Treatment Of Acute Kidney Injury Research Articles

Synaptotagmin-1 antagonizes paraquat intracellular accumulation and nephrocyte toxicity by up-regulating SERBP1/GLUT2 expression

Acute kidney injury (AKI) is common and an independent risk factor for mortality in patients with paraquat (PQ) poisoning. Currently, no specific antidote is available. Synaptotagmin-1 (SYT1) has been identified as a key protein that facilitates PQ efflux in PQ-resistant A549 cells, thereby preventing PQ-induced lung injury. However, the protective effect of STY1 on PQ-induced AKI remains to be elucidated. This study exposed human kidney 2 (HK-2) cells overexpressing SYT1 to PQ. These cells exhibited significantly lower levels of growth inhibition, reactive oxygen species production, early apoptosis, and PQ accumulation compared to the parent HK-2 cells. Transcriptomic screening and Western blot analysis revealed that SYT1 overexpression significantly promoted the expression of glucose transporter 2 (GLUT2). Inhibition of GLUT2 completely abolished the protective effects of SYT1 overexpression in HK-2 cells and restored intracellular PQ concentrations. Further immunoprecipitation-shotgun and RNA interference experiments revealed that SYT1 binds to and stabilizes the protein SERPINE1 mRNA-binding protein 1 (SERBP1), enhancing the stability of GLUT2 mRNA and its protein levels. In summary, SYT1 antagonizes PQ intracellular accumulation and prevents nephrocyte toxicity by up-regulating SERBP1/GLUT2 expression. This study identifies a potential target for the treatment of PQ-induced AKI.

Kim-1 targeted black phosphorus nanoplatforms: Antioxidation and efferocytosis recovery for acute kidney injury treatment

Efferocytosis, the clearance of apoptotic cells, is an essential process for resolving inflammation. Current evidence suggests that in acute kidney injury (AKI), the inflammatory cascade triggered by oxidative stress in damaged tissues can impair efferocytosis. This disrupts the clearance of apoptotic cells, exacerbates inflammatory reactions, and ultimately leads to tissue damage. To address this challenge, we developed a novel renal dual-targeting nanoplatform for AKI treatment based on black phosphorus nanosheets (BPNSs). Surface modification with LTH and 4-Octyl itaconate (4OI) endowed BPNSs with both renal tubulars targeting specificity and sustained antioxidant properties. This nanoplatform could effectively target damaged renal tubular epithelial cells, scavenge excess reactive oxygen species (ROS), alleviate oxidative stress, enhance efferocytosis, inhibit inflammatory responses, and ultimately achieve the specific therapeutic goal of AKI.

Multifunctional Nanosystem Based on Ultrasmall Carbon Dots for the Treatment of Acute Kidney Injury.

Acute kidney injury (AKI) is a critical medical condition characterized by high morbidity and mortality rates. The pathogenesis of AKI potentially involves bursts of reactive oxygen species (ROS) bursts and elevated levels of inflammatory mediators. Developing nanoparticles (NPs) that downregulate ROS and inflammatory mediators is a promising approach to treat AKI. However, such NPs would be affected by the glomerular filtration barrier (GFB). Typically, NPs are too large to penetrate the glomerular system and reach the renal tubules─the primary site of AKI injury. Herein, we report the development of ultrasmall carbon dots-gallic acid (CDs-GA) NPs (∼5 nm). These NPs exhibited outstanding biocompatibility and were shown not only to efficiently eliminate ROS and alleviate oxidative stress but also to suppress the activation of the NF-κB signaling pathway, leading to a reduction in the release of inflammatory factors. Importantly, CDs-GA NPs were shown to be able to rapidly accumulate rapidly in the renal tissues without the need for intricate targeting strategies. In vivo studies demonstrated that CDs-GA NPs significantly reduced the incidence of cisplatin (CDDP)-induced AKI in mice, surpassing the efficacy of the small molecular drug, N-acetylcysteine. This research provides an innovative strategy for the treatment of AKI.

