Search Results (43)

Background: Healthcare-associated infection drives morbidity and unplanned hospital use in haemodialysis. We aimed to determine whether an adapted British Renal Society Infection Risk Screening Tool, applied during a nurse-led vascular access consultation, identifies patients at increased risk of subsequent infection-related hospitalisation and can inform de-selection of buttonhole puncture. Methods: We conducted a retrospective cohort of 404 adults reviewed between 1 January 2022 and 31 December 2024. Baseline demographics, comorbidities, vascular access status and screening classification (“risk present/absent”) were retrieved from records. The primary outcome was ≥1 infection-related hospitalisation within 12 months; the number of such admissions was secondary. Results: Mean age was 70.2 years; 47% had diabetes; 27.8% screened “risk present”. Forty-eight patients (11.9%) were hospitalised for infection. “Risk present” showed higher—though imprecise—odds of infection-related admission versus “risk absent” (adjusted OR 1.73; 95% CI 0.90–3.27). Older age increased risk, whereas higher body-mass index appeared protective; diabetes, central venous catheter and dialysis vintage were not significant. Conclusions: The dichotomised screening classification identified only a modest elevation in risk, with age and nutritional status exerting greater influence. The tool may support cautious de-selection of buttonhole in higher-risk individuals, but refinement and prospective validation are required. Full article

Sepsis is characterized by the over-production of pro-inflammatory cytokines. Cecal ligation and puncture (CLP) is a well-accepted model for recreating sepsis-induced renal injury in mice. The current study investigates how citronellol, a naturally occurring substance with a variety of biological characteristics, can prevent acute kidney inflammation brought on by CLP. In the CLP mouse model, citronellol was administered orally at doses of 50 and 100 mg/kg. Serum levels of creatinine and urea were used as markers of renal function, and the Murine Sepsis Score (MSS) was used to assess the severity of sepsis. According to our findings, CLP caused a decline in renal function, as shown by higher serum urea and creatinine levels in comparison to control mice. Nevertheless, administering citronellol as pretreatment at doses of 50 and 100 mg/kg alleviated the deterioration in renal functions. Citronellol decreased levels of serum urea and creatinine. Citronellol demonstrated an anti-inflammatory effect by reducing pro-inflammatory cytokines (TNF-α, NF-κB, AP-1) and KIM-1. Overall, our study suggests that citronellol holds a promise as a potential therapeutic agent for mitigating kidney inflammation. Full article

Sirtuin 3 (sirt3), a mitochondrial NAD⁺-dependent deacetylase, is an important enzyme in the maintenance of kidney functions, with critical roles in renal homeostasis, attenuation of oxidative stress, and preservation of mitochondrial homeostasis. This review aims to summarize the current literature on the mechanisms by which sirt3 impacts kidney health and disease, as well as highlight the therapeutic implications of sirt3 targeting. We conducted a PubMed search using the title word “sirt3” and the keyword “kidney” to generate our literature review sources. The animal studies that are explored in this review include cisplatin-induced acute kidney injury, cadmium-induced kidney injury, cecal ligation and puncture (CLP) and lipopolysaccharide-induced sepsis, diabetic kidney fibrosis, high-fat induced kidney disease, and ischemic kidney injury. Increasing evidence points towards a deficiency in sirt3 being an aggravator of mitochondrial dysfunction, promoting abnormal glycolysis, and contributing to the progression of diabetic kidney disease, renal fibrosis, and acute kidney injury. In contrast, pharmacological and dietary activation of sirt3 has been observed to enhance mitochondrial biogenesis, mitigate production of reactive oxygen species (ROS), and preserve the integrity of renal tubular cells under stressful conditions. Collectively, studies point towards sirt3 as a central metabolic and antioxidant regulator within the kidney, and link chronic kidney disease, as well as age-related decline in kidney function, to this enzyme. The conclusion of this review identifies future directions for translational research regarding sirt3 and NAD⁺-dependent regulation of mitochondrial homeostasis in renal medicine. Full article

