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CD36 promotes tubular ferroptosis by regulating the ubiquitination of FSP1 in Acute kidney injury

Genes & Diseases 2024年第1期11卷 449-463页

作者： Yixin Ma Lili Huang Zheng Zhang Pengfei Yang Qingsong Chen Xujia Zeng Fangyan Tan Chunxia Wang Xiongzhong Ruan Xiaohui Liao Department of Nephrology The Second Affiliated HospitalChongqing Medical UniversityChongqing 400010China Department of Cell Biology and Genetics Chongqing Medical UniversityChongqing 400016China Centre for Nephrology Royal Free and University College Medical SchoolUniversity College LondonRoyal Free CampusRowland Hill StreetLondon NW32PFUnited Kingdom Centre for Lipid Research Key Laboratory of Molecular Biology on Infectious DiseasesMinistry of EducationChongqing Medical UniversityChongqing 400016China Kuanren Laboratory of Translational Lipidology Centre for Lipid ResearchSecond Affiliated Hospital of Chongqing Medical UniversityChongqing 400010China

Reactive oxidative species(ROos)production-driven ferroptosis plays a role in Acute kidney injury(Akl).However,its exact molecular mechanism is poorly understood.Scavenger receptor CD36 has important roles in oxidizing lipids,lipid accumulation,metabolic syndrome,and insulin resistance in chronic kidney disease,but its roles remain unexplored in AKl.The present study investigated the role and mechanism of CD36 in regulating proximal tubular cell ferroptosis and AKl.The expression of CD36 was found to be significantly up-regulated in AKI renal tissues and correlated with renal function,which might serve as an independent biomarker for AKl patients.Moreover,in adult mice subjected to AKl,deletion of CD36(CD36-/-)induced tubular cell Ros accumulation,ferroptosis activation,and renal injury.Mechanistically,combining LC-MS/MS,co-IP,and ubiquitination analyses revealed that CD36 could specifically bind to ferroptosis suppressor protein 1(FSP1)and regulate its ubiquitination at sites K16 and K24,leading to FSP1 degradation and progression of ferroptosis in AKl.The present results emphasize a novel mechanism of CD36 in cisplatin-induced AKl.The discovery of the special CD36 roles in promoting ferroptosis and AKI development by regulating the ubiquitination of FSP1 in proximal tubular cells may be potential therapeutic targets for AKl.Moreover,CD36 may play a key role in the progression of AKl.Therefore,targeting CD36 may provide a promising treatment option for AKI.

关键词： Acute kidney injury CD36 Ferroptosis FSP1 Ubiquitin-dependent degradation

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Data driven analysis reveals prognostic genes and immunological targets in human sepsis-associated Acute kidney injury

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World Journal of Emergency Medicine 2024年第2期15卷 91-97页

作者： Qing Zhao Jinfu Ma Jianguo Xiao Zhe Feng Hui Liu Department of Diagnosis and Treatment of Cadres the First Medical CenterChinese PLA General HospitalBeijing 100853China Intensive Care Unit the 305th Hospital of Chinese PLABeijing 100032China Department of Critical Care Medicine the First Medical CenterChinese PLA General HospitalBeijing 100853China Nephrology Department the First Medical CenterChinese PLA General HospitalBeijing 100853China

BACKGROUND:The molecular mechanism of sepsis-associated Acute kidney injury(SA-AKI)is unclear.We analyzed co-differentially expressed genes(co-DEGs)to elucidate the underlying mechanism and intervention targets of SA-AKI.METHODS:The microarray datasets GSE65682,GSE30718,and GSE174220 were downloaded from the Gene Expression Omnibus(GEO)database.We identified the co-DEGs and constructed a gene co-expression network to screen the hub genes.We analyzed immune correlations and disease correlations and performed functional annotation of the hub genes.We also performed single-cell and microenvironment analyses and investigated the enrichment pathways and the main transcription factors.Finally,we conducted a correlation analysis to evaluate the role of the hub genes.RESULTS:Interleukin 32(IL32)was identified as the hub gene in SA-AKI,and the main enriched signaling pathways were associated with hemopoiesis,cellular response to cytokine stimulus,inflammatory response,and regulation of kidney development.Additionally,IL32 was significantly associated with mortality in SA-AKI patients.Monocytes,macrophages,T cells,and NK cells were closely related to IL32 and were involved in the immune microenvironment in SA-AKI patients.IL32 expression increased significantly in the kidney of septic mouse.Toll-like receptor 2(TLR2)was significantly and negatively correlated with IL32.CONCLUSION:IL32 is the key gene involved in SA-AKI and is significantly associated with prognosis.TLR2 and relevant immune cells are closely related to key genes.

