Oral Adsorbents, Probiotics an Inexpensive Way to Eliminate Uremic Toxics in CKD Patients
Probiotics could correct derangements of the GI tract.
Ultimately, this translates into a diet low in fiber and micronutrients and high in fat. While the conventional diet, if followed as prescribed, may keep serum potassium and phosphorus within normal ranges, it can also contribute to altered gastrointestinal (GI) function and, potentially, micronutrient inadequacies.
The GI tract is a metabolically active organ that contributes to immune function and availability of amino acids, glucose, lipids, and micronutrients for further metabolic conversion by the liver. Additionally, the GI tract harbors a huge populations of bacteria, which in turn contribute to the metabolic status of the body. It is thought that the human intestinal tract contains over 1014 bacteria with over 500 different types (J Renal Nutr 2005;15:77-80).
It has been suggested that derangements of the GI tract occur when chronic kidney disease (CKD) develops. For instance, bacteria in the gut become more aerobic verses anaerobic. Escherichia coli and Bifidobacterium are examples of aerobic and anaerobic bacteria, respectively.
The balance between these two bacteria types can become altered and may result in an increase in toxins and a decrease in available nutrients. Potential therapies to improve mortality and overall health could target the GI tract by correcting the balance between aerobic and anaerobic microbes via bacteria supplementation (e.g., probiotics), eliminating toxins through fecal waste (gut sorbents), or providing substrate, such as fiber, to support a particular type of bacteria (e.g. prebiotics).
Indoxylsulfate and p-cresolsulfate are two uremic toxins that have been studied as they relate to CKD. Both toxins are associated with negative outcomes in the CKD population.
Indoxylsulfate causes inflammation, endothelial dysfunction, and disturbances of bone metabolism, and is associated with a loss of renal function (Blood Purif 2010;29:130-136); p-cresolsulfate is a pro-inflammatory molecule that impacts monocytes and lymphocytes. Additionally, in observational studies, p-cresol, which is converted to p-cresolsulfate, is associated with mortality, cardiovascular disease, infectious complications, and uremic symptoms.
The production of indoxylsufate and p-cresolsulfate begins in the GI tract. Aerobic bacteria have an enzyme called tryptophanase, which converts tryptophan in the bowel to indole. Indole is absorbed into the blood from the GI tract and travels to the liver, where it is converted into indoxyl sulfate. Similarly, tryosine in the bowel is converted to p-cresol.
To reduce the amount of toxins produced, patients would need to consume less tryptophan or tyrosine, both of which are found in high-protein foods, or absorb and eliminate the precursors before they leave the bowel. Low-protein diets are recommended for pre-dialysis patients; however, that type of diet would not be recommended for dialysis patients. Therefore, oral adsorbents and pre- and probiotics have been suggested. An oral adsorbent “absorbs” the urea and other toxins and eliminates them via feces.
AST-120 is an oral adsorbent that has been studied in rats and humans. In a Japanese study with CKD patients, AST-120 was compared with standard care. The dialysis-initiation-free rate was significantly higher in the AST-120 group compared with the non-AST-120 group at 12 and 24 months (25% and 13.7%, respectively vs. 10.5% and 5.7%, respectively). However, this improved rate did not translate into improved survival rates in the AST-120 group (Int J Nephrol 2012; published online ahead of print. Curr Med Res Opin. 2009;25:1913-1918).
Finally, pre- and probiotics together in a symbiotic have been tested in hemodialysis (HD) patients to see if the amount of p-cresol could be reduced (Nephrol Dial Transplant 2011;26:1094-1098). The symbiotic was tested in nine HD patients for two weeks. The patients were surveyed on their bowel habits and p-cresol was measured pre and post treatment. At the end of treatment, p-cresol significantly decreased and stool volume and consistency had improved.
These types of interventions may be less expensive and have far reaching positive effects on patients' overall health, but substantially more research needs to be done in this area before these therapies can become standard practice.