Septic shock has an unacceptably high mortality rate and unmet need for new therapeutics. Murine models are crucial for research, yet methodologies often differ. This study characterised standard- and high-grade caecal ligation and puncture (CLP) murine models of septic shock by integrating ultraminiature arterial telemetry with comprehensive plasma biomarker analysis. Standard-grade and high-grade CLP was performed in 8–10 week old, male C57BL/6 mice (n = 98), with a subset implanted with arterial telemetry to monitor real-time circulatory function. Plasma markers of inflammation and organ damage were measured at multiple intervals up to 168 h post-CLP. Standard-grade and high-grade CLP showed distinct progressions; episodes of hypotension began 5–6 h after CLP in 30% of standard-grade and all high-grade CLP mice, with respective 168 h mortality of 40% and 71%. Recurrent episodes of hypotension 5–39 h after CLP were universally lethal. The coincidence of hypotension and elevated plasma lactate defined the onset of septic shock after high-grade CLP, which was always lethal. Inflammatory cytokines and markers of liver, renal, and cardiac damage were markedly elevated to 168 h after high-grade CLP, in contrast to standard-grade CLP, which returned to baseline by 48 h. Elevated plasma IL-6, TNFα, and corticosterone, along with reduced albumin, were significantly correlated with mortality. In conclusion, this research refines murine CLP models by providing a precise, dynamic map of the progression to septic shock. The high-grade CLP model consistently models early and late-stage physiological deterioration and serves as a robust model for evaluating the efficacy of novel therapies aimed at human septic shock. Full article

Sepsis is a life-threatening condition driven by a dysregulated host response to infection, with high mortality and few treatment options. Decades of failed drug development underscore the urgent need for therapies with novel mechanisms of action. Vimentin, an intermediate filament protein, acts as a network hub that senses and integrates cellular signals. Its involvement in key sepsis pathologies, including infection, hyperinflammation, immunosuppression, coagulopathy and metabolic dysregulation, positions it as a potential therapeutic target. This study evaluated the efficacy of ALD-R491, a novel small-molecule vimentin modulator, in a murine model of polymicrobial sepsis induced by cecal ligation and puncture (CLP). Mice received ALD-R491 prophylactically or therapeutically, alone or with ceftriaxone. The treatment significantly reduced serum levels of key biomarkers of sepsis, including C-reactive protein (CRP), lactate (Lac), tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6), and dose-dependently improved the survival of septic mice. Organ-specific analysis confirmed the effects of ALD-R491 in mitigating hyperinflammation and multi-organ injury. The treatment reduced pulmonary edema and inflammation; preserved liver tissue architecture and improved hepatic function with lowered alanine aminotransferase/aspartate aminotransferase (ALT/AST); decreased kidney tubular damage; and improved renal function with lowered creatinine/blood urea nitrogen (BUN). These preclinical findings indicate that the vimentin-targeting agent ALD-R491 represents a promising therapeutic candidate for sepsis and merits further clinical investigation. Full article

Background: Three-dimensional (3D) printing technology has rapidly emerged as a transformative tool in medicine, enabling the conversion of two-dimensional scans into highly accurate 3D models. This technology, especially when combined with artificial intelligence (AI) and advanced materials, offers numerous applications in surgical planning, simulation-based training, and patient-specific care. Methods: This review examines current literature and case studies on the use of 3D printing technology in various fields of medicine, especially in surgical specialties. Key applications include surgical planning, mock surgeries, biopsy guide creation, and customized implant fabrication across various surgical fields. Results: 3D printing is transforming surgery by enabling precise visualization of tumors and critical structures, significantly enhancing preoperative planning for conditions such as bone, soft tissue (e.g., neuroblastomas), renal, and maxillofacial tumors. In reconstruction surgeries, patient-specific 3D-printed implants ensure better anatomical compatibility, particularly in maxillofacial, neurosurgical, and vascular applications. Puncture guides improve procedural accuracy in interventions like percutaneous nephrolithotripsy. Detailed anatomical models aid in simulation-based training, increasing preparedness for complex procedures. Additionally, patient-specific implants and AI-integrated decision support systems are paving the way for more personalized and efficient surgical care. Conclusions: 3D printing technology, especially when combined with AI, is reshaping modern surgery by improving both accuracy, safety, and personalized healthcare. Its applications extend across multiple specialties, offering new possibilities in surgical planning, training, and patient-specific treatments. As AI and bioprinting continue to evolve, the potential for real-time applications, such as live-printed tissue implants and enhanced decision support, could drive the next phase of innovation in various fields. Full article