关键词： Sepsis Acute kidney injury Interleukin 32 Toll-like receptor 2 Bioinformatics analysis

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

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World Journal of Stem Cells 2024年第5期16卷 525-537页

作者： Fang Li Bin Zhao Lei Zhang Guo-Qing Chen Li Zhu Xiao-Ling Feng Meng-Jia Gong Cheng-Chen Hu Yuan-Yuan Zhang Ming Li Yong-Qiang Liu Department of General Surgery Chongqing General HospitalChongqing 401147China Department of Pediatric Research Institute Children’s Hospital of Chongqing Medical UniversityChongqing 401147China

BACKGROUND 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.METHODS 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).RESULTS 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 prolif-eration 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 proliferatio

关键词： Urine-derived stem cells Regenerative medicine Acute kidney injury Renal function recovery Cell therapy

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Efficacy and safety of Yiqi Peiyuan granules for improving the short-term prognosis of patients with Acute kidney injury:A multicenter,double-blind,placebo-controlled,randomized trial

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Journal of Integrative Medicine 2024年第3期22卷 279-285页

作者： Jia-jia Wu Tian-yi Zhang Ying-hui Qi Min-yan Zhu Yan Fang Chao-jun Qi Li-ou Cao Ji-fang Lu Bo-han Lu Lu-min Tang Jian-xiao Shen Shan Mou Department of Nephrology Molecular Cell Lab for Kidney DiseaseShanghai Peritoneal Dialysis Research CenterUremia Diagnosis and Treatment CenterRenji Hospital Affiliated to Shanghai Jiaotong University School of MedicineShanghai 200127China Department of Nephrology Shanghai Pudong New Area Punan HospitalShanghai 200125China Department of Nephrology Ningbo Hangzhou Bay HospitalNingbo 315336Zhejiang ProvinceChina

Background:Yiqi Peiyuan(YQPY)prescription,a composite prescription of traditional Chinese medicine,has been used to prevent or delay the continued deterioration of renal function after Acute kidney injury(AKI)in some institutions and has shown considerable efficacy.Objective:This is the first randomized controlled trial to assess efficacy and safety of YQPY for improving short-term prognosis in adult patients with AKI.Design,setting,participants and interventions:This is a prospective,double-blind,multicenter,randomized,and placebo-controlled clinical trial.A total of 144 enrolled participants were randomly allocated to two groups according to a randomization schedule.Participants,caregivers and investigators assessing the outcomes were blinded to group assignment.Patients in the YQPY group received 36 g YQPY granules twice a day for 28 days.Patients in the placebo group received a placebo in the same dose as the YQPY granules.Main outcome measures:The primary outcome was the change in the estimated glomerular filtration rate(eGFR)between baseline and after 4 and 24 weeks of treatment.The secondary outcomes were the change of serum creatinine(Scr)level between baseline and after treatment,and the incidence of endpoint events,defined as eGFR increasing by more than 25%above baseline,eGFR>75 mL/min per1.73 m2or the composite endpoint,which was defined as the sum of patients meeting either of the above criteria.Results:Data from a total of 114 patients(59 in the YQPY group and 55 in the control group)were analyzed.The mean changes in eGFR and Scr in weeks 4 and 24 had no difference between the two groups.In further subgroup analysis(22 in the YQPY group and 31 in the control group),the mean change in eGFR after treatment for 4 weeks was 27.39 mL/min per 1.73 m2in the YQPY group and 5.78 mL/min per1.73 m2in the placebo group,and the mean difference between groups was 21.61 mL/min per 1.73 m2(P<0.001).Thirteen(59.1%)patients in the YQPY group and 5(16.1%)in the placebo group reached the composite endpoints(P=0.002).Du

关键词： Chinese herbal medicine Randomized controlled trial Acute kidney injury Renal function

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MicroRNA-30a inhibits cell proliferation in a sepsis-induced Acute kidney injury model by targeting the YAP-TEAD complex

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Journal of Intensive Medicine 2024年第2期4卷 231-239页

