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Are Probiotics Safe For Kidney Transplant Patients

Microbial Therapies In Kidney Transplantation

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The treatment of gut dysbiosis can be divided into probiotics, prebiotics, symbiotics, and FMT. Probiotics are defined by the World Health Organization as live organisms that, when administered in adequate amounts, confer a health benefit to the host.56 They have the characteristics to be able to survive the harsh conditions of the digestive tract, to proliferate in the lower gastrointestinal tract, to be stable, and to have a positive healthy effect in human studies.57 Probiotics compete with pathogens for adhesion to the gastrointestinal epithelium, inhibit the production of bacterial toxins, and produce their own antimicrobial substances.58 Plain yoghurt, cottage cheese, and vinegar are among the substances containing probiotics. Probiotics such as Lactobacilli and Streptococci have been used principally in liver transplantation,59-61 documenting significant activity in reducing infection rates.

Prebiotics are defined as a non-viable food component that confers health benefits on the host associated with modulation of the microbiota. Prebiotics must be resistant to the actions of acid in the stomach, bile salts, and other enzymes in the intestines and should not be absorbed by the upper gastrointestinal tract. They act by producing SCFA, mucin, and increasing IgA production. To date, only insulin and trans-galacto-olisaccharides may be considered probiotics.62

Mr Bacteria Please Eat Some Uremic Toxins

Give me some of that uremic-toxin eating bacteria! you say. Yes, that is possible! Let me tell you what that really means as far as what you do. Also consider that we are not just concerned about a strain of bacteria but also must always consider overall gut health because of how it impacts inflammation.

Gut health and kidney disease is not just about uremic toxins. Theres a lot more. There hasnt been one huge study, perfectly randomized, placebo-controlled study that shows the relationship between gut health and CKD progression. But theres been plenty of smaller studies focusing on correcting gut bacterial balance with reported findings of delaying kidney progression, reducing inflammation, and improving iron status .

There is also some interesting data showing that probiotics may help improve the health, strength, and overall condition of the gut barrier . The gut barrier is an absolutely essential point to understand when looking at the connection between gut health and inflammation.

The gut barrier is pretty important since it houses 70% or so of our immune system . It also is supposed to be a semi-permeable barrier meaning it lets some little things through and some big things out . If the gut barrier becomes more permeable, aka leaky, then unwelcome things pass into the blood that shouldnt.

When your guts epithelial tight junctions start to loosen up, some ugly things that should stay in your gut and be metabolized by bacteria begin toenter the bloodstream.

Does It Matter Which Probiotic I Use

Multiple probiotics have been studied with a specific focus on kidney disease. Bacillus pasteurii, Sporlac, Lactobacillus acidophilus, Escherichia coli-DH5, and others . There are many researchers in a variety of universities that study probiotics and prebiotics with kidney disease. Kibow Biotech, who produces Renadyl, is the only company that specifically studied probiotics for kidneys. Their probiotic consists of (S thermophilus-KB19, L acidophilus-KB27, and B longum-KB3 in a dosage of about 90 billion organisms. Dr. Ranganathan, the founder of Kibow Biotech, and one of the primary researchers has been studying this formula for 20+ years.

Current studies with Renadyl show that especially in later stages of CKD that uremic toxins were able to be broken down and excreted with help of their probiotic strains. Plus, remember I just mentioned bacterial production of ammonia and ammonium hydroxide from breaking down uremic toxins? There is some interesting data that Renadyl can help reduce that as well . Each of the different strains of bacteria has been chosen for a specific purpose. For example, per their report S. thermophils-KB19 breaks down urea, uric acid and creatinine, while B. longum-KB31 helps reduce levels of protein bound uremic toxins like p-cresol and indoles .

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How Safe are Probiotics Really?

In last weeks article, we discussed that while the use of probiotics is generally safe for most patients, caution is advised in individuals who areimmunocompromised or have a severely damagedgastrointestinaltract. Today, were going to delve deeper on the safety of probiotics in immunocompromised individuals, particularly those who received transplants.