Background: Hepcidin not only sustains systemic iron homeostasis but also functions as an antimicrobial peptide. During this study, we sought to analyze the ability of hepcidin to protect against sepsis-associated acute kidney injury (SAKI) and elucidated its underlying mechanisms in mediating ferroptotic pathways. Methods: A SAKI mouse model was created via cecal ligation and puncture (CLP), along with an LPS-induced Human Kidney-2 (HK-2) cell model, to study the protective mechanism of hepcidin against SAKI. Through the analysis of renal injury biomarkers and ferroptosis-related molecules, combined with quantitative detection of nuclear factor-erythroid 2-related factor-2 (Nrf2) nuclear translocation and glutathione peroxidase 4 (GPX4), a regulatory protein of ferroptosis, we uncovered the hepcidin-mediated mechanisms underlying ferroptosis in SAKI. Results: Hepcidin significantly attenuated renal function impairment in mice with SAKI and reduced the sepsis-driven increase in inflammatory mediators. As sepsis was associated with enhanced renal ferroptosis, hepcidin exerted a therapeutic effect by mitigating ferroptosis to a degree comparable with that of the ferroptosis inhibitor Ferrostatin-1 (Fer-1). Furthermore, hepcidin conferred renoprotective effects in SAKI by promoting the nuclear translocation of Nrf2, which in turn mediated the upregulation of the downstream anti-ferroptotic protein GPX4. Importantly, the Nrf2 inhibitor ML385 abrogated both the hepcidin-induced nuclear translocation of Nrf2 and the subsequent increase in GPX4 expression. Conclusions: Protective effects of hepcidin against SAKI are mediated by the Nrf2/GPX4 ferroptosis pathway, underscoring its therapeutic potential for SAKI. Full article

Sepsis is a life-threatening condition caused by an abnormal host response to infection, leading to organ dysfunction and potentially death. Acute kidney injury (AKI) is a critical complication of sepsis. Various pathways, especially signaling through Toll-like receptors (TLRs) and the nucleotide-binding oligomerization domain, leucine-rich repeat and pyrin domain-containing protein 3 (NLRP3) inflammasome, contribute to inflammation and tissue damage. Cilastatin, a renal dehydropeptidase I inhibitor, has shown promise in protecting against AKI induced by nephrotoxic drugs. This study assessed cilastatin’s effectiveness in preventing AKI and inflammation caused by sepsis and its impact on survival. Sepsis was induced in male Sprague-Dawley rats using the cecal ligation puncture (CLP) model, with four groups: sham (control), CLP, sham + cilastatin, and CLP + cilastatin. Cilastatin (150 mg/kg) was administered immediately and 24 h after sepsis induction. Kidney injury was evaluated 48 h later by assessing serum creatinine, blood urea nitrogen, glomerular filtration rate, proteinuria, kidney injury molecule-1 levels, and renal morphology. Inflammatory and fibrotic biomarkers, particularly related to the TLR4 and NLRP3 pathways, were also measured. Cilastatin treatment prevented kidney dysfunction, reduced inflammatory markers, and improved survival by 33%. These results suggest that cilastatin could be a beneficial therapeutic strategy for sepsis-related AKI, improving outcomes and reducing mortality. Full article

Background/Objectives: Achieving renal access is a key step in percutaneous nephrolithotomy (PNL), with transpapillary access considered the safest anatomical approach. This prospective pilot study aimed to compare the effectiveness of freehand ultrasound-guided (F-UG) versus fluoroscopy-guided (FG) punctures in achieving anatomically accurate transpapillary access during supine PNL, confirmed by endoscopic visualization. Perioperative and postoperative outcomes were also evaluated. Methods: Forty-three patients undergoing supine PNL for renal pelvic or lower calyceal stones were prospectively enrolled and assigned to either the FG group (n = 23) or F-UG group (n = 20). Following renal access, intraoperative flexible ureteroscopy confirmed the anatomical nature of the puncture (transpapillary vs. nonpapillary). The puncture time, fluoroscopy time, operative time, complications (Clavien–Dindo classification), transfusion requirement, hospital stay, and one-month stone-free rates were recorded. Results: Transpapillary access was achieved in 95.7% of FG cases and 55.0% of F-UG cases (p = 0.003). Radiation exposure was significantly lower in the F-UG group (p < 0.001). Complication (15.0% vs. 0.0%) and transfusion rates (10.0% vs. 0.0%) were higher in the F-UG group but not statistically significant (p = 0.092 and p = 0.210, respectively). Other outcomes, including the operative time, hospital stay, and stone-free rates, were similar between groups. Conclusions: FG puncture is more effective for achieving transpapillary access, while F-UG significantly reduces radiation exposure. The endoscopic confirmation method may provide a reference for future comparative studies on access techniques in PNL. Full article