作者： Junfeng Su Ying Wang Jing Xie Long Chen Xinxin Lin Jiandong Lin Xiongjian Xiao Department of General Intensive Care Unit The Second Affiliated Hospital of Zhejiang University School of MedicineHangzhouChina Department of Critical Care Medicine The First Affiliated HospitalFujian Medical UniversityFuzhouChina Department of Critical Care Medicine National Regional Medical CenterBinhai Campus of the First Affiliated HospitalFujian Medical UniversityFuzhouChina

Background Acute kidney injury(AKI)is a primary feature of renal complications in patients with sepsis.MicroRNA(miRNA/miR)-30a is an essential regulator of cardiovascular diseases,tumors,phagocytosis,and other physical processes,but whether it participates in sepsis-induced AKI(sepsis-AKI)is unknown.We aimed to elucidate the functions and molecular mechanism underlying miR-30a activity in sepsis-AKI.Methods The classical cecal ligation and puncture(CLP)method and lipopolysaccharide(LPS)-induced Human kidney 2(HK-2)cells were used to establish in vivo and in vitro sepsis-AKI models.Specific pathogen-free and mature male Sprague-Dawley(SD)rats,aged 6–8 weeks(weight 200–250 g),were randomly divided into five-time phase subgroups.Fluid resuscitation with 30 mL/kg 37°C saline was administered after the operation,without antibiotics.Formalin-fixed,paraffin-embedded kidney sections were stained with hematoxylin and eosin.SD rat kidney tissue samples were collected for analysis by real-time quantitative polymerase chain reaction and enzyme-linked immunosorbent assay.HK-2 cells were transfected with hsa-miR-30a-3p mimics or inhibitors,and compared with untreated normal controls.RNA,protein,and cell viability were evaluated by quantitative reverse transcription-polymerase chain reaction(qRT-PCR),western blot,and cell counting kit-8 methods.A Dual-Luciferase Assay Kit(Promega)was used to measure luciferase activity 48 h after transfection with miR-30a-3p mimics.Results Expression levels of miR-30a-3p and miR-30a-5p in renal tissues of the sepsis group were significantly reduced at 12 h and 24 h(P<0.05).Tumor necrosis factor-α(TNF-α)and interleukin-1β(IL-1β)were significantly increased in renal tissue 3 h after the operation in rats(P<0.05),and gradually decreased 6 h,12 h,and 24 h after CLP.Levels of miR-30a-5p and miR-30a-3p were significantly down-regulated at 3 h after LPS treatment(P<0.05),and gradually decreased in HK-2 cells.One hour after LPS(10µg/mL)treatment,TNF-αand IL-1βlevels in HK-2 cells were significantly up-

关键词： MicroRNA-30a TEAD1 YAP-TEAD complex Sepsis Acute kidney injury

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Effect of Angiotensin Receptor-neprilysin Inhibitor on Acute kidney injury in Patients With acute Decompensated Heart Failure

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Cardiology Discovery 2024年第1期4卷 23-29页

作者： Gonghao Li Yanli Zhao Zhongxing Peng Kun Liu Delu Yin Yunfeng Zhao Department of Cardiology Nanjing Medical University Kangda College First Affiliated Hospitalthe First People’s Hospital of LianyungangLianyungangJiangsu 222061China

Objective:The risk of Acute kidney injury(AKI)is high in patients with acute decompensated heart failure(ADHF).The aim of this study is to analyze the role of urinary neutrophil gelatinase-associated lipocalin(uNGAL)in diagnosing AKI in patients with ADHF and evaluate the therapeutic effect of angiotensin receptor-neprilysin inhibitor(ARNI)on AKI.Method:Sixty patients with ADHF were enrolled at the First Affiliated Hospital of Kangda College of Nanjing Medical University from January 2020 to June 2021,and randomized into 2 groups(ARNI group:30 patients treated with tablets of sacubitril valsartan sodium;and angiotensin-converting enzyme inhibitor(ACEI)group:30 patients treated with benazepril).The uNGAL level was measured immediately after as well as 1,2,3,and 7 d after hospital admission.The serum creatinine(sCr)level and estimated glomerular filtration rate(eGFR)were measured immediately as well as 2 and 7 d after hospital admission.The urine volume,dose of loop diuretics,and duration of hospital stay(DoHS)were recorded.Result:The most valuable diagnostic metric for AKI in patients with ADHF was the uNGAL level 1 d after hospital admission,which had a sensitivity of 0.94,specificity of 0.84,and optimal cutoff of 125.62μg/L.In the presence of AKI,during the first 2 d,patients in the ARNI-AKI and ACEI-AKI groups showed an increase in the sCr level and a reduction in the eGFR level,but there was no significant difference between the 2 groups(P>0.05).After 7 d of treatment,the sCr level decreased and the eGFR level increased in both groups,with a significantly greater changes being observed in the ARNI-AKI group than in the ACEI-AKI group(P<0.05,respectively).In the absence of AKI,the difference in the sCr level and eGFR between the 2 groups was not significant.The DoHS((11.25±2.38)d vs.(14.11±2.89)d),urinary microalbumin level((22.95±6.04)mg/L vs.(31.91±2.18)mg/L),and daily dose of loop diuretics((19.03±3.04)mg/d vs.(23.62±4.46)mg/d)were significantly lower in patients with AKI in the ARNI group than in the ACEI g

