Link between obstructive uropathy and acute kidney injury

Obstructive uropathy represents a major risk of acute kidney injury.From an epidemiological point of view,it is responsible for 5%to 10%of cases of acute renal failure and 4%of cases of end-stage kidney disease.Although obstructive uropathy is a recognized disease,there is a significant lack of detailed research on this topic from both a nephrological and urological perspective.The majority of published research focuses on the pathophysiology of the topic and neglects a comprehensive analysis of diagnostic and treatment approaches supported by current data.In this context,it is crucial to assess the overall hemodynamic status,especially in the presence of urosepsis.Once clinical stability is assured,it is important to focus on symptom management,usually by controlling pain.Ultimately,it is crucial to decide immediately whether the patient should receive a prompt urinary diversion.Urinary diversion is an essential part of the treatment of obstructive uropathy and should be initiated promptly and without unnece-ssary delay once the diagnosis has been confirmed.Functional recovery of the obstructed kidney after decompression of the urinary tract depends on the degree of obstruction,the duration of the obstruction and the presence of a concomitant urinary tract infection.The timing and proper treatment of this condition determines the recovery of kidney function after an obstruction and prevents the development of chronic kidney disease.In this editorial,we emphasized the pathophysiological role and clinical significance of obstructive uropathy in the context of acute kidney injury.

Transition from acute kidney injury to chronic kidney disease in liver cirrhosis patients:Current perspective

In liver cirrhosis patients,acute kidney injury(AKI)is a common and severe complication associated with significant morbidity and mortality,often leading to chronic kidney disease(CKD).This progression reflects a complex interplay of renal and hepatic pathophysiology,with AKI acting as an initiator through maladaptive repair mechanisms.These mechanisms—such as tubular cell cycle arrest,inflammatory cascades,and fibrotic processes—are exacerbated by the hemodynamic and neurohormonal disturbances characteristic of cirrhosis.Following AKI episodes,persistent kidney dysfunction or acute kidney disease(AKD)often serves as a bridge to CKD.AKD represents a critical phase in renal deterioration,characterized by prolonged kidney injury that does not fully meet CKD criteria but exceeds the temporal scope of AKI.The progression from AKD to CKD is further influenced by recurrent AKI episodes,impaired renal autoregu-lation,and systemic comorbidities such as diabetes and metabolic dysfunction-associated steatotic liver disease,which compound kidney damage.The clinical management of AKI and CKD in cirrhotic patients requires a multidimensional approach that includes early identification of kidney injury,the application of novel biomarkers,and precision interventions.Recent evidence underscores the inadequacy of traditional biomarkers in predicting the AKI-to-CKD progression,necessitating novel biomarkers for early detection and intervention.

Pegaspargase induced multiple organ failure with acute lymphoblastic leukemia:A case report

BACKGROUND The introduction of pegaspargase has greatly advanced the treatment of acute lymphoblastic leukemia(ALL).In the literature,only one case of pegaspargaseinduced multiple organ failure has been reported,and the patient died due to multiple organ failure.CASE SUMMARY Herein,we present a rare case of a 40-year-old man with ALL who developed multiple organ failure after treatment with pegaspargase.The patient had two rare phenomena reflecting poor prognosis,including the discrepancy between clinical manifestations and liver function and persistently low alpha-fetoprotein(AFP)levels from subacute liver failure.However,the patient was successfully treated using a multidisciplinary team approach.CONCLUSION This is the first case report of successful treatment of pegaspargase-induced multiple organ failure.The findings emphasize the importance of a multidisciplinary team approach in treating pegaspargase-induced multiple organ failure.

Current role of biomarkers in the initiation and weaning of kidney replacement therapy in acute kidney injury

The occurrence of acute kidney injury(AKI)in critically ill patients is often associated with increased morbidity and mortality rates.Despite extensive research,a consensus is yet to be arrived,especially regarding the optimal timing and indications for initiation of kidney replacement therapy(KRT)for critically ill patients.There is no clear guidance available on the timing of weaning from KRT.More recently,various biomarkers have produced promising prognostic pre-diction in such patients,regarding the need for KRT and its termination.Most of these biomarkers are indicative of kidney damage and stress,rather than re-covery.However,large-scale validation studies are required to guide the cutoff values of these biomarkers among different patient cohorts so as to identify the optimum timing for KRT.This article reviews the kidney biomarkers in detail and summarizes the individual roles of biomarkers in the decision-making process for initiation and termination of the KRT among critically ill AKI patients and the supportive literature.

