A study published in 2012 found that more than 64 million Americans aged 30 or older had periodontal (gum) disease. Gum disease, also known as periodontitis, is a severe infection of the gums caused by an immune response to imbalanced oral bacteria. Inflammation from periodontal disease can damage gums, destroy the jawbone, and lead to tooth loss. Several studies have shown an association between periodontal disease and other systemic diseases such as heart disease, diabetes, cancer, and dementia. But what about the association between dental health and kidney disease? In this blog, I am going to explore that link.
Periodontal disease and systemic inflammation
The oral microbiome produces metabolic by-products in the mouth. Some of these by-products leak into the blood stream and lead to a low-grade systemic inflammation. Studies have shown that patients with severe periodontitis have elevated levels of pro-inflammatory mediators and increased neutrophil numbers in the blood. In fact, successful treatment of gum disease was associated with improvement in inflammatory markers. Many of these inflammatory markers have been linked to heart disease, diabetes, and other diseases. This may explain the link between periodontal disease and systemic diseases.
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CKD is an inflammatory state
Low-grade inflammation has been shown to be an integral aspect of chronic kidney disease (CKD). Here, too, inflammatory markers were found to be elevated. As kidney function worsens, the levels of these markers increase in the body. They also increase with increasing urine protein (albuminuria), which is common in CKD.
On the other hand, an evaluation of the Chronic Renal Insufficiency Cohort (CRIC) study found that elevated inflammatory markers were associated with rapid progression of kidney disease. So, the relationship between inflammation and kidney disease is bidirectional. CKD can lead to inflammation and inflammation can lead to and worsen CKD.
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Can gum disease cause kidney problems?
Periodontitis can increase the risk of CKD by direct and indirect effects. Directly, periodontitis increases systemic inflammatory burden leading to an increased incidence of CKD. In a recent review of 37 studies, researchers found strong evidence that periodontitis is associated with an increased risk for CKD. This association remained strong after adjusting for other risk factors.
Periodontitis can also increase the risk for CKD indirectly by increasing the risk for insulin resistance and diabetes. In this study, diabetes increased the odds of CKD by twofold, and 6.5% of this effect was mediated by periodontitis.
In addition, some of the increased risk of CKD may have to do with genetics. For example, variants in vitamin D receptor gene were associated with CKD during inflammatory conditions caused by periodontal disease.
There is not a lot of data on how treating gum disease affects CKD. However, in this pilot study, researchers found that treating severe chronic periodontitis for 180 days led to improvement of all periodontal clinical parameters. This was associated with statistically significant improvement in kidney function and markers of inflammation.
CKD and periodontitis: Does kidney disease affect oral health?
On the other hand, CKD can affect oral health by inducing gum overgrowth (known as gingival hyperplasia), dry mouth, calcification of root canals, and delayed eruption of teeth in children. These can lead to increased risk of periodontal disease. In addition, severe periodontal disease was found to be more common in patients with more severe CKD.
Kidney disease, gum disease, and nutrition
There is a triangular interaction between nutrients, CKD, and periodontal disease. Protein wasting that is common in kidney disease, for example, can increase the risk of periodontal disease. Omega-3 fatty acids, on the other hand, were found to be beneficial in the management of chronic periodontitis. Many other nutrients and micronutrients that can be altered in CKD were also associated with periodontal disease.
CKD medications may cause gum and teeth problems
Some of the medications that are used for patients with CKD can also increase the risk for periodontitis. Medications such as calcium channel blockers that are used to treat blood pressure can lead to gum swelling and overgrowth. This was also noted in some transplant medications such as cyclosporine. Other medications can be associated with dry mouth, which can promote gum and teeth problems. These include ACE inhibitors, calcium channel blockers, betablockers, and diuretics.
The bottom line on chronic kidney disease and oral health
Both periodontal disease and CKD are associated with low-level systemic inflammation. The association between the two is bidirectional. Periodontal disease can increase the risk for CKD and the rate of its progression. On the other hand, CKD can also worsen periodontal disease. Paying attention to oral health is essential for the prevention of many chronic diseases. It is also crucial for preventing or slowing down the progression of CKD.
