Bogdan Cimpineanu

Advanced chronic kidney disease (CKD) presents a complex hemostatic paradox, characterized by a simultaneous increase in bleeding and thromboembolic risks. This study aimed to evaluate and compare the safety and efficacy of apixaban versus acenocoumarol in a real-world cohort of patients across advanced CKD stages (pre-dialysis and hemodialysis). We conducted a retrospective observational study including 84 adults with CKD stages 4 and 5 (40.5% in stage 4; 59.5% in stage 5, of whom 86.0% were on chronic hemodialysis) receiving oral anticoagulation for at least 3 months. Patients were stratified by CKD stage and anticoagulant type (apixaban vs. acenocoumarol). Clinical outcomes included major and clinically relevant bleeding, anticoagulant overdose, and thromboembolic events. Bleeding events were more frequent in CKD stage 5 than in stage 4 (66.0% vs. 44.1%, p = 0.06), highlighting a pronounced hemorrhagic burden that increases with disease progression. Apixaban was associated with significantly fewer total bleeding events (44.4% vs. 66.7%, p = 0.04) and a lower rate of anticoagulant overdoses (5.6% vs. 18.8%, p = 0.04) compared with acenocoumarol. Thromboembolic event rates did not differ significantly between the two anticoagulant groups (13.9% vs. 16.7%, p = 0.72). Conventional risk scores (CHA₂DS₂-VASc and HAS-BLED) showed limited discriminatory capacity for actual clinical events in this advanced CKD population. In patients with advanced CKD, oral anticoagulation is associated with a high hemorrhagic burden that intensifies as renal function declines. Apixaban demonstrated a more favorable safety profile than acenocoumarol without a loss of thromboembolic protection. These findings suggest that stage-specific biological factors, rather than conventional risk models alone, should guide anticoagulation strategies in this population.

This systematic review examines chronic kidney disease-associated pruritus (CKD-aP) as a complex clinical manifestation in patients undergoing hemodialysis. Traditionally considered a secondary symptom of end-stage renal disease, emerging evidence now positions CKD-aP as a multidimensional disorder with substantial pathogenic influence on patient outcomes. Using the PRISMA 2020 methodology, we critically evaluated 54 peer-reviewed studies published between 2020 and 2025. Our synthesis highlights a convergence of five mechanistic frameworks underpinning CKD-aP: elevated levels of uremic toxins originating from gut microbial dysbiosis, immune activation driven by IL-31 and other pro-inflammatory cytokines, heightened peripheral and central neural sensitization, dysregulation of endogenous opioid receptor pathways favoring μ-receptor activation, and xerosis-related epidermal barrier dysfunction. These mechanisms contribute to a systemic cycle of microinflammation, pruritogenic signaling, and neural hyperexcitability. We also identified and compared validated assessment tools—including the NRS, VAS, Skindex-10, and the UP-Dial scale—that facilitate standardized quantification of disease burden. While available treatments such as gabapentinoids and phototherapy offer partial relief, targeted therapies—including κ-opioid receptor agonists—represent a major advancement, although long-term effectiveness and accessibility remain under investigation. Growing scientific consensus establishes CKD-aP as a priority therapeutic target in hemodialysis care, underscoring the need for integrated, mechanism-based management strategies to improve quality of life and clinical outcomes. This work represents a narrative systematic review, integrating evidence from mechanistic, translational, and clinical studies to critically examine the biological pathways underlying CKD-associated pruritus.

Background: Anticoagulation in patients with advanced chronic kidney disease (CKD) and atrial fibrillation (AF) remains challenging due to the concurrent risks of thrombosis and bleeding driven by endothelial dysfunction, uremic inflammation, and impaired hemostasis. Evidence comparing vitamin K antagonists (VKAs) with direct oral anticoagulants (NOACs) in this high-risk population, particularly in dialysis, is still limited. Methods: We conducted a single-center, retrospective observational study including 93 patients with CKD stages 4–5 and AF treated between January 2021 and February 2025. Fifty patients received apixaban (2.5–5 mg twice daily), and forty-three received acenocoumarol with a target INR of 2.0–3.0. Thirty-eight patients (41%) were on maintenance hemodialysis. Demographics, comorbidities, and risk scores (CHA₂DS₂-VASc and HAS-BLED) were analyzed. Bleeding events were classified per ISTH criteria. Statistical comparisons used t-tests and χ² tests, with p < 0.05 considered significant. Results: The mean age was 67.8 ± 9.1 years, and 51.6% were male. Major bleeding occurred in 9.7%, minor in 15.8%, and overdose-related bleeding in 10.0% of patients. The overall bleeding rate was significantly lower in the apixaban group (16.0%) than in the acenocoumarol group (53.5%; p = 0.01). No thromboembolic events were observed in either group. Dialysis patients had higher bleeding rates overall (13.2% vs. 7.4%), mainly among those on VKAs. The HAS-BLED score moderately correlated with bleeding incidence (r = 0.43, p < 0.01). Conclusions: Apixaban provided comparable thromboembolic protection with significantly fewer bleeding events than acenocoumarol, including in patients on dialysis. These findings support apixaban as a safer and more practical anticoagulant option in advanced CKD, consistent with its limited renal clearance and reduced influence on the inflammation–coagulation axis. Further multicenter prospective studies are warranted to validate these real-world results.

