BACKGROUND Transplant teams often hesitate to use the right kidney(RK)in living donor(LD)transplants due to the complexities of anastomosing the short,thin-walled right renal veins,which can potentially lead to graft ...BACKGROUND Transplant teams often hesitate to use the right kidney(RK)in living donor(LD)transplants due to the complexities of anastomosing the short,thin-walled right renal veins,which can potentially lead to graft loss or graft dysfunction.Nevertheless,circumstances may arise where selecting the RK over the left kidney(LK)is unavoidable.Consequently,it is crucial to thoroughly examine the implications of such a choice on the overall transplant outcome.AIM To compare transplant outcomes between recipients of RK and LK while examining the factors that influence these outcomes.METHODS We retrospectively analyzed data from adult patients who received LD kidney transplants involving meticulous patient selection and surgical techniques at our center from January 2020 to December 2023.We included all kidney donors who were over 18,fit to donate,and had undergone diethylenetriamine pentaacetic acid split function and/or computed tomography based volumetry.The variables examined comprised donor and recipient demographics,and outcome measures included technical graft loss(TGL),delayed or slow graft function(SGF),and post-transplant serum creatinine(SC)trends.We used a logistic regression model to assess the likelihood of adverse outcomes considering the donor kidney side.RESULTS Of the 250 transplants performed during the period,56(22%)were RKs.The recipient demographics and transplant factors were comparable for the right and LKs,except that the donor warm and cold ischemia time were shorter for RKs.TGL and SGF each occurred in 2%(n=1)of RKs and 0.5%(n=1)of LKs,the difference being insignificant.These complications,however,were not related to the venous anastomosis.One RK(2%)developed delayed graft function after 48 hours,which was attributable to postoperative hypoxia rather than the surgical technique.The post-transplant SC trend and mean SC at the last follow-up were similar across both kidney sides.CONCLUSION The donor kidney side has little impact on post-transplant adverse events and graft function in LD transplants,provided that careful patient selection and precise surgical techniques are employed.展开更多
Chronic kidney disease(CKD),which represents a significant global health concern,is characterized by a gradual decline in kidney function,leading to complications such as electrolyte imbalance,cardiovascular disease,a...Chronic kidney disease(CKD),which represents a significant global health concern,is characterized by a gradual decline in kidney function,leading to complications such as electrolyte imbalance,cardiovascular disease,and immune dysfunction.Standard CKD management includes dietary modifications,ketoana-logues supplementation,blood pressure and blood glucose control,hydration maintenance,and treatment of the underlying causes.Emerging evidence has indicated a significant role of the gut microbiota in CKD,and that dysbiosis of the gut microbiota contributes to the progression of CKD towards end-stage renal disease.Probiotics and prebiotics have recently garnered attention owing to their potential to enhance gastrointestinal health and well-being by restoring the balance of the gut microbiota.Specific probiotic strains,including Lactobacillus and Bifidobacterium,promote beneficial bacterial growth,suppress harmful bacteria,and exert anti-inflammatory,antihypertensive,and antidiabetic effects.The combination of Streptococcus thermophilus,Lactobacillus acidophilus,Bifidobacterium longum,and Bacillus coagulans has demonstrated potential as a therapeutic formulation for CKD management in various studies,highlighting its promise in treating CKD;however,supporting evidence remains limited,making it crucial to conduct further investigations to determine the specific effects of different probiotic formulations on outcomes in patients with CKD.展开更多
Khan et al’single-centre,retrospective study on the use of right or left kidneys in living-donor renal transplantation,offers the opportunity to further discuss a complex and debated topic in clinical transplantation...Khan et al’single-centre,retrospective study on the use of right or left kidneys in living-donor renal transplantation,offers the opportunity to further discuss a complex and debated topic in clinical transplantation.In brief,the authors confirm that,despite the historical preference for left kidneys,attributed to their anatomical advantages during donor nephrectomy and recipient transplantation,right kidneys can provide excellent outcomes when donors and recipients are carefully selected,and a meticulous surgical technique is applied in every step of the process.Usefully,the article includes some practical tips to help less experienced surgeons address the technical challenges of right kidney transplantation,such as extended renal vein dissection or full mobilization of the iliac vein of the recipient to minimize tension during anastomosis.Although limited by the selective use of minimally invasive(MI)nephrectomy for left kidneys,this work underscores the importance of expanding the living-donor pool,challenging the traditional taboos,and facilitating access to transplantation for a wider population of patients around the globe.Properly designed studies with larger sample size,comparable MI surgical techniques,prospective data collection,and long-term donor and recipient outcomes are warranted.展开更多
BACKGROUND Transplantectomy has long been considered the preferred treatment for spontaneous renal graft rupture,prioritizing patient safety over kidney salvage.In the last decade,there has been an increasing number o...BACKGROUND Transplantectomy has long been considered the preferred treatment for spontaneous renal graft rupture,prioritizing patient safety over kidney salvage.In the last decade,there has been an increasing number of reports showing that,in selected scenarios,conservative management through graft repair represents a feasible option,challenging traditional approaches.CASE SUMMARY We describe the case of a 37-year-old sensitized XY patient who experienced early spontaneous graft rupture after receiving his second deceased donor kidney transplant.Following temporary hemodynamic stabilization and abdominal contrast enhanced computed tomography scan assessment,the recipient was brought back to theatre for surgical exploration.Possible causes of irreversible graft damage were immediately ruled out.The fractured upper pole of the transplanted kidney was repaired using a fibrin sealant,external compression,and a tailored polyglactin 910 mesh wrapped around the graft.The post-operative course was uneventful.After 20 months of follow up,the patient is doing very well,with excellent renal function and complete reabsorption of the mesh,as demonstrated by serial ultrasound evaluations of the graft.CONCLUSION Amid organ shortages and sensitized patients,graft nephrectomy is reserved for severe injuries;repair using sealants and mesh is effective.展开更多
Kenya, a lower-middle-income country in East Africa, faces a rising burden of chronic kidney disease (CKD), with an estimated 12,500 individuals suffering from end-stage renal disease (ESRD). Renal transplantation—th...Kenya, a lower-middle-income country in East Africa, faces a rising burden of chronic kidney disease (CKD), with an estimated 12,500 individuals suffering from end-stage renal disease (ESRD). Renal transplantation—the preferred treatment option for ESRD, remains underutilized. Since the first transplant in 1978, seven centers have been established, with 829 transplants performed by 2022. Living-related renal transplants (LRRT) dominate, while deceased donor renal transplantation (DDRT) is yet to be implemented. Recent data show improved outcomes, with one-year graft survival rates up to 96%, but challenges such as acute rejection rates (32.8%) and limited donor outcome data persist. Barriers include high costs, limited insurance coverage, inadequate laboratory infrastructure, and a transplant workforce shortage. Efforts to establish DDRT programs are underway but are hampered by the absence of organ procurement systems and insufficient laboratory capabilities. Future priorities include reducing costs and expanded insurance coverage for transplant care. Investments in laboratory infrastructure, local tissue typing, and surgical training are essential. Strengthening international collaborations and public education campaigns can improve donor pools and transplantation access. Strategic policy reforms and resource allocation are vital to scaling up Kenya’s kidney transplant program and addressing the unmet needs of its ESRD population.展开更多