关键词： Acute kidney injury acute decompensated heart failure Angiotensin receptor-neprilysin inhibitor Angiotensin-converting enzyme inhibitor Sacubitril valsartan Benazepril

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Sound waves and solutions:Point-of-care ultrasonography for Acute kidney injury in cirrhosis

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World Journal of Critical Care Medicine 2024年第2期13卷 83-92页

作者： David Aguirre-Villarreal Mario Andrés de Jesús Leal-Villarreal Ignacio García-Juárez Eduardo R Argaiz Abhilash Koratala Departamento de Gastroenterología Instituto Nacional de Ciencias Médicas y Nutrición Salvador ZubiránMexico City 14080Mexico Cardiología Instituto Nacional de Cardiología Ignacio ChávezMexico City 14080Mexico Unidad de Hepatología y Trasplante Departamento de GastroenterologíaInstituto Nacional de Ciencias Medicas y Nutricion Salvador ZubiranMexico City 14080Mexico Departamento de Nefrología y Metabolismo Mineral Instituto Nacional de Ciencias Médicas y Nutrición Salvador ZubiránMexico City 14080Mexico Tecnológico de Monterrey Escuela de Medicina y Ciencias de la SaludMexico City 64710Mexico Department of Nephrology Medical College of WisconsinMilwaukeeWI 53226United States

This article delves into the intricate challenges of Acute kidney injury(AKI)in cirrhosis,a condition fraught with high morbidity and mortality.The complexities arise from distinguishing between various causes of AKI,particularly hemodynamic AKI,in cirrhotic patients,who experience hemodynamic changes due to portal hypertension.The term"hepatocardiorenal syndrome"is introduced to encapsulate the intricate interplay among the liver,heart,and kidneys.The narrative emphasizes the often-overlooked aspect of cardiac function in AKI assessments in cirrhosis,unveiling the prevalence of cirrhotic cardiomyopathy marked by impaired diastolic function.The conventional empiric approach involving volume expansion and vasopressors for hepatorenal syndrome is critically analyzed,highlighting potential risks and variable patient responses.We advocate for a nuanced algorithm for AKI evaluation in cirrhosis,prominently featuring point-of-care ultrasonography(POCUS).POCUS applications encompass assessing fluid tolerance,detecting venous congestion,and evaluating cardiac function.

关键词： Point-of-care ultrasonography Bedside ultrasound Cirrhosis Congestion Acute kidney injury Congestive nephropathy

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Spontaneous Tumor Lysis Syndrome Secondary to Iatrogenic Acute kidney injury: A Case Report

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Case Reports in Clinical Medicine 2024年第5期13卷 155-161页

作者： Joseph Capito Mitchell Hoyson Amie M. Ashcraft Hassan Suleiman Courtney S. Pilkerton Department of Family Medicine West Virginia University Morgantown WV USA Department of Clinical Family Medicine University of Rochester Medical Center Rochester NY USA Departments of Critical Care Medicine & Nephrology Mount Sinai New York City NY USA

Spontaneous Tumor Lysis Syndrome (STLS) is a rare oncologic condition caused by the breakdown of neoplastic tissue in the absence of traditional anti-tumor therapy. It is postulated that cancers with rapidly dividing cells lead to increased cell turnover which exceeds the kidneys’ ability to adequately filtrate by-products of cellular breakdown (i.e., phosphate, potassium, anduric acid), leading to end organ damage. It has been reported in the past that kidney failure is a sequelae of Tumor Lysis Syndrome (TLS), but there have been no reports that demonstrate Acute kidney injury (AKI) preceding TLS. The case presented here demonstrates TLS in a patient with no formal cancer diagnosis, who had received no chemotherapy or radiation that was precipitated by an iatrogenic AKI with chlorthalidone and ibuprofen. This unusual pattern of AKI preceding STLS may provide insight into the pathophysiology of the condition and could possibly lead to greater understanding of this phenomenon.

