Background: A bidirectional kidney–gut axis was described in patients with chronic kidney disease (CKD). On the one hand, gut dysbiosis could promote CKD progression, but on the other hand, studies reported specific gut microbiota alterations linked to CKD. Therefore, we aimed to systematically review the literature on gut microbiota composition in CKD patients, including those with advanced CKD stages and end-stage kidney disease (ESKD), possibilities to shift gut microbiota, and its impact on clinical outcomes. Materials and methods: We performed a literature search in MEDLINE, Embase, Scopus, and Cochrane databases to find eligible studies using pre-specified keywords. Additionally, key inclusion and exclusion criteria were pre-defined to guide the eligibility assessment. Results: We retrieved 69 eligible studies which met all inclusion criteria and were analyzed in the present systematic review. Microbiota diversity was decreased in CKD patients as compared to healthy individuals. Ruminococcus and Roseburia had good power to discriminate between CKD patients and healthy controls (AUC = 0.771 and AUC = 0.803, respectively). Roseburia abundance was consistently decreased in CKD patients, especially in those with ESKD (p < 0.001). A model based on 25 microbiota dissimilarities had an excellent predictive power for diabetic nephropathy (AUC = 0.972). Several microbiota patterns were observed in deceased ESKD patients as compared to the survivor group (increased Lactobacillus, Yersinia, and decreased Bacteroides and Phascolarctobacterium levels). Additionally, gut dysbiosis was associated with peritonitis and enhanced inflammatory activity. In addition, some studies documented a beneficial effect on gut flora composition attributed to synbiotic and probiotic therapies. Large randomized clinical trials are required to investigate the impact of different microbiota modulation strategies on gut microflora composition and subsequent clinical outcomes. Conclusions: Patients with CKD had an altered gut microbiome profile, even at early disease stages. Different abundance at genera and species levels could be used in clinical models to discriminate between healthy individuals and patients with CKD. ESKD patients with an increased mortality risk could be identified through gut microbiota analysis. Modulation therapy studies are warranted.

Cardiovascular kidney metabolic (CKM) syndrome represents a complex interplay of cardiovascular disease (CVD), chronic kidney disease (CKD), and metabolic comorbidities, posing a significant public health challenge. Gender exerts a critical influence on CKM syndrome, affecting the disease severity and onset through intricate interactions involving sex hormones and key physiological pathways such as the renin–angiotensin system, oxidative stress, inflammation, vascular disease and insulin resistance. It is widely known that beyond the contribution of traditional risk factors, men and women exhibit significant differences in CKM syndrome and its components, with distinct patterns observed in premenopausal women and postmenopausal women compared to men. Despite women generally experiencing a lower incidence of CVD, their outcomes following cardiovascular events are often worse compared to men. The disparities also extend to the treatment approaches for kidney failure, with a higher prevalence of dialysis among men despite women exhibiting higher rates of CKD. The impact of endogenous sex hormones, the correlations between CKM and its components, as well as the long-term effects of treatment modalities using sex hormones, including hormone replacement therapies and gender-affirming therapies, have drawn attention to this topic. Current research on CKM syndrome is hindered by the scarcity of large-scale studies and insufficient integration of gender-specific considerations into treatment strategies. The underlying mechanisms driving the gender disparities in the pathogenesis of CKM syndrome, including the roles of estrogen, progesterone and testosterone derivatives, remain poorly understood, thus limiting their application in personalized therapeutic interventions. This review synthesizes existing knowledge to clarify the intricate relationship between sex hormones, gender disparities, and the progression of CVD within CKM syndrome. By addressing these knowledge gaps, this study aims to guide future research efforts and promote tailored approaches for effectively managing CKD syndrome.

Background/Objectives: Chronic kidney disease (CKD) progression is strongly influenced by systemic inflammation. The neutrophil-to-lymphocyte ratio (NLR), derived from routine blood counts, reflects the balance between innate and adaptive immunity and has been proposed as a marker of adverse renal outcomes. We hypothesized that elevated baseline NLR is associated with reduced kidney function and increased risk of progression to end-stage kidney disease (ESKD) in adults with non-dialysis CKD. Methods: Following PRISMA guidelines, we systematically searched MEDLINE, Embase, and Scopus for studies enrolling adults with CKD stages 1–4 that reported renal outcomes according to baseline NLR. The primary outcome was progression to ESKD or renal replacement therapy (RRT) initiation. Results: Six eligible studies were identified, of which four provided sufficient data for meta-analysis. Across cohorts, elevated baseline NLR was consistently associated with adverse renal outcomes. In pooled analyses, high NLR nearly doubled the risk of ESKD or RRT (RR 1.96, 95% CI 1.30–2.97). Leave-one-out sensitivity analysis strengthened the association while reducing heterogeneity. For kidney function, higher NLR was associated with lower baseline eGFR (SMD −1.59, 95% CI −2.38 to −0.80). Conclusions: Elevated NLR is a robust prognostic marker of renal function decline and progression to ESKD or RRT in non-dialysis CKD. As a simple and inexpensive biomarker, NLR offers additional predictive value beyond eGFR and albuminuria. Incorporating NLR into risk models may refine stratification, guide follow-up, and enable earlier therapeutic optimization. Prospective large studies are warranted to establish thresholds and validate its role in clinical practice.