BACKGROUND In France,nitazoxanide is available through compassionate use authorization,as there is no summary of product characteristics for this medication.However,it has been marketed in the United States for severa...BACKGROUND In France,nitazoxanide is available through compassionate use authorization,as there is no summary of product characteristics for this medication.However,it has been marketed in the United States for several years,with evidence supporting its use in the treatment of chronic norovirus infections in immunocompromised individuals.Due to its limited use,data on the efficacy and safety of this drug remain sparse.CASE SUMMARY We report the case of a 79-year-old immunocompromised patient,a renal transplant recipient undergoing treatment with mycophenolate mofetil and tacrolimus,who developed toxic agranulocytosis,as absolute neutrophil count dropped from 2.93 G/L to 0.09 G/L within 17 days following the introduction of nitazoxanide for the treatment of chronic diarrhea caused by norovirus infection.Clinical and laboratory findings suggest a toxic mechanism,most likely attributable to nitazoxanide.CONCLUSION This case highlights the potential of nitazoxanide to induce dose-dependent toxic agranulocytosis.While this adverse effect does not necessarily contraindicate reintroduction of the drug,it underscores the necessity for close hematological monitoring in such cases.展开更多
Objective To predict the autophagy-related pathogenesis and key diagnostic genes of diabetic kidney disease(DKD)through bioinformatics analysis,and to identify related Chinese medicines.Methods Data from sequencing mi...Objective To predict the autophagy-related pathogenesis and key diagnostic genes of diabetic kidney disease(DKD)through bioinformatics analysis,and to identify related Chinese medicines.Methods Data from sequencing microarrays GSE30528,GSE30529,and GSE1009 in the Gene Expression Omnibus(GEO)were employed.Differentially expressed genes(DEGs)with adjusted P<0.05 from GSE30528 and GSE30529 were identified.Combining these DEGs with the human autophagy gene database,Gene Ontology(GO),Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses,and protein-protein interaction(PPI)network analysis were conducted on the obtained DKD autophagy-related genes.Subsequently,the least absolute shrinkage and selection operator(LASSO)regression and support vector machinerecursive feature elimination(SVM-RFE)algorithms were adopted to select autophagy-related genes.The diagnostic capability of these genes was assessed through analysis with the external validation set from microarray GSE1009,and relevant Chinese medicines were inversely predicted using the SymMap database.Results A total of 2014 DEGs were selected from GSE30528 and GSE30529,leading to the identification of 37 DKD autophagy-related genes.GO analysis indicated 681 biological mechanisms,including autophagy regulation and plasma membrane microdomain activity.KEGG enrichment analysis identified 112 related signaling pathways.PPI network analysis showed a marked enrichment of autophagy-related genes in DKD.Through LASSO regression and SVM-RFE,four core diagnostic genes for autophagy in DKD were identified:protein phosphatase 1 regulatory subunit 15A(PPP1R15A),hypoxia inducible factor 1 alpha subunit(HIF1α),deleted in liver cancer 1(DLC1),and ceroid lipofuscinosis neuronal 3(CLN3).The external validation set demonstrated high diagnostic efficiency for these genes.Finally,146 kinds of potential Chinese medicines were predicted using the SymMap database,with heatclearing and detoxifying medicine and blood-activating and stasis-eliminating medicine accounting for the largest proportion(25/146 and 13/146,respectively).Conclusion This study analyzed and validated bioinformatics sequencing databases to elucidate the potential molecular mechanisms of DKD autophagy and predicted key diagnostic genes,potential therapeutic targets,and related Chinese medicines,laying a solid foundation for clinical research and application.展开更多
OBJECTIVE:To investigate the impact of Shenhua tablet(肾华片,SHT)on renal macrophage polarization and renal injury in mice with diabetic kidney disease(DKD)and to explore the potential mechanism involving the hypoxia-...OBJECTIVE:To investigate the impact of Shenhua tablet(肾华片,SHT)on renal macrophage polarization and renal injury in mice with diabetic kidney disease(DKD)and to explore the potential mechanism involving the hypoxia-inducible factor-1α(HIF-1α)and pyruvate kinase M2(PKM2)signaling pathway,along with the glycolysis metabolism pathway.METHODS:The animals were divided into the following groups:Model,Control,dapagliflozin,SHT low-dose,SHT medium-dose,and SHT high-dose.We assessed 24-hour urine protein(24 h-UTP)levels,urinary albuminto-creatinine ratio,and regularly monitored fasting blood glucose during the treatment period.After treatment,we examined renal tissue structure,renal function(urea nitrogen,uric acid,creatinine,cystatin C,β2-microglobulin),and glycolysis in renal macrophages.Additionally,we observed macrophage polarization in renal tissue and measured inflammatory factors(tumor necrosis factor-α,interleukin-1β,interleukin-6,interleukin-10,monocyte chemoattractant protein-1)to assess the immunoinflammatory status of the renal tissue.Finally,we investigated the expression of the HIF-1α/PKM2 signaling pathway in macrophages to explore its role in the glycolysis process.RESULTS:SHT shows a beneficial effect in treating DKD by reducing 24 h-UTP,regulating blood glucose levels,improving renal tissue structure,protecting renal function,inhibiting macrophage glycolysis,reducing macrophage transformation to the M1 state,and suppressing the expression of the HIF-1α/PKM2 signaling pathway.CONCLUSION:SHT may exert renoprotective effects by inhibiting macrophage glycolysis via the HIF-1α/PKM2 signaling pathway.This inhibition decreases macrophage M1 polarization and reduces immunoinflammatory injury in the renal tissue of DKD mice.展开更多
BACKGROUND Pediatric kidney transplantation is the treatment of choice for children with endstage renal disease;however,access to transplantation remains limited in lowand middle-income countries.Uzbekistan had no pri...BACKGROUND Pediatric kidney transplantation is the treatment of choice for children with endstage renal disease;however,access to transplantation remains limited in lowand middle-income countries.Uzbekistan had no prior institutional experience in performing pediatric living donor kidney transplantation(LDKT).AIM To report the implementation,surgical protocols,and clinical outcomes of the first pediatric LDKT program in Uzbekistan.METHODS This retrospective single-center study analyzed the first 20 pediatric LDKTs performed between April 2023 and February 2025.All donors were related family members who underwent either open or laparoscopic hand-assisted nephrectomy.Pre-transplant immunologic workup included HLA typing and anti-HLA antibody screening using solid-phase assays.Perioperative management was guided by Enhanced Recovery After Surgery Society principles.Primary outcomes included operative metrics,perioperative complications,graft function,biopsyproven rejection,and patient/graft survival.Statistical analysis utilized descriptive statistics,Kaplan–Meier survival estimates,and Fisher’s exact test where applicable.RESULTS Donors included 13 women and 7 men(median age:38 years;range:31–50).Median operative times were 182.5 minutes for open nephrectomy and 198.5 minutes for laparoscopic nephrectomy.No major intraoperative complications occurred;one donor developed a postoperative wound seroma.All recipients(aged 87–207 months)exhibited immediate graft function,with no delayed graft function observed.Median cold and warm ischemia times were 15 minutes(range:10–138)and 35 minutes(range:18–40),respectively.Median serum creatinine decreased from 198μmol/L on postoperative day 1 to 54μmol/L by day 7.Three rejection episodes were reported,two of which occurred in sensitized recipients.Two graft losses were attributed to late rejection.One patient died from hemorrhagic stroke six months post-transplant.At 24 months,patient and graft survival rates were 95%and 90%,respectively.CONCLUSION The successful implementation of a pediatric living donor kidney transplantation program in Uzbekistan yielded favorable short-and intermediate-term outcomes,with high graft survival and low complication rates.This experience may provide a practical framework for initiating similar programs in other resource-constrained healthcare settings.展开更多