关键词： Spontaneous Tumor Lysis Acute kidney injury Lymphoma Chlorthalidone NSAID

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Revaccination after Acute kidney injury Associated with Prior COVID-19 Vaccination: Case Report

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Advances in Infectious Diseases 2024年第1期14卷 196-205页

作者： Senyo Tagboto Laurette Geldenhuys Department of Internal Medicine Yarmouth Regional Hospital Yarmouth Canada Department of Medicine Dalhousie University Halifax Canada Department of Internal Medicine University of Health and Allied Sciences Ho Ghana Department of Pathology Dalhousie University Halifax Canada Department of Pathology and Laboratory Medicine Central Zone Nova Scotia Health Halifax Canada

Background: Acute kidney injury associated with proteinuria has been reported following vaccination against SARS-CoV-2 several times since 2021. Decisions about subsequent revaccination in these patients have been difficult because of the uncertainty of the consequences of doing so, and the absence of publications to help determine whether revaccination may be considered safe or not. Purpose: We present a case report of a 59-year-old Canadian man who developed severe Acute kidney injury associated with moderate proteinuria following his first COVID-19 vaccine with the Moderna vaccine (an mRNA vaccine). He required haemodialysis for 2 weeks, which was initiated when his creatinine reached 1002 μmol/l. A kidney biopsy showed changes consistent with acute tubular necrosis. The patient was cautioned that repeat vaccination might result in further kidney injury which might be irreversible. However, he badly wanted to attempt a second COVID-19 vaccination, to facilitate a family vacation across several countries in Europe, at a time when travel restrictions were in place in many countries for persons who had not completed a course of vaccines. Method: Following deliberations, the patient chose to try a different type of Covid-19 vaccine. On this occasion, he was vaccinated with the Novavax vaccine (a subunit COVID-19 vaccine). Following this, close monitoring of his urine to detect proteinuria and blood testing for Acute kidney injury were carried out on days 1, 3, 7, and 60 after vaccination. Furthermore, a year after his repeat vaccination, his kidney function and urinalysis were again assessed. Result and Conclusions: The patient did not develop Acute kidney injury or worsening proteinuria following repeat vaccination. It remains unclear if Acute kidney injury with proteinuria is caused by Covid-19 vaccination, or simply an incidental association. This case report suggests that it is may be reasonable for patients with Acute kidney injury after COVID-19 vaccination to consider trying a different type of vaccine. In

关键词： Covid-19 Vaccination Acute kidney injury Proteinuria Haemodialysis Revaccination

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Exertional Rhabdomyolysis Induced Acute kidney injury: A Case Report and Literature Review

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Case Reports in Clinical Medicine 2024年第3期13卷 53-62页

作者： Yu Zhang Department of Geriatric The Second Hospital of Tianjin Medical University Tianjin China

Background: The exRML (exertional rhabdomyolysis) is a pathophysiologic condition of skeletal muscle cell damage and breakdown associated with high intensity or prolonged exercise, normal exercise under extreme circumstances, or sudden and excessive skeletal muscle contraction. It may manifest from the increase in CK (creatine kinase) or MYO (myoglobin), a protein that can cause life-threatening injury to the kidney (AKI, Acute kidney injury), and may or may not be associated with myoglobinuria. Here, we presented a case of exRML with AKI, and then reviewed the related reports. Vigorous hydration, sodium bicarbonate and furosemide are key treatments. Aim: To examine an elderly patient with exRML induced AKI and the key treatment process. Case summary: A 61-year-old man left our hospital without permission after his admission and has been walking for almost 30 kms with no water and food intake, then was diagnosed exRML and exRML induced AKI with an obvious elevation of CK, MYO and decrease of eGFR (estimated glomerular filtration rate) after coming back, and was treated with vigorous hydration, loop diuresis, sodium bicarbonate, prostaglandin and Shenkang injection. After vigorous resuscitation, the patient’s renal function, CK and MYO returned normal. Conclusions: The exRML can cause serious complications such as AKI and death. Delayed diagnosis can be critical;therefore, manner of time should be taken to achieve a favorable prognosis.

关键词： Exertional Rhabdomyolysis Serum Creatine Kinase Myoglobin Acute kidney injury

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