Targeting the transmembrane cytokine co-receptor neuropilin-1 in distal tubules improves renal injury and fibrosis

Neuropilin-1 (NRP1), a co-receptor for various cytokines, including TGF-β, has been identified as a potential therapeutic target for fibrosis. However, its role and mechanism in renal fibrosis remains elusive. Here, we show that NRP1 is upregulated in distal tubular (DT) cells of patients with transplant renal insufficiency and mice with renal ischemia-reperfusion (I-R) injury. Knockout of Nrp1 reduces multiple endpoints of renal injury and fibrosis. We find that Nrp1 facilitates the binding of TNF-α to its receptor in DT cells after renal injury. This signaling results in a downregulation of lysine crotonylation of the metabolic enzyme Cox4i1, decreases cellular energetics and exacerbation of renal injury. Furthermore, by single-cell RNA-sequencing we find that Nrp1-positive DT cells secrete collagen and communicate with myofibroblasts, exacerbating acute kidney injury (AKI)-induced renal fibrosis by activating Smad3. Dual genetic deletion of Nrp1 and Tgfbr1 in DT cells better improves renal injury and fibrosis than either single knockout. Together, these results reveal that targeting of NRP1 represents a promising strategy for the treatment of AKI and subsequent chronic kidney disease.

Neutrophil-Mediated Nanozyme Delivery System for Acute Kidney Injury Therapy.

Reactive oxygen species (ROS) scavenging of nanozymes toward acute kidney injury (AKI) is a current promising strategy, however, the glomerular filtration barrier (GFB) limits their application for treating kidney related diseases. Here, a neutrophil-mediated delivery system able to hijack neutrophil to transport nanozyme-loaded cRGD-liposomes to inflamed kidney for AKI treatment by cRGD targeting integrin αvβ1 is reported. The neutrophil-mediated nanozyme delivery system demonstrated great antioxidant and anti-apoptosis ability in HK-2 and NRK-52E cell lines. Moreover, in ischemia-reperfusion (I/R) induced AKI mice, a single dose of LM@cRGD-LPs 12h post-ischemia significantly reduces renal function indicators, alleviates renal pathological changes, and inhibits apoptosis of renal tubular cells and the expression of renal tubular injured marker, thus remarkably reducing the damage of AKI. Mechanistically, the treatment of LM@cRGD-LPs markedly inhibits the process of Nrf2 to the nucleus and reduces the expression of the downstream HO-1, achieves a 99.51% increase in renal tissue Nrf2 levels, and an 86.31% decrease in HO-1 levels after LM@cRGD-LPs treatment. In short, the strategy of neutrophil-mediated nanozyme delivery system hold great promise as a potential therapy for AKI or other inflammatory diseases.

Ultrasmall Polyphenol-NAD+ Nanoparticle-Mediated Renal Delivery for Mitochondrial Repair and Anti-Inflammatory Treatment of AKI-to-CKD Progression.

As a central metabolic molecule, nicotinamide adenine dinucleotide (NAD+) can potentially treat acute kidney injury (AKI) and chronic kidney disease (CKD); however, its bioavailability is poor due to short half-life, instability, the deficiency of targeting, and difficulties in transmembrane transport. Here a physiologically adaptive gallic acid-NAD+ nanoparticle is designed, which has ultrasmall size and pH-responsiveness, passes through the glomerular filtration membrane to reach injured renal tubules, and efficiently delivers NAD+ into the kidneys. With an effective accumulation in the kidneys, it restores renal function, immune microenvironment homeostasis, and mitochondrial homeostasis of AKI mice via the NAD+-Sirtuin-1 axis, and exerts strong antifibrotic effects on the AKI-to-CKD transition by inhibiting TGF-β signaling. It also exhibits excellent stability, biodegradable, and biocompatible properties, ensuring its long-term safety, practicality, and clinical translational feasibility. The present study shows a potential modality of mitochondrial repair and immunomodulation through nanoagents for the efficient and safe treatment of AKI and CKD.

Incidence of acute kidney injury and attributive mortality in acute respiratory distress syndrome randomized trials.