Antibody-mediated rejection(ABMR)and recurrent primary renal disease(PRD)represent major causes of kidney transplant(KT)loss.The standard of care for desensitization,ABMR,and relapsing autoimmune glomerulopathies or n...Antibody-mediated rejection(ABMR)and recurrent primary renal disease(PRD)represent major causes of kidney transplant(KT)loss.The standard of care for desensitization,ABMR,and relapsing autoimmune glomerulopathies or nephrotic syndrome includes apheresis for antibody removal and polyclonal immunoglobulin for antibody blockage.Although frequently used to achieve B-cell depletion,the administration of the type 1 anti-CD20 monoclonal antibodies(mAb)rituximab(RTX)or ofatumumab(OFA)has failed to demonstrate a significant survival benefit.Obinutuzumab(OBI)is a humanized glycoengineered type 2 anti-CD20 mAb.Compared to RTX or OFA,OBI-induced B-cell depletion is not related to complement-dependent cytotoxicity,mostly operating through antibody-dependent cell-mediated cytotoxicity,antibody-dependent phagocytosis,and direct cell death.These characteristics could play a pivotal role in the development of new anti-rejection strategies,enabling the simultaneous administration of complement inhibitors and B-cell-depleting agents.OBI has also demonstrated more powerful peripheral and central B-cell depletion capacities than RTX,with enhanced effects on memory B cells and plasmablasts.In patients with autoimmune glomerulopathies or multidrug-dependent nephrotic syndrome,OBI has shown encouraging results,representing a potential evolution of the treatment of post-transplant relapsing PRD.The present review summarizes the current knowledge on OBI use in KT setting.展开更多
BACKGROUND Kidney transplant recipients(KTRs)are most vulnerable to infection in the first year after transplantation.Tixagevimab and cilgavimab are neutralizing monoclonal antibodies directed against different epitop...BACKGROUND Kidney transplant recipients(KTRs)are most vulnerable to infection in the first year after transplantation.Tixagevimab and cilgavimab are neutralizing monoclonal antibodies directed against different epitopes of the receptor-binding domain of the severe acute respiratory syndrome coronavirus 2 spike protein.The purpose of this study is to report experience with tixagevimab/cilgavimab administered to KTRs who were within 1 year of transplantation.AIM To describe outcomes of KTRs who received tixagevimab/cilgavimab early posttransplant to prevent coronavirus disease 2019(COVID-19).METHODS This is a single-center retrospective cohort study of adult KTRs who underwent kidney transplantation from January 1,2022 to September 30,2022 and received tixagevimab/cilgavimab 300 mg/300 mg for prevention of COVID-19.Outcomes of interest were adverse events associated with tixagevimab/cilgavimab,COVID-19 breakthrough infection and COVID-19-associated hospitalization and complications.We also conducted a systematic review of the literature for the use of tixagevimab/cilgavimab as pre-exposure prophylaxis for COVID-19 in solid organ transplant recipients(SOTRs)from inception to December 31,2023.RESULTS There were 104 patients included with median age of 50 years(range 21-72 years).Omicron strain of the COVID-19 virus was the predominantly circulating variant at the time of current study.Patients testing positive for COVID-19 were given tixagevimab/cilgavimab for prophylaxis of complications during the median of 3 days(range 0-201 days)after kidney transplant,of whom 97(93.3%)received the antibodies prior to discharge.No discernable adverse effects attributable to the medication were observed during the time they received prophylaxis.The efficacy of the drug assessed through the absence of breakthrough infections were observed in 91 patients.13(12.5%)patients developed COVID-19 breakthrough infections during an overall median follow-up period of 125 days(range 10-257 days)after tixagevimab/cilgavimab.These infections were observed at median 105 days(range 6-211 days)after receiving the prophylactic medication.5(4.8%)of overall patients required hospitalization and there were no reported deaths in the cohort.Findings of the systematic review were consistent with our findings wherein tixagevimab/cilgavimab was well tolerated by SOTRs.CONCLUSION Tixagevimab/cilgavimab has a favorable safety profile when administered in newly transplanted kidney recipients.Although breakthrough infections were not uncommon,there was a low rate of hospitalization and no deaths.This study highlights the need to examine the efficacy of novel monoclonal antibodies administered for COVID-19 prophylaxis in newly transplanted recipients.展开更多
Objective:To investigate the mechanism by which advanced glycation end products(AGEs)promote diabetic kidney disease fibrosis by regulating the tyrosine phosphatase SHP1/SHP2 balance and activating the epidermal growt...Objective:To investigate the mechanism by which advanced glycation end products(AGEs)promote diabetic kidney disease fibrosis by regulating the tyrosine phosphatase SHP1/SHP2 balance and activating the epidermal growth factor receptor(EGFR)pathway.Methods:Animal experiments and in vitro cell experiments were conducted using Western blot analysis and tissue cell staining to detect the expression of relevant proteins and cellular morphological changes.Results:AGEs disrupt the SHP1/SHP2 balance,activate the EGFR and TGFβpathways,and promote fibrosis in diabetic nephropathy.Conclusion:AGEs regulate the balance of tyrosine phosphatases SHP1/SHP2,activate the EGFR-mediated signaling pathway,promote the release of inflammatory factors,and ultimately lead to fibrosis in diabetic nephropathy through a novel mechanism.展开更多
BACKGROUND Hyperphosphatemia(HP)is a common complication in an advanced stage of chronic kidney disease(CKD)and is associated with cardiovascular issues,metabolic bone abnormalities and worsening of secondary hyperpar...BACKGROUND Hyperphosphatemia(HP)is a common complication in an advanced stage of chronic kidney disease(CKD)and is associated with cardiovascular issues,metabolic bone abnormalities and worsening of secondary hyperparathyroidism.Most patients on dialysis require phosphate binders to control HP.Sucroferric oxyhydroxide(SO)(Dynulta^(TM))is a calcium-free,polynuclear iron(III)based oral phosphate binder,for the treatment of HP.In this phase IV,open-label,singlearm,multi-center,12-week,SOLO CKD study evaluated efficacy and safety of Dynulta^(TM)in Indian CKD patients undergoing hemodialysis.AIM To investigate the efficacy,safety and tolerability of SO Chewable Tablet(Dynulta^(TM))in patients with CKD on hemodialysis.METHODS Hyperphosphatemic patients on hemodialysis and fulfilling eligibility criteria were included in the study for at least 12 weeks and received SO 1500 mg chewable tablet per day.The key endpoint was change in mean serum phosphorus levels after 12 weeks.Data were analysed using analysis of variance,Paired test,Wilcoxon test,and post-hoc comparisons,with P<0.05 considered statistically significant,using Graph Pad software.RESULTS A total of 114 patients were enrolled and 94 patients completed the study.The mean±SD serum phosphorous level was reduced from 7.62 mg/dL±2.02 mg/dL at baseline to 5.13 mg/dL±1.88 mg/dL after 12 weeks of treatment.At each follow-up visit,the reduction in mean serum phosphorous levels was statistically significant(P value<0.05)compared to baseline,confirming the efficacy of SO.A total of 33.33%of patients experienced adverse events(AEs).The most frequently reported AEs were pyrexia,nasopharyngitis and headache,which were considered unlikely to be related to the study drug treatment.No serious AEs was reported during the study period and no patients discontinued treatment due to AEs.CONCLUSION This first real-world study in Indian CKD patients on hemodialysis shows SO as a safe,and effective monotherapy for HP,though its small sample size limits generalizability.展开更多
BACKGROUND Descending thoracic aortic aneurysms are dangerous and have to be treated quickly.The primary treatment methods are thoracic endovascular aortic repair(TEVAR)and open surgical repair(OSR).The comparative ef...BACKGROUND Descending thoracic aortic aneurysms are dangerous and have to be treated quickly.The primary treatment methods are thoracic endovascular aortic repair(TEVAR)and open surgical repair(OSR).The comparative effectiveness and safety of TEVAR and OSR were evaluated in this meta-analysis,focusing on perioperative and long-term outcomes.AIM To compare and contrast the efficacy and safety of TEVAR vs OSR in the treatment of descending thoracic aortic aneurysms.This study aims to assess both perioperative and long-term outcomes through a systematic review and metaanalysis.METHODS A comprehensive search of PubMed,EMBASE,and Cochrane was conducted from inception to January 2025.Baseline characteristics and outcomes were evaluated.Odds ratios(OR)for dichotomous data and mean differences for continuous data with 95%confidence intervals(CI)were analyzed using random-effects models.RESULTS A meta-analysis of 21 studies involving 29465 patients(8261 TEVAR;21204 OR)showed TEVAR associated with lower operative mortality(OR=0.60,95%CI:0.42-0.85,P=0.004),shorter intensive care unit(-2.94 days,95%CI:-4.76 to-1.12,P=0.002)and hospital stays(-7.35 days,95%CI:-10.54 to-4.17,P<0.00001),and reduced rates of paraplegia(OR=0.44,95%CI:0.27-0.73,P=0.002),spinal ischemia(OR=0.30,95%CI:0.16-0.56,P=0.0002),renal failure(OR=0.29,95%CI:0.14-0.61,P=0.001),and wound infections(OR=0.28,95%CI:0.13-0.61,P=0.001).However,TEVAR had higher rates of vascular complications.No significant differences were noted in 1-year and 5-year mortality rates,the rate of non-elective surgery,neurological complications,or stroke rates.CONCLUSION Compared to EVAR,TEVAR revealed lower operative mortality and better perioperative outcomes across all indicators,including hospital and intensive care unit stays,as well as fewer complications,except for those related to vascular problems.Mortality results were also similar in the long run;consequently,more research is required concerning the long-term durability.展开更多
