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.
Fibronectin glomerulopathy (FNGP) is an extremely rare glomerulopathy with an autosomal dominant pattern of inheritance. Sporadic cases of the disease are also described. Currently, several types of FN1 gene mutations are known that underlie conformational changes in the fibronectin molecule and lead to its deposition in the renal tissue. The clinical manifestations of FNGP may be very heterogeneous, but in most cases are characterized by proteinuria, microscopic hematuria, arterial hypertension, and long-term progressive renal failure. Renal biopsy is the main method for diagnosing the disease. Histologically, GFND is characterized by a lobular glomerular architecture with mesangial expansion and obliteration of capillary loops due to the accumulation of an acellular, periodic acid–Schiff positive, silver Jones-negative material. Immunofluorescence is usually negative. Electron microscopy shows finely granular or fibrillary mesangial and subendothelial electron-dense deposits. At higher magnifications, the fibrils have a diameter of 12-16 nm and are randomly arranged. Standard protocols for the etiopathogenetic therapy of FNGP are not currently developed. Improvement of clinical status and prognosis can be achieved by optimizing blood pressure and proteinuria control by renin–angiotensin–aldosterone system blockers. The recurrence risk of FNGP after renal transplantation remains uncertain due to the rare prevalence of the pathology. In this article, we report a 25-year-old man with nephrotic syndrome, which occurred after a previous upper respiratory tract infection. Histological changes specific to FNGP were found in the kidney biopsy. Genetic analysis was not performed. The absence of a family history of kidney disease suggests that this is a sporadic case of FNGP.
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.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.