The development of acute kidney injury (AKI) after the acute respiratory distress syndrome (ARDS) reduces the chance of organ recovery and survival. The purpose of this study was to examine the AKI rate and attributable mortality in ARDS patients. We performed an individual patient-data analysis including 10 multicenter randomized controlled trials conducted over 20years. We employed a Super Learner ensemble technique, including a time-dependent analysis, to estimate the adjusted risk of AKI. We calculated the mortality attributable to AKI using an inverse probability of treatment weighting estimator integrated with the Super Learner. There were 5148 patients included in this study. The overall incidence of AKI was 43.7% (n = 2251). The adjusted risk of AKI ranged from 38.8% (95% confidence interval [CI], 35.7 to 41.9%) in ARMA, to 55.8% in ROSE (95% CI, 51.9 to 59.6%). 37.1% recovered rapidly from AKI, with a significantly lower recovery rate in recent trials (P < 0.001). The 90-day excess in mortality attributable to AKI was 15.4% (95% CI, 12.8 to 17.9%). It decreased from 25.4% in ARMA (95% CI, 18.7 to 32%), to 11.8% in FACTT (95% CI, 5.5 to 18%) and then remained rather stable over time. The 90-dayoverall excess in mortality attributable to acute kidney disease was 28.4% (95% CI, 25.3 to 31.5%). The incidence of AKI appears to be stable over time in patients with ARDS enrolled in randomized trials. The development of AKI remains a significant contributing factor to mortality. These estimates are essential for designing future clinical trials for AKI prevention or treatment.

Unraveling the genetic and molecular landscape of sepsis and acute kidney injury: A comprehensive GWAS and machine learning approach

ObjectivesThis study aimed to explore the underlying mechanisms of sepsis and acute kidney injury (AKI), including sepsis-associated AKI (SA-AKI), a frequent complication in critically ill sepsis patients. MethodsGWAS data was analyzed for genetic association between AKI and sepsis. Then, we systematically applied three distinct machine learning algorithms (LASSO, SVM-RFE, RF) to rigorously identify and validate signature genes of SA-AKI, assessing their diagnostic and prognostic value through ROC curves and survival analysis. The study also examined the functional and immunological aspects of these genes, potential drug targets, and ceRNA networks. A mouse model of sepsis was created to test the reliability of these signature genes. ResultsLDSC confirmed a positive genetic correlation between AKI and sepsis, although no significant shared loci were found. Bidirectional MR analysis indicated mutual increased risks of AKI and sepsis. Then, 311 key genes common to sepsis and AKI were identified, with 42 significantly linked to sepsis prognosis. Six genes, selected through LASSO, SVM-RFE, and RF algorithms, showed excellent predictive performance for sepsis, AKI, and SA-AKI. The models demonstrated near-perfect AUCs in both training and testing datasets, and a perfect AUC in a sepsis mouse model. Significant differences in immune cells, immune-related pathways, HLA, and checkpoint genes were found between high- and low-risk groups. The study identified 62 potential drug treatments for sepsis and AKI and constructed a ceRNA network. ConclusionsThe identified signature genes hold potential clinical applications, including prognostic evaluation and targeted therapeutic strategies for sepsis and AKI. However, further research is needed to confirm these findings.

Research on the global trends of COVID-19 associated acute kidney injury: a bibliometric analysis

Critically ill COVID-19 patients may exhibit various clinical symptoms of renal dysfunction including severe Acute Kidney Injury (AKI). Currently, there is a lack of bibliometric analyses on COVID-19-related AKI. The aim of this study is to provide an overview of the current research status and hot topics regarding COVID-19 AKI. The literature was retrieved from the Web of Science Core Collection (WoSCC) database. Subsequently, we utilized Microsoft Excel, VOSviewer, Citespace, and Pajek software to revealed the current research status, emerging topics, and developmental trends pertaining to COVID-19 AKI. This study encompassed a total of 1507 studies on COVID-19 AKI. The United States, China, and Italy emerged as the leading three countries in terms of publication numbers, contributing 498 (33.05%), 229 (15.20%), and 140 (9.29%) studies, respectively. The three most active and influential institutions include Huazhong University of Science and Technology, Wuhan University and Harvard Medical School. Ronco C from Italy, holds the record for the highest number of publications, with a total of 15 papers authored. Cheng YC’s work from China has garnered the highest number of citations, totaling 470 citations. The co-occurrence analysis of author keywords reveals that ‘mortality’, ‘intensive care units’, ‘chronic kidney disease’, ‘nephrology’, ‘renal transplantation’, ‘acute respiratory distress syndrome’, and ‘risk factors’ emerge as the primary areas of focus within the realm of COVID-19 AKI. In summary, this study analyzes the research trends in the field of COVID-19 AKI, providing a reference for further exploration and research on COVID-19 AKI mechanisms and treatment.