BACKGROUND Tacrolimus(TAC)is metabolized primarily by the CYP3A-encoded enzyme family(CYP3A4,CYP3A5,and CYP3A7).Individuals expressing the CYP3A51 allele are considered fast metabolizers and generally require higher T...BACKGROUND Tacrolimus(TAC)is metabolized primarily by the CYP3A-encoded enzyme family(CYP3A4,CYP3A5,and CYP3A7).Individuals expressing the CYP3A51 allele are considered fast metabolizers and generally require higher TAC doses to reach therapeutic levels.AIM To evaluate the predictive value of the TAC concentration-to-dose(C0/D)ratio for identifying CYP3A5 poly-morphisms in renal transplant recipients.METHODS Eighty-six de novo kidney transplant recipients with TAC-based immunosuppression from the Department of Nephrology and Dialysis at Military Hospital 103(Hanoi,Vietnam)were included in this retrospective study.Blood samples were collected within the first week post-transplantation to monitor TAC levels and to perform genotyping for CYP3A5 genetic polymorphisms.RESULTS The CYP3A53/3 genotype was identified in 37 patients(43%),CYP3A51/3 in 40 patients(46.5%),and CYP3A51/1 in 9 patients(10.5%).Patients carrying the CYP3A51/3 or CYP3A51/1 genotype,classified as fast metabolizers(CYP3A5 expressers),had significantly lower TAC C0 concentrations and C0/D ratios compared to slow meta-bolizers(CYP3A53/3 genotype)at multiple time points during follow-up(all P<0.001).Notably,the TAC C0/D ratio obtained on day 1(0.91)was shown to predict CYP3A5 polymorphism with a sensitivity of 84.6%and a specificity of 84.6%.CONCLUSION This study demonstrates that the TAC C0/D ratio provides a reliable predictive value for CYP3A5 polymorphisms,which can be used to individualize TAC dosing in renal transplant recipients in Vietnam and other low-income countries.展开更多
Acute kidney injury(AKI)is a prevalent clinical syndrome characterized by a rapid loss of renal filtration function,with high incidence and mortality rates that are steadily rising.AKI not only affects the shortterm p...Acute kidney injury(AKI)is a prevalent clinical syndrome characterized by a rapid loss of renal filtration function,with high incidence and mortality rates that are steadily rising.AKI not only affects the shortterm prognosis of patients but also considerably raises the risk of progression to chronic kidney disease and end-stage renal disease,making it a significant threat to human health.Nanomedicine offers innovative therapeutic strategies for AKI and shows considerable potential in its treatment.This review comprehensively summarizes the application of nanomedicines in AKI therapy,with a particular focus on recent advances in the development of antioxidant,anti-inflammatory,and combined nanomedicine-based therapies targeting oxidative stress and inflammation,two primary pathological features of AKI.Additionally,this review also summarizes recent progress in AKI model construction to facilitate a better understanding and investigation of AKI.Overall,the review provides insights into innovative nanomedicine application in the effective treatment of AKI,hoping to provide new ideas for the clinical treatment of AKI.展开更多
BACKGROUND The NOD-like receptor thermal protein domain associated protein 3(NLRP3)inflammasome may play an important role in diabetic kidney disease(DKD).However,the exact link remains unclear.AIM To investigate the ...BACKGROUND The NOD-like receptor thermal protein domain associated protein 3(NLRP3)inflammasome may play an important role in diabetic kidney disease(DKD).However,the exact link remains unclear.AIM To investigate the role of the NLRP3 inflammasome in DKD.METHODS Using datasets from the Gene Expression Omnibus database,30 NLRP3 inflammasome-related genes were identified.Differentially expressed genes were selected using differential expression analysis,whereas intersecting genes were selected based on overlapping differentially expressed genes and NLRP3 inflammasome-related genes.Subsequently,three machine learning algorithms were used to screen genes,and biomarkers were identified by overlapping the genes from the three algorithms.Potential biomarkers were validated by western blotting in a db/db mouse model of diabetes.RESULTS Two biomarkers,sirtuin 2(SIRT2)and caspase 1(CASP1),involved in the Leishmania infection pathway were identified.Both biomarkers were expressed in endothelial cells.Pseudo-temporal analysis based on endothelial cells showed that DKD mostly occurs during the mid-differentiation stage.Western blotting results showed that CASP1 expression was higher in the DKD group than in the control group(P<0.05),and SIRT2 content decreased(P<0.05).CONCLUSION SIRT2 and CASP1 provide a potential theoretical basis for DKD treatment.展开更多
Dear Editor,Heart failure(HF)is a common multi-faceted and life-threatening syndrome,of which up to 23%occur acute kidney injury(AKI)[1].HF-related AKI is largely overlooked or delayed in identification[2].Approximate...Dear Editor,Heart failure(HF)is a common multi-faceted and life-threatening syndrome,of which up to 23%occur acute kidney injury(AKI)[1].HF-related AKI is largely overlooked or delayed in identification[2].Approximately 85%of AKI cases that occurred during cardiac hospitalization in China were either ignored or identifi ed too late[3].Currently,there are no specific guidelines for the management of HF-related AKI.Hence,it is essential to identify patients at the risk of developing AKI and intervene promptly.展开更多
AIM To review negative pressure wound therapy(NPWT) as animportant addition to the conventional methods of wound management.METHODS A systematic review, performed by searching the PubM ed, EMBASE and Cochrane Library ...AIM To review negative pressure wound therapy(NPWT) as animportant addition to the conventional methods of wound management.METHODS A systematic review, performed by searching the PubM ed, EMBASE and Cochrane Library databases, showed 11 case reports comprising a total of 22 kidney transplantation(KT) patients(range, 1 to 9), who were treated with NPWT. Application of NPWT was associated with successful healing of wounds, leg ulcer, lymphocele and urine leak from ileal conduit.RESULTS No complications related to NPWT were reported. However, there was paucity of robust data on the effectiveness of NPWT in KT recipients; therefore, prospective studies assessing its safety and efficacy of NPWT and randomised trials comparing the effectiveness of NPWT with alternative modalities of wound management in KT recipients is recommended.CONCLUSION Negative pressure incision management system, NPWT with instillation and endoscopic vacuum-assisted closure system are in investigational stage.展开更多
OBJECTIVE: To analyze the distribution of Traditional Chinese medicine(TCM) syndromes in patients with diabetic kidney disease(DKD) and its related factors.METHODS: We enrolled 435 patients with DKD, who were not unde...OBJECTIVE: To analyze the distribution of Traditional Chinese medicine(TCM) syndromes in patients with diabetic kidney disease(DKD) and its related factors.METHODS: We enrolled 435 patients with DKD, who were not undergoing dialysis, admitted to the Department of Nephrology, First Medical Center, Chinese PLA General Hospital from April 2020 to August 2021.Analysis of their TCM syndromes and related factors was carried out.RESULTS: The 435 patients included 109, 117, 86, and 123 chronic kidney disease(CKD) 1-2, CKD3, CKD4, and CKD5 cases, respectively. With the progression of CKD1-5, the proportion of Yin deficiency and dry heat syndrome,and that of Qi and Yin deficiency syndrome showed a downward trend, whereas the proportion of spleen-kidney Yang deficiency, blood deficiency, blood stasis, water stagnation, and phlegm turbidity syndromes showed an upward trend;the differences were statistically significant(P < 0.05). Multivariate logistic regression analysis showed that Yin deficiency and dry heat syndrome was positively correlated with hemoglobin [odds ratio(OR) =1.022, P = 0.005], albumin(OR = 1.058, P = 0.006), and estimated glomerular filtration rate(eGFR)(OR = 1.020,P < 0.001) but negatively correlated with male sex(OR =0.277, P = 0.004). Qi and Yin deficiency syndrome was positively correlated with albumin(OR = 1.056, P < 0.001)and eGFR(OR = 1.008, P = 0.022) but negatively correlated with age(OR = 0.977, P = 0.023). Liver-kidney Yin deficiency syndrome was positively correlated with age(OR = 1.028, P = 0.021) and glycosylated hemoglobin(OR = 1.223, P = 0.007) but negatively correlated with total cholesterol(OR = 0.792, P = 0.006).Spleen-kidney Yang deficiency syndrome was negatively correlated with hemoglobin(OR = 0.977, P < 0.001),albumin(OR = 0.891, P < 0.001), and eGFR(OR = 0.978,P < 0.001) but positively correlated with high density lipoprotein(OR = 3.376, P = 0.001). CONCLUSION: With CKD1-5 progression, TCM syndromes changed from Yin deficiency and dry heat syndrome to syndrome of deficiency of both Qi and Yin, liver-kidney Yin, and spleen-kidney Yang deficiency syndromes. TCM syndromes were correlated with laboratory test results.展开更多