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The root cause of IgA nephropathy
IgA nephropathy is a kidney disease that is defined by the pathologic appearance of glomerular deposition of IgA immune complexes. However, this definition does not address the root cause of the disease.
It has been increasingly recognized that IgA immune complex that deposit in the kidneys predominantly contain polymeric IgA1 lacking galactose within its O-glycosylated hinge region.
In this study, researchers found that patients with IgA nephropathy have elevated levels of certain B cells that are enriched for λ light chains. These cells are predestined for homing to upper respiratory and digestive tract mucosal tissues. In the mucosal tissues, these B cells mature and excrete abnormal IgA in the setting of upper respiratory or digestive infection. You can read more IgA nephropathy by reading our blog here.
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Metformin: Some people love it and some people hate it… But it sure is getting a lot of attention lately
This study was done in rats with “non-diabetic kidney disease.” CKD was established in these rats by feeding them high adenine diet. Then they were randomized to receive either metformin or canagliflozin (an SGLT-2 inhibitor).
Metformin, but not canagliflozin, halted the decline in kidney function. Additionally, kidneys of metformin-treated animals showed less interstitial area and inflammation as compared to the vehicle group.
Metformin is increasingly being studied in humans for various kidney diseases. If used judiciously it may be a cheap alternative to preserving kidney function.
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Tremor + gum disease + nephrotic Syndrome = ?
In this study, investigators in Beijing looked into the manifestation of mercury poisoning in 172 patients. 26.74% of these patients had kidney injury (3/4 were women) and most of them had nephrotic syndrome. The most common finding on the biopsy was membranous nephropathy.
Other findings of chronic mercury poisoning were neurotoxicity and gingivitis. Chelation with DMPS alone was as effective as chelation and prednisone in reversing kidney injury.
The most common source of exposure without kidney disease was industrial exposure. Interestingly, the most common source of exposure leading to kidney disease was cosmetics containing ionic mercury (mercury concentration in one of the patients cosmetic was 4600 mg/kg – national standards are < 1 mg/kg).
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Root Causes of Itching in Kidney Disease
Uremic toxin-induced neurologic changes
Several studies showed that patients with CKD have an imbalance of opioid receptors in the central and peripheral nervous system. Interestingly, itching in CKD correlates better with the level of uremic toxins than with glomerular filtration rate (GFR, a measurement of how well the kidneys are working). These toxins play an important role in these neurologic changes that are common in CKD. Most of these toxins are generated by the gut microbiome and are excreted by the renal tubules and not by glomerular filtration (or GFR). Measuring these toxins can be helpful. This can be done by a metabolomic test such as Genova’s Metabolomix+.
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Inflammation
CKD is an inflammatory disorder. Elevated inflammatory markers have been found to be associated with itching in kidney disease. Measuring inflammatory markers such as hsCRP, Th-1 cells, and IL-6 can be helpful in the assessment of the root cause of itching in CKD.
Dehydration
Dehydration can also lead to dry skin and worsens itching in CKD patients. Correcting the dehydration can be important in the management of itching.
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Drug-induced itching
Many medications that are used in CKD have been associated with itching. These include calcium channel blockers, hydrochlorothiazide, and ACE inhibitors. In addition, other medications such as opioids, anticoagulants, and antibiotics can cause itching.
The itch-scratch-itch cycle
One of the major problems with itching is that it leads to scratching, and this can cause skin damage. The latter can cause further itching and the cycle continues.
Natural Treatments for itching in kidney disease
There are many steps you can take to get rid of itching in kidney disease and a kidney disease rash. The first step is to visit a healthcare provider to help you determine the root cause. You can download this two-page handout to guide you in the natural treatment of itching. There is hope that you’ll relieve this frustrating problem and have comfortable skin once again.
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Air pollution is linked to kidney disease
PM 2.5 refers to particulate matters that are up to 2.5 microns in size. Because of their small size, they are considered to be the worst of all air pollutants. They reach the alveoli and enter the blood stream. This study looked at the link between PM 2.5 and chronic kidney disease (CKD) in the Twin-cities area of Minnesota. Researchers found that the risk of CKD increases with higher levels of PM 2.5. This remained true after adjusting to all other variable.