Innovative approaches beyond periprocedural hydration for preventing contrast-induced acute kidney injury

Contrast-induced acute kidney injury(CI-AKI)is a major concern in clinical practice,particularly among high-risk patients with preexisting renal and cardiovascular conditions.Although periprocedural hydration has long been the primary approach for CI-AKI prevention,recent advancements have led to the development of novel approaches such as RenalGuard and contrast removal systems.This editorial explores these emerging approaches and highlights their potential for enhancing CI-AKI prevention.By incorporating the latest evidence into clinical practice,health-care professionals can more effectively maintain renal function and improve outcomes for patients undergoing contrast-enhanced procedures.

Navigating nephrotoxic waters:A comprehensive overview of contrast-induced acute kidney injury prevention

Contrast-induced acute kidney injury(CI-AKI)is the third leading cause of acute kidney injury deriving from the intravascular administration of contrast media in diagnostic and therapeutic procedures and leading to longer in-hospital stay and increased short and long-term mortality.Its pathophysiology,although not well-established,revolves around medullary hypoxia paired with the direct toxicity of the substance to the kidney.Critically ill patients,as well as those with pre-existing renal disease and cardiovascular comorbidities,are more susceptible to CI-AKI.Despite the continuous research in the field of CI-AKI prevention,clinical practice is based mostly on periprocedural hydration.In this review,all the investigated methods of prevention are presented,with an emphasis on the latest evidence regarding the potential of RenalGuard and contrast removal systems for CI-AKI prevention in high-risk individuals.

Clinical Presentation and Treatment Outcomes of Pregnancy-Related Acute Kidney Injury among Pregnant Women Admitted at the Benjamin Mkapa Hospital in Tanzania

Background: Globally, PRAKI is among the leading causes of death in pregnant women. The prevalence, causes and outcome of this condition vary among countries due to differences in environmental, socioeconomic, and health delivery systems. The common causes that have been reported in several studies are PIH, Haemorrhages and Sepsis while the outcomes may be either complete renal recovery, progression to CKD and hence dialysis dependency or death. This study aimed at determining clinical presentation and treatment outcomes of Pregnancy-Related Acute Kidney Injury in Pregnant women admitted at the Benjamin Mkapa Hospital, Dodoma, Tanzania. Results: Out of 4007 pregnant women who were admitted to the maternity ward 51 pregnant women were found to have PRAKI. Of those with PRAKI, 74.5% were between 21 to 25 years. The leading causes of PRAKI were PPH 12 (23.53%), Eclampsia 12 (23.53%), and pre-eclampsia 12 (23.5%). Hemodialysis therapy was provided to 22 (43.1%) patients, 15 (29.4%) individuals recovered spontaneously with medical management and 14 (27.5%) missed haemodialysis therapy due to various reasons. The mortality due to PRAKI was 17 (33.3%). Conclusion and Recommendation: Pre-eclampsia/eclampsia and post-partum haemorrhage were found to be the main causes of PRAKI. The mortality related to PRAKI is high and Hemodialysis therapy is vital help to prevent deaths for pregnant women with PRAKI. Pregnant women who develop acute kidney injury should be followed closely and a nephrologist should be consulted early. Early referral should be done by the lower level facilities for all at-risk pregnant women to a specialized multidisciplinary health facility.

