Kidney countdown: exposure to myrcobiota will help delay dialysis

The gut microbiota may become a new key to the treatment of chronic kidney disease and help patients go longer without dialysis. This conclusion was reached by doctors at Sechenov University, who are investigating the effect of intestinal bacteria on the progression of the disease and related cognitive impairments. The results of the work can form the basis of new personalized approaches to CKD therapy and change the management strategy of millions of patients. For more information about the proposed approach, see the Izvestia article.

How is the microbiome related to chronic kidney disease

For the first time in Russia, nephrologists are studying the effect of microbiota on the course of chronic kidney disease (CKD). The findings of the clinicians will form the basis of a comprehensive approach to treating patients and prolonging their life without the need for dialysis. At this stage, specialists from the E.M. Tareev Clinic of Rheumatology, Nephrology and Occupational Pathology at Sechenov University have found out that an increase in the proportion of conditionally pathogenic organisms in the microbiota of a person with CKD can have a negative impact on the cardiovascular system, kidneys and even the brain.

— The human microbiome consists of beneficial and conditionally pathogenic bacteria that are in balance. In CKD, a decrease in the filtration function of the kidneys leads to the release of excess urea into the intestinal lumen. There it is broken down to ammonia, which inhibits the beneficial flora. The situation is aggravated by an excess of dietary protein: it provokes the growth of bacteria that produce uremic toxins, such as indoxyl sulfate. In conditions of increased permeability of the intestinal barrier, these toxins freely enter the systemic bloodstream, where they cause vascular inflammation, accelerate kidney damage, and overcome the blood—brain barrier, leading to cognitive disorders — deterioration of memory, attention and thinking, - said Lyudmila Milovanova, professor of the Department of Internal, Occupational Diseases and Rheumatology at Sechenov University.

The accumulated evidence suggests that changes in the gut microbiome may contribute to the development of cognitive impairments within the framework of the "kidney—brain—intestine" axis. Systemic inflammation, oxidative stress, toxins, and increased intestinal permeability ("leaky gut syndrome") are key components of such problems.

Therefore, the treatment of CKD requires an integrated approach, in which the role of the microbiota is of particular importance, the scientists said. To this end, they are launching a study on "Chronic kidney disease and cognitive impairment. The role of diet and microbiota".

— For the first time in our country, we propose to evaluate the effect of a low-protein diet in patients with CKD and changes in the composition of the microbiota on the cognitive abilities of patients with chronic kidney disease. This information is a serious clinical tool for predicting the course of the disease and slowing its further development," explained Lyudmila Milovanova.

Recommendations include a low—protein diet, mainly of plant origin, the replacement of part of animal protein with soy isolate, the use of ketoanalogs of essential amino acids, as well as the use of means to modify the microbiota - prebiotics ("food" of beneficial bacteria), probiotics (living microorganisms), synbiotics (a combination of probiotic and prebiotic) and metabiotics (waste products of beneficial microbes).

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How studying the microbiota can change approaches to the treatment of CKD

Chronic kidney disease and the intestinal microbiota are linked in a chain of mutual reinforcement: the worse the kidneys work, the more the balance of bacteria is disrupted, and this accelerates organ damage, molecular biologist Arina Kholkina told Izvestia.

— The data obtained opens the way to personalized nephroprotection. Analyzing the composition of the microbiota and the level of bacterial toxins will help predict in advance who will develop complications faster. A low-protein diet, probiotics, and toxin sorbents can adjust the composition of the microbiota, break the chain of damage, and delay dialysis. The nephrology study lays the foundation for this approach," she said.

The results of the study open up new opportunities for early diagnosis, prevention, prognosis and treatment of chronic kidney disease through microbiota correction. In the future, this may change patient management tactics by adding microbiome-modulating therapy to standard regimens, Evgeny Kanaev, head of the Department of Urology with kidney transplantation at the SamSMU clinic of the Russian Ministry of Health, urologist, surgeon, market expert at NTI Helsnet, told Izvestia.

— The work of scientists can become the basis for a personalized approach to the treatment of CKD, from microbiota correction and diet therapy to the use of fecal transplantation in cases where it is proven that dysbiosis worsens the course of the disease. The approach can also be used as prognostic markers: analysis of the intestinal microflora will allow assessing the risk of CKD progression and the development of cardiovascular complications, and regular monitoring will help timely adjust therapy at an early stage," he said.

According to the expert, the data obtained can be useful not only for the treatment, but also for the prevention of complications of chronic kidney disease. If it is confirmed that certain microorganisms contribute to increased uremic intoxication or inflammatory processes, this will allow the development of more accurate antimicrobial strategies aimed at correcting the composition of the microbiota.