Stevioside protects against acute kidney injury by inhibiting gasdermin D pathway

AbstractRecent studies indicate a significant upregulation of gasdermin D (GSDMD) in acute kidney injury (AKI), a severe medical condition characterized by high morbidity and mortality globally. In this study, we identified and validated the therapeutic effects of small molecule inhibitors targeting the GSDMD pathway for AKI treatment. Using a drug screening assay, we evaluated thousands of small molecules from DrugBank against Lipopolysaccharide (LPS) and Nigericin‐stimulated immortalized bone marrow‐derived macrophages (iBMDMs) to discern GSDMD pathway activators. We simulated AKI in primary renal tubular epithelial cells using hydrogen peroxide (H2O2) exposure. Furthermore, AKI in mouse models was induced via cisplatin and ischemia/reperfusion. Our findings highlight stevioside as a potent GSDMD activator exhibiting minimal toxicity. Experimental results, both in vitro and in vivo, demonstrate stevioside's significant potential in alleviating renal tubular epithelial cell injury and AKI histological damage. After stevioside treatment, a notable decrease in cleaved GSDMD‐N terminal levels was observed coupled with diminished inflammatory factor release. This observation was consistent in both cisplatin‐ and ischemia/reperfusion‐induced AKI mouse models. Collectively, our research suggests that stevioside could be a promising candidate for modulating GSDMD signaling in AKI treatment.

Protective Effect of CXCR7 Against Hypoxia/Reoxygenation Injury in Renal Tubular Epithelial Cells

Acute kidney injury (AKI) is a multifactorial syndrome with complex pathophysiology and prognosis. Ischaemia‒reperfusion injury (IRI) is a major cause of induced AKI. The aim of this study was to investigate the effect of upregulated CXCR7 expression on renal tubular epithelial cell apoptosis induced by hypoxia/reoxygenation (H/R). HK-2 cells were divided into three groups: control group (pcDNA3.1), hypoxia/reoxygenation + pcDNA3.1 group (H/R+pcDNA3.1) and CXCR7 overexpression + hypoxia/reoxygenation group (H/R+ Flag-CXCR7). Protein levels of renal tubular epithelial cell injury-, apoptosis- and autophagy-related markers were assessed by qRT‒PCR, Western blotting, flow cytometry (FCM), immunofluorescence and transmission electron microscopy (TEM). In addition, HK-2 cells were treated with the autophagy inhibitor 3-MA and divided into 3 groups: control group, 3-MA + pcDNA3.1 group, and 3-MA + Flag-CXCR7 group. Changes in autophagy and apoptosis in renal tubule epithelial cells were assessed by Western blotting and FCM. Compared with those in the control group, the protein and mRNA expression levels of CXCR7 in HK-2 cells were significantly lower under H/R conditions. Under H/R conditions, CXCR7 overexpression in HK-2 cells significantly downregulated the expression of NGAL. Moreover, CXCR7 overexpression significantly decreased H/R-induced cleaved PARP-1 and cleaved Caspase 3 levels, increased the level of the antiapoptotic protein BCL-2 and the autophagy-related molecules ATG5 and LC3B II, and significantly inhibited the expression of P62. Autophagy flow and TEM also showed that CXCR7 significantly promoted autophagy. CXCR7 significantly alleviated the 3-MA-induced inhibition of autophagy and increase in apoptosis. Upregulated CXCR7 expression can inhibit renal tubular epithelial cell apoptosis and damage by regulating autophagy. In conclusion, CXCR7 is a promising target for the prevention and/or treatment of AKI.

