With advances in solid organ transplantation,the option of combined kidney with other solid organ transplantation is an enticing option for patients with advanced kidney disease and concomitant other solid organ failu...With advances in solid organ transplantation,the option of combined kidney with other solid organ transplantation is an enticing option for patients with advanced kidney disease and concomitant other solid organ failure.Kidney allograft dysfunction is well known to be associated with increased adverse outcomes post solitary kidney transplant however,outcomes for patients and the kidney allograft are somewhat understudied in the setting of kidney transplantation when combined with other solid organ transplantation such as in a simultaneous liverkidney transplant.We will provide an overview of the current literature available on kidney allograft clinical outcome measures in combined solid organ transplant recipients such as delayed kidney allograft function,kidney allograft rejection,kidney allograft and patient survival metrics and how they compare to patients with kidney transplants alone.Worse kidney allograft survival outcomes were noted in most combined other organ with kidney transplantation(liver-kidney,heart-kidney,and lung-kidney)due to comorbidities attributed to non-renal organ dysfunction whereas improved kidney allograft survival outcomes were noted for pancreas-kidney transplantation.展开更多
Cardiovascular disease(CVD)is often accompanied by chronic kidney disease(CKD)and metabolic disorders such as obesity and type 2 diabetes^([1]).The coexistence of these conditions can lead to systemic dysfunction and ...Cardiovascular disease(CVD)is often accompanied by chronic kidney disease(CKD)and metabolic disorders such as obesity and type 2 diabetes^([1]).The coexistence of these conditions can lead to systemic dysfunction and substantially increase adverse cardiovascular outcomes.To describe this interplay,the American Heart Association(AHA)recently proposed the concept of cardiovascular-kidney-metabolic(CKM)syndrome^([1]).However,its risk-enhancing factors and underlying mechanisms remain unclear.展开更多
Acute kidney injury(AKI)is a critical condition with limited effective therapies.Akkermansia muciniphila(A.muciniphila)is a probiotic with multiple beneficial effects,including the regulation of epithelial cell tight ...Acute kidney injury(AKI)is a critical condition with limited effective therapies.Akkermansia muciniphila(A.muciniphila)is a probiotic with multiple beneficial effects,including the regulation of epithelial cell tight junctions.Since renal pathophysiology is associated with gut barrier integrity,we hypothesized that A.muciniphila may have preventive effects on AKI.We established a lipopolysaccharide(LPS)-induced AKI mouse model to evaluate the effects of A.muciniphila.Our findings showed that pretreatment with A.muciniphila significantly attenuated kidney injury,as evidenced by reduced serum creatinine and urea nitrogen levels,alongside decreased tubular necrosis and apoptosis.A.muciniphila preserved intestinal barrier integrity and induced marked shifts in gut microbial ecology and the metabolome.A.muciniphila notably induced an increase in the relative abundance of the phylum Proteobacteria while decreasing in that of the phylum Bacteroidetes.At the genus level,Prevotella,Faecalibaculum,Moraxella,and Lactobacillus were more abundant in A.muciniphilapretreated mice.Metabolomic analysis revealed that A.muciniphila altered the gut metabolome,with changes involving pathways such as tyrosine metabolism,alanine/aspartate/glutamate homeostasis,cancer-related carbon flux,and GABAergic synaptic signaling.In conclusion,our findings indicate that A.muciniphila exerts renoprotective effects by modulating the gut-kidney axis,thereby establishing a foundation for future studies to explore the connection between gut microbiota and AKI.展开更多
