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Decreasing blood urea & S. creatinine In chronic kidney disease patients (stage 3&4)Dr. Alaa Hussain A. AwnConsultant nephrologist

Today we will discuss how probiotics are providing new hope for people living with kidney problems. We will examine how the probiotic microorganisms work and promising new data that show the potential of Kibow Biotics, a probiotic supplement, to promote kidney health and quality of life of those living with kidney problems.1

Kidney functionsa dynamic equilibrium

SecretoryErythropoietin, vitamin D, reninExcretoryUrea, uric acid, creatinine,nitrogenous wasteRegulatoryMaintains homeostasis; Na, K, PO4, trace elements

As you may know, kidneys perform 3 main functions to keep the blood clean and physiologically balanced.

They work to excrete waste products that would otherwise build up and damage all organs in the body, especially the cardiac and vascular systems.

They are responsible for regulating the volume and concentration of body fluids to maintain homeostasis. This requires selective filtration of chemicals in and out of the bloodstream.

Meanwhile, the kidneys secrete important proteins that are essential to the human body.

Typically, when dysfunction occurs, each of the 3 main functions of the kidneys are treated separately by nephrologists.

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Healthy kidneys remove nitrogenous waste

UrineExcreted nitrogenous wasteClean blood back to bodyBlood w/uric acid, creatinine,and urea

Most nitrogeneous waste comes from amino acids (via dietary protein) that are broken down by the liver into ammonia and is extremely toxic. The liver then converts the ammonia into urea, a less toxic waste product that is dissolved in the blood. Urea is subsequently filtered and excreted by the kidneys as urine, along with other waste products, such as creatinine and uric acid.3

Chronic kidney disease (CKD)CKD = failure of kidneys to filter waste from the bloodstreamAffects more than 26 million Americans2 main causes: diabetes and hypertensionOn the rise due to aging populationProgresses to end-stage renal disease, requiring dialysis or transplantationSource: National Kidney Foundation

Unfortunately, this type of impaired kidney function is widespread and growing. Chronic kidney disease, or CKD, affects more than 26 million Americans, and millions more are at risk because people with diabetes and hypertension are predisposed to developing CKD. Due to the aging population, these conditions are on the rise, which means so is CKD. CKD eventually leads to end-stage renal disease, where dialysis and transplantation are the only treatment options.

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- Worldwide, the number of patients with Chronic Kidney Disease (CKD) is rising and it now being recognized as a major public health concern that is threatening to reach epidemic proportions in the next decade.

CKD stage 3 = creatinine clearence is 60-30 cc/ min.CKD stage 4 = creatinine clearence is 30-15 cc/min.

-In recent studies. 4.5% of the US adult population have Stage 3 and stage 4 CKD.

- Reducing protein intake modifies the Creatinine and lowers the blood urea in patients with CKD.

Reducing protein intake in patients with chronic renal failure reduces the occurrence of death by about 40% as compared with larger or unrestricted protein intake.

Is there a promise of usingthe probiotics for kidney health?

Probiotics??Hope for people with kidney problems

Today we will discuss how probiotics are providing new hope for people living with kidney problems. We will examine how the probiotic microorganisms work and promising new data that show the potential of Kibow Biotics, a probiotic supplement, to promote kidney health and quality of life of those living with kidney problems.7

- Gut normal flora ( good bacteria).

- Probiotics.

- Use of probiotics in chronic kidney disease.

- The human gut is home to a highly complex ecosystem of micro-organisms. These micro-organisms are vital to the healthy functioning of the digestive system. They are collectively known as gut flora.

- Indeed, research indicates that this microflora can have a positive effect on the overall health of the individual and have subsequently been termed the good bacteria of the gut.

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The average human body potentially contains around 100,000 billion of these organisms /gram, within the digestive tract.

There are billions more found in the skin, the genito-urinary and respiratory tracts.

The greatest variety of species is however concentrated in the large intestine.

- The gut microflora plays a vital role in health, particularly in relation to nutrition, immune function, protection and detoxification. - They help to synthesize certain vitamins, such as folic acid, vitamin K and a number of the B vitamins, as well as assisting the synthesis of amino acids (proteins).

- These good bacteria also provide an important line of immune defense in the digestive tract by helping to avoid the invasion of bad bacteria in the gut.