It is, therefore, important to think of air pollution as a mediator of CKD and minimize exposure to it.
Block "fundamentals" not found
A Study reaffirms the role of the gut kidney connection in diabetic kidney disease
You know we discussed the role of the gut-kidney connection in the progression of CKD. You can find many of our blogs discussing this here. Dysbiosis can be a predisposing factor or a mediator when it comes to kidney disease. This study looked at the contribution of impairment in the intestinal barrier (leaky gut) to kidney injury in diabetic kidney disease (DKD). In diabetic mice with impaired intestinal integrity intestine-derived Klebsiella oxytoca and elevated IL-17 were detected in the circulation. This was associated with epithelial renal tubular injury and faster progression to kidney failure as compared to control.
So, always think about the gut when it comes to kidney disease. A personalized comprehensive gut restoration protocol is a must to heal the gut.
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A gut-derived uremic toxin is associated with inflammation
Speaking of the gut, we discussed monocyte to HDL ration (MHR) in a previous email. If you missed it, you can read about it on our Instagram page. This study looked at the connection between Indole-3-acetic acid which is a gut-derived uremic toxin and MHR in patients with kidney disease. The study was conducted on 67 patients with CKD. Researchers found that Indole-3-acetic acid levels are directly related to MHR levels. The latter was associated with higher levels of fibrinogen, arterial hypertension, CRP.
So, as they say, when in doubt think about the gut.
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By Lara Zakaria, PharmD, CNS, CDN, IFMCP
The Gut-Kidney Connection
In this series we examine the comprehensive gut restoration protocol used to as a foundational approach to heal gut integrity. 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 blogs, we discussed the impact of exposure to food and environmental triggers that impact the gut lining (or mucosa)integrity and microbiome balance leading to intestinal permeability (aka “leaky gut”).
So far we have looked at how the first and second steps of the 5R protocol, Remove and Replace, help to address the underlying factors associated with leaky gut that include a combination of factors like exposure to food and environmental triggers causing local and systemic inflammation, disruption of digestion and nutrient absorption, altered bowel motility, and dysbiosis.
Below, we will explore step 3, Reinoculate. Let’s first 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 are:
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 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.
Reinoculate
The basic premise of the third stage of gut restoration is to foster an environment that allows beneficial microflora (aka good bacteria) to thrive in the gastrointestinal (GI) tract. This is achieved by leveraging diet, supplementation, and lifestyle modification.
In previous blogs, we have explored the connection between dysbiosis and kidney health. An increasing number of studies have demonstrated a significant relationship between the health of the microbiome and the progression of kidney disease, a relationship referred to as gut-kidney axis.
Those with a healthy microbiome, abundance of good bacteria and no overgrowth of bad bacteria, are less likely to develop chronic kidney disease. In fact, the presence of certain strains of bacteria in the gut can actually slow the progression of chronic kidney disease and even reduce the need for dialysis.
Where to start?
Prebiotics (aka Fiber)
Most Americans fall significantly short of the recommended fiber intake of 30+ g/day. High fiber intake is associated with reducing the risk of heart disease, obesity, diabetes, and even certain kinds of cancers like colorectal cancer. These benefits are linked to to improved bowel movements, neutralizing and removing toxins, and “feeding” gut bacteria contributing to a favorable microbiome balance.
Research even suggests that dietary fiber-intake may be one of the most significant predictors not only of gut health, but overall health and risk of disease!
Remember to always choose whole, fresh, fiber-rich fruits and veggies whenever possible to maximize nutrients and prebiotics simultaneously. Whole grains and legumes make good fiber sources as well, but always avoid processed foods that claim to have “added fiber”. They are usually packed full of fillers, sugars, grains, cereals and artificial ingredients.
High-sugar diets can be a major disrupter of your gut microbiome, primarily because it feeds bad bacteria and yeast overgrowth. This is one of the proposed mechanisms contributing to metabolic diseases like diabetes and heart disease, two conditions associated with KD.