文摘BACKGROUND Transplant teams often hesitate to use the right kidney(RK)in living donor(LD)transplants due to the complexities of anastomosing the short,thin-walled right renal veins,which can potentially lead to graft loss or graft dysfunction.Nevertheless,circumstances may arise where selecting the RK over the left kidney(LK)is unavoidable.Consequently,it is crucial to thoroughly examine the implications of such a choice on the overall transplant outcome.AIM To compare transplant outcomes between recipients of RK and LK while examining the factors that influence these outcomes.METHODS We retrospectively analyzed data from adult patients who received LD kidney transplants involving meticulous patient selection and surgical techniques at our center from January 2020 to December 2023.We included all kidney donors who were over 18,fit to donate,and had undergone diethylenetriamine pentaacetic acid split function and/or computed tomography based volumetry.The variables examined comprised donor and recipient demographics,and outcome measures included technical graft loss(TGL),delayed or slow graft function(SGF),and post-transplant serum creatinine(SC)trends.We used a logistic regression model to assess the likelihood of adverse outcomes considering the donor kidney side.RESULTS Of the 250 transplants performed during the period,56(22%)were RKs.The recipient demographics and transplant factors were comparable for the right and LKs,except that the donor warm and cold ischemia time were shorter for RKs.TGL and SGF each occurred in 2%(n=1)of RKs and 0.5%(n=1)of LKs,the difference being insignificant.These complications,however,were not related to the venous anastomosis.One RK(2%)developed delayed graft function after 48 hours,which was attributable to postoperative hypoxia rather than the surgical technique.The post-transplant SC trend and mean SC at the last follow-up were similar across both kidney sides.CONCLUSION The donor kidney side has little impact on post-transplant adverse events and graft function in LD transplants,provided that careful patient selection and precise surgical techniques are employed.
文摘Chronic kidney disease(CKD),which represents a significant global health concern,is characterized by a gradual decline in kidney function,leading to complications such as electrolyte imbalance,cardiovascular disease,and immune dysfunction.Standard CKD management includes dietary modifications,ketoana-logues supplementation,blood pressure and blood glucose control,hydration maintenance,and treatment of the underlying causes.Emerging evidence has indicated a significant role of the gut microbiota in CKD,and that dysbiosis of the gut microbiota contributes to the progression of CKD towards end-stage renal disease.Probiotics and prebiotics have recently garnered attention owing to their potential to enhance gastrointestinal health and well-being by restoring the balance of the gut microbiota.Specific probiotic strains,including Lactobacillus and Bifidobacterium,promote beneficial bacterial growth,suppress harmful bacteria,and exert anti-inflammatory,antihypertensive,and antidiabetic effects.The combination of Streptococcus thermophilus,Lactobacillus acidophilus,Bifidobacterium longum,and Bacillus coagulans has demonstrated potential as a therapeutic formulation for CKD management in various studies,highlighting its promise in treating CKD;however,supporting evidence remains limited,making it crucial to conduct further investigations to determine the specific effects of different probiotic formulations on outcomes in patients with CKD.
文摘Khan et al’single-centre,retrospective study on the use of right or left kidneys in living-donor renal transplantation,offers the opportunity to further discuss a complex and debated topic in clinical transplantation.In brief,the authors confirm that,despite the historical preference for left kidneys,attributed to their anatomical advantages during donor nephrectomy and recipient transplantation,right kidneys can provide excellent outcomes when donors and recipients are carefully selected,and a meticulous surgical technique is applied in every step of the process.Usefully,the article includes some practical tips to help less experienced surgeons address the technical challenges of right kidney transplantation,such as extended renal vein dissection or full mobilization of the iliac vein of the recipient to minimize tension during anastomosis.Although limited by the selective use of minimally invasive(MI)nephrectomy for left kidneys,this work underscores the importance of expanding the living-donor pool,challenging the traditional taboos,and facilitating access to transplantation for a wider population of patients around the globe.Properly designed studies with larger sample size,comparable MI surgical techniques,prospective data collection,and long-term donor and recipient outcomes are warranted.
文摘BACKGROUND Transplantectomy has long been considered the preferred treatment for spontaneous renal graft rupture,prioritizing patient safety over kidney salvage.In the last decade,there has been an increasing number of reports showing that,in selected scenarios,conservative management through graft repair represents a feasible option,challenging traditional approaches.CASE SUMMARY We describe the case of a 37-year-old sensitized XY patient who experienced early spontaneous graft rupture after receiving his second deceased donor kidney transplant.Following temporary hemodynamic stabilization and abdominal contrast enhanced computed tomography scan assessment,the recipient was brought back to theatre for surgical exploration.Possible causes of irreversible graft damage were immediately ruled out.The fractured upper pole of the transplanted kidney was repaired using a fibrin sealant,external compression,and a tailored polyglactin 910 mesh wrapped around the graft.The post-operative course was uneventful.After 20 months of follow up,the patient is doing very well,with excellent renal function and complete reabsorption of the mesh,as demonstrated by serial ultrasound evaluations of the graft.CONCLUSION Amid organ shortages and sensitized patients,graft nephrectomy is reserved for severe injuries;repair using sealants and mesh is effective.
文摘Kenya, a lower-middle-income country in East Africa, faces a rising burden of chronic kidney disease (CKD), with an estimated 12,500 individuals suffering from end-stage renal disease (ESRD). Renal transplantation—the preferred treatment option for ESRD, remains underutilized. Since the first transplant in 1978, seven centers have been established, with 829 transplants performed by 2022. Living-related renal transplants (LRRT) dominate, while deceased donor renal transplantation (DDRT) is yet to be implemented. Recent data show improved outcomes, with one-year graft survival rates up to 96%, but challenges such as acute rejection rates (32.8%) and limited donor outcome data persist. Barriers include high costs, limited insurance coverage, inadequate laboratory infrastructure, and a transplant workforce shortage. Efforts to establish DDRT programs are underway but are hampered by the absence of organ procurement systems and insufficient laboratory capabilities. Future priorities include reducing costs and expanded insurance coverage for transplant care. Investments in laboratory infrastructure, local tissue typing, and surgical training are essential. Strengthening international collaborations and public education campaigns can improve donor pools and transplantation access. Strategic policy reforms and resource allocation are vital to scaling up Kenya’s kidney transplant program and addressing the unmet needs of its ESRD population.
文摘BACKGROUND In France,nitazoxanide is available through compassionate use authorization,as there is no summary of product characteristics for this medication.However,it has been marketed in the United States for several years,with evidence supporting its use in the treatment of chronic norovirus infections in immunocompromised individuals.Due to its limited use,data on the efficacy and safety of this drug remain sparse.CASE SUMMARY We report the case of a 79-year-old immunocompromised patient,a renal transplant recipient undergoing treatment with mycophenolate mofetil and tacrolimus,who developed toxic agranulocytosis,as absolute neutrophil count dropped from 2.93 G/L to 0.09 G/L within 17 days following the introduction of nitazoxanide for the treatment of chronic diarrhea caused by norovirus infection.Clinical and laboratory findings suggest a toxic mechanism,most likely attributable to nitazoxanide.CONCLUSION This case highlights the potential of nitazoxanide to induce dose-dependent toxic agranulocytosis.While this adverse effect does not necessarily contraindicate reintroduction of the drug,it underscores the necessity for close hematological monitoring in such cases.
