Could Delayed Kidney Function Leading To Gut Dysfunction Favor Rejection
The structure of the gut microbiome is known to be altered in individuals with kidney disease . Investigations in humans and rat models have shown differences between the gut microbiome in uremic subjects with ESRD and healthy controls . The effect of renal transplantation has, however, not been extensively investigated. Renal dysfunction with increased serum urea leads to intestinal barrier dysfunction and disruption of the epithelial tight junction . Such disruptions allow bacterial fragments and toxins to translocate from the gut microbiome into the bloodstream, promoting chronic systemic inflammation whether this has a causal or exacerbating affect in co-morbidities associated with ESRD is unclear. After transplantation, there is some degree in variability as to how quickly the kidney allograft begins to function, although in recent years the incidence of delayed graft function has increased, possibly due to the use of expanded donor criteria, to within the range of 2045% of cases . Delayed graft function may expose the patient to a longer period of uremia and an increased risk of gut dysfunction, systemic inflammation, and allograft rejection. A delayed graft function of more than six days has been found to strongly decrease the long-term survival of transplanted kidneys .
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.
Practical Applications For Probiotics
While these findings show exciting promise, probiotic therapy may not be necessary for all patients. Understanding which patients might benefit and what type of probiotics to use takes a lot of careful research and trial and error.
Lets start by examining why probiotics may be helpful and when to use caution.
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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.
Probiotic Prophylaxis For Immunosuppressant Associated Diarrhea Following Kidney Transplantation
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.|
|First Posted : August 15, 2006Last Update Posted : July 26, 2011|
|Drug: Probiotic SupplementOther: Placebo||Not Applicable|
Repopulation of the normal intestinal microflora in kidney transplant patients after kidney transplantation may maintain normal bowel function. This study is designed to test the hypothesis that the administration of a food supplement probiotic consisting of high amounts of six strains of lactic acid bacteria normally found in the human colon will favorably support and maintain bowel function moderating or obviating IAD.
- subjects who are pregnant, lactating or nursing
- subjects with active peptic ulcer disease
- child bearing women not willing to use a reliable form of contraception
- subjects with prior history of C. difficile
- subjects receiving other medications considered to be experimental for control of diarrhea
Information from the National Library of Medicine
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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.
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.
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Urinary Microbiome May Hold Key To Early Rejection Detection
Since the recognition of its medical relevance, the urinary microbiome has been receiving growing attention . The most frequently reported genera are Lactobacillus and Streptococcus, with Alloscardovia, Burkholderia, Jonquetella, Klebsiella, Saccharofermentans, Rhodanobacter, and Veillonella also found less frequently . Whilst the importance of the urinary microbiome in health is still emerging, evidence from several studies confirm its composition is altered by some post-transplant situations . A study comparing the urinary microbiome of 21 kidney transplant recipients with that of 8 healthy controls reported marked differences between the two groups . Under the multiple stressors of kidney transplantation the urinary microbiota of kidney-transplant recipients suggested an overall decrease in diversity when compared to healthy controls, alongside an increased abundance of opportunistic pathogens and may select for promotion of antibiotic resistance. The effect of elevated urinary urea concentrations on urinary tract infections caused by urealytic pathogens also warrants further investigation. In the future, frequent, longitudinal sampling of the patients urinary microbiome might be implemented to detect deviations from microbiome stability. If these changes are shown to precede organ damage or loss, this may be useful as a non-invasive method of early detection.
Bidirectional Relationship Between Microbiota And The Immune System After Allotransplantation
While the microbiota clearly influences immune pathways, dysregulated immune responses also impact the microbiome in a bidirectional manner. For example, absence of Treg in mice was associated with pronounced Th2 type inflammation in the gut and airways, as well as altered gut microbiota, suggesting that Treg maintain eubiosis in the gut by regulating Th2 inflammation . Independent of cause, inflammation in the gut leads to changes in microbiota composition , leading to dysbiosis. Dysbiosis in turn disrupts the immune thresholds set by ânormalâ commensals, resulting in chronic, recurrent infection or inflammation and inability to clear âabnormalâ microbiota .
Host factors in transplant patients that influence this bidirectional relationship include antibiotics, immunosuppression, and chronic kidney disease . Germ-free or antibiotic-treated mice are deficient in Th17 cells and have impaired Treg function . These deficiencies are associated with dysregulation of immunity, inflammation, and response to infection, leading to an increased burden of pathogens and the potential to develop cross-reactive alloantibodies. Thus, dysbiosis associated with chronic antibiotic use may have immune consequences in allograft recipients beyond simply the emergence of antibiotic-resistant organisms.
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Nutrition After Kidney Transplant
It’s important for your child to eat a healthy diet after receiving a kidney transplant. Good eating habits help prevent health complications from post-transplant medications.
A healthy diet can:
- Keep blood sugar levels within normal limits, which prevents diabetes. Blood sugar can go up after a transplant.
