Introduction: Numerous studies to date have shown that the development of dysbiotic gut microbiota is a characteristic finding in chronic kidney disease (CKD). A number of uremic toxins progressively accumulate in the course of CKD, some of them generated by the intestinal microbiome, such as indoxyl sulfate (IS) and p-cresyl sulfate (p-CS). They are found to be involved in the pathogenesis of certain complications of uremic syndrome, including low-grade chronic inflammation and oxidative stress. The aim of the present study is to research the serum concentration of IS and p-CS in end stage renal disease (ESRD) patients undergoing conventional hemodialysis, as well as to study the possibilities of influencing some markers of inflammation and oxidative stress after taking a synbiotic. Materials and Methods: Thirty patients with end-stage renal disease (ESRD) undergoing hemodialysis treatment who were taking a synbiotic in the form of Lactobacillus acidophilus La-14 2 × 10¹¹ (CFU)/g and prebiotic fructooligosaccharides were included in the study. Serum levels of total IS, total p-CS, Interleukin-6 (IL-6), and Malondialdehyde (MDA) were measured at baseline and after 8 weeks. Results. The baseline values of the four investigated indicators in the patients were significantly higher—p-CS (29.26 ± 58.32 pg/mL), IS (212.89 ± 208.59 ng/mL), IL-6 (13.84 ± 2.02 pg/mL), and MDA (1430.33 ± 583.42 pg/mL), compared to the results obtained after 8 weeks of intake, as we found a significant decrease in the parameters compared to the baseline—p-CS (6.40 ± 0.79 pg/mL, p = 0.041), IS (47.08 ± 3.24 ng/mL, p < 0.001), IL-6 (9.14 ± 1.67 pg/mL, p < 0.001), and MDA (1003.47 ± 518.37 pg/mL, p < 0.001). Conclusions: The current study found that the restoration of the intestinal microbiota in patients with CKD significantly decreases the level of certain uremic toxins. It is likely that this favorably affects certain aspects of CKD, such as persistent low-grade inflammation and oxidative stress.

Background and Objectives: The worldwide prevalence of chronic kidney disease (CKD) continues to increase, representing a major concern for public health systems. CKD is associated with gut microbiota dysbiosis, which may exacerbate disease progression by increasing the levels of uremic toxins, systemic inflammation, and oxidative stress. Modulation of the gut microbiota through biotic supplementation has been proposed as a potential therapeutic strategy to slow CKD progression and mitigate its complications. This study aimed to evaluate the effect of 10-month synbiotic supplementation on estimated glomerular filtration rate (eGFR), circulating concentrations of indoxyl sulfate (IS), p-cresyl sulfate (p-CS), interleukin-6 (IL-6), and malondialdehyde (MDA) in patients with stage IV–V CKD not receiving dialysis, in comparison to placebo. Materials and Methods: Fifty non-dialysis CKD IV–V patients were assigned (n = 25 each) via matched, non-randomized allocation (age, sex, and primary disease) to synbiotic or placebo. This single-blind, placebo-controlled trial blinded participants and laboratory personnel. The synbiotic group received daily capsules containing Lactobacillus acidophilus La-14 (2 × 10¹¹ CFU/g) + fructooligosaccharides; controls received identical placebo. Adherence was monitored monthly (pill counts, diaries), with < 80% over two visits resulting in withdrawal. The eGFR, IS, p-CS, IL-6, and MDA were measured at baseline and month 10. Results: Forty-two patients (21/arm) completed the study; eight withdrew (4 per arm). At 10 months, the change in eGFR was −1.2 ± 2.5 mL/min/1.73 m² (synbiotic) vs. −3.5 ± 3.0 mL/min/1.73 m² (placebo); between-group difference in change was 2.3 mL/min/1.73 m² (95% CI: 0.5–4.1; p = 0.014; adjusted p = 0.07). IS decreased by −15.4 ± 8.2 ng/L vs. −3.1 ± 6.5 ng/L; between-group difference in change was −12.3 ng/L (95% CI: −17.8 to −6.8; p < 0.001; adjusted p = 0.005). No significant differences were observed for p-CS, IL-6, or MDA after correction. Conclusions: Synbiotic supplementation over a 10-month period resulted in a trend toward decreased serum IS levels in patients with advanced CKD, suggesting potential benefits of microbiota-targeted therapies. However, no significant effects were observed on renal function, inflammatory, or oxidative stress markers. Further large-scale studies are warranted to confirm these findings and explore the long-term impact of synbiotics in CKD management.

Membranous nephropathy (MN) is a disease with an etiology and pathogenesis that are still not fully understood, and it represents a great challenge. It is characterized by a variable course, spontaneous remissions and relapses. The inability to rely entirely on antibodies and the continuous threat of a malignant disease make the differentiation of MN types extremely difficult. Data of twelve patients with membranous nephropathy, ranging in age between 28 and 67 years, are presented; in total, seven men and five women were observed for a period of 2 to 10 years. In all patients, the diagnosis was confirmed through kidney biopsy and laboratory tests, including immunological, histopathological, and immunohistochemical tests. Histopathological and immunohistochemical tests were applied on available material from the thyroid gland in two patients and the gallbladder in two patients with MN. Data of 102 patients with MN and their comorbidities are evaluated in order to establish correlations. These and other data are used to build a hypothetical pathogenetic model that explains the etiology and the likely pattern of disease occurrence. We found a connection between chronic cholecystitis, thyroiditis, hepatitis, and other diseases in the occurrence of MN and disease course. From our practice and cases, we drew the conclusion that chronic inflammation in sites that express PLA2R leads to the formation of antibodies against PLA2R. These antibodies occur as a preformed immune complex or separately and are deposited in the subepithelial space, leading to MN appearance.

Membranous nephropathy is a disease that has been well documented, yet its etiopathogenesis has not been fully clarified and the distinction between its primary and secondary forms has not been completely categorized. The discovery of new antigens and antibodies reveals different percentages of positivity in secondary membranous nephropathy, which is a cause of great confusion and ambiguity not only in diagnosis but also in the choice of a therapeutic approach. The aim of this review is to summarize the literature on newly discovered antigens and antibodies, and to propose a pathogenetic model based on the role of the complement system and its activation pathways. In this model, antigens are categorized based on the type of immunoglobulin deposits and the putative complement pathways that they activate, which can help to differentiate primary from secondary membranous nephropathy. The model also reflects how the deposition of foreign antigens in the basement membrane can activate both the lectin and classical complement pathways, which may explain why positive antibodies are observed in both primary and secondary forms of membranous nephropathy.