Structural and functional intestinal barrier abnormalities and chronic kidney disease. Literature review. Part I

Pyatchenkov, M. O.; Markov, Alexander G.; Rumyantsev, A. Sh.

doi:10.36485/1561-6274-2022-26-1-10-26

Cited by 7 publications

(1 citation statement)

References 108 publications

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“…Понимание фундаментальных основ каждого метода имеет важное значение для оценки их преимуществ и ограничений. Учитывая, что почки играют ключевую роль в поддержании гомеостаза внутренней среды организма благодаря регулируемому выведению избыточной жидкости, электролитов, органических соединений, а также токсичных продуктов жизнедеятельности, изучение особенностей функционирования пищеварительной системы в условиях почечной недостаточности, является чрезвычайно интересным и актуальным направлением научных и клинических исследований [25].…”

Section: методы оценки барьерной функции и проницаемости кишечной стенкиunclassified

Features of assessing the intestinal barrier permeability in chronic kidney disease

Pyatchenkov

Власов

Sherbakov

et al. 2023

jour

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Numerous studies have shown that changes in the intestinal microbial-tissue complex are a risk factor for the progression of chronic kidney disease (CKD) to end-stage renal disease and, therefore, a potential target for new therapeutic interventions. Thus, reliable and sensitive diagnostic tools for measuring intestinal permeability in the clinical setting are necessary. Modern genome sequencing and multi-omics technologies have established that patients with CKD are characterized by a specific imbalance between the saccharolytic and proteolytic microbiota, contributing to the accumulation of numerous toxic microbial products, such as indoxyl sulphate, p-cresyl sulphate, trimethylamine-N-oxide. Progressive kidney function decline leads to compensatory urea accumulation in the gastrointestinal tract. In the intestinal lumen, urea is hydrolyzed by microbial urease, forming a large amount of ammonium hydroxide, which may be accompanied by disruption of the epithelial barrier integrity with an increase in intestinal permeability for microbial molecules that initiate systemic inflammation. Experimental approaches to studying the intestinal barrier in CKD include the assessment of electrophysiological parameters of the intestinal epithelium and the transport of fluorescently labelled tracers in the Ussing chamber. Actively improving various cell-based in vitro methods, which may be useful for studying the effect of microbiota on the barrier functions of the intestinal epithelium. Gene expression and protein content of tight junctions are estimated using polymerase chain reaction, immunohistochemical methods and Western blotting. Using various biomolecular methods, it was found that renal failure is characterized by the presence of inflammatory and atrophic changes throughout the gastrointestinal tract, destruction of the mucin layer, damage to tight junctions with a decrease in the amount of claudine-1, occludin and ZO-1 as well as a decrease in transepithelial electrical resistance. Clinical examination of intestinal permeability by methods based on the urine excretion of orally administered sugars, polyethylene glycol polymers and labelled tracers indicate a distortion of the results in patients with CKD due to altered renal clearance. Alternatively, quantitative determination of bacterial DNA and D-lactate levels in the blood is considered. Identification of serum non-coding microRNAs, confocal laser endomicroscopy and impedance spectroscopy have the potential to be used as methods for assessing intestinal barrier function.

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Section: методы оценки барьерной функции и проницаемости кишечной стенкиunclassified

Features of assessing the intestinal barrier permeability in chronic kidney disease

Pyatchenkov

Власов

Sherbakov

et al. 2023

jour

Self Cite

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The state of the intestinal microbial-tissue complex in patients with chronic kidney disease