基金National Natural Science Foundation of China(82170747),and Shanghai Key Laboratory of Traditional Chinese Clinical Medicine(20DZ2272200).
文摘Objective To predict the autophagy-related pathogenesis and key diagnostic genes of diabetic kidney disease(DKD)through bioinformatics analysis,and to identify related Chinese medicines.Methods Data from sequencing microarrays GSE30528,GSE30529,and GSE1009 in the Gene Expression Omnibus(GEO)were employed.Differentially expressed genes(DEGs)with adjusted P<0.05 from GSE30528 and GSE30529 were identified.Combining these DEGs with the human autophagy gene database,Gene Ontology(GO),Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses,and protein-protein interaction(PPI)network analysis were conducted on the obtained DKD autophagy-related genes.Subsequently,the least absolute shrinkage and selection operator(LASSO)regression and support vector machinerecursive feature elimination(SVM-RFE)algorithms were adopted to select autophagy-related genes.The diagnostic capability of these genes was assessed through analysis with the external validation set from microarray GSE1009,and relevant Chinese medicines were inversely predicted using the SymMap database.Results A total of 2014 DEGs were selected from GSE30528 and GSE30529,leading to the identification of 37 DKD autophagy-related genes.GO analysis indicated 681 biological mechanisms,including autophagy regulation and plasma membrane microdomain activity.KEGG enrichment analysis identified 112 related signaling pathways.PPI network analysis showed a marked enrichment of autophagy-related genes in DKD.Through LASSO regression and SVM-RFE,four core diagnostic genes for autophagy in DKD were identified:protein phosphatase 1 regulatory subunit 15A(PPP1R15A),hypoxia inducible factor 1 alpha subunit(HIF1α),deleted in liver cancer 1(DLC1),and ceroid lipofuscinosis neuronal 3(CLN3).The external validation set demonstrated high diagnostic efficiency for these genes.Finally,146 kinds of potential Chinese medicines were predicted using the SymMap database,with heatclearing and detoxifying medicine and blood-activating and stasis-eliminating medicine accounting for the largest proportion(25/146 and 13/146,respectively).Conclusion This study analyzed and validated bioinformatics sequencing databases to elucidate the potential molecular mechanisms of DKD autophagy and predicted key diagnostic genes,potential therapeutic targets,and related Chinese medicines,laying a solid foundation for clinical research and application.
基金National Natural Science Foundation of China:Basic Research on the Mechanism of Organ Immune Damage and the Diagnosis and Treatment of Integrated Traditional Chinese and Western Medicine(No.32141005)。
文摘OBJECTIVE:To investigate the impact of Shenhua tablet(肾华片,SHT)on renal macrophage polarization and renal injury in mice with diabetic kidney disease(DKD)and to explore the potential mechanism involving the hypoxia-inducible factor-1α(HIF-1α)and pyruvate kinase M2(PKM2)signaling pathway,along with the glycolysis metabolism pathway.METHODS:The animals were divided into the following groups:Model,Control,dapagliflozin,SHT low-dose,SHT medium-dose,and SHT high-dose.We assessed 24-hour urine protein(24 h-UTP)levels,urinary albuminto-creatinine ratio,and regularly monitored fasting blood glucose during the treatment period.After treatment,we examined renal tissue structure,renal function(urea nitrogen,uric acid,creatinine,cystatin C,β2-microglobulin),and glycolysis in renal macrophages.Additionally,we observed macrophage polarization in renal tissue and measured inflammatory factors(tumor necrosis factor-α,interleukin-1β,interleukin-6,interleukin-10,monocyte chemoattractant protein-1)to assess the immunoinflammatory status of the renal tissue.Finally,we investigated the expression of the HIF-1α/PKM2 signaling pathway in macrophages to explore its role in the glycolysis process.RESULTS:SHT shows a beneficial effect in treating DKD by reducing 24 h-UTP,regulating blood glucose levels,improving renal tissue structure,protecting renal function,inhibiting macrophage glycolysis,reducing macrophage transformation to the M1 state,and suppressing the expression of the HIF-1α/PKM2 signaling pathway.CONCLUSION:SHT may exert renoprotective effects by inhibiting macrophage glycolysis via the HIF-1α/PKM2 signaling pathway.This inhibition decreases macrophage M1 polarization and reduces immunoinflammatory injury in the renal tissue of DKD mice.
文摘BACKGROUND Pediatric kidney transplantation is the treatment of choice for children with endstage renal disease;however,access to transplantation remains limited in lowand middle-income countries.Uzbekistan had no prior institutional experience in performing pediatric living donor kidney transplantation(LDKT).AIM To report the implementation,surgical protocols,and clinical outcomes of the first pediatric LDKT program in Uzbekistan.METHODS This retrospective single-center study analyzed the first 20 pediatric LDKTs performed between April 2023 and February 2025.All donors were related family members who underwent either open or laparoscopic hand-assisted nephrectomy.Pre-transplant immunologic workup included HLA typing and anti-HLA antibody screening using solid-phase assays.Perioperative management was guided by Enhanced Recovery After Surgery Society principles.Primary outcomes included operative metrics,perioperative complications,graft function,biopsyproven rejection,and patient/graft survival.Statistical analysis utilized descriptive statistics,Kaplan–Meier survival estimates,and Fisher’s exact test where applicable.RESULTS Donors included 13 women and 7 men(median age:38 years;range:31–50).Median operative times were 182.5 minutes for open nephrectomy and 198.5 minutes for laparoscopic nephrectomy.No major intraoperative complications occurred;one donor developed a postoperative wound seroma.All recipients(aged 87–207 months)exhibited immediate graft function,with no delayed graft function observed.Median cold and warm ischemia times were 15 minutes(range:10–138)and 35 minutes(range:18–40),respectively.Median serum creatinine decreased from 198μmol/L on postoperative day 1 to 54μmol/L by day 7.Three rejection episodes were reported,two of which occurred in sensitized recipients.Two graft losses were attributed to late rejection.One patient died from hemorrhagic stroke six months post-transplant.At 24 months,patient and graft survival rates were 95%and 90%,respectively.CONCLUSION The successful implementation of a pediatric living donor kidney transplantation program in Uzbekistan yielded favorable short-and intermediate-term outcomes,with high graft survival and low complication rates.This experience may provide a practical framework for initiating similar programs in other resource-constrained healthcare settings.
文摘Antibody-mediated rejection(ABMR)and recurrent primary renal disease(PRD)represent major causes of kidney transplant(KT)loss.The standard of care for desensitization,ABMR,and relapsing autoimmune glomerulopathies or nephrotic syndrome includes apheresis for antibody removal and polyclonal immunoglobulin for antibody blockage.Although frequently used to achieve B-cell depletion,the administration of the type 1 anti-CD20 monoclonal antibodies(mAb)rituximab(RTX)or ofatumumab(OFA)has failed to demonstrate a significant survival benefit.Obinutuzumab(OBI)is a humanized glycoengineered type 2 anti-CD20 mAb.Compared to RTX or OFA,OBI-induced B-cell depletion is not related to complement-dependent cytotoxicity,mostly operating through antibody-dependent cell-mediated cytotoxicity,antibody-dependent phagocytosis,and direct cell death.These characteristics could play a pivotal role in the development of new anti-rejection strategies,enabling the simultaneous administration of complement inhibitors and B-cell-depleting agents.OBI has also demonstrated more powerful peripheral and central B-cell depletion capacities than RTX,with enhanced effects on memory B cells and plasmablasts.In patients with autoimmune glomerulopathies or multidrug-dependent nephrotic syndrome,OBI has shown encouraging results,representing a potential evolution of the treatment of post-transplant relapsing PRD.The present review summarizes the current knowledge on OBI use in KT setting.