Complement system inhibitors are emerging as promising therapies in nephrology, particularly for diseases where complement dysregulation is central to pathogenesis. This review summarizes the role of complement activation in kidney diseases and current evidence supporting complement-targeted treatments. As the complement system can be involved in the pathogenesis of different diseases to varying degrees, several research works have been conducted. These research efforts aim, firstly, to understand the mechanisms and role of complement cascade components in the most prevalent nephrological diseases and, secondly, to explore the potential of complement system inhibitors in these conditions and their possible clinical applications. Clinical trials demonstrate that complement inhibitors are most effective in conditions with significant complement involvement, such as C3 glomerulopathy (C3G), atypical hemolytic uremic syndrome (aHUS), and immune complex membranoproliferative glomerulonephritis (IC-MPGN). These agents show variable benefits in diseases with partial complement activation, including lupus nephritis and ANCA-associated vasculitis, while their role in disorders like diabetic nephropathy and focal–segmental glomerulosclerosis remains limited. Complement inhibition offers a targeted strategy to prevent disease progression and improve outcomes in selected nephrological disorders.

Patients with chronic kidney disease have an increased risk of all-cause death. The value of collagen biomarkers such as procollagen type I carboxy-terminal propeptide (PICP) and procollagen type III N-terminal peptide (P3NP), in end-stage renal disease (ESRD), has not yet been defined (in the literature and in clinics). The purpose of this study was to determine the potential value of these new biomarkers in the prediction of mortality in this population. Plasma PICP and P3NP levels were determined in 140 patients with ESRD, not yet on dialysis, who were followed up for 36 ± 5.3 months. During follow-up, 58 deaths were recorded (41.4%), with the majority of them being cardiovascular deaths (43, 74.13%). Using the ROC curve, the cut-off value for the prediction of mortality for PICP was 297.31 µg/L, while for P3NP, the cut-off value was 126.67 µg/L. In univariate analysis, a value of PICP above the cut-off point was associated with a fivefold increased risk of mortality (hazard ratio (HR) 5.071, 95% confidence interval 1.935–13.29, p = 0.001) and a value of P3NP above the cut-off point was associated with a twofold increased risk of mortality (HR 2.089, 95% CI 1.044–4.178, p = 0.002). In a multivariable Cox proportional hazards model, PICP values remained independent predictors of mortality (HR 1.22, 95% CI 1.1–1.31, p < 0.0001). Our data suggest that the collagen biomarker PICP is an independent predictor of mortality in ESRD patients who are not yet on dialysis.

Increasing evidence sustains the potential of periodontitis as a risk factor for chronic kidney disease (CKD). Our study aimed to analyze several periodontal specific inflammatory biomarkers within the gingival crevicular fluid (GCF) of patients with CKD, compared to patients with normal kidney function, providing an inflammatory profile of the dialysis patient. The study comprised 79 patients divided into: group 1 (59 subjects with periodontitis and CKD) and group 2 (20 patients with periodontitis, without other systemic conditions). Clinical diagnosis was performed via dental and periodontal examination. GCF samples were collected from each patient, and the levels of TNF-α, IL-1β and MMP-8 were determined by using ELISA assay. In group 1, the average values were: 22.85 ± 5.87 pg/mL for TNF-α, 33.00 ± 39.68 pg/mL for IL-1β and 18.80 ± 27.75 ng/mL for MMP-8. In group 2, the mean values were: 2.10 ± 1.34 pg/mL for TNF-α, 0.71 ± 2.42 pg/mL for IL-1β and 5.35 ± 0.37 ng/mL for MMP-8. Statistical analysis revealed significant differences between groups as referring to all three biomarkers and, TNF-α and MMP-8, in certain stages of periodontitis. The level of TNF-α, IL-1β and MMP-8 points out the increased inflammatory status of the dialysis patient with PD, supporting the mutual connection of the two pathologies.