- . When imbalance occurs it means that the numbers of beneficial bacteria in the gut have reduced, which can result in undesirable symptoms such as:

irregular bowel movements, diarrhoea, constipation and abdominal pain.

It can also result in the overgrowth of yeasts and fungal infections in the gut.

Factors affecting the good flora:- The use of antibiotics. Antiobiotics will help destroy bad bacteria in the body, including in the gut, but they will also destroy beneficial bacteria in the digestive tract.

Intestinal upset such as diarrhoea, from food poisoning or other causes, can result in microflora being lost.

Starvation, perhaps in the form of a low-calorie diet, can result in an imbalance of gut bacteria.

General illness, a stressful lifestyle and excessive alcohol consumption can all contribute to an imbalance of gut bacteria.

The beneficial effect of probiotics

-Probiotics are defined by the World Health Organisation as:

living organisms which when administered in adequate amounts confer a health benefit on the host.

L. casei DN-114 001B. animalis DN-173 010Foods containing probioticsL. casei ShirotaL. rhamnosus GG

Where do probiotics come from? Most people associate probiotics with yogurt and fermented drinks, which have been heavily promoted for their health benefits over the past several years. However, because probiotic organisms are killed during pasteurization, live probiotic cultures must be added to yogurt after pasteurization. Once consumed, they then become subject to degradation by acids in the stomach, before they have a chance to reach the intestines.

As such, by the time they reach the intestine, the availability of live probiotics is markedly reduced. For this reason, Kibow Biotics is enteric-coated to deliver a large number of viable microbes.

Dannon, the manufacturer of Activia and DanActive, was fined in December 2010 for overstating the health benefits of these probiotic products.

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IndicationProbioticAntibiotic-associated diarrhea Lactobacillus rhamnosus GG (LGG)Irritable bowel syndromeLGG, VSL#3, Bifidobacterium infantisUlcerative colitis VSL#3, SaccharomycesboulardiiCrohns diseaseSaccharomycesboulardiiPouchitisVSL#3

Probiotics for specific conditions Note: All health applications are highly strain-specific.

Specific probiotic strains are increasingly used to provide health benefits related to medical conditions of the digestive tract, such as antibiotic-associated diarrhea, irritable bowel syndrome, ulcerative colitis, Crohns disease, and pouchitis. 20

Other possibilities of probioticsFecal transplant applications, in diarrhea patients infected by Clostridium difficile

Fecal bacteria was transplanted into a patients gutSymptoms improved, beneficial effect was observed over time

Although liver, heart, and kidney transplants are well documented, fecal transplants are an emerging form of treatment.

Among promising applications of probiotics is the reintroduction of bacterial flora from stool through a process of fecal transplantation. This is done to restore a healthy balance of microorganisms in the gut for patients suffering from chronic diarrhea caused byClostridium difficile. Patients who received the bacteria obtained from a healthy donor saw their symptoms improve and enjoyed a beneficial effect over time.22

(contd) Other possibilities of probiotics Obesity applicationsLink found between intestinal microbes and obesityMicrobes from gut of obese mice were transplanted into lean miceMice that received microbes from obese donors gained more weightPotential use of probiotics to reduce obesity

Researchers have found that intestinal microorganisms are markedly different in obese and lean individuals. In one study, the totality of microbes, or microbiome, were transplanted from the gut of obese mice into lean mice. It was found that the mice that received the microbes from obese donors gained weight.

This illustrates a possible link between microorganisms and obesity, as well as the potential probiotic applications in managing obesity.23

In this regard, in patients with CKD,uremic toxins constitute over 100 different metabolites, most of which diffuse into the bowel as a result of the kidney inability to filter these waste metabolites.

Are the probiotics useful for removal & detoxification of these nitrogenous waste products from the bowel of those patients?

I.e., using the colon to maintain health in CKD patients, ( enteric toxic reduction technology).

Health benefits of probioticsHOPE

But there is hope for people who have early stage CKD. And it comes from a unique application of selected strains of probiotics. It has been found that certain strains of probiotic microorganisms can metabolize the nitrogenous waste that builds up as a result of impaired kidney function.

In fact, these microbes actually utilize urea, uric acid, creatinine, and other toxins as nutrients for growth, which causes them to multiply and further disperse more uremic toxins. As a result, the toxic waste is eliminated in the feces.

This process is called enteric toxin reduction and can reduce the burden on the kidneys and help maintain kidney function.