This systematic review investigates the role of the gut microbiota in patients with advanced chronic kidney disease (CKD), specifically stages 4 and 5. Increasing evidence suggests that dysbiosis—an alteration in the normal balance of gut microbial populations—is not merely a secondary consequence of renal decline but a significant driver of disease progression. Such microbial imbalances are closely linked to a range of CKD-associated complications, including systemic inflammation, accumulation of uremic toxins, and heightened cardiovascular risk. Using PRISMA 2020 guidelines, we analyzed 87 peer-reviewed studies published between 2019 and 2025. The review revealed a consistent decline in beneficial microbes such as short-chain fatty acid-producing bacteria were markedly reduced, while populations of uremic toxin-generating microbes were notably increased. This microbial imbalance was associated with elevated concentrations of indoxyl sulfate and p-cresyl sulfate, heightened systemic inflammation, and impaired intestinal barrier integrity. Five conceptual frameworks—including the gut—kidney axis and endotoxemia—inflammation loop—were discussed. Ten microbiome assessment tools were reviewed, including 16S rRNA sequencing and LC-MS/MS for uremic toxin detection. Although probiotics, prebiotics, and synbiotics are gaining attention as potential therapeutic options, questions remain regarding their long-term efficacy and incorporation into standard clinical practice. Increasing scientific evidence underscores the gut microbiome’s pivotal role in CKD progression and management, reinforcing the need for carefully designed, long-term interventions aimed at restoring a healthier microbial balance to support renal function.

Background: Hepatic encephalopathy (HE) is a severe neuropsychiatric complication of advanced liver disease, driven primarily by ammonia accumulation due to impaired hepatic detoxification and portosystemic shunting. Lactulose is a cornerstone therapy, while rifaximin serves as an effective adjunct for reducing recurrence and hospitalizations. Methods: We conducted a retrospective cohort study at Constanța Emergency County Hospital from January 2022 to March 2025, including 120 adult patients diagnosed with HE. Inclusion criteria were confirmed diagnosis of cirrhosis with clinical and/or biochemical evidence of HE. Patients with other primary neurological disorders or incomplete medical records were excluded. Data on demographics, comorbidities, laboratory results, and medications were collected. Statistical analyses were performed employing descriptive statistics, Friedman’s two-way ANOVA by ranks for medication use, and Cox proportional hazards regression to assess survival associations. Results: The mean age was 61.19 years, with high prevalence of anemia (mean hemoglobin: 9.35 g/dL) and thrombocytopenia (mean: 121.86 × 10³/µL). Inflammatory markers were elevated (mean CRP: 36.95 mg/L; ESR: 55.83 mm/h), and INR averaged 1.86. Lactulose was administered to 63.3% of patients, rifaximin to 52.5%, with diuretics, pantoprazole, and albumin being frequently used. Friedman’s analysis ranked lactulose highest in usage frequency. Cox regression indicated no significant short-term survival difference associated with toxic encephalopathy or rifaximin use. Conclusion: In this cohort, lactulose remained the primary treatment for HE, often complemented by supportive pharmacotherapy. While rifaximin use was limited, the overall medication patterns reflected standard practice priorities in HE management.

Background: End-stage renal disease (ESRD) patients on haemodialysis present a high burden of cardiovascular comorbidities and require anticoagulation, which increases bleeding risk. Methods: We performed a retrospective observational study (2021–2024) in the Haemodialysis Centre of The Clinical Emergency Hospital of Constanta County, Romania, including 50 adults with stage G5 CKD on haemodialysis for ≥3 months and receiving anticoagulant therapy. We collected from electronic medical records detailed demographic data (age, sex, place of residence), comorbidities (hypertension, atrial fibrillation, ischaemic heart disease, diabetes, deep-vein thrombosis, stroke, myocardial infarction, pulmonary embolism, cirrhosis), lifestyle factors (smoking and alcohol consumption), vascular access type (arteriovenous fistula or central venous catheter) and laboratory parameters (haemoglobin, haematocrit, creatinine, albumin, total protein, electrolytes, LDL- and HDL-cholesterol, total cholesterol, INR, APTT, D-dimer, BNP, CK-MB, troponin). All laboratory units were standardised and checked for plausibility. Results: Median age was 71 years; 48% were female. The most common comorbidities were: hypertension (100%), atrial fibrillation (100%) and ischaemic heart disease (62–81%). Patients exhibited severe anaemia (mean Hb ~9.7 g/dL), nephrotic-range proteinuria, hypoalbuminaemia, and impaired coagulation profiles (INR ~1.8–1.9; prolonged APTT in men). Female patients had higher platelet counts and D-dimer levels, suggesting a stronger prothrombotic profile, while males showed longer APTT. Cardiovascular strain was reflected by elevated BNP in men and also troponin/CK-MB. Correlations included smoking with leukocytosis, alcohol with increased urine density, diabetes with higher urea and lower protein, and subtherapeutic INR in cerebrovascular disease. Conclusions: Patients with ESRD on haemodialysis and anticoagulant therapy display a complex interplay of cardiovascular comorbidities, anemia, overlapping thrombotic and bleeding risks, with sex-specific differences. Therefore, systematic monitoring of proteinuria, haemoglobin, D-dimer, and coagulation markers is crucial to balance thrombotic and bleeding risks. Objective: To characterise the clinical and paraclinical profile and comorbidity–laboratory correlations of ESRD patients undergoing haemodialysis and anticoagulant therapy.