Timing of Continuous Renal Replacement Therapy Initiation in Sepsis-Associated Acute Kidney Injury: A Comprehensive Review and Future Directions

This review examines the application of continuous renal replacement therapy(CRRT)in patients with sepsis-associated acute kidney injury(S-AKI),with a particular focus on the timing of CRRT initiation.This review addresses the controversy surrounding initiation timing and proposes future research directions.Through a systematic review of recent literature on CRRT for S-AKI,working principles,therapeutic mechanisms,initiation timing of CRRT,and related meta-analyses were summarized.Current studies indicate that the optimal timing for CRRT initiation in S-AKI patients remains inconclusive,with ongoing debate regarding whether early initiation significantly improves patient survival and renal function.This lack of consensus reflects the heterogeneity of the S-AKI patient population and the limitations of existing research methodologies.Future studies should focus on advancing the application of precision medicine in S-AKI and developing individualized treatment strategies by integrating multidimensional information to optimize CRRT utilization and improve patient outcomes.

Silent information regulator sirtuin 1 ameliorates acute liver failure via the p53/glutathione peroxidase 4/gasdermin D axis

BACKGROUND Acute liver failure(ALF)has a high mortality with widespread hepatocyte death involving ferroptosis and pyroptosis.The silent information regulator sirtuin 1(SIRT1)-mediated deacetylation affects multiple biological processes,including cellular senescence,apoptosis,sugar and lipid metabolism,oxidative stress,and inflammation.AIM To investigate the association between ferroptosis and pyroptosis and the upstream regulatory mechanisms.METHODS This study included 30 patients with ALF and 30 healthy individuals who underwent serum alanine aminotransferase(ALT)and aspartate aminotransferase(AST)testing.C57BL/6 mice were also intraperitoneally pretreated with SIRT1,p53,or glutathione peroxidase 4(GPX4)inducers and inhibitors and injected with lipopolysaccharide(LPS)/D-galactosamine(D-GalN)to induce ALF.Gasdermin D(GSDMD)^(-/-)mice were used as an experimental group.Histological changes in liver tissue were monitored by hematoxylin and eosin staining.ALT,AST,glutathione,reactive oxygen species,and iron levels were measured using commercial kits.Ferroptosis-and pyroptosis-related protein and mRNA expression was detected by western blot and quantitative real-time polymerase chain reaction.SIRT1,p53,and GSDMD were assessed by immunofluorescence analysis.RESULTS Serum AST and ALT levels were elevated in patients with ALF.SIRT1,solute carrier family 7a member 11(SLC7A11),and GPX4 protein expression was decreased and acetylated p5,p53,GSDMD,and acyl-CoA synthetase long-chain family member 4(ACSL4)protein levels were elevated in human ALF liver tissue.In the p53 and ferroptosis inhibitor-treated and GSDMD^(-/-)groups,serum interleukin(IL)-1β,tumour necrosis factor alpha,IL-6,IL-2 and C-C motif ligand 2 levels were decreased and hepatic impairment was mitigated.In mice with GSDMD knockout,p53 was reduced,GPX4 was increased,and ferroptotic events(depletion of SLC7A11,elevation of ACSL4,and iron accumulation)were detected.In vitro,knockdown of p53 and overexpression of GPX4 reduced AST and ALT levels,the cytostatic rate,and GSDMD expression,restoring SLC7A11 depletion.Moreover,SIRT1 agonist and overexpression of SIRT1 alleviated acute liver injury and decreased iron deposition compared with results in the model group,accompanied by reduced p53,GSDMD,and ACSL4,and increased SLC7A11 and GPX4.Inactivation of SIRT1 exacerbated ferroptotic and pyroptotic cell death and aggravated liver injury in LPS/D-GalNinduced in vitro and in vivo models.CONCLUSION SIRT1 activation attenuates LPS/D-GalN-induced ferroptosis and pyroptosis by inhibiting the p53/GPX4/GSDMD signaling pathway in ALF.