- Keep blood cholesterol levels within normal limits, which keeps the heart healthy. Cholesterol levels can become elevated after a transplant.
- Prevent excessive weight gain. Some patients gain too much weight after a transplant.
- Help keep blood pressure normal directly after the transplant, through appropriate salt intake.
- Provide enough calcium to keep your child’s bones strong and support growth. Patients taking prednisone after transplant need more calcium.
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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Literature Search And Data Collation
The following databases were searched: MEDLINE, Embase, Lexi-Natural Products, PubMed Dietary Supplement Subset, and Natural Medicines . Keywords for the search were the specific name of each NHP , chronic renal failure OR chronic kidney failure OR renal insufficiency, hemodialysis, peritoneal dialysis, kidney graft OR renal transplant, immunomodulating OR immunology OR immunomodulation, pharmacokinetics, nephrotoxicity, CYP450, cyclosporine OR tacrolimus, mycophenolate, warfarin. There were no restrictions on the search strategy with the exception of citations that did not pertain to patients with renal disease. Authors of pertinent papers were contacted if information was incomplete . References of pertinent articles were also hand-searched for additional studies.
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.
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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.
Probiotics And Chronic Kidney Disease
- Laetitia KoppeAffiliationsDepartment of Nephrology and Nutrition, Centre Hospitalier Lyon SUD, Carmen, CENS, Univ Lyon, UCBL, Pierre Bénite, France
- Denis FouqueCorrespondenceDepartment Nephrology and Nutrition, Centre Hospitalier Lyon SUD, Chemin du Grand Revoyet, Univ Lyon, UCBL, 69495 Pierre Bénite, FranceAffiliationsDepartment of Nephrology and Nutrition, Centre Hospitalier Lyon SUD, Carmen, CENS, Univ Lyon, UCBL, Pierre Bénite, France
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Clinical Manifestations Of Microbiome Disruption
Differences in microbiota after transplantation can be associated with clinically significant events. Decreased Firmicutes in small bowel recipients has been associated with acute rejection . In lung transplant patients, restoration of microbiota diversity decreased the risk of bronchiolitis obliterans syndrome . Bronchial samples containing greater than 10% Pseudomonas aeruginosa were associated with symptomatic infection, while those containing greater than 10% P.fluorescens were not. No sample had greater than 10% of both species . Such changes, however, are difficult to interpret in the presence of concomitant antimicrobial administration.
Fricke et al. demonstrated that major shifts in microbiota composition were identifiable at one month after renal transplant . In another study of 26 renal transplant recipients, Lee at al. identified increased Proteobacteria species in rectal microbiota at 90 days . Patients with post-transplant diarrhea had reduced microbiota diversity, with reduced Bacteroides, Ruminococcus, Coprococcus, and Dorea. Patients with abundant Enterococcus in rectal stool samples were more likely to have an Enterococcus urinary tract infection .
The Need To Monitor Kidney Function With Certain Drugs
Experts have suggested that after the initial assessment of kidney function, physicians should consider regular monitoring after starting or increasing the dosage of drugs associated with nephrotoxicity, especially those used chronically in patients with multiple risk factors for impaired kidney function, Dr. Naughton noted. If there is any sign of kidney harm, the provider should review the medications you are taking in order to identify which one is causing the problem.
If multiple medications are present and the patient is clinically stable, physicians should start by discontinuing the drug most recently added to the patients medication regimen. Once that has been taken care of, further harm to the kidneys may be minimized by keeping blood pressure stable, staying hydrated, and temporarily avoiding the use of other medications that may cause nephrotoxicity.
These safety tips can ensure you get the care you need while keeping your kidneys safe. That way, they can tend to essential functions like keeping things flowing .Originally published May 11, 2017
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What Does The Research Say About Probiotics For Kidney Disease
The role of probiotics as a treatment for CKD is an emerging area of research. Although we see more and more studies on this topic, high-quality interventional studies are lacking. So, what are the significant findings in studies so far?
A meta-analysis conducted by Jia et al. reviewed the literature in human studies found that the primary conclusions of probiotics in the CKD population are reductions of PCS and the pro-inflammatory cytokine Interleukin-6 .
Viramontes-Horner et al. conducted a small double-blinded, placebo-controlled, randomized clinical trial in hemodialysis patients. The trial compared a control group that received only nutritional counseling to the interventional group that received nutrition counseling and a symbiotic gel that contained Omega-3s, vitamins, inulin, and L. Acidophilus and Bifidobacterium lactis.
The studys primary outcomes included improvement in gastrointestinal symptoms and decreased serum CRP in the intervention group compared to the control.
A randomized, double-blind placebo-controlled study in PD patients found that patients receiving one capsule daily of Bifidobacterium bifidum A218, 109 CFU Bifidobacterium catenulatum A302, 109 CFU Bifidobacterium longum A101, and 109 CFU Lactobacillus Plantarum A87 for six months decreased the pro-inflammatory markers TNF-a, IL-5, IL-6 and preserved residual renal function compared to those who did not receive treatment