The Benefits of Probiotics for Chronic Kidney Disease Patients

The Role of Human Intestinal Microbiota

The human intestinal microbiota is an extensive collection of helpful microorganisms that live in human guts. They help with essential things like metabolism, nutrition, and immunity. Gut dysbiosis is when this balance gets messed up that could cause problems like atherosclerosis and hypertension.

Intestinal Dysbiosis in Patients with Chronic Kidney Disease

Chronic kidney disease (CKD) is a health problem that affects many people and can result in poor quality of life, high management costs, and increased death risk. Studies have found that intestinal dysbiosis (an imbalance of bacteria in the intestine) is common in people with end-stage renal disease (ESRD). It is caused by uremic (related to kidney disease) and non-uremic factors, such as diet and medicines for CKD patients. In advanced CKD stages, vegetables and fruit intake must be restricted to prevent the risk of hyperkalemia (above the normal level of potassium in the blood) and fluid overload. The lack of fiber can worsen dysbiosis by slowing intestinal transit, causing edema (swelling) in the intestine wall, and increasing metabolic acidosis.

Effect of Oral Supplement Intake in ESRD Patients

Additionally, ESRD patients often take oral drugs (supplements like iron and vitamin D analogs, potassium and phosphate-chelating agents, diuretics) that can cause pro-inflammatory gastrointestinal overload. This overload changes the balance of bacteria in the intestine, increasing the production and absorption of intestinal bacterial metabolites, like indican and 3-methyl-indole (3-MI). Furthermore, patients with ESRD have to be on a low-protein diet to reduce their kidneys’ workload, leading to gut dysbiosis. Intestinal dysbiosis in CKD patients has been linked to an increased risk of death, heart problems, and poor nutrition.

Tests that are Used to Determine Bacterial Imbalances in the Intestines

Two tests can diagnose either a fermentative intestinal dysbiosis or an overgrowth of harmful bacteria in the gut. The first test is called 3-methyl-indole, and it is used to measure the number of harmful bacteria in your system. The second test is called indican, and it is used to measure the amount of sugar that bacteria have fermented in the gut. If either of these test results is positive, then there is a bacterial imbalance in the intestines that must be corrected. Fermentative dysbiosis is due to non-absorbed sugar hydrolyzation by several bacteria strains that can cause swelling, diarrhea, and a change in the function of the gut-associated lymphoid tissue (GALT) and mucosa-associated lymphoid tissue (MALT). Putrefactive dysbiosis is a problem that is caused by an overgrowth of intestinal putrefactive microorganisms that can result in constipation, digestive difficulties, and impaired GALT and MALT functions.

Moreover, it has been found that metabolites are directly involved in causing heart and kidney damage. We studied a group of people with stage 3a CKD to see if taking probiotics could help improve their health. Probiotics are “live microorganisms” that provide health benefits to the host when administered in proper amounts. ProbiotiCKD was tested in a clinical trial to see the impact of a new mode of probiotics administration on indican and 3-MI levels, all fecal Lactobacillales and Bifidobacteria concentrations, and serum biochemistry lab parameters. This new protocol used different complexes of high concentration and stable probiotics in a ‘sequential’ manner.

The Study Method on Probiotics for Chronic Kidney Disease

This study would test the efficacy of a new protocol for probiotics administration to correct an imbalance in the intestinal microbiota of 28 CKD patients randomly and equally assigned to ProbiotiCKD treatment or placebo. Blood, stool, and morning spot urine samples were taken at baseline and after the treatment. 

The treated group underwent three phases: Phase 1: cleaning the intestines by taking one capsule of Enterelle (a complex of probiotics) during main meals (breakfast, lunch, and supper) for one week; Phase 2: colonizing the intestines by taking one capsule each of Bifiselle (a complex of Bifidobacterium strains) and Ramnoselle (a complex of Lactobacillus strains) during main meals for two weeks; Phase 3: maintaining the microbiota by taking one capsule each of Bisifelle and Ramnoselle, twice per day during breakfast and dinner for three months.

The primary outcome of the ProbiotiCKD study was the urinary indican and 3-MI concentration after the treatment period. The secondary outcomes were the after-treatment concentrations of fecal Lactobacillales and Bifidobacteria and biochemistry laboratory parameters.

The Results

In both groups at baseline, fecal Lactobacillales and Bifidobacteria concentrations were abnormally low, while high urinary indican and 3-MI levels indicated the excessive presence of a mixed (fermentative and putrefactive) dysbiosis. An inverse correlation was also evident between these urinary metabolites and fecal Lactobacillales and Bifidobacteria concentrations. 

Notably, after treatment, fecal Lactobacillales and Bifidobacteria concentrations significantly improved in the probiotics group, while no change was observed in the placebo group. The changes from baseline to after intervention were significantly different between the placebo and probiotic groups. The urinary indican and 3-MI levels were substantially lower in the probiotics patients than in the placebo group. Compared with the placebo group, significant improvements in C-reactive protein, iron, ferritin, transferrin saturation, and β2-microglobulin were observed only in the probiotics group.

Of note, compliance to treatment was overall good. None of the patients discontinued the treatment, and no one reported any relevant side effects.

The Conclusion

ProbiotiCKD is the first intervention study showing that intestinal mixed dysbiosis is present in the early CKD stage. This imbalance can be effectively corrected by improving inflammatory indices with the application of a new and optimized administration protocol of high-quality probiotics. This novel mode of administration was based on the rationale that creating a favorable intestinal environment before colonization with probiotics is vital to the effective management of gut dysbiosis.


An Open-Label, Randomized, Placebo-Controlled Study on the Effectiveness of a Novel Probiotics Administration Protocol (ProbiotiCKD) in Patients with Mild Renal Insufficiency (Stage 3a of CKD)

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