Antibody-mediated rejection(AMR)remains a leading cause of kidney allograft failure,posing significant clinical and economic challenges.Donor-specific antibodies against human leukocyte antigens or non-human leukocyte...Antibody-mediated rejection(AMR)remains a leading cause of kidney allograft failure,posing significant clinical and economic challenges.Donor-specific antibodies against human leukocyte antigens or non-human leukocyte antigens are critical risk factors for AMR and graft loss.The diagnostic criteria and classification of AMR have evolved considerably over the past three decades,driven largely by the Banff classification.The latest Banff 2022 classification introduced two additional subcategories of“microvascular inflammation,donor-specific antibody-negative,C4d-negative”and“probable AMR”.Traditionally,graft monitoring has relied on non-specific markers such as serum creatinine and proteinuria,and the invasive biopsies.Noninvasive tools using blood and urine biomarkers,including cellular assays and molecular profiling,are increasingly being investigated.Technologies such as the Molecular Microscope Diagnostic System show promise,with studies reporting 80%sensitivity and 90%specificity in detecting AMR.Treatment of AMR remains inconsistent.Recent advances,including CD38 antibodies,have demonstrated up to 60%efficacy in reversing AMR,while complement inhibition shows potential in severe early cases.Ongoing clinical trials evaluating high-dose intravenous immunoglobulin,efgartigimod,fostamatinib,and other novel therapies aim to expand treatment options.These developments highlight the need for well-designed clinical trials to validate biomarkers and therapies and to improve long-term outcomes for kidney transplant recipients.展开更多
BACKGROUND The use of induction immunosuppression agents has improved kidney transplant outcomes,but selecting the optimal agent remains a point of debate.AIM To compare the long-term outcomes of kidney transplant rec...BACKGROUND The use of induction immunosuppression agents has improved kidney transplant outcomes,but selecting the optimal agent remains a point of debate.AIM To compare the long-term outcomes of kidney transplant recipients receiving alemtuzumab vs basiliximab induction,focusing on graft function,acute rejection,infection,malignancy,post-transplant glomerulonephritis,and survival,using a propensity score matched cohort design.METHODS Kidney transplant recipients who received alemtuzumab or basiliximab induction from 2014 to 2019 across two nephrology centres in Northwest England were evaluated.Propensity score matching at a 1:1.5 ratio ensured comparability between cohorts.Baseline characteristics,immunosuppression regimens,and outcomes were analyzed.Linear,binary logistic and Cox proportional hazard regression models.RESULTS A total of 436 recipients were included,with a median follow-up of 5.2 years.The matched cohort(n=262)had a mean age of 51.1±13.5 years;39%were female and 92%were white.There was no significant difference in the cumulative incidence of acute rejection[odds ratio(OR)=2.10;95%CI:0.9-4.9;P=0.110].Compared with basiliximab,alemtuzumab was associated with lower estimated glomerular filtration rate at 12 months(-6.6 mL/minute/1.73 m2;95%CI:-10.5 to-2.7;P<0.001)and higher risks of cytomegalovirus viremia(OR=3.2;95%CI:1.6-6.5;P<0.001),BK viremia(OR=2.4;95%CI:1.1-5.5;P=0.02),post-transplant malignancy(OR=6.2;95%CI:1.6-29.9;P=0.013),and death-censored graft loss(hazard ratio=3.6;95%CI:1.2-11.4;P=0.03).No significant differences were observed in post-transplant glomerulonephritis or recipient mortality.CONCLUSION In this propensity score-matched analysis,alemtuzumab induction was associated with lower graft function at 12 months and higher risks of viral infection,post-transplant malignancy,and graft loss compared with basiliximab.These findings highlight the need for further studies to confirm the long-term safety and effectiveness of alemtuzumab in kidney transplantation.展开更多
