck, A., Nagler, E. V., & Glorieux, G. (2014). The uremic toxicity of indoxyl sulfate and p-cresyl sulfate: a systematic review. Journal of the American Society of Nephrology, 25(9), 1897-1907.