文摘BACKGROUND Kidney transplant recipients(KTRs)are most vulnerable to infection in the first year after transplantation.Tixagevimab and cilgavimab are neutralizing monoclonal antibodies directed against different epitopes of the receptor-binding domain of the severe acute respiratory syndrome coronavirus 2 spike protein.The purpose of this study is to report experience with tixagevimab/cilgavimab administered to KTRs who were within 1 year of transplantation.AIM To describe outcomes of KTRs who received tixagevimab/cilgavimab early posttransplant to prevent coronavirus disease 2019(COVID-19).METHODS This is a single-center retrospective cohort study of adult KTRs who underwent kidney transplantation from January 1,2022 to September 30,2022 and received tixagevimab/cilgavimab 300 mg/300 mg for prevention of COVID-19.Outcomes of interest were adverse events associated with tixagevimab/cilgavimab,COVID-19 breakthrough infection and COVID-19-associated hospitalization and complications.We also conducted a systematic review of the literature for the use of tixagevimab/cilgavimab as pre-exposure prophylaxis for COVID-19 in solid organ transplant recipients(SOTRs)from inception to December 31,2023.RESULTS There were 104 patients included with median age of 50 years(range 21-72 years).Omicron strain of the COVID-19 virus was the predominantly circulating variant at the time of current study.Patients testing positive for COVID-19 were given tixagevimab/cilgavimab for prophylaxis of complications during the median of 3 days(range 0-201 days)after kidney transplant,of whom 97(93.3%)received the antibodies prior to discharge.No discernable adverse effects attributable to the medication were observed during the time they received prophylaxis.The efficacy of the drug assessed through the absence of breakthrough infections were observed in 91 patients.13(12.5%)patients developed COVID-19 breakthrough infections during an overall median follow-up period of 125 days(range 10-257 days)after tixagevimab/cilgavimab.These infections were observed at median 105 days(range 6-211 days)after receiving the prophylactic medication.5(4.8%)of overall patients required hospitalization and there were no reported deaths in the cohort.Findings of the systematic review were consistent with our findings wherein tixagevimab/cilgavimab was well tolerated by SOTRs.CONCLUSION Tixagevimab/cilgavimab has a favorable safety profile when administered in newly transplanted kidney recipients.Although breakthrough infections were not uncommon,there was a low rate of hospitalization and no deaths.This study highlights the need to examine the efficacy of novel monoclonal antibodies administered for COVID-19 prophylaxis in newly transplanted recipients.
基金Baoding Municipal Science and Technology Plan Project(Project No.:2441ZF089)。
文摘Objective:To investigate the mechanism by which advanced glycation end products(AGEs)promote diabetic kidney disease fibrosis by regulating the tyrosine phosphatase SHP1/SHP2 balance and activating the epidermal growth factor receptor(EGFR)pathway.Methods:Animal experiments and in vitro cell experiments were conducted using Western blot analysis and tissue cell staining to detect the expression of relevant proteins and cellular morphological changes.Results:AGEs disrupt the SHP1/SHP2 balance,activate the EGFR and TGFβpathways,and promote fibrosis in diabetic nephropathy.Conclusion:AGEs regulate the balance of tyrosine phosphatases SHP1/SHP2,activate the EGFR-mediated signaling pathway,promote the release of inflammatory factors,and ultimately lead to fibrosis in diabetic nephropathy through a novel mechanism.
文摘BACKGROUND Hyperphosphatemia(HP)is a common complication in an advanced stage of chronic kidney disease(CKD)and is associated with cardiovascular issues,metabolic bone abnormalities and worsening of secondary hyperparathyroidism.Most patients on dialysis require phosphate binders to control HP.Sucroferric oxyhydroxide(SO)(Dynulta^(TM))is a calcium-free,polynuclear iron(III)based oral phosphate binder,for the treatment of HP.In this phase IV,open-label,singlearm,multi-center,12-week,SOLO CKD study evaluated efficacy and safety of Dynulta^(TM)in Indian CKD patients undergoing hemodialysis.AIM To investigate the efficacy,safety and tolerability of SO Chewable Tablet(Dynulta^(TM))in patients with CKD on hemodialysis.METHODS Hyperphosphatemic patients on hemodialysis and fulfilling eligibility criteria were included in the study for at least 12 weeks and received SO 1500 mg chewable tablet per day.The key endpoint was change in mean serum phosphorus levels after 12 weeks.Data were analysed using analysis of variance,Paired test,Wilcoxon test,and post-hoc comparisons,with P<0.05 considered statistically significant,using Graph Pad software.RESULTS A total of 114 patients were enrolled and 94 patients completed the study.The mean±SD serum phosphorous level was reduced from 7.62 mg/dL±2.02 mg/dL at baseline to 5.13 mg/dL±1.88 mg/dL after 12 weeks of treatment.At each follow-up visit,the reduction in mean serum phosphorous levels was statistically significant(P value<0.05)compared to baseline,confirming the efficacy of SO.A total of 33.33%of patients experienced adverse events(AEs).The most frequently reported AEs were pyrexia,nasopharyngitis and headache,which were considered unlikely to be related to the study drug treatment.No serious AEs was reported during the study period and no patients discontinued treatment due to AEs.CONCLUSION This first real-world study in Indian CKD patients on hemodialysis shows SO as a safe,and effective monotherapy for HP,though its small sample size limits generalizability.
文摘BACKGROUND Descending thoracic aortic aneurysms are dangerous and have to be treated quickly.The primary treatment methods are thoracic endovascular aortic repair(TEVAR)and open surgical repair(OSR).The comparative effectiveness and safety of TEVAR and OSR were evaluated in this meta-analysis,focusing on perioperative and long-term outcomes.AIM To compare and contrast the efficacy and safety of TEVAR vs OSR in the treatment of descending thoracic aortic aneurysms.This study aims to assess both perioperative and long-term outcomes through a systematic review and metaanalysis.METHODS A comprehensive search of PubMed,EMBASE,and Cochrane was conducted from inception to January 2025.Baseline characteristics and outcomes were evaluated.Odds ratios(OR)for dichotomous data and mean differences for continuous data with 95%confidence intervals(CI)were analyzed using random-effects models.RESULTS A meta-analysis of 21 studies involving 29465 patients(8261 TEVAR;21204 OR)showed TEVAR associated with lower operative mortality(OR=0.60,95%CI:0.42-0.85,P=0.004),shorter intensive care unit(-2.94 days,95%CI:-4.76 to-1.12,P=0.002)and hospital stays(-7.35 days,95%CI:-10.54 to-4.17,P<0.00001),and reduced rates of paraplegia(OR=0.44,95%CI:0.27-0.73,P=0.002),spinal ischemia(OR=0.30,95%CI:0.16-0.56,P=0.0002),renal failure(OR=0.29,95%CI:0.14-0.61,P=0.001),and wound infections(OR=0.28,95%CI:0.13-0.61,P=0.001).However,TEVAR had higher rates of vascular complications.No significant differences were noted in 1-year and 5-year mortality rates,the rate of non-elective surgery,neurological complications,or stroke rates.CONCLUSION Compared to EVAR,TEVAR revealed lower operative mortality and better perioperative outcomes across all indicators,including hospital and intensive care unit stays,as well as fewer complications,except for those related to vascular problems.Mortality results were also similar in the long run;consequently,more research is required concerning the long-term durability.
基金Supported by the Vietnam National Foundation for Science and Technology Development,No.NAFOSTED 04/2020/TN.
文摘BACKGROUND Tacrolimus(TAC)is metabolized primarily by the CYP3A-encoded enzyme family(CYP3A4,CYP3A5,and CYP3A7).Individuals expressing the CYP3A51 allele are considered fast metabolizers and generally require higher TAC doses to reach therapeutic levels.AIM To evaluate the predictive value of the TAC concentration-to-dose(C0/D)ratio for identifying CYP3A5 poly-morphisms in renal transplant recipients.METHODS Eighty-six de novo kidney transplant recipients with TAC-based immunosuppression from the Department of Nephrology and Dialysis at Military Hospital 103(Hanoi,Vietnam)were included in this retrospective study.Blood samples were collected within the first week post-transplantation to monitor TAC levels and to perform genotyping for CYP3A5 genetic polymorphisms.RESULTS The CYP3A53/3 genotype was identified in 37 patients(43%),CYP3A51/3 in 40 patients(46.5%),and CYP3A51/1 in 9 patients(10.5%).Patients carrying the CYP3A51/3 or CYP3A51/1 genotype,classified as fast metabolizers(CYP3A5 expressers),had significantly lower TAC C0 concentrations and C0/D ratios compared to slow meta-bolizers(CYP3A53/3 genotype)at multiple time points during follow-up(all P<0.001).Notably,the TAC C0/D ratio obtained on day 1(0.91)was shown to predict CYP3A5 polymorphism with a sensitivity of 84.6%and a specificity of 84.6%.CONCLUSION This study demonstrates that the TAC C0/D ratio provides a reliable predictive value for CYP3A5 polymorphisms,which can be used to individualize TAC dosing in renal transplant recipients in Vietnam and other low-income countries.