Objective: Study the mechanism of ginsenoside Rg₁ in ameliorating hyperuricemia (HUA) induced by high-purine diet. Methods: Rats were randomly divided into groups, and the HUA model was established by administering a high-purine diet containing potassium oxonate combined with yeast. After the experiment, blood was collected via cardiac puncture, and the organ indices of the rats were calculated. Serum biochemical markers including aspartate aminotransferase (AST), alanine aminotransferase (ALT), triglyceride (TG), total cholesterol (TC), xanthine oxidase (XOD), creatinine (CREA), uric acid (UA), and blood urea nitrogen (BUN) were measured. Histopathological sections of the kidney and intestine were prepared. Western blot was used to assess the expression levels of intestinal occludin and zonula occludens-1 barrier proteins and key proteins in IL-17/NF-κB inflammatory pathways. After the experiment, fecal samples were collected from the rats. The gut microbiota of HUA-induced rats was analyzed via 16S rRNA sequencing, and the levels of short-chain fatty acids in the fecal samples were quantified using gas chromatography–mass spectrometry. Results: Ginsenoside Rg₁ significantly increased body weight and organ indexes as well as reduced serum levels of BUN, CREA, ALT, AST, XOD, and UA. Pathologic analysis showed that ginsenoside Rg₁ improved renal cell injury, glomerulosclerosis, and renal interstitial fibrosis while restoring intestinal barrier function. Ginsenoside Rg₁ down-regulated the expression of inflammatory proteins and up-regulated the levels of intestinal barrier proteins. The results of 16S rRNA sequencing showed that ginsenoside Rg₁ significantly increased the diversity index of gut microbiota and enhanced the number of beneficial bacteria in HUA rats. Short-chain fatty acids analysis demonstrated that ginsenoside Rg₁ markedly elevated the levels of acetate, propionate, butyrate, and valerate in HUA rats. Conclusions: Ginsenoside Rg₁ ameliorates and treats HUA by improving the composition of intestinal flora and inhibiting the IL-17/NF-κB signaling pathway to reduce inflammatory factors in the intestinal tract in HUA rats. Full article

Sepsis-associated acute kidney injury (S-AKI) is a severe complication in critically ill patients, marked by inflammation, oxidative stress, and renal dysfunction. This study aimed to evaluate the renoprotective effects of Fasudil (Fas), a Rho-associated kinase inhibitor, in a rat model of S-AKI induced by cecal ligation and puncture (CLP). Thirty-six Wistar albino rats were divided into control, CLP with saline, and Fas (100 mg/kg/day intraperitoneally) groups. Biochemical, histopathological, and molecular analyses were conducted to assess kidney function, oxidative stress, and inflammation. Fas treatment significantly decreased plasma malondialdehyde and TNF-α levels, reducing oxidative stress and systemic inflammation. Kidney function markers, including BUN and creatinine, showed marked improvement. Furthermore, Fas suppressed the expression of STAT-3 and NLRP-3 in renal tissues, highlighting its role in modulating key inflammatory pathways. Histological evaluation revealed alleviated renal damage, with less tubular necrosis and interstitial inflammation in the Fas-treated group. In conclusion, Fas demonstrates significant anti-inflammatory, antioxidant, and nephroprotective effects in S-AKI, primarily by inhibiting STAT-3 and NLRP-3 signaling. These results support its potential as a therapeutic agent in sepsis-induced kidney injury and suggest the need for further clinical evaluation. Full article

Background and Objectives: To evaluate the effectiveness and outcomes of supine percutaneous nephrolithotomy (PCNL) using the Barts ‘flank-free’ position and ultrasound-guided puncture, assessing the feasibility of the tubeless technique for discharge within 24 h. Materials and Methods: We conducted a retrospective analysis of 208 patients across 220 renal units who underwent supine PCNL at a tertiary university hospital between May 2019 and December 2024. All procedures were performed by a single surgeon. Patient demographics, stone characteristics, and surgical outcomes were analyzed. The tubeless technique was applied in most cases, and outcomes were assessed in terms of operative time, complication rates, stone-free rates (SFRs), and length of hospital stay. Results: The mean operating time was 50.34 ± 30.80 min. Single-tract PCNL was performed in 94.55% of cases, with the tubeless technique used in 90% of patients. The overall complication rate was 9.55%, with no Clavien–Dindo grade IV–V complications observed. On the first postoperative day, 68.18% of patients were discharged, demonstrating 24 h discharge feasibility. SFR and complication rates aligned with existing literature. Conclusions: The Barts ‘flank-free’ position and ultrasound-guided puncture considerably improved surgical access and safety in supine PCNL. The tubeless technique facilitates faster recovery, making early discharge feasible, even with standard sheath sizes. Further research is warranted to validate these findings and optimize renal stone management outcomes. Full article