Background:Acute kidney injury(AKI),characterized by rapid renal dysfunction(KDIGO 2022 criteria:48-hour doubling of serum creatinine or<0.5 mL/kg/h urine output for>6 h),affects 13.3 million people annually wit...Background:Acute kidney injury(AKI),characterized by rapid renal dysfunction(KDIGO 2022 criteria:48-hour doubling of serum creatinine or<0.5 mL/kg/h urine output for>6 h),affects 13.3 million people annually with>20%mortality.Its progression involves metabolic imbalances,toxin accumulation,and multiorgan failure,often culminating in chronic kidney disease.Current therapies(fluid resuscitation,diuretics,renal replacement therapy)remain limited.Inflammation drives AKI pathogenesis:renal insults(ischemia,toxins)trigger tubular cell release of pro-inflammatory mediators(TNF-α,IL-1β,IL-6),activating neutrophil gelatinase-associated lipocalin(NGAL)and dysregulating P38 MAPK/ERK pathways.This cascade promotes leukocyte infiltration,oxidative stress,and apoptosis,exacerbating renal damage.Ononin,a flavonoid from Astragali Radix,shows multi-target potential by suppressing pro-inflammatory cytokines,modulating signaling,and mitigating oxidative stress.Its dual anti-inflammatory/antioxidant properties position it as a promising candidate for AKI intervention.Exploring the ameliorative effect of ononin on the inflammatory response Ameliorative effect of ononin on the inflammatory response in doxorubicin-induced AKI mice.Methods:We used network pharmacology to explore ononin’s target molecules and AKI-related disease molecules,identified their intersections,and predicted potential mechanisms via enrichment analysis,followed by molecular docking verification.For in-vivo validation,50 mice were randomly divided into five groups(n=10/group):Control,Model,Ononin-L(15 mg/kg),Ononin-H(60 mg/kg),and Dexamethasone(2.6 mg/kg).An AKI model was established by intravenous tail-vein injection of Doxorubicin(15 mg/kg).Samples were collected 12 h post-induction.We calculated the renal coefficient,examined renal histopathology using hematoxylin and eosin(HE),periodic acid-Schiff(PAS),and Masson’s trichrome(MASSON)staining,and observed mitochondrial morphology by electron microscopy(EM).ELISA was used to measure NGAL,serum creatinine(Scr),and blood urea nitrogen(BUN)levels in serum.Immunofluorescence(IF)evaluated the expression of P-P38,P-ERK,NGAL,and KIM-1 in renal tissues.RT-qPCR assessed the gene expression of pro-inflammatory cytokines,MAPK pathway components,and renal injury markers in kidney tissues.Western Blot(WB)quantified P-P38,P38 MAPK,P-ERK,ERK,NGAL,and KIM-1 in renal tissues.Results:Network pharmacology analysis suggested that ononin could attenuate AKI through its anti-inflammatory properties and regulation of the MAPK signaling pathway.The Model group exhibited a significantly elevated renal coefficient(P<0.05),severe histopathological damage,and mitochondrial dysfunction compared to controls.Serum levels of NGAL,Scr,and BUN were markedly increased(P<0.05),indicating impaired renal function.Enhanced fluorescence signals of P-P38 MAPK,P-ERK,NGAL,and KIM-1 suggested activation of MAPK pathways and renal injury.Upregulation of pro-inflammatory cytokines(IL-1β,IL-6,TNF-α)and MAPK-related genes(P38 MAPK,ERK)alongside injury markers(NGAL,KIM-1)(P<0.05).Increased ratios of phosphorylated-to-total proteins(P-P38/P38,P-ERK/ERK)and elevated NGAL/KIM-1 protein levels confirmed pathway dysregulation.Treatment significantly reduced the renal coefficient(P<0.05),attenuated histological damage,and restored mitochondrial integrity.NGAL,Scr,and BUN levels were lowered,reflecting functional recovery.Diminished fluorescence intensities of P-P38,P-ERK,NGAL,and KIM-1 indicated suppression of injury pathways.Downregulation of inflammatory cytokines(IL-1β,IL-6,TNF-α),MAPK components(P38 MAPK,ERK),and injury markers(NGAL,KIM-1)(P<0.05).Reduced phosphorylation ratios(P-P38/P38,P-ERK/ERK)and decreased NGAL/KIM-1 protein expression demonstrated therapeutic efficacy.Conclusion:Ononin ameliorates inflammatory responses in AKI mice via the P38 MAPK/ERK pathway.展开更多
BACKGROUND An echocardiogram is an essential tool in the evaluation of potential kidney transplant recipients(KTRs).Despite cardiac clearance,potential KTRs still have structural and functional abnormalities.Identifyi...BACKGROUND An echocardiogram is an essential tool in the evaluation of potential kidney transplant recipients(KTRs).Despite cardiac clearance,potential KTRs still have structural and functional abnormalities.Identifying the prevalence of these abnormalities and understanding their predictors is vital for optimizing pretransplant risk stratification and improving post-transplant outcomes.