Background: Chronic ethanol consumption is a major global health concern traditionally associated with liver disease. Ethanol disrupts gut microbial communities, compromises intestinal barrier function, and contributes to hepatic, metabolic, and neurocognitive disorders. Methods: We conducted a systematic PubMed search and meta-analysis of 11 human and 19 animal studies evaluating ethanol-induced gut microbiota alterations. Studies were assessed for microbial diversity, taxonomic shifts, barrier integrity, and systemic effects. Effect sizes were calculated where possible, and interventional outcomes were examined. Results: Across species, ethanol exposure was consistently associated with reduced microbial diversity and depletion of beneficial commensals such as Faecalibacterium, Lactobacillus, Akkermansia, and Bifidobacterium, alongside an expansion of proinflammatory taxa (Proteobacteria, Enterococcus, Veillonella). Our analysis uniquely highlights discrepancies between human and animal studies, including opposite trends in specific genera (e.g., Akkermansia and Bifidobacterium) and the impact of confounders such as antibiotic exposure in human cohorts. We also demonstrate that microbiota-targeted interventions can partially restore diversity and improve clinical or behavioral outcomes. Conclusions: This meta-analysis highlights reproducible patterns of ethanol-induced gut dysbiosis across both human and animal studies.

Background/Objectives: The diversity of the oral microbiota exerts its effects in maintaining dental and overall health. The unique genetic profile of each individual influences the composition of the oral microbiota, determining susceptibility to certain diseases. The aim is to observe its role by highlighting the pathogenic mechanisms involved in oral dysbiosis and identify genetic determinism’s influence in maintaining balance. Methods: This study was designed as a narrative review of the oral microbiota, utilizing some of the principles and guidelines of systematic review to increase methodological rigor. We examined 121 articles such as reviews, meta-analyses, editorials, and observational studies, which met the inclusion and exclusion criteria. The inclusion criteria for studies were as follows: (1) studies that evaluated the impact of the microbiota in oral or/and systemic diseases; (2) studies that observed pathogenic mechanisms in the oral microbiota; (3) studies that evaluated the interaction of the microbiota with the immune system (4); studies that evaluated genetic implications in the microbiota. Results: Host genes regulate inflammatory and immunological reactions that play a role in microbiological balance. This explains the increased resistance of some to diseases, including gingivitis or periodontitis. Also, the implications of oral dysbiosis are reflected not only locally, but also generally, being associated with various systemic conditions. Conclusions: Understanding the pathogenic mechanisms and genetic determinants involved in oral dysbiosis may help create individualized therapies for preventing and managing oral and systemic disorders. A healthy lifestyle and adequate oral hygiene can facilitate a diverse and balanced microbiome, crucial for overall health.

Diabetes is one of the leading causes of chronic kidney disease (CKD), and multiple underlying mechanisms involved in pathogenesis of diabetic nephropathy (DN) have been described. Although various treatments and diagnosis applications are available, DN remains a clinical and economic burden, considering that about 40% of type 2 diabetes patients will develop nephropathy. In the past years, some research found that hypoxia response and hypoxia-inducible factors (HIFs) play critical roles in the pathogenesis of DN. Hypoxia-inducible factors (HIFs) HIF-1, HIF-2, and HIF-3 are the main mediators of metabolic responses to the state of hypoxia, which seems to be the one of the earliest events in the occurrence and progression of diabetic kidney disease (DKD). The abnormal activity of HIFs seems to be of crucial importance in the pathogenesis of diseases, including nephropathies. Studies using transcriptome analysis confirmed by metabolome analysis revealed that HIF stabilizers (HIF-prolyl hydroxylase inhibitors) are novel therapeutic agents used to treat anemia in CKD patients that not only increase endogenous erythropoietin production, but also could act by counteracting the metabolic alterations in incipient diabetic kidney disease and relieve oxidative stress in the renal tissue. In this review, we present the newest data regarding hypoxia response and HIF involvement in the pathogenesis of diabetic nephropathy and new therapeutic insights, starting from improving kidney oxygen homeostasis.