基金supported by the National Natural Science Foundation of China(Nos.82272147,32271450,U21A20417,31930067,82472138,32200323)the Science and Technology Project of Sichuan Province(Nos.2023YFS0118,2024YFFK0322)the China Postdoctoral Science Foundation(No.2023M732144)。
文摘Acute kidney injury(AKI)is a prevalent clinical syndrome characterized by a rapid loss of renal filtration function,with high incidence and mortality rates that are steadily rising.AKI not only affects the shortterm prognosis of patients but also considerably raises the risk of progression to chronic kidney disease and end-stage renal disease,making it a significant threat to human health.Nanomedicine offers innovative therapeutic strategies for AKI and shows considerable potential in its treatment.This review comprehensively summarizes the application of nanomedicines in AKI therapy,with a particular focus on recent advances in the development of antioxidant,anti-inflammatory,and combined nanomedicine-based therapies targeting oxidative stress and inflammation,two primary pathological features of AKI.Additionally,this review also summarizes recent progress in AKI model construction to facilitate a better understanding and investigation of AKI.Overall,the review provides insights into innovative nanomedicine application in the effective treatment of AKI,hoping to provide new ideas for the clinical treatment of AKI.
基金Joint Funds for the Innovation of Science and Technology,Fujian Province,No.2021Y9106Fujian Provincial Health Technology Project,No.2021GGA033the Natural Science Foundation of Fujian Province,No.2024J011234.
文摘BACKGROUND The NOD-like receptor thermal protein domain associated protein 3(NLRP3)inflammasome may play an important role in diabetic kidney disease(DKD).However,the exact link remains unclear.AIM To investigate the role of the NLRP3 inflammasome in DKD.METHODS Using datasets from the Gene Expression Omnibus database,30 NLRP3 inflammasome-related genes were identified.Differentially expressed genes were selected using differential expression analysis,whereas intersecting genes were selected based on overlapping differentially expressed genes and NLRP3 inflammasome-related genes.Subsequently,three machine learning algorithms were used to screen genes,and biomarkers were identified by overlapping the genes from the three algorithms.Potential biomarkers were validated by western blotting in a db/db mouse model of diabetes.RESULTS Two biomarkers,sirtuin 2(SIRT2)and caspase 1(CASP1),involved in the Leishmania infection pathway were identified.Both biomarkers were expressed in endothelial cells.Pseudo-temporal analysis based on endothelial cells showed that DKD mostly occurs during the mid-differentiation stage.Western blotting results showed that CASP1 expression was higher in the DKD group than in the control group(P<0.05),and SIRT2 content decreased(P<0.05).CONCLUSION SIRT2 and CASP1 provide a potential theoretical basis for DKD treatment.
基金supported by the National Key Research and Development Program of China(2021YFC2500200,2021YFC2500204)the Key Technologies Research and Development Program of Guangdong Province(2023B1111030004)the Guizhou Science and Technology Department(QKHPTRC2018-5636-2,QKHCG2023-ZD010).
文摘Dear Editor,Heart failure(HF)is a common multi-faceted and life-threatening syndrome,of which up to 23%occur acute kidney injury(AKI)[1].HF-related AKI is largely overlooked or delayed in identification[2].Approximately 85%of AKI cases that occurred during cardiac hospitalization in China were either ignored or identifi ed too late[3].Currently,there are no specific guidelines for the management of HF-related AKI.Hence,it is essential to identify patients at the risk of developing AKI and intervene promptly.
文摘AIM To review negative pressure wound therapy(NPWT) as animportant addition to the conventional methods of wound management.METHODS A systematic review, performed by searching the PubM ed, EMBASE and Cochrane Library databases, showed 11 case reports comprising a total of 22 kidney transplantation(KT) patients(range, 1 to 9), who were treated with NPWT. Application of NPWT was associated with successful healing of wounds, leg ulcer, lymphocele and urine leak from ileal conduit.RESULTS No complications related to NPWT were reported. However, there was paucity of robust data on the effectiveness of NPWT in KT recipients; therefore, prospective studies assessing its safety and efficacy of NPWT and randomised trials comparing the effectiveness of NPWT with alternative modalities of wound management in KT recipients is recommended.CONCLUSION Negative pressure incision management system, NPWT with instillation and endoscopic vacuum-assisted closure system are in investigational stage.
基金the Beijing Science and Technology Plan Project:Study on Multidimensional Precise Diagnosis and Treatment Technology and Clinical Transformation of Type 2 Diabetic Nephropathy (No. Z221100007422121)the Beijing Science and Technology Plan Project:Correlation between Clinical Phenotype and Pathological Diagnosis of Type 2 Diabetic Nephropathy (D171100002817002)+2 种基金the State Key Research and Development Program:Study on the Core Pathogenesis and Clinical Evolution of Damp-heat Symptom in Diabetic Nephropathy (2018YFC1704203)National Key R&D Program of China (2018YFC1704200)Natural Science Foundation of China:Mechanism of Organ Immune Injury and Basic Research of Integrated Traditional Chinese and Western Medicine Diagnosis and Treatment (No. 32141005)。
文摘OBJECTIVE: To analyze the distribution of Traditional Chinese medicine(TCM) syndromes in patients with diabetic kidney disease(DKD) and its related factors.METHODS: We enrolled 435 patients with DKD, who were not undergoing dialysis, admitted to the Department of Nephrology, First Medical Center, Chinese PLA General Hospital from April 2020 to August 2021.Analysis of their TCM syndromes and related factors was carried out.RESULTS: The 435 patients included 109, 117, 86, and 123 chronic kidney disease(CKD) 1-2, CKD3, CKD4, and CKD5 cases, respectively. With the progression of CKD1-5, the proportion of Yin deficiency and dry heat syndrome,and that of Qi and Yin deficiency syndrome showed a downward trend, whereas the proportion of spleen-kidney Yang deficiency, blood deficiency, blood stasis, water stagnation, and phlegm turbidity syndromes showed an upward trend;the differences were statistically significant(P < 0.05). Multivariate logistic regression analysis showed that Yin deficiency and dry heat syndrome was positively correlated with hemoglobin [odds ratio(OR) =1.022, P = 0.005], albumin(OR = 1.058, P = 0.006), and estimated glomerular filtration rate(eGFR)(OR = 1.020,P < 0.001) but negatively correlated with male sex(OR =0.277, P = 0.004). Qi and Yin deficiency syndrome was positively correlated with albumin(OR = 1.056, P < 0.001)and eGFR(OR = 1.008, P = 0.022) but negatively correlated with age(OR = 0.977, P = 0.023). Liver-kidney Yin deficiency syndrome was positively correlated with age(OR = 1.028, P = 0.021) and glycosylated hemoglobin(OR = 1.223, P = 0.007) but negatively correlated with total cholesterol(OR = 0.792, P = 0.006).Spleen-kidney Yang deficiency syndrome was negatively correlated with hemoglobin(OR = 0.977, P < 0.001),albumin(OR = 0.891, P < 0.001), and eGFR(OR = 0.978,P < 0.001) but positively correlated with high density lipoprotein(OR = 3.376, P = 0.001). CONCLUSION: With CKD1-5 progression, TCM syndromes changed from Yin deficiency and dry heat syndrome to syndrome of deficiency of both Qi and Yin, liver-kidney Yin, and spleen-kidney Yang deficiency syndromes. TCM syndromes were correlated with laboratory test results.