AGK2 pre-treatment protects against thioacetamide-induced acute liver failure via regulating the MFN2-PERK axis and ferroptosis signaling pathway

Background:Acute liver failure(ALF)is an unpredictable and life-threatening critical illness.The pathological characteristic of ALF is massive necrosis of hepatocytes and lots of inflammatory cells infiltration which may lead to multiple organ failure.Methods:Animals were divided into 3 groups,normal,thioacetamide(TAA,ALF model)and TAA+AGK2.Cultured L02 cells were divided into 5 groups,normal,TAA,TAA+mitofusin 2(MFN2)-siRNA,TAA+AGK2,and TAA+AGK2+MFN2-siRNA groups.The liver histology was evaluated with hematoxylin and eosin staining,inositol-requiring enzyme 1(IRE1),activating transcription factor 6β(ATF6β),protein kinase R(PKR)-like endoplasmic reticulum kinase(PERK)and phosphorylated-PERK(p-PERK).C/EBP homologous protein(CHOP),reactive oxygen species(ROS),MFN2 and glutathione peroxidase 4(GPX4)were measured with Western blotting,and cell viability and liver chemistry were also measured.Mitochondriaassociated endoplasmic reticulum membranes(MAMs)were measured by immunofluorescence.Results:The liver tissue in the ALF group had massive inflammatory cell infiltration and hepatocytes necrosis,which were reduced by AGK2 pre-treatment.In comparison to the normal group,apoptosis rate and levels of IRE1,ATF6β,p-PERK,CHOP,ROS and Fe2+in the TAA-induced ALF model group were significantly increased,which were decreased by AGK2 pre-treatment.The levels of MFN2 and GPX4 were decreased in TAA-induced mice compared with the normal group,which were enhanced by AGK2 pretreatment.Compared with the TAA-induced L02 cell,apoptosis rate and levels of IRE1,ATF6β,p-PERK,CHOP,ROS and Fe2+were further increased and levels of MFN2 and GPX4 were decreased in the MFN2-siRNA group.AGK2 pre-treatment decreased the apoptosis rate and levels of IRE1,ATF6β,p-PERK,CHOP,ROS and Fe2+and enhanced the protein expression of MFN2 and GPX4 in MFN2-siRNA treated L02 cell.Immunofluorescence observation showed that level of MAMs was promoted in the AGK2 pre-treatment group when compared with the TAA-induced group in both mice and L02 cells.Conclusions:The data suggested that AGK2 pre-treatment had hepatoprotective role in TAA-induced ALF via upregulating the expression of MFN2 and then inhibiting PERK and ferroptosis pathway in ALF.

Acute kidney injury in acute-on-chronic liver failure is different from in decompensated cirrhosis

AIM To evaluate the differences in acute kidney injury(AKI) between acute-on-chronic liver failure(ACLF) and decompensated cirrhosis(DC) patients. METHODS During the period from December 2015 to July 2017, 280 patients with hepatitis B virus(HBV)-related ACLF(HBV-ACLF) and 132 patients with HBV-related DC(HBV-DC) who were admitted to our center were recruited consecutively into an observational study. Urine specimens were collected from all subjects and the levels of five urinary tubular injury biomarkers were detected,including neutrophil gelatinase-associated lipocalin(NGAL), interleukin-18(IL-18), liver-type fatty acid binding protein(L-FABP), cystatin C(CysC), and kidney injury molecule-1(KIM-1). Simultaneously, the patient demographics, occurrence and progression of AKI, and response to terlipressin therapy were recorded. All patients were followed up for 3 mo or until death after enrollment. RESULTS AKI occurred in 71 and 28 of HBV-ACLF and HBV-DC patients, respectively(25.4% vs 21.2%, P = 0.358). Among all patients, the levels of four urinary biomarkers(NGAL, CysC, L-FABP, IL-18) were significantly elevated in patients with HBV-ACLF and AKI(ACLF-AKI), compared with that in patients with HBV-DC and AKI(DC-AKI) or those without AKI. There was a higher proportion of patients with AKI progression in ACLF-AKI patients than in DC-AKI patients(49.3% vs 17.9%, P = 0.013). Fortythree patients with ACLF-AKI and 19 patients with DC-AKI were treated with terlipressin. The response rate of ACLFAKI patients was significantly lower than that of patients with DC-AKI(32.6% vs 57.9%, P = 0.018). Furthermore, patients with ACLF-AKI had the lowest 90 d survival rates among all groups(P < 0.001).CONCLUSION AKI in ACLF patients is more likely associated with structural kidney injury, and is more progressive, with a poorer response to terlipressin treatment and a worse prognosis than that in DC patients.