Impaired renal function can influence biomarker levels through mechanisms involving blood–brain barrier integrity and clearance pathways; however, the impact of variations within normal renal function remains unclear. The main aim of this study was to determine whether adjustment for the specific level of renal function is necessary when renal function remains within physiological levels. We studied n = 183 patients (NID n = 122; other neurological diseases n = 39; somatoform controls n = 22) who underwent lumbar puncture at University Hospital Frankfurt. Serum and cerebrospinal fluid (CSF) levels of neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), total tau protein (tTAU), and ubiquitin C-terminal hydrolase-L1 (UCHL1) were measured using the single molecule array (SIMOA) technique. Estimated glomerular filtration rate (eGFR) correlated negatively with CSF GFAP (r = −0.217, p = 0.004) and serum NfL (r = −0.164, p = 0.032). Patients with impaired renal function exhibited higher CSF NfL (p = 0.036) and CSF GFAP (p = 0.026) levels. However, these findings did not remain significant after adjusting for BMI and age. Importantly, in patients with normal renal function, no significant correlations with eGFR and biomarker levels were observed after adjustment. Our findings indicate that serum and CSF concentrations of NfL, GFAP, tTAU, and UCHL1 are not significantly affected by fluctuations in physiological kidney function but emphasize the importance of considering comorbidities in impaired renal function when interpreting biomarker levels. Full article

In CT-guided percutaneous punctures—an image-guided puncture method using CT images—physicians treat targets such as lung tumors, liver tumors, renal tumors, and intervertebral abscesses by inserting a puncture needle into the body from the exterior while viewing images. By recognizing two-dimensional CT images prior to a procedure, a physician determines the least invasive puncture route for the patient. Therefore, the candidate puncture route is limited to a two-dimensional region along the cross section of the human body. In this paper, we aim to construct a three-dimensional puncture space based on multiple two-dimensional CT images to search for a safer and shorter puncture route for a given patient. If all puncture routes starting from a target in the three-dimensional space were examined from all directions (the brute-force method), the processing time to derive the puncture route would be very long. We propose a more efficient method for three-dimensional puncture route selection in CT-guided percutaneous punctures. The proposed method extends the ray-tracing method, which quickly derives a line segment from a given start point to an end point on a two-dimensional plane, and applies it to three-dimensional space. During actual puncture route selection, a physician can use CT images to derive a three-dimensional puncture route that is safe for the patient and minimizes the puncture time. The main novelty is that we propose a method for deriving a three-dimensional puncture route within the allowed time in an actual puncture. The main goal is for physicians to select the puncture route they will use in the actual surgery from among the multiple three-dimensional puncture route candidates derived using the proposed method. The proposed method derives a three-dimensional puncture route within the allowed time in an actual puncture. Physicians can use the proposed method to derive a new puncture route, reducing the burden on patients and improving physician skills. In the evaluation results of a computer simulation, for a 3D CT image created by combining 170 two-dimensional CT images, the processing time for deriving the puncture route using the proposed method was approximately 59.4 s. The shortest length of the puncture route from the starting point to the target was between 20 mm and 22 mm. The search time for a three-dimensional human body consisting of 15 CT images was 4.77 s for the proposed method and 2599.0 s for a brute-force method. In a questionnaire, physicians who actually perform puncture treatments evaluated the candidate puncture routes derived by the proposed method. We confirmed that physicians could actually use these candidates as a puncture route. Full article

Hemorheological factors may show arterio-venous differences. Alterations in acid-base and metabolic parameters may also influence these factors. However, little is known about changes in micro-rheological parameters during abdominal surgery, influencing splanchnic circulation. In anesthetized pigs, the external jugular vein, femoral artery and vein were cannulated unilaterally, and paramedian laparotomy was performed. In the anastomosis group, after resecting a bowel segment, end-to-end jejuno-jejunostomy was completed. Blood samples (from cannulas and by puncturing the portal vein) were taken before and after the intervention. Hematological, acid-base and blood gas parameters, metabolites, red blood cell (RBC) deformability and aggregation were determined. The highest hematocrit was found in portal blood, increasing further by the end of operation. A significant pH decrease was seen, and portal blood showed the highest lactate and creatinine concentration. The highest RBC aggregation values were found in arterial, the lowest in renal venous blood. The RBC aggregation increased with higher lactate concentration and lower pH. Osmotic gradient deformability declined, with the lowest values in portal and renal venous samples. In conclusion, micro-rheological parameters showed arterio-venous and porto-renal venous differences, influenced by oxygenation level, pH and lactate concentration. The intestinal anastomosis operation caused an immediate micro-rheological deterioration with portal venous dominancy in this experiment. Full article