Pyatchenkov

Саликова

Sherbakov

et al. 2023

Bulletin of the Russian Military Medical Academy

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The gut microbiota plays a fundamental role in maintaining normal organism homeostasis, regulating a wide range of metabolic, biosynthetic, and immune functions. This complex ecosystem, together with cellular, and stromal components of the intestinal wall, forms the intestinal microbial-tissue complex, which pathology is considered a universal mechanism for the development of many diseases, including chronic kidney disease. Accumulation of nitrogen metabolism products in the intestine, specific diet, polypharmacy, sedentary lifestyle, limited fluid intake, and violation of gastrointestinal motility in patients with chronic kidney disease lead to a decrease in the number of bacteria synthesizing short-chain fatty acids with crucial physiological effects, along with an increase in the content of anaerobic proteolytic bacteria expressing uricase, urease, and p-cresol-, and indole-forming enzymes. The features of gut dysbiosis depend on the etiology of chronic kidney disease and severity of renal insufficiency and differ significantly in individuals receiving various renal replacement therapies (hemodialysis, peritoneal dialysis, kidney transplant recipients). Abnormal microbial metabolism enhances the production and accumulation of microbial-derived uremic toxins: p-cresyl sulfate, indoxyl sulfate, and trimethylamine-N-oxide. Renal insufficiency, through mechanisms mainly associated with the hydrolysis of accumulated in the lumen of the intestine urea, leads to inflammation, and swelling of the intestinal wall, which is accompanied by disorders of the immune tolerance of the mucous layer and disorganization of intercellular junctional complexes, which are critical modulators of intestinal intercellular transepithelial transport. Uremia-induced impairment of the gut epithelial barrier integrity induces the systemic translocation of numerous immunogenic substances generated by the aberrant microbiota, followed by the development of oxidative stress and chronic subclinical inflammation that causes the progression of chronic kidney disease and related complications. The most pronounced changes were observed in people with end-stage chronic kidney disease. Further study of the bidirectional relationship between the kidneys and intestinal microbial-tissue complex will contribute to the development of new directions of pathogenetic therapy and prevention of adverse outcomes in patients with chronic kidney disease.

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Evaluation of the nephroprotective strategy effectiveness in the late stages of chronic kidney disease

Sadovskaya

Vishnevskii

Konakova

et al. 2023

HERALD of North-Western State Medical University named after I.

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Background. Classical nephroprotection reduces its effectiveness at the late CKD stages; the search for effective algorithms is hampered by accelerating decline in GFR, therefore there are no generally accepted ways to evaluate the effectiveness. Aim: to build a model for predicting the GFR decline rate in order to assess the effectiveness of the intensive follow-up. Methods. A representative group of regular follow-up (N=540) was allocated from the city database (N=7696) to built-up the polynomial model that predicts GFR annual decline. We used the model to evaluate the intensive monitoring effectiveness (N=100) by the difference between predicted and actual rates of GFR decline. We also selected well matched subgroup of 200 patients for direct comparison of hard and surrogate outcomes. Results. During last year before need in dialysis, the rate of GFR decline in intensive group was 5.981.69 vs. the predicted 9.060.59ml/min/1.73 m/year. We used that assessment of the intervention effectiveness as dependent variable in regression and categorical analysis. The significant components of the nephroprotection: phosphatemia decrease (0.25 mmol/l), hemoglobin increase (1 g/dl), effective administration of RAAS blockers (to reduce proteinuria by 0.1 g/l), systolic blood pressure decrease (5 mmHg), calcemia deviations decrease from the target (0.1 mmol/l), acidosis correction (2 mmol/l), inflammation reduction and albumin increase (1.5 g/l) -were associated with the smaller GFR decrease rate by 15%. In intensive group, the dialysis risk was 2.2 times lower, the death risk was 4 times. The only planned dialysis start was ensured in intensive group, 67% chose peritoneal dialysis. Conclusions. The prediction of GFR decline rate calculated by nonlinear model in comparison with the actual one can evaluate the nephroprotection effectiveness; it differs significantly from the classical ones at the CKD late stages.

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Structural and functional intestinal barrier abnormalities and chronic kidney disease. Literature review. Part I

Cited by 7 publications

References 108 publications

Features of assessing the intestinal barrier permeability in chronic kidney disease

Features of assessing the intestinal barrier permeability in chronic kidney disease

The state of the intestinal microbial-tissue complex in patients with chronic kidney disease

Evaluation of the nephroprotective strategy effectiveness in the late stages of chronic kidney disease

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