UREMIC DYSBIOSIS: a unique CKD truth

by Robin Rose MD

I had the honor of being interviewed by Vivian Asamoah MD, a functional gastroenterologist [the video will get posted here once its available]. I gathered some notes together to do this interview and decided to share them as a blog. Understanding the nature of dysbiosis and leaky gut is critical to CKD success - making it a priority in lifestyle choices is necessary self-care. Teaching our patients about the what why and how is not optional.

Uremia means toxins are accumulating because filtration is inadequate to remove dangerous substances from the body via the urine. Many things that are apparently safe for non-CKD people can be uremic toxins in CKD - the list grows longer as we recognize this hazardous array. Recognition is a gift when action follows to remediate.

Let's look.

In CKD, uremia plus leaky gut can lead to progression of kidney decline with enhanced inflammation and cardiovascular compromise [which is the way to demise in the majority of CKD cases]. When there is decreased waste excretion ---:::> uremic toxins accumulate --::> this leads to organ effects --::> changes in the array of gut microbes then leads to an excess of 'bad' microbes that induce disease.

1. Increased Uremic Toxins - [known as uremic retention solutes] cause production of bacterially-metabolized proteins --::> this results in formation of [toxic] indoles, phenols, and ammonia. These are usually cleared by healthy kidneys. So unfortunately in CKD... these uremic toxins can rise and threaten homeostasis and health.

2. Leaky gut - means there's a breach in the integrity of the gut barrier, allowing substances meant for excretion [endotoxins, uremic toxins] to slip through the colon cells and enter the blood --::> leading to enhanced inflammation, CKD progression and cardiovascular assault.

3. Abnormal metabolism of dietary components - there is a decrease in the fermenting bacteria needed to thrive --::> we see decreased short chain fatty acid production, which are kidney protective

4. Altered microbiome - this presents a serious challenge to the body, remedied by awareness, testing, lifestyle changes, dietary willingness, and supplementation

   
   

   DYSMOTILITY means that the rhythmic pulsatile action of the gut [from stomach to anus] becomes altered, a notable problem often presenting in CKD. There are many consequences [a separate conversation]. Suffice it to say that one big consequence in CKD is diminished small intestinal water produced after eating --::> this results in increased endotoxins - unpleasant players in the inflammatory surge that makes CKD worse.

   
   

   STUDIED UREMIC TOXINS

   There are many of these players, and some have been studied extensively- I will review these briefly. These begin forming in early CKD, so exploring/testing and remediating the gut microbiome has a definite role in slowing down the inflammation common to all kinds of CKD - early bird intervention means less twang to nephrons trying to repair themselves.

   
   

   The assimilation - digestion, metabolism, and absorption - of dietary proteins is impaired in CKD . When proteins aren't metabolized in the small intestine, they are further metabolized in the large intestine by proteolytic bacteria --::> these cause toxins to form. Comorbidities like diabetes and metabolic acidosis and liver problems enhance this undesirable effect.

   
   

   INDOXYL SULFATE -:> IS <:- this cardiotoxin can result in vascular disease, with the dread outcome of glomerular sclerosis and interstitial fibrosis [unfortunate scarring in the kidney that interferes with function]. It is made by 'bad bugs' in the GI tract [like E. coli] affecting amino acid tryptophan from the diet. This results in TMA = tri-methyl-amine,= as a result of carnitine and choline in the diet. My book Renology Peptides explains this in detail, - but when TMA is oxidized, it becomes TMAO and is a very bad actor - causing vasciular disease and kidney decline.

   
   

   Treatment is very important for achieving kidney success. Dietary protein needs to be monitored [cronometer.com makes it possible to actually know how much protein is in your daily diet - otherwise its mere guess work]. A ballpark recommendation for CKD is 0.6-0.8grams of protein per kilo of optimal body weight. Increasing fiber in the diet is important. Each case must be personalized, but the diet is the saving grace.

   
   

   And acacia senegal- a fiber supplement that is a powder - is slowly added to the daily fare [start with 1 teaspoon and increase slowly over time to max 5 teaspoons, honoring the requirement to optimize hydration lest it cause impacted stool]. Acacia senegal also swabs up uremic toxins in the gut [including creatinine], assisting in their excretion - using the gut to support the kidneys is wise. It functions as a prebiotic and feeds the colon cells the beneficial short chain fatty acid butyrate.

   
   

   Also probiotics are essential players. Diet first - many ways to include fermented foods and drinks into the daily fare [learn to make them at home]. Include Spore-biotics to support gut health. Activated charcoal has been observed to help [research looked at AST-120].

   
   

   pCRESYL SULFATE --:> pCS <:-- similar story - caused by many different bad endotoxic microbes in the gut - acting this time on the aromatic amino acids tyrosine and phenylalanine from the diet. Endothelial damage and oxidative damage are enhanced, with NADPH oxidase and reactive oxygen species produced in cardiomyocytes and diastolic dysfunction as a consequence. Toxic effects on tubular cells suppresses Klotho expression by hypermethylation. There is activation of the RAAS system, with "epithelial-to-mesenchymal" transition - meaning scarring. pCS's role in insulin resistance is also known. This uremic toxin is not cleared by dialysis. Again, as noted above, therapeutic strategies can mediate these untoward effects. Make good choices and enjoy positive consequences. Providing laxative interventions to avoid any dysmotility-induced constipation is really useful.

   
   

   LIVER-KIDNEY AXIS

   From the Renology Peptide Bioregulator perspective, including liver awareness makes it more possible to succeed.

   
   

   Gut endotoxins translocate from the colon to mesenteric lymph nodes --::> through the portal circulation --::> excretion of PAMPs [pathogen associated molecular patterns] is decreased in CKD.

   
   

   When urea increases in CKD, microbes make ammonia --::> this increases gut permeability - more leaky! --::> producing more nephrotoxic molecules. Uremic toxins in the liver convert to ROS [reactive oxygen species] causing vascular injury. That's when TMA becomes TMAO, with decreased cholesterol transport and worsenining of atherosclerosis [enhanced by CKD].

   
   

   Liver bioregulators can be integrated into a protocol in this situation, along with consideration of kidney, vascular, and [see below] stomach. Vilon is a useful helper in this situation as well. Including BPC157, KPV, and Larazotide has been suggested by our functional gastroenterologist - each case personalized and supported by an educated clinician. Knowing when the place these, how to sequence and cycle them is the art.

   
   

   KIDNEY-STOMACH AXIS

   Gastroparesis is a common dysmotility issue in CKD, especially in diabetics. The stomach pulsation slows down. This can dysregulate electrolytes, cause mucosal edema, and cause direct effects of the uremic toxins. We know!!!! that the PPI medications like prilosec are kidney-hazardous and contraindicated in CKD [worsening nephritis, cardiovascular diease, decreasing iron, magnesium, causing bone changes and infections]. The reknowned nephrologist Dr. Vaziri teaches us that the uremic toxins cause epithelial barrier changes along the entire GIT. Zonulin [the regulator of intestinal permeability] is significantly lower in CKD, even early on.

The stomach bioregulator peptide can be bundled with kidney and liver and vascular PBs. Again, Renology Peptides is a guide for how to use these therapeutic tools in CKD

GUT HEALTH is KIDNEY HEALTH and SUCCESS! Keep learning about this. I will add more content as time goes on. Be well!!