Cystatin C is a biomarker for predicting acute kidney injury in patients with acute-on-chronic liver failure

AIM:To investigate serum cystatin C level as an early biomarker for predicting acute kidney injury(AKI)in patients with acute-on-chronic liver failure(ACLF).METHODS:Fifty-six consecutive patients with hepatitis B virus-related ACLF who had normal serum creatinine(Cr)level(<1.2 mg/dL in men,or<1.1 mg/dL in women)were enrolled in the Liver Failure Treatment and Research Center of Beijing 302 Hospital between August 2011 and October 2012.Thirty patients with chronic hepatitis B(CHB)and 30 healthy controls in the same study period were also included.Measurement of serum cystatin C(CysC)was performed by a particle-enhanced immunonephelometry assay using the BN Prospec nephelometer system.The ACLF patients were followed during their hospitalization period.RESULTS:In the ACLF group,serum level of CysC was 1.1±0.4 mg/L,which was significantly higher(P<0.01)than those in the healthy controls(0.6±0.3mg/L)and CHB patients(0.7±0.2 mg/L).During the hospitalization period,eight ACLF patients developed AKI.Logistic regression analysis indicated that CysC level was an independent risk factor for AKI development(odds ratio=1.8;95%CI:1.4-2.3,P=0.021).The cutoff value of serum CysC for prediction of AKI in ACLF patients was 1.21 mg/L.The baseline CysC-based estimated glomerular filtration rate(eGFR CysC)was significantly lower than the creatinine-based eGFR(eGFR CG and eGFR MDRD)in ACLF patients with AKI,suggesting that baseline eGFR CysC represented early renal function in ACLF patients while the Cr levels were still within the normal ranges.CONCLUSION:Serum CysC provides early prediction of renal dysfunction in ACLF patients with a normal serum Cr level.

Rhabdomyolysis-related acute kidney injury in patients with COVID- 19

BACKGROUND Viral and bacterial infections may be complicated by rhabdomyolysis,which has a spectrum of clinical presentations ranging from asymptomatic laboratory abnor-malities to life-threatening conditions such as renal failure.Direct viral injury as well as inflammatory responses may cause rhabdomyolysis in the course of coronavirus disease 2019(COVID-19).When presented with acute kidney injury(AKI),rhabdomyolysis may be related to higher morbidity and mortality.AIM To compare rhabdomyolysis-related AKI with other AKIs during COVID-19.METHODS A total of 115 patients with COVID-19 who had AKI were evaluated retrospec-tively.Fifteen patients had a definite diagnosis of rhabdomyolysis(i.e.,creatine kinase levels increased to>5 times the upper normal range with a concomitant increase in transaminases and lactate dehydrogenase).These patients were aged 61.0±19.1 years and their baseline creatinine levels were 0.87±0.13 mg/dL.Patients were treated according to national COVID-19 treatment guidelines.They were compared with patients with COVID-19 who had AKI due to other reasons.RESULTS For patients with rhabdomyolysis,creatinine reached 2.47±1.17 mg/dL during follow-up in hospital.Of these patients,13.3%had AKI upon hospital admission,and 86.4%developed AKI during hospital follow-up.Their peak C-reactive protein reached as high as 253.2±80.6 mg/L and was higher than in patients with AKI due to other reasons(P<0.01).Peak ferritin and procalcitonin levels were also higher for patients with rhabdomyolysis(P=0.02 and P=0.002,respective-ly).The mortality of patients with rhabdomyolysis was calculated as 73.3%,which was higher than in other patients with AKI(18.1%)(P=0.001).CONCLUSION Rhabdomyolysis was present in 13.0%of the patients who had AKI during COVID-19 infection.Rhabdomyolysis-related AKI is more proinflammatory and has a more mortal clinical course.

