Xianghong Yang

Sepsis-associated acute kidney injury (SA-AKI) is a critical complication in intensive care units (ICUs) with a high mortality rate, and current treatments

Acute kidney injury (AKI) is a serious condition associated with high incidence, mortality and poor prognosis. The optimal time for discontinuing continuous renal replacement therapy (CRRT) in AKI remains controversial. This study aimed to explore the predictive value of the furosemide stress test (FST) for determining the optimal timing to discontinue CRRT in critically ill patients with AKI. This prospective, multicenter, randomized controlled study was conducted across eight centers. Patients with AKI who were admitted into the ICU were included and grouped into the FST or non-FST control groups. FST was performed on patients enrolled in the FST group by randomization. The probability of renal replacement therapy (RRT) re-initiation within 7 and 28 days post-FST was assessed to evaluate the capability of FST in determining CRRT discontinuation time in AKI. A total of 240 patients were included after screening. Ninety-five patients (81.2%) in the FST group were successfully weaned, compared to 79 patients (64.2%) in the non-FST group (p = 0.003). Within 7 days after weaning, 22 patients (18.8%) in the FST group restarted RRT, compared to 44 patients (35.8%) in the non-FST group (p = 0.003). Within 28 days after weaning, 35 patients (29.9%) in the FST group restarted RRT, compared to 45 (36.6%) in the non-FST group (p = 0.273). FST is validated as a reliable and safe method for predicting successful CRRT weaning in critically ill AKI patients. It significantly improves the CRRT weaning success rate.

Acute kidney injury (AKI) has high incidence and mortality rates, with its vicious cycle involving inflammation, oxidative stress, and apoptosis often leading to rapid decline in renal function. Current treatments face multiple challenges: lack of targeted drugs, limited efficacy of conventional therapies with significant systemic side effects, difficulty in drug delivery to the kidney's unique structure, susceptibility to re-injury, rapid disease progression, a narrow intervention window, and high risk of irreversible damage. To address these issues, we developed the near-infrared II (NIR-II)-excited photothermal nanocomposite Cu_2-XSe@AHI. Constructed via coordination self-assembly, this material offers advantages of structural controllability, spatiotemporal precision, and non-invasive treatment. Upon NIR-II laser activation, it achieves deep tissue penetration and low-toxicity photothermal conversion, generating mild thermal stimulation in the kidney to specifically induce heat shock protein 70 (HSP70) expression. HSP70 stabilizes the IκBα–IKKβ complex, inhibiting the NF-κB pathway to synergistically exert anti-inflammatory, antioxidant, and anti-apoptotic effects. Furthermore, HSP70 upregulation enhances cellular resilience and promotes tissue repair, enabling a dual mechanism from injury blockade to active restoration. This strategy overcomes limitations of existing therapies, offering a novel pathway with high translational potential for AKI treatment.

Objective To explore the potential of honeysuckle-derived exosome-like nanovesicles (HELNVs) for preventing cisplatin-induced acute kidney injury (AKI). Methods The renoprotective efficacy of HELNVs against cisplatin-induced AKI was assessed in human kidney cell-2 (HK-2) cells exposed to 100 μmol/L cisplatin for 24 h, followed by HELNVs (50–200 μg/mL) for another 24 h; the optimal therapeutic concentration was determined as 100 μg/mL. At this concentration, oxygen species (ROS) levels were measured by flow cytometry. Male C57BL/6 mice received a single intraperitoneal injection of cisplatin (30 mg/kg) to establish an AKI model and were then computer-randomized into 3 groups (n=6 per group): control group, daily intraperitoneal administration of normal saline (0.9% NaCl); the cisplatin-injured group, same NaCl regimen; the HELNVs treatment group, daily intraperitoneal administration of HELNVs (30 mg/kg) for 5 consecutive days, with euthanasia on day 6. Renal accumulation of HELNVs was tracked by small-animal multispectral imaging (peak uptake at 8–10 h). Functional assessment included serum creatinine and blood urea nitrogen (BUN) quantified with an automated biochemical analyzer. Molecular analyses included enzyme-linked immunosorbent assay (ELISA) quantification of interleukin (IL)-1β, IL-6, IL-10, and tumor necrosis factor-α (TNF-α). Results HELNVs significantly reduced ROS, inflammatory responses, and apoptosis in cisplatin-treated HK-2 cells (PPPP<0.01). Conclusion HELNVs may serve as a promising therapeutic approach for ameliorating cisplatin-induced AKI, offering a potential novel treatment option for managing this condition in clinical settings.

Effective anticoagulation is essential for maintaining extracorporeal circuit patency during continuous renal replacement therapy (CRRT), yet commonly used anticoagulants have limitations. Herein, we present an innovative hybrid anticoagulation strategy for CRRT. A 98-year-old female admitted with a left sacroiliac joint abscess developed decompensated heart failure and acute kidney injury, necessitating CRRT. Conventional-dose regional citrate anticoagulation (RCA) was projected to be intolerable in this ultra-elderly patient with progressive hepatic dysfunction, coagulopathy, and hyperlactatemia, whereas low-dose RCA failed to prevent filter clotting within hours. A modified anticoagulation protocol combining low-dose citrate with nafamostat infusion successfully sustained extracorporeal circuit patency without citrate-related metabolic complications or bleeding. Despite this success, the patient ultimately died of unrelated respiratory failure. The innovative hybrid anticoagulation strategy effectively prolonged CRRT circuit longevity in an ultra-elderly patient at high risk of citrate accumulation without procedure-associated complications. This approach represents a promising alternative for patients who have contraindications to conventional citrate anticoagulation.

