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Background and Objectives: The present study aims to investigate the association between gut microbiota's oxalate-degrading activity (ODA) and the risk of developing cardiovascular disease (CVD) over a three-year follow-up period in a cohort of patients undergoing kidney replacement therapy (KRT). Additionally, various factors were examined to gain insight into the potential mechanisms underlying the ODA-CVD link. Materials and Methods: A cohort of 32 KRT patients and 18 healthy volunteers was enrolled in this prospective observational pilot study. Total fecal ODA, routine clinical data, plasma oxalic acid (POx), serum indoxyl sulfate, lipid profile, oxidative stress, and proinflammatory markers were measured, and the patients were followed up for three years to assess CVD events. Results: The results revealed that patients with kidney failure exhibited significantly lower total fecal ODA levels compared to the healthy control group (p = 0.017), with a higher proportion showing negative ODA status (≤-1% per 0.01 g) (p = 0.01). Negative total fecal ODA status was associated with a significantly higher risk of CVD events during the three-year follow-up period (HR = 4.1, 95% CI 1.4-16.3, p = 0.003), even after adjusting for potential confounders. Negative total fecal ODA status was significantly associated with elevated POx and indoxyl sulfate levels and linked to dyslipidemia, increased oxidative stress, and inflammation, which are critical contributors to CVD. Conclusions: The findings contribute novel insights into the relationship between gut microbiota's ODA and cardiovascular health in patients undergoing KRT, emphasizing the need for further research to elucidate underlying mechanisms and explore potential therapeutic implications of targeting gut microbiota's ODA in this vulnerable population.

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BACKGROUND: Little evidence is available on oxalate balance in peritoneal dialysis (PD) patients. PATIENTS AND METHODS: We performed a cross-sectional observational pilot study with 62 adult PD patients to document oxalate balance and explore its association with PD-related peritonitis. Plasma oxalate concentration, levels of oxalate excretion in 24-h urine, and peritoneal dialysis effluent were evaluated. The peritoneal oxalate transport status and renal and peritoneal oxalate clearances were calculated according to the PD-related peritonitis history. RESULTS: PD patients with a history of peritonitis had a statistically significantly lower peritoneal oxalate clearance, daily peritoneal oxalate excretion, and overall oxalate removal rate compared with the peritonitis-free PD patients. They had a 4-fold risk of plasma oxalic acid increase, and even a single episode of dialysis-related peritonitis resulted in plasma oxalate elevation. CONCLUSION: Peritoneal oxalate clearance plays an important role in oxalate balance in PD patients and, therefore, dialysis-related peritonitis is a significant predictor for hyperoxalemia. Further well-designed clinical trials need to be undertaken before the association between peritonitis and oxalate balance in PD patients is more clearly understood.

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The present study aimed (i) to evaluate whether ceftriaxone treatment could affect not only intestinal oxalate-degrading bacteria number but also their total activity to degrade oxalate and influence oxalate homeostasis in rats, (ii) and to estimate the ability of commercially available inulin-contained synbiotic to restore fecal oxalate-degrading activity and ceftriaxone-induced disruption of oxalate homeostasis in rats. Twenty-eight female Wistar rats (200-300 g) were randomly divided into four groups (n = 7). Group 1 was treated with vehicle sterile water (0.1 ml, i.m., 14 days); Group 2 received synbiotic (30 mg/kg, per os, 14 days); Group 3 was treated with ceftriaxone (300 mg/kg, i.m., 7 days); Group 4 was supplemented with ceftriaxone and synbiotic. Oxalate-degrading bacteria number and their total activity, urinary and plasma oxalate concentrations were measured on days 1 and 57 after the treatment withdrawal. The redoximetric titration with KMnO4 was adopted to evaluate the total oxalate-degrading activity in highly selective Oxalate Medium. Ceftriaxone treatment reduced total fecal oxalate-degrading activity independently on oxalate-degrading bacteria number and increased urinary and plasma oxalate concentrations. The synbiotic had higher oxalate-degrading activity vs probiotics and was able to restore fecal oxalate-degrading activity and significantly decrease urinary oxalate excretion in antibiotic-treated rats. Total fecal oxalate-degrading activity but not oxalate-degrading bacteria number should be thoroughly examined in the future to develop predictive diagnostics methods, targeted prevention and personalized treatment in kidney stone disease. Synbiotic supplementation had a beneficial effect on the total oxalate-degrading activity of gut microbiota, which resulted in decreased UOx excretion in rats.

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BACKGROUND: We have hypothesized that the problem of dyslipidemia in peritoneal dialysis (PD) patients lies beyond certain levels of plasma lipoprotein and involves cardiovascular risk, but can also influence the development of chronic intraperitoneal inflammation. OBJECTIVES: The aim of our work was to define whether the association of dyslipidemia with intraperitoneal inflammation really exists and if it could it be used in a prospective cohort of PD patients. PATIENTS AND METHODS: We performed a cross-sectional, single-center, pilot study involving 40 nondiabetic PD patients (27 men and 13 women with an average age of 49.3 ± 12.2 years). The median time on PD was 29 (18.5-37) months. The parameters dialysis adequacy, blood lipid profile, and the concentrations of tumor necrosis factor (TNF)-α, monocyte chemoattractant protein (MCP)-1, and interleukin (IL)-10 in peritoneal dialysate effluent (PDE) were determined. Cohen's d effect size was computed post hoc to determine the differences between groups in the concentrations of pro- and anti-inflammatory mediators. RESULTS: PD patients with atherogenic dyslipidemia had significantly high levels of MCP-1 compared with dyslipidemia-free patients (Cohen's d = 1.32). A reduced high-density lipoprotein cholesterol level was associated with a high intraperitoneal production of the proinflammatory mediator TNF-α (p < 0.0001) and anti-inflammatory IL-10 (p < 0.0001). Atherogenic index of plasma was directly correlated with MCP-1 (p < 0.0001) and TNF-α (p < 0.0001). In multiple regression analysis, MCP-1 appeared to predict PD inadequacy (R 2 = 0.58; F ratio = 9.4; p = 0.006) independently of age and blood C-reactive protein level. Effect size was 1.38 with α = 0.05, n = 40, and 3 predictors. CONCLUSIONS: Our cross-sectional pilot study first demonstrated a close interaction between the atherogenic lipid profile and a high concentration of MCP-1 in PDE; this might be a prognostic marker for PD inadequacy. The potential significance of our finding is that it provides useful preliminary information necessary for further research into this area.