Self-Assembling P38 Peptide Inhibitor Nanoparticles Ameliorate the Transition from Acute to Chronic Kidney Disease by Suppressing Ferroptosis.

Accumulating evidence highlights p38 as a crucial factor highly activated during the process of acute kidney injury (AKI), but the application of p38 inhibitor in AKI is quite limited due to the low efficiency and poor kidney-targeting ability. Herein, a novel self-assembling peptide nanoparticle with specific p38-inhibiting activity is constructed, which linked mitogen-activated protein kinase kinase 3b (MKK3b), the functional domain of p38, with the cell-penetrating TAT sequence, ultimately self-assembling into TAT-MKK3b nanoparticles (TMNPs) through tyrosinase oxidation. Subsequent in vitro and in vivo studies demonstrated that TMNPs preferably accumulated in the renal tubular epithelial cells (RTECs) through forming protein coronas by binding to albumin, and strongly improved the reduced renal function of ischemia-reperfusion injury (IRI)-induced AKI and its transition to chronic kidney disease (CKD). Mechanically, TMNPs inhibited ferroptosis via its solute carrier family 7 member 11 (SLC7A11)/glutathione peroxidase 4 (GPX4) axis-inducing capacity and synergistic potent antioxidant property in AKI. The findings indicated that the multifunctional TMNPs exhibited renal targeting, ROS-scavenging, and ferroptosis-mitigating capabilities, which may serve as a promising therapeutic agent for the treatment of AKI and its progression to CKD.

Lactate metabolism and acute kidney injury.

Acute kidney injury (AKI) is a common clinically critical syndrome in hospitalized patients with high morbidity and mortality. At present, the mechanism of AKI has not been fully elucidated, and no therapeutic drugs exist. As known, glycolytic product lactate is a key metabolite in physiological and pathological processes. The kidney is an important gluconeogenic organ, where lactate is the primary substrate of renal gluconeogenesis in physiological conditions. During AKI, altered glycolysis and gluconeogenesis in kidneys significantly disturb the lactate metabolic balance, which exert impacts on the severity and prognosis of AKI. Additionally, lactate-derived posttranslational modification, namely lactylation, is novel to AKI as it could regulate gene transcription of metabolic enzymes involved in glycolysis or Warburg effect. Protein lactylation widely exists in human tissues and may severely affect non-histone functions. Moreover, the strategies of intervening lactate metabolic pathways are expected to bring a new dawn for the treatment of AKI. This review focused on renal lactate metabolism, especially in proximal renal tubules after AKI, and updated recent advances of lactylation modification, which may help to explore potential therapeutic targets against AKI.

Therapeutic potential of urine-derived stem cells in renal regeneration following acute kidney injury: A comparative analysis with mesenchymal stem cells.

Acute kidney injury (AKI) is a common clinical syndrome with high morbidity and mortality rates. The use of pluripotent stem cells holds great promise for the treatment of AKI. Urine-derived stem cells (USCs) are a novel and versatile cell source in cell-based therapy and regenerative medicine that provide advantages of a noninvasive, simple, and low-cost approach and are induced with high multidifferentiation potential. Whether these cells could serve as a potential stem cell source for the treatment of AKI has not been determined. To investigate whether USCs can serve as a potential stem cell source to improve renal function and histological structure after experimental AKI. Stem cell markers with multidifferentiation potential were isolated from human amniotic fluid. AKI severe combined immune deficiency (SCID) mice models were induced by means of an intramuscular injection with glycerol. USCs isolated from human-voided urine were administered via tail veins. The functional changes in the kidney were assessed by the levels of blood urea nitrogen and serum creatinine. The histologic changes were evaluated by hematoxylin and eosin staining and transferase dUTP nick-end labeling staining. Meanwhile, we compared the regenerative potential of USCs with bone marrow-derived mesenchymal stem cells (MSCs). Treatment with USCs significantly alleviated histological destruction and functional decline. The renal function was rapidly restored after intravenous injection of 5 × 105 human USCs into SCID mice with glycerol-induced AKI compared with injection of saline. Results from secretion assays conducted in vitro demonstrated that both stem cell varieties released a wide array of cytokines and growth factors. This suggests that a mixture of various mediators closely interacts with their biochemical functions. Two types of stem cells showed enhanced tubular cell proliferation and decreased tubular cell apoptosis, although USC treatment was not more effective than MSC treatment. We found that USC therapy significantly improved renal function and histological damage, inhibited inflammation and apoptosis processes in the kidney, and promoted tubular epithelial proliferation. Our study demonstrated the potential of USCs for the treatment of AKI, representing a new clinical therapeutic strategy.