Understanding the molecular crossroads in acute liver failure:A pathway to new therapies

In this editorial we comment on the article published in a recent issue of the World Journal of Gastroenterology.Acute liver failure(ALF)is a critical condition characterized by rapid hepatocellular injury and organ dysfunction,and it often necessitates liver transplant to ensure patient survival.Recent research has eluci-dated the involvement of distinct cell death pathways,namely ferroptosis and pyroptosis,in the pathogenesis of ALF.Ferroptosis is driven by iron-dependent lipid peroxidation,whereas pyroptosis is an inflammatory form of cell death;both pathways contribute to hepatocyte death and exacerbate tissue damage.This comprehensive review explores the interplay between ferroptosis and pyroptosis in ALF,highlighting the role of key regulators such as silent information regulator sirtuin 1.Insights from clinical and preclinical studies provide valuable perspectives on the dysregulation of cell death pathways in ALF and the therapeutic potential of targeting these pathways.Collaboration across multiple disciplines is essential for translating the experimental insights into effective treatments for this life-threatening condition.

Viral etiologies of acute liver failure

Acute liver failure(ALF)is a rare cause of liver-related mortality worldwide,with an estimated annual global incidence of more than one million cases.While drug-induced liver injury,including acetaminophen toxicity,is the leading cause of ALF in the Western world,viral infections remain a significant cause of ALF and the most common cause in many developing nations.Given the high mortality rates associated with ALF,healthcare providers should be aware of the broad range of viral infections that have been implicated to enable early diagnosis,rapid treatment initiation when possible,and optimal management,which may include liver transplantation.This review aims to provide a summary of viral causes of ALF,diagnostic approaches,treatment options,and expected outcomes.

Prognostic impact of atrial fibrillation on clinical outcomes of acute coronary syndromes,heart failure and chronic kidney disease

Atrial fibrillation(AF) is the most common type of sustained arrhythmia,which is now on course to reach epidemic proportions in the elderly population. AF is a commonly encountered comorbidity in patients with cardiac and major non-cardiac diseases. Morbidity and mortality associated with AF makes it a major healthcare burden. The objective of our article is to determine the prognostic impact of AF on acute coronary syndromes,heart failure and chronic kidney disease. Multiple studies have been conducted to determine if AF has an independent role in the overall mortality of such patients. Our review suggests that AF has an independent adverse prognostic impact on the clinical outcomes of acute coronary syndromes,heart failure and chronic kidney disease.

Neutrophil gelatinase-associated lipocalin does not predict acute kidney injury in heart failure

BACKGROUND Acute cardiorenal syndrome type 1(CRS-1)is defined by a rapid cardiac dysfunction leading to acute kidney injury(AKI).Neutrophil gelatinaseassociated lipocalin(NGAL)is expressed on the surface of human neutrophils and epithelial cells,such as renal tubule cells,and its serum(sNGAL)and urinary have been used to predict AKI in different clinical settings.AIM To characterize CRS-1 in a cohort of patients with acute heart diseases,evaluating the potentiality of sNGAL as an early marker of CRS-1.METHODS We performed a retrospective cohort,multi-centre study.From January 2010 to December 2011,we recruited 202 adult patients admitted to the coronary intensive care unit(CICU)with a diagnosis of acute heart failure or acute coronary syndrome.We monitored the renal function to evaluate CRS-1 development and measured sNGAL levels within 24 h and after 72 h of CICU admission.RESULTS Overall,enrolled patients were hemodynamically stable with a mean arterial pressure of 92(82-107)mmHg,55/202(27.2%)of the patients developed CRS-1,but none of them required dialysis.Neither the NGAL delta value(AUC 0.40,95%CI:0.25-0.55)nor the NGAL peak(AUC 0.45,95%CI:0.36-0.54)or NGAL cutoff(≥140 ng/mL)values were statistically significant between the two groups(CRS-1 vs no-CRS1 patients).The area under the ROC curve for the prediction of CRS-1 was 0.40(95%CI:0.25-0.55)for the delta NGAL value and 0.45(95%CI:0.36-0.54)for the NGAL peak value.Finally,in multivariate analysis,the risk of developing CRS-1 was correlated with age>60 years,urea nitrogen at admission and 24 h-urine output(AUC 0.83,SE=60.5%SP=93%),while sNGAL was not significantly correlated.CONCLUSION In our population,sNGAL does not predict CRS-1,probably as a consequence of the mild renal injury and the low severity of heart disease.So,these data might suggest that patient selection should be taken into account when considering the utility of NGAL measurement as a biomarker of kidney damage.