Acute kidney injury (AKI) is frequently attributed to the lack of effective early diagnosis and incorrect timing for treatment, resulting in a high incidence rate and mortality. Currently, there is no precise clinical treatment available for AKI. In this study, we developed a good approach utilizing injured renal cell membrane-coated ICG/CORM-401 nanosystem (IRICP), which can specifically target to the injured kidney site through homologous targeting of the injured renal cell membrane. Through in vivo experiments, we demonstrated that indocyanine green (ICG), acting as a near-infrared (NIR) contrast agent, enables clear visualization of its distribution using fluorescence imaging and photoacoustic imaging (PAI) techniques. The addition of CORM-401 effectively mitigates AKI-induced oxidative stress by consuming reactive oxygen species and generating carbon monoxide for anti-inflammatory, anti-apoptotic, and anti-oxidative effects, thereby effectively inhibiting the progression of AKI and facilitating its recovery. In conclusion, this targeted theranostic strategy presents high efficiency and promise potential for the future clinical treatment of AKI.

Intestinal barrier damage is crucial for the development of sepsis. Ghrelin (GHS) can restore intestinal barrier function. However, the mechanisms of GHS on intestinal barrier damage in sepsis remain unclear. We aimed to explore the mechanisms of GHS against intestinal barrier damage in sepsis. Septic models were established by cecal ligation and puncture surgery for rats and lipopolysaccharides exposure for IEC-6 cells. Furthermore, these septic models were overexpressed miR-143 and treated with GHS. In vivo, small intestinal pathological injury and D-lactic acid level were detected. Tight junction protein (Claudin-1, Occludin and ZO-1) expressions and autophagosome number were evaluated. In vitro, cell viability, autolysosome number, and relationship between miR-143 and ATG2B were determined. miR-143, ATG2B and autophagy-related protein (Beclin-1, p62 and LC3I/LC3II) levels were evaluated in rats and cells. GHS mitigated small intestinal pathological injury and decreased D-lactic acid level for septic rats. Additionally, GHS elevated tight junction protein expressions, ATG2B, Beclin-1 and LC3I/LC3II levels, and autophagosome number, but reduced miR-143 and p62 levels for septic rats. However, miR-143 overexpression presented the opposite results. Consistently, cellular experiments found that GHS increased cell viability, autolysosome number, and presented similar results for miR-143, ATG2B and autophagy-related protein levels for lipopolysaccharides-exposed cells. Additionally, ATG2B directly targeted miR-143 in IEC-6 cells. Both animal and cellular experiments found the effects of GHS on sepsis-induced small intestinal barrier damage were reversed by miR-143 overexpression. GHS may improve small intestinal barrier damage in sepsis through miR-143/ATG2B-mediated autophagy, indicating miR-143/ATG2B was an underlying therapeutic target for sepsis.

Background: Currently, there is a lack of serum biomarkers that can accurately predict the short-term prognosis of enterogenic sepsis. Methods: 99 patients with enterogenic sepsis were categorized based on their Acute Gastrointestinal Injury (AGI) grade on the third day of ICU admission into four groups: no AGI, AGI grade I, AGI grade II, and AGI (III+IV). Additionally, patients were classified into survival and death groups according to their 28-day clinical outcomes. Peripheral venous blood samples were collected to measure levels of interleukin (IL)-27, intestinal fatty acid-binding protein (IFABP), and diamine oxidase (DAO). Receiver operating characteristic (ROC) curves were generated to assess the ability of IL-27, IFABP, and DAO to predict the short-term prognosis of patients with enterogenic sepsis. Results: On the third day, both the survival and death groups exhibited elevated serum levels of IL-27 and IFABP compared to the first day, while levels of DAO were lower than those observed on day one. Furthermore, a significant positive correlation was observed between IL-27 and both IFABP and DAO, with stronger correlations evident on day three compared to day one. As the Acute Gastrointestinal Injury (AGI) grading increased, levels of IL-27, IFABP, and DAO rose correspondingly, correlating with a gradual decrease in survival rates, all demonstrating statistical significance (all P < 0.05). The Area Under the Curve (AUC) values for IL-27, IFABP, and DAO on the third day, predicting short-term prognosis for intestinal sepsis patients, were 0.714, 0.772, and 0.724, respectively. Notably, these values surpassed those of the first day, with IFABP on the third day exhibiting the highest predictive capability. Conclusion: IL-27, IFABP, and DAO levels measured on the third day of hospitalization can accurately predict the short-term prognosis of enterogenic sepsis.

Non-invasive imaging in the near-infrared region (NIR) offers enhanced tissue penetration, reduced spontaneous fluorescence of biological tissues, and improved signal-to-noise ratio (SNR), rendering it more suitable for in vivo deep tissue imaging. In recent years, a plethora of NIR photoresponsive materials have been employed for disease diagnosis, particularly acute kidney injury (AKI). These encompass inorganic nonmetallic materials such as carbon (C), silicon (Si), phosphorus (P), and upconversion nanoparticles (UCNPs); precious metal nanoparticles like gold and silver; as well as small molecule and organic semiconductor polymer nanoparticles with near infrared responsiveness. These materials enable effective therapy triggered by NIR light and serve as valuable tools for monitoring AKI in living systems. The review provides a concise overview of the current state and pathological characteristics of AKI, followed by an exploration of the application of nanomaterials and photoresponsive nanomaterials in AKI. Finally, it presents the design challenges and prospects associated with NIR photoresponsive materials in AKI.