The inhibitory impact of Schisandrin on inflammation and oxidative stress alleviates LPS-induced acute kidney injury.

Inflammation and oxidative stress (OS) are the major pathogenic characteristics of acute kidney injury (AKI). Studies have shown that Schisandrin (Sch) could regulate inflammatory disease. However, the function and mechanism of Sch in AKI progression are still unknown. Here, we investigated Sch's potential effects and mechanism on mice's renal damage and macrophages induced by lipopolysaccharide (LPS). Sch decreased LPS-induced inflammatory factor production while increasing the activity of related antioxidant enzymes in macrophages and mouse kidney tissues. Hematoxylin and eosin staining revealed that Sch may have the ability to profoundly inhibit inflammatory cell invasion and tissue damage caused by LPS in renal tissue. Furthermore, Western blot and immunohistochemical studies showed that Sch exerted its effects mainly through up-regulation of nuclear factor erythroid 2-related factor 2/heme oxygenase-1 and inhibition of Toll-like receptor 4‒mitogen-activated protein kinases/nuclear factor-kappa B pathways. Collectively, this study illustrates that Sch suppresses LPS-stimulated AKI by descending inflammation and OS, illuminating prospective AKI treatment options.

Exploring Acute Kidney Injury Following Aortic Dissection: A Comprehensive Review of Machine Learning Models for Predicting Risk, Management Strategies, Complications, and Racial and Gender Disparities.

Both types of aortic dissection (AD), Stanford type A and type B, can result in complications such as acute kidney injury (AKI) and aortic rupture. Renal complications in AD arise from compromised renal perfusion affecting the renal arteries. Understanding the intricate connection between AD and AKI is crucial for navigating the complexities of tailored treatment and formulating specific management plans. Concerning machine learning models, in patients with type A aortic dissection, factors such as decreased platelet count on admission, increased D-dimer level, longer cardiopulmonary bypass duration, elevated white blood cell levels, the need for blood transfusion, longer aortic clamp time, extended surgery duration, advanced age, and an elevated body mass index were positively associated with the development of AKI. For the risk of AKI after type B aortic dissection, elevated Nt-pro brain natriuretic peptide, prolonged activated partial thromboplastin time, elevated admission systolic blood pressure, and a higher contrast agent requirement during operative repair were found to predict the risk. Male gender was associated with a higher risk of AKI, and nonwhite race was linked to a higher risk of AKI, a greater likelihood of requiring more urgent procedures, and lower levels of insurance coverage. The treatment of AKI following AD requires a multifaceted approach. Identifying and addressing the underlying cause, such as low blood pressure, renal artery involvement, or medication-induced injury, is crucial for effective management and preventing further kidney damage. Maintaining proper fluid balance is essential for improving renal perfusion, but careful monitoring is necessary to avoid complications. The evolving landscape of research, particularly in biomarkers and AI programs, reveals a promising role in predicting the risk for and managing AKI post-AD.

The novel potential therapeutic target PSMP/MSMP promotes acute kidney injury via CCR2