Fetal kidney stem cells ameliorate cisplatin induced acute renal failure and promote renal angiogenesis

AIM: To investigate whether fetal kidney stem cells(f KSC) ameliorate cisplatin induced acute renal failure(ARF) in rats and promote renal angiogenesis.METHODS: The f KSC were isolated from rat fetuses of gestation day 16 and expanded in vitro up to 3rd passage. They were characterized for the expression of mesenchymal and renal progenitor markers by flow cytometry and immunocytochemistry, respectively. The in vitro differentiation of f KSC towards epithelial lineage was evaluated by the treatment with specific induction medium and their angiogenic potential by matrigel induced tube formation assay. To study the effect of f KSC in ARF, f KSC labeled with PKH26 were infused in rats with cisplatin induced ARF and, the blood and renal tissues of the rats were collected at different time points. Blood biochemical parameters were studied to evaluate renal function. Renal tissues were evaluated for renal architecture, renal cell proliferation and angiogenesis by immunohistochemistry, renal cell apoptosis by terminal deoxynucleotidyl transferase nickend labeling assay and early expression of angiogenic molecules viz. vascular endothelial growth factor(VEGF), hypoxia-inducible factor(HIF)-1α and endothelial nitric oxide synthase(eN OS) by western blot.RESULTS: The fK SC expressed mesenchymal markers viz. CD29, CD44, CD73, CD90 and CD105 as well asrenal progenitor markers viz. Wt1, Pax2 and Six2. They exhibited a potential to form CD31 and Von Willebrand factor expressing capillary-like structures and could be differentiated into cytokeratin(CK)18 and CK19 positive epithelial cells. Administration of fK SC in rats with ARF as compared to administration of saline alone, resulted in a significant improvement in renal function and histology on day 3(2.33 ± 0.33 vs 3.50 ± 0.34, P < 0.05) and on day 7(0.83 ± 0.16 vs 2.00 ± 0.25, P < 0.05). The infused PKH26 labeled fK SC were observed to engraft in damaged renal tubules and showed increased proliferation and reduced apoptosis(P < 0.05) of renal cells. The kidneys of fK SC as compared to saline treated rats had a higher capillary density on day 3 [13.30 ± 1.54 vs 7.10 ± 1.29, capillaries/high-power fields(HPF), P < 0.05], and on day 7(21.10 ± 1.46 vs 15.00 ± 1.30, capillaries/HPF, P < 0.05). In addition, kidneys of fK SC treated rats had an upregulation of angiogenic proteins hypoxia-inducible factor-1α, VEGF and eN OS on day 3(P < 0.05).CONCLUSION: Our study shows that fK SC ameliorate cisplatin induced ARF in rats and promote renal angiogenesis, which may be an important therapeutic mechanism of these stem cells in the disease.

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

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.

Overview of ferroptosis and pyroptosis in acute liver failure

In this editorial,we comment on the article by Zhou et al published in a recent issue.We specifically focus on the crucial roles of ferroptosis and pyroptosis in acute liver failure(ALF),a disease with high mortality rates.Ferroptosis is the result of increased intracellular reactive oxygen species due to iron accumulation,glutathione(GSH)depletion,and decreased GSH peroxidase 4 activity,while pyroptosis is a procedural cell death mediated by gasdermin D which initiates a sustained inflammatory process.In this review,we describe the characteristics of ferroptosis and pyroptosis,and discuss the involvement of the two cell death modes in the onset and development of ALF.Furthermore,we summarize several interfering methods from the perspective of ferroptosis and pyroptosis for the alleviation of ALF.These observations might provide new targets and a theoretical basis for the treatment of ALF,which are also crucial for improving the prognosis of patients with ALF.