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20 billion CFU

30 billion CFUProbiotic supplements available

15 billion CFU1 billion CFU

1.5 billion CFU

100 million CFU1 billion CFU

As an alternative to yogurt products, a variety of probiotic supplements have come to market in recent years. Kibow Biotics stands out among these products because it is enteric-coated. This coating allows capsules to pass intact through the highly acidic environment of the stomach and release probiotics into the intestines where they can provide a beneficial effect.

Kibow Biotics also has a high CFU of 30 billion. CFU, which stands for colony-forming unit, is a measure of viable bacterial microbes provided by the supplement.

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How Kibow Biotics supports healthy kidney function

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- Kibow biotic (K.B.)=( Renadyl ) is formulated with food grade, gram positive bacteria.

Each enteric coated (for targeted ileo- cecal delivery) size 1 gel capsule contain a mix of:

Streptococcus thermophilus (KB19), Lactobacillus acidophilus (KB27), Bifidobacterium longum (KB31),

_ For a total of 30 billion colony forming unit(CFU).

Probiotics to remove uremic toxinsBifidobacterium longumKB31Lactobacillus acidophilusKB27Streptococcus thermophilusKB19

Kibow Biotics features a patented combination of 3 naturally occuring probiotic strains: Streptococcus thermophilus, Lactobacillus acidophilus, and Bifidobacterium longum.

These microbes help cleanse the bloodstream of several uremic toxins, including urea, uric acid, creatinine, and other toxins that, while present in lower concentrations, are extremely toxic. This process is called enteric toxin reduction.

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- Streptococcus thermophilus (KB19): Actually utilize urea/ creatinine/uric acid as nutrients for its increased growth and survival.

Lactobacillus acidophilus (KB27): have reduced concentration of toxins (methylamine, nitrosamines and several other carcinogenic amines) in blood stream. In addition, it also helps to prevent the growth of pathogenic bacteria in small bowel.

Bifidobacterium longum (KB31): Utilize various phenolic and indole metabolic toxic compounds in colonic region as its nutrients for growth.

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How does Kibow Biotics work?Nitrogenous waste enters the gut from the bloodCarefully screened probiotic microbes bind with toxinsMicrobes break down toxins and multiplyToxins are carried out of the bowel and eliminated in the feces

1234See full animation at www.youtube.com/kibowbiotech

Enteric toxin reduction is the process through which the probiotics contained in Kibow Biotics break down and eliminate the nitrogenous waste that builds up in the colon as a result of impaired kidney function.

(1) As the toxins accumulate in the bloodstream, they gather in the gut.

(2) The special enteric coating of Kibow Biotics prevents the release of the probiotic strains before they reach the colon. There, the carefully screened microbes bind with toxins and (3) break them down. Using the toxins as nutrients, the microbes multiply, which accelerates the breakdown of additional toxins.

(4) Toxins are then carried out of the bowel and eliminated in the feces.

You can see a full animation that shows how Kibow Biotics works at www.youtube.com/kibowbiotech.31

- Because these microbes literally use these toxic waste products as their food, these three bacteria help cleanse the blood stream of urea, creatinine and uric acid, giving the kidney a rest by taking on some of their work.

We are using the bowel as an assistant organ helping for removing the nitrogenous waste products in the patients with CKD.

- consumption of 90 Billion CFU per day is clinically safe .

The oral ingestion of a probiotic bacterial regimen in patients with CKD was well tolerated, with decreases in blood urea nitrogen and uric acid, possibly contributing to improved quality of life.

Key findings: effectivenessBUN levelsReduced in 63% of patients*Quality of lifeImproved in 85% of patients*Creatinine levelsReduced in 43% of patientsUric acid levelsReduced in 33% of patients

Outcomes of the trial were assessed using biochemical parameters. The blood urea nitrogen, or BUN, levels were reduced in 63% of patients; serum creatinine levels were reduced in 43% of patients; and uric acid levels were reduced in 33% of patients.

Perhaps more significant, however, was that a large majority of subjects85%perceived a substantial overall improvement to their quality of life. 34

Key findings: safetyIngestion found to be safeMild side effects, eg, diarrhea, bloating, flatulenceLasted 2 weeks; then disappeared and did not recurNo adverse effects reported from any sites

Kibow Biotics was also shown to be safe when taken for the trial period of 6 months. Only mild side effects were seen, which were self-limited, and no adverse events were reported from any of the sites.35