Acute kidney injury (AKI) is a major worldwide health concern that currently lacks effective medical treatments. PSMP is a damage-induced chemotactic cytokine that acts as a ligand of CCR2 and has an unknown role in AKI. We have observed a significant increase in PSMP levels in the renal tissue, urine, and plasma of patients with AKI. PSMP deficiency improved kidney function and decreased tubular damage and inflammation in AKI mouse models induced by kidney ischemia-reperfusion injury, glycerol, and cisplatin. Single-cell RNA sequencing analysis revealed that Ly6Chi or F4/80lo infiltrated macrophages (IMs) were a major group of proinflammatory macrophages with strong CCR2 expression in AKI. We observed that PSMP deficiency decreased CCR2+Ly6Chi or F4/80lo IMs and inhibited M1 polarization in the AKI mouse model. Moreover, overexpressed human PSMP in the mouse kidney could reverse the attenuation of kidney injury in a CCR2-dependent manner, and this effect could be achieved without CCL2 involvement. Extracellular PSMP played a crucial role, and treatment with a PSMP-neutralizing antibody significantly reduced kidney injury invivo. Therefore, PSMP might be a therapeutic target for AKI, and its antibody is a promising therapeutic drug for the treatment of AKI.

#1280 Temporal trends in chronic kidney disease and mortality after acute kidney injury

Abstract Background and Aims In 2015, the International Society of Nephrology formulated the “0by25” initiative, which aims to eliminate all preventable deaths due to acute kidney injury (AKI) by 2025. Numerus publications have added focus to the importance of clinical awareness and improved treatment for AKI. Ideally, this should translate to lower rates of AKI-associated adverse outcomes such as chronic kidney disease (CKD) and death. To our knowledge, there are no studies describing temporal trends in the incidence of CKD following AKI. Moreover, only a few studies have examined the temporal trends in mortality following AKI and these studies included highly selected groups of patients not representative of general hospitalized patients and to an even lesser degree the general population. Hence, further examination of the prognosis after AKI is required to understand temporal trends in the quality of care for AKI and establish a foundation for both preventive and therapeutic measures. Therefore, we examined the temporal trends in CKD and mortality after AKI in Denmark. Method We identified adult individuals with AKI from 1 January 2007 to 31 December 2018 using population-based plasma creatinine (pCr) data covering both the primary care and hospital settings. AKI was defined in accordance with the Kidney Disease: Improving Global Outcomes (KDIGO) creatinine criteria. CKD after AKI was defined as ≥2 eGFR measurements from primary care or planned outpatient hospital visits &amp;lt;60 mL/min/1.73 m2 separated by a period of ≥90 days or by a hospital diagnoses code related to chronic dialysis or kidney transplantation. Information on all-cause death was obtained from the Danish Civil Registration System. Annual crude and sex-and-age-standardized 1-year incidence rates of CKD and mortality after AKI were estimated using direct standardization. Results During the 2007-2018 period, 406,207 AKIs were identified in 274,269 distinct Danish residents. The mean age at the time of first AKI was 72 years (IQR, 61; 81) and 137,185 (50%) of first-time AKIs occurred in males. Twenty-eight percent of individuals had a Charlson Comorbidity Index (CCI) score of 0, while 42% had a CCI score of 1-2, and 30% a CCI score ≥3. The mean age, sex, and CCI score distributions were stable across the study period. The age- and sex-standardized incidence rate of CKD after AKI ranged from 102 (95% CI, 99-106) per 1000 person-years in 2018 to 126 (95% CI, 119-133) per 1000 person-years in 2014. Besides a peak in 2014, the incidence of CKD after AKI showed little variation throughout the period. The age-and sex-standardized mortality rate after AKI ranged from 317 (95% CI, 311-323) per 1000 person-years in 2018 to 392 (95% CI, 379-406) per 1000 person-years in 2007. From 2007 to 2013 there was a stable decline in the mortality rate after AKI. From 2014 to 2018 the rate showed little variation. Conclusion The rate of CKD after AKI was stable throughout the period, while there was a decline in mortality after AKI, especially in the years from 2007 to 2013. The decline in mortality after AKI is encouraging; however, the stable rate of CKD after AKI, despite increasing knowledge on AKI treatment and CKD prevention, warrants an evaluation of the contemporary quality of care for AKI in Denmark.

