This is part of a series of blogs discussing an individualized comprehensive gut restoration protocol in chronic kidney disease.

The Gut-Kidney Connection

Researchers have established a relationship between gut integrity and microbiome diversity with various chronic diseases, including kidney disease. Increased intestinal permeability, also known colloquially as “leaky gut” has been shown to be at the root of this connection. This gut-kidney relationship is the result of complex biochemical and immune mechanisms. 

In our previous blog, we discussed the impact of exposure to food and environmental triggers that impact the gut lining (or mucosa)integrity and microbiome balance. Intestinal permeability (aka “leaky gut”) is the result of inflammatory assault to the gut lining that results in breaks in the integrity of the wall. Imagine it like breaks in a “fence” that let undigested food, bacteria, and metabolites “leak” through the holes.


The physiologic changes associated with this leaky state include a combination of factors including hypochlorhydria (insufficient stomach acid to break down food adequately), reduced production of digestive enzymes, altered bowel motility (often leading to constipation, but not always), and dysbiosis.

As a result of these pathologies, leaky gut leads to increased local and systemic inflammation, poor digestion, reduced nutrient absorption, and reduced ability to remove toxins and digestive byproducts. 

Though we address step two, Replace in more detail below, let’s review the five steps of the comprehensive gut restoration protocol. The 5R Protocol addresses leaky gut as a foundational approach to reduce the risk of progression of CKD. The five areas of GI mucosal integrity: 

1) Remove potential triggers, including polypharmacy, pathogenic organisms, food intolerances, sensitivities and allergies, or toxic exposure.  

2) Replace digestive aid to support improved nutrient absorption and metabolism, including digestive enzymes, or agents that promote improved motility and regular bowel movements.  

3) Reinoculate to provide an environment where good bacteria can thrive and where bad ones cannot. 

4) Repair support of the cellular repair process through the above, as well as by providing specific nutritional support for the regeneration of the GI protective barrier. 

5) Rebalance lifestyle factors that influence the gut bacteria such as stress, sleep, exercise and relationships and assure ongoing gut health.


Due to diet quality, food sensitivities, pathogenic microbes, epithelial inflammation leads to damage to the gut mucosa integrity. This causes damage to the structure of the villi and reduction in the intestinal surface area leading to reduced absorption of nutrients. This is referred to as malabsorption, or poor absorption of nutrients across the gut wall into circulation to be used by the body. 

A second pathology is maldigestion, or ineffective breakdown of nutrients from food. This might be one or more of the major macronutrients, fat, protein, and/or carbohydrates. In these cases, you’ll notice GI distress after eating, bloating, distention, and or excessive flatulence. This not only reduces the effective absorption of essential nutrients necessary for healthy metabolism, but also creates a backup that contributes to increased inflammation, buildup of endotoxins, and further contributing to dysbiosis. 

Furthermore, poor motility can contribute to chronic constipation. It’s been estimated that 20% of the adult population suffers from chronic constipation – that’s 1 in 5 adults! Ideally bowel movements should be daily, easy to pass and as characterized by the Bristol Stool Scale below, smooth soft and formed.

Constipation is not only uncomfortable, but leads to inefficient removal of toxins, recirculation of endogenous hormones, and alteration of the microbiome balance. Furthermore, stool consistency and frequency can be used as clues for clinicians signaling the need for a gut restoration protocol. From there, integrative and functionally trained practitioners can use advanced stool testing that employs a technique called PCR technology as discussed in Part 1 Remove blog.

Where to start?

Assess Nutrient status

Often, we begin by assessing the baseline nutrition status for any micro- or macronutrient deficiencies. These tend to be more significant with long-term maldigestion and malabsorption, depriving the body of necessary vitamins, minerals, amino acids, and essential fats needed for healthy function. Supplementation is often necessary, but dietary adjustments can be made to optimize absorption from food as long as digestion and motility are also addressed (see below)

Assessment can be done by physical exam to detect signs and symptoms of nutrient deficiency – for example dry hair and skin, brittle nails, bleeding gums, and difficulty digesting animal protein or fat can all be indications of various nutrient malabsorption/depletion or maldigestion. 

Furthermore, laboratory assessment of nutrient status can confirm specific deficiency and help us target key nutrients strategically to customize the therapeutic approach. 

Address Maldigestion and Malabsorption

To enhance digestion, use of broad-spectrum digestive enzymes such as lipase and bile salts, proteases, and cellulases that break down fats, proteins and carbohydrates, respectively is necessary because the digestive tract isn’t producing sufficient enzymes to breakdown and absorb nutrients form food. In addition, betaine HCL, a digestive aid that address low hydrochloric acid (hypochlorhydria) in the stomach may also be necessary to improve gastric pH.

Herbs and foods can also be useful for improving nutrient absorption and motility. For example, pineapple, papaya, and bitter foods like dandelion greens can be helpful for aiding digestion, stimulating motility and digestive enzyme production. Eating beets and staying hydrated promotes bile salt flow. Fermented and fiber-rich foods can also help promote motility and healthy microbial balance (though sometimes we don’t introduce these until step 3: Reinoculate). Last but not least, traditional concoctions of herbal bitters and teas can be very helpful in promoting this process.    

Address Motility

We cannot emphasize enough how important it is to have at least one daily bowel movement for overall health. That is why integrative and functional practitioners will often prioritize resolving constipation. Bulk laxatives, stool softeners, and stimulants can be useful as a short-term strategy but are only a band-aid. It’s important to understand the underlying causes and address it: slow motility and dysbiosis.

Restoring stool frequency and consistency to ideal can be a challenging and time-consuming process with involves multiple aspects of the 5R protocol. Useful tools include supplements like magnesium citrate, triphala, Swedish bitters, electrolyte replacement and hydration, increasing fiber (dietary and supplemental) as well as stimulating the migrating motor complex and balancing the HPA axis (stress response) through lifestyle modifications including exercise, massage, gargling and stress management.     

Bottom Line

The second step in an individualized comprehensive gut restoration protocol involves promoting improved nutrient status and motility by exogenously replacing the necessary enzymes and nutrients needed. This is often done simultaneously to the Remove step, but in some cases, it’s addressed in sequence. It’s important to work with an integrative or functional medicine provider trained in the comprehensive gut restoration protocol to help you navigate this successfully.

Next, we will tackle the third “R” in the gut restoration protocol: Reinoculate.