Prebiotic supplementation might also be necessary in some cases. Supplemental powders and capsules of resistant starch, arabinogalactan, and mastic gum, among others, might be useful in many situations. Your integrative or functional medicine provider can help you determine which, if any, are appropriate for your unique situation.
Probiotics
Supplementation with high intensity probiotics may be very useful in the Reinoculation phase of the 5R protocol. There are a variety of strains of bacteria and even beneficial yeast that are used to help to “seed” the gut (though technically more recent studies suggest the benefit is transient, it can still be helpful). Depending on your individual needs, your integrative and functional medicine provider may choose a particular strain or opt for a broad-spectrum formulation. Either way, the quality and potency of the probiotic is important to consider (not all brands are created equal).
That said, research seems to support that the best long-term strategy is to increase the intake of probiotics coupled with prebiotic fiber intake through diet. Traditionally fermented foods are a great source of naturally found probiotics, these include non-pasteurized traditionally made kefir, sauerkraut, kimchi, miso, and pickled vegetables.
Other factors impacting the microbiome
Interestingly, exercise impacts microbiome balance and promote changes that improve gut health. Aim for at least 20 minutes of exercise daily at a level appropriate to your physical fitness and make it priority to get up and move – you and your kidneys are worth it!
Furthermore, stress has been found to negatively alter the balance of the microbiome by reducing the presence of friendly flora and promote the growth of bad bacteria. Although we know that stress cannot always be avoided, everyone can find a stress management practice to reduce its negative impact. Breathing exercises, meditation, long walks, listening to music, adult coloring books – the options are endless. Find what works best for you!
Bottom Line
The third step in an individualized comprehensive gut restoration protocol involves promoting microbiome balance. This is often done after the Remove step but might be simultaneous to the Replace step. Sequencing the steps of the protocol is case-by-case dependent. 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 fourth “R” in the gut restoration protocol: Repair.
The post The 5R Protocol Part 3: Reinoculate appeared first on Integrative Kidney.]]>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.
Past studies have attempted to explore the impact of dietary changes shifting the gut microbiome to help restore the lining of the gut and reduce the resulting inflammation. However, many of the studies in the literature looking at the use of probiotics to reduce uremic load show some limited benefit in reducing the chronic kidney disease (CKD) burden.
But these studies failed to present a comprehensive approach that reveres damage to the gut while simultaneously inoculating the necessary bacteria. This single dimensional approach does not acknowledge all the different factors involved in the gut-kidney Axis.
To assure that the patient is getting a comprehensive gut restoration protocol, all the mechanisms that underlie probiotic use should be addressed. These include modification of microbiota, competitive adherence to the mucosa and epithelium, strengthening of gut barrier and modulation of the immune system.
The 5R gut restoration program addresses these gaps and help reduce the risk of progression of CKD.
This program is designed to address five areas of GI mucosal integrity repair:
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 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.
Remove
The first step of this protocol focuses on removing any exposures that may be contributing to increase inflammation in the gut. This includes food exposures, toxins, as well as screening for and treating pathogenic bacteria, fungi, parasites, or viruses that maybe disrupting the normal microbiota balance, which may require antimicrobial treatment to eradicate.
First, food known to cause sensitivities and allergies should be eliminated as part of an elimination diet. There are multiple categories of foods that contribute to inflammatory response that disrupts the lining of the gut. For example, gluten has been found to be associated with the development of leaky gut and IgA nephropathy. At the same time, we should be emphasizing the inclusion of key nutrient-dense foods that help to restore gut integrity and reduce inflammation, including antiinflammatory fats, organic fiber and phytonutrient-rich vegetables and fruit.
Typically, an elimination diet removes common food triggers like gluten, dairy, eggs, and soy. Depending on the root of the food reactivity, sometimes the removal or reduction of grains, legumes, FODMAPS, or night-shade vegetables is also necessary.
A nutritionist or clinician trained in implementing the elimination diet can help guide on which foods to eliminate or reduce. The decision may be done empirically, using symptom monitoring to guide the progress. Alternatively, the program can be personalized by using specialized testing for immune response against food can help guide this process.
Second, exposure to environmentally derived toxic substances should also be minimized, this includes mercury, arsenic as well as pesticides and other environmental pollutants whenever possible. We are exposed to toxic chemicals on a daily basis including pesticides in conventionally-farmed food, non-stick cookware, plastic use, and flame retardants and off-gassing released from furniture.
Addressing this aspect involves focusing on consuming organic produce and animal products and addressing environmental sources of toxicity. This topic is covered in more detail in this blog here.
Lastly, remove also entail identifying potential microbial triggers that might be contributing to inflammatory response. As mentioned above this may be “bad” bacteria, viruses, candida, and/or parasites. The presence of these offenders can be detected through symptoms as well as through advanced stool testing that employs a technique called PCR. Once identified, your practitioner can use antimicrobials to help eradicate the pathogenic organism, using prescriptive antibiotics or even herbal antimicrobials if appropriate.
Where to start?
Inflammatory foods
Some foods can be inflammatory or induce allergic reactivity. Furthermore, they may provide an environment that allows for the growth of pathogenic microbes, including low-fiber diets and high sugar diets. Furthermore, depending on your genetics, some foods can even lead to autoimmune conditions that may affect the kidneys. Eliminating food that is known to cause sensitivities varies dependent on the individual and their genetic predisposition.
An elimination diet can help with identifying what food an individual should avoid. This diet involves the removal of foods commonly associated with food sensitivities or immune reactivity. There are many variations of the elimination diet, and it’s very important to work with a nutritionist who can ensure you’re doing the protocol correctly and not missing any essential nutrients.
After a period of removal lasting at least 4 weeks, and assuming improvement in symptoms that suggests improved gut integrity, your integrative or functional medicine provider will work with you on gradual and careful reintroduction of foods to assess if tolerance has improved.
Decrease/Eliminate Exposure to Toxins
It is very hard to eliminate all sources of toxin exposure, but these steps can help minimize it:
1. Water filtration: we discussed options for water filtration in a previous blog.
2. Cookware: gradually eliminate all toxic non-stick cookware from your kitchen.
3. Avoid plastic containers or utensils: gradually switch from plastic to non-plastic containers and utensils.
4. Eat organic when possible: we know that choosing organic food can be expensive. If you are on a budget, there are certain fruits and vegetables that you should buy organic because of their high toxic burden. Visit the Environmental Working Group website to learn about their “Dirty dozen” T. This list gets updated yearly depending on their tests.
5. Be careful of processed drinks and juices. Not only do these contain excessive amounts of sugar, but they can also be a source of heavy metals and toxins because of poor regulations.
Eliminate Pathogens
As discussed above, laboratory analysis of the patient’s stool and serum can help give insight to the extent of intestinal permeability (leaky gut), as well as the status of microbiota. Establishment of baseline status is essential for measuring outcomes at designated milestones to give quantifiable outcomes. A comprehensive stool analysis can be a good start. In addition, a good dietary intake can help identify issues that could be related to food intake to guide this process.
Depending on the results of the individual’s comprehensive stool analysis, certain bacterial or yeast overgrowth can be detected. Also, parasites can sometimes be identified. Any of these should be treated by various medications, dietary changes, and/or herbal supplements as indicated and advised by an integrative or functional medicine provider.
Remove stress
Stress can have a bad influence on digestion and absorption. People who are stressed tend to eat too fast, make poor choices, and may eat too much at various intervals. This can lead to food choices that can lead to feeding the bad bacteria in the gut and poor digestion causing nutritional deficiencies. Furthermore, stress itself can influence epigenetic changes that impact dysbiosis as well as disease expression in general.
Bottom Line
The first step in an individualized comprehensive gut restoration protocol involves the removal of food sensitivities, environmental toxins, pathogenic organisms, stress. It’s important to work with an integrative or functional medicine provider trained to guide patients with elimination diets can help you navigate this successfully.
Next, we will tackle the second “R” in the gut restoration protocol: Replace.
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