#2561 Association of acute kidney injury stage with in-hospital mortality in elderly patients with hip fractures

Abstract Background and Aims Elderly individuals often experience hip fractures and acute kidney injury (AKI), both of which are associated with higher rates of morbidity and mortality. This study aimed to evaluate whether the severity of AKI is associated with higher mortality rates in elderly patients with hip fractures. Method Patients aged 65 years and older, who underwent surgery for hip fracture between October 2015 and October 2020, were retrospectively evaluated. Those with known chronic kidney disease stages 4, 5, or end-stage kidney disease were excluded. AKI was defined and categorized into stages 1, 2, and 3 according to the Kidney Disease Improving Global Outcomes (KDIGO) guidelines. Results In the study, 780 elderly patients with hip fractures were included, with a median age of 82.0 years (interquartile range 77.0–87.0) and 22.4% of them being men. Of these, 172 patients (22.1%) experienced AKI, with 125 (72.7%), 26 (15.1%), and 21 (12.2%) of these patients categorized as having stage 1, 2, and 3 AKI, respectively. Higher AKI stages were independently associated with increased in-hospital mortality compared to patients without AKI (odds ratio [OR] 1.07, 95% confidence interval [CI] 0.18–6.55, P=0.940 for AKI stage 1; OR 14.09, 95% CI 1.47–135.52, P=0.022 for AKI stage 2; and OR 413.79, 95% CI 45.84–3735.28, P&amp;lt;0.001 for AKI stage 3). Furthermore, compared to patients without AKI, those with AKI stage 3 had a significantly increased risk of mortality (hazard ratio 15.30, 95% CI 2.65–88.48, P=0.002). Conclusion A higher stage of AKI is independently associated with increased in-hospital mortality in elderly patients with hip fractures. Prevention and prompt treatment of AKI, especially higher AKI stages, is important in elderly patients with hip fractures.

#2977 Pregnancy-related acute kidney injury in a second level care hospital in Merida, Yucatan, Mexico

Abstract Background and Aims Pregnancy-related acute kidney injury (PRAKI) is a public health problem associated with an increased risk of adverse maternal and fetal outcomes. The causes of PRAKI varies according to the age of gestation. Mexico lacks a national acute kidney injury (AKI) registry, and the access to AKI treatment is limited due to lack of financial coverage, lack of nephrologists, and poor infrastructure. The General Hospital Dr. Agustín O'Horán is a second level unit that attends to the uninsured pregnant population from the southeast of Mexico. The aim of this study was to investigate the prevalence, clinical characteristics, and outcomes of PRAKI in a Mexican population. Method This was a retrospective study in an obstetric intensive care unit (OICU) in the General Hospital Dr. Agustín O'Horán in Merida, Yucatan, Mexico. Women during pregnancy and postpartum periods admitted to the OICU between January to December 2023 were included. Demographical, clinical and laboratory data were collected from medical records, and AKI was diagnosed according to the Kidney Disease Improving Global Outcomes (KDIGO) creatinine criteria. We evaluated the prevalence, clinical characteristics, and outcomes of PRAKI. Results During the study period, 188 women were admitted to the OICU, and the mean age was 24.9 years. Eight women presented in the first trimester, 19 in the second trimester, 21 in the third trimester, and 140 in the postpartum period. Fifty-five women met AKI creatinine criteria: 31 (56.3%) had stage 1, 15 (27.3%) had stage 2, and 9 (16.4%) had stage 3. The most common causes of PRAKI were obstetric hemorrhage (27.3%), eclampsia (21.8%), and preeclampsia (18.2%) (Table 1). There was no difference in vital signs on admission and baseline creatinine level between both groups. Women who developed PRAKI had a longer stay in the OICU (4.2 days vs 2.3 days, p &amp;lt; 0.001), and greater use of vasopressor (30.9% vs 9.0%, p &amp;lt; 0.001), and mechanical ventilation (34.5% vs 11.3%, p &amp;lt; 0.001). Women with AKI had higher mortality (9.1% vs 1.5%, p = 0.012), and perinatal mortality (9.1% vs 2.3%, p = 0.035) (Table 2). Conclusion Women during pregnancy and postpartum periods who developed PRAKI had more adverse clinical and obstetric outcomes (maternal and perinatal mortality). Hence, women in pregnancy and postpartum periods admitted to an intensive care unit should be closely monitored and implement strategies for early diagnosis and aggressive therapy of PRAKI regardless of KDIGO stage.