This article was inspired by a real-life case at work, where a patient in the nephrology clinic inquired about the potential effects of probiotics on her transplanted kidney. Although the pharmacist and I were unsure about the evidence supporting its use, the theory of probiotics potentially boosting the immune system to cause transplant failure and the importance of maintaining a state of immunosuppression formed the basis of the recommendation.

Lets look at the evidence surrounding probiotic use in transplant patients.

What Does the Evidence Say?

A quick look at the available studies did not yield many results on the topic. One article that evaluated the current evidence on the safety of probiotics found that the main side-effects found were . Individuals who were at an increased risk for these complications included:1

  • Critically ill in intensive care units
  • Critically sick infants
  • Postoperative and hospitalized patients
  • Patients with immune-compromised complexity
  • Systemic infections
  • Excessive immune stimulation in susceptible individuals
  • Gene transfer
  • The Bottom Line


    Dysbiosis And Renal Fibrosis

    Pre And Probiotic Capsules

    In a recent study on transplant patients, Modena et al.42 collected urinary samples from 25 patients after kidney transplantation. All of these patients developed interstitial fibrosis/tubular atrophy at 6 months after transplantation at kidney biopsy. Patients were compared with 23 kidney transplant recipients who did not develop IF/TA. Patients with IF/TA had a decreased number of Lactobacillus and Streptococcus genera. The authors concluded that modification of the urinary microbiota could develop IF/TA by altering the host immune response.

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    Predisposing Factors For Utis After Rtx

    Many factors are believed to contribute to the high incidence of UTI in RTx recipients. Some exist prior to transplant, including female gender, diabetes mellitus and underlying urinary tract abnormalities. Peri-transplant factors are often related to instrumentation of the urinary tract, including ureteral stenting and prolonged urinary catheterization. Additional risk factors contributing to UTI post-transplant include immunosuppression and graft dysfunction or rejection. It is noteworthy that so far no direct association has been found between the risk of UTI and dose or type of maintenance immunosuppression. It is the net state of immunosuppression that impairs host defense capability against infections in general. Various authors have suggested different potential UTI risk factors, and their findings are not always consistent. The potential pre-, peri- and post-transplant risk factors for UTI in RTx recipients are shown in Table 1.


    Ways I Help My Clients Support Their Kidneys Through Gut Health

    Okay, so now you know balancing your gut is important and probiotics for kidneys make a difference. The gut, the microbiome, and probiotics are involved with relieving uremic toxins, decreasing inflammation, and helping with better nutrient absorption.

    Supporting a healthy gut is not just about getting the right probiotics for kidneys. That is a big piece for sure. You also need to support your army meaning feed them and not send extra stress their way. For my clients with kidney disease I really like to talk about a few gut healthy strategies.

    1. Yes, get a good probiotic. You need to consider quantity, quality, and length of time of administration . If my client has stage 3 or 4 kidney disease, we definitely use at least 90 days of Renadyl. I also like to add in spore-based probiotics as they have some specific functions with healing the gut lining .

    2. Use some prebiotics. Prebiotics are the food of the microbiota. You can get this in the form of food, like fresh fruits, vegetables, and whole grains. In general, a diet that is full of more fresh foods and more fiber is going to give you the best results. Plant-based diets are powerful for people with kidney disease any ways, good to work with a renal dietitian to make this a new habit. More info coming soon on prebiotics so I wont belabor the point here. You can also use a product like Kibow Fortis®.

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    Small Intestine Bacterial Overgrowth

    Probiotics were previously thought to be contraindicated for individuals with SIBO. However, a recent meta-analysis by Zhong et al. showed that probiotics decreased abdominal pain and diagnostic markers of SIBO.

    In conclusion, However, it is necessary to use even more discernment for patients at a higher risk for infection.

    How Do We Know If Probiotic Therapy Is Working

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    Although measuring fecal samples before and after introducing probiotic therapy would be fantastic to see what positive changes ensue, unfortunately, this is impossible for many of us.

    So how do we know if probiotic therapy is effective and beneficial?

    There are several potential markers of success in the effectiveness of probiotics. Closely monitoring for improvements in gastrointestinal symptoms, lab changes, and even quality of life are all telltale signs that probiotics are benefiting our patients. Some of the improved GI symptoms to watch for include:

    • Improved IBS symptoms
    • Less gas or bloating

    While there are considerable benefits to utilizing these available therapies, we cant overshadow the importance of a healthy balanced diet.

    Taking a pill or powder cannot undo or improve the effects of a poor diet. Instead, the use of probiotics in addition to a healthy balanced diet full of fiber and prebiotics may result in significant improvements in kidney and gut health in our CKD patients!

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    Living With Transplant Recipients

    A person who is living with a loved one who has contracted COVID-19 is at risk of also becoming infected. This is especially true for posttransplant patients.

    Therefore, it is important for anyone to limit going into the public, especially if there is an active and expanding outbreak in their area, or if local and state authorities recommend remaining in place in an effort to maintain social distancing to help control the spread of the virus.

    If people need to go into public, then they should take certain precautions, including limiting the time spent outside as much as possible, avoiding large crowds, and maintaining social distances . People with a kidney transplant should also consult with their healthcare team to find out what precautions should be taken by them and their caregivers. This might include additional hand washing/sanitizing, face coverings, or other measures.

    The Oral Microbiome During Immunosuppression

    There is a longstanding association between immunosuppressive agents and oral disease. Gingival hyperplasia, for example, has been associated with the immunosuppressant ciclosporin, and kidney-transplantation where bacteria-induced inflammation could be affected by transplant-driven microbiome changes . In a large study of kidney transplant patients, 60% had at least one type of oral mucosal ulcer . Similar studies indicate that these lesions are common in transplant or immunocompromised cohorts with causal links to oral microbiome constituents. Oral candidiasis is also more common in transplant recipients and immunosuppressed cohorts . Whether the overgrowth and increased prevalence of Candida spp. in this context is caused by failure of the immunocompromised host to maintain normal suppression of its growth, or a side effect of prophylactic antibiotic use , remains to be discerned.

    Table 1 Summary of recent studies reporting microbiome-associated differences using kidney transplant recipient cohorts.

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    Will I Have To Watch My Diet After A Transplant

    Yes, your diet still plays a big role after a kidney transplant. It is important to keep a healthy weight and exercise regularly. A healthy, balanced diet will help prevent high blood pressure, high blood sugar, excess weight gain and promote overall wellness and health.

    After a kidney transplant, plan to follow a diet low in salt and high in fiber. A balanced diet includes a variety of fresh fruits and vegetables, lean meats, reduced-fat dairy products, whole grains, and plenty of water.

    Additionally, you may need to avoid eating certain types of foods. Your healthcare team can help you understand which foods you should avoid and why. The dietitian at your transplant center can help you find a diet that is right for you.

    Evaluation After Having Covid

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    You can still receive an evaluation after having COVID-19, but your healthcare team will need to tell you when you will be free from infection. Also, depending on your current health status and the impact of COVID-19 on hospital staff and supplies, your transplant may be delayed or postponed. You should discuss this with your transplant center.

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    Another Study Shows Probiotics Are Great For Kidney Health

    Findings presented at the National Kidney Foundation Spring Clinical Meetings shed more light on the benefits of probiotic supplements on kidney issues.

    Probiotics can help significantly reduce inflammation, improve gastrointestinal health, and even help in reducing uremic toxins. The study most notably revealed a total body reduction in inflammation and a reduction in serum C-reactive protein following a course of probiotics. This, in turn, helped improve mortality rates in laboratory rats suffering from end-stage renal disease.

    Unfortunately, the study, which followed 178 end-stage renal disease patients, revealed no significant impact upon serum tumor necrosis or albumin, but overall GI symptoms were definitely improved.

    Past studies highlighting the effects of probiotics on kidney problems have shown its ability to regulate hemoglobin and help with anemia. Probiotics are the good bacteria that line the gut and aid in digestion and when kidney health is compromised, they become ten times more important.

    If youre looking for a good probiotic, check out Kidney Restore on our shop page.

    Determination Of Nhp Usage

    In British Columbia, services for CKD and kidney transplant patients are coordinated by the BC Provincial Renal Agency . Each patients clinical information, including medication regimen, is collected and entered into the agencys Patient Records and Outcome Management Information System . The number of NHP entries for CKD-ND, dialysis, and renal transplant patients was obtained from this database, using data derived from entries listed on August 1, 2014. Vitamins were excluded, because they were to be evaluated in a second phase. Calcium supplements were also excluded, because they are primarily used as phosphate binders in the renal population. Nutritional supplements and herbal teas were excluded, because these items are not entered into PROMIS. Input was solicited from other renal pharmacists across Canada to identify NHPs commonly used in other renal practices, in addition to the ones identified through the PROMIS database. The demographic characteristics of NHP users and non-users were also determined from the PROMIS database. Statistical tests, specifically t tests and 2 tests, were performed to compare the demographic characteristics of NHP users and non-users. Access to the PROMIS database was approved by the Research Committee of the BCPRA.

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    Uremic Toxins Damage Your Gut And Kidneys

    Lets start with uremic toxins. Probiotics may be helpful in reducing uremic toxins generated in your gut . .

    You may or may not be familiar with the word uremia. Its been around since 1847 and a big deal with kidney disease. Uremia is more or less defined as urine in the blood.. Sounds gross, right?

    Healthy working kidneys normally filter out something called uremic toxins, thus the word urine. Urea is one of the most well-known uremic toxins but there are many others. When the kidneys arent working at full capacity some uremic toxins stay in the blood and can damage the kidneys, heart, and bones .

    Protein is the precursor of uremic toxins. Thus, when you eat protein some of it gets broken down into these uremic toxins. There are many uremic toxins, but I wrote about two of these in my recent post about kidney care and the gut. Uremic toxins normally are absorbed through the gut lining into the blood stream and then processed out through the kidneys.

    What some scientists have found is that protein is not the only source of uremic toxins. Bacteria in the gut can produce uremic toxins. Bacteria can also eat uremic toxins. This is why the gut in kidney disease is so very important. The toxic load that is part of the progression of kidney disease can be modulated by the bacteria in the gut both for good and ill.

    Probiotic Supplements Might Not Be Universally

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    Probiotics plausibly restore gut microflora as dietary and therapeutic supplements.

    Probiotics display varying efficacies and risk factors in at-risk population groups.

    Probiotics may affect certain infections, allergies, or antibiotic gene transfer.

    Stringent regulation is required toward the therapeutic usage of probiotics.

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    Intestinal Microbiota And The Kidney

    An inter-relationship between the gut and the kidney occurs either by the activation of the immune system or by the microbiota-derived metabolites. While the indigenous resident microbiota induces a normal balance between Treg and Th17 cells, pathobionts may activate Th17 cells and favour renal inflammation and injury.21

    Similarly, microbiota-derived metabolites may affect kidney function. The protective role of SCFA has been already highlighted. In addition, SCFA have beneficial effects by reducing the production of cytokines and chemokines such as IL-, IL-6, TNF, and monocyte chemoattractant protein.22

    On the contrary, pathobionts such as E. coli have deleterious effects. The phenomenon is bilateral. Indeed, dysbiosis may facilitate acute kidney injury by modifying SCFA composition and generating high quantities of toxic indoxylsulfate and trimethylamine N oxide . This fact may favour the transition from AKI to chronic kidney disease . On the other hand, AKI may modify the gut bacterial composition . 23

    Figure 2: Relationship between acute kidney injury, chronic kidney disease, and toxic substances.Dysbiosis may facilitate AKI by modifying the SCFA composition and generating high quantities of toxic indoxysulfate and TMAO.AKI: acute kidney injury CKD: chronic kidney disease CVD: cardiovascular disease LPS: lipopolysaccharides SCFA: short-chain fatty acids TMA: trimethylamine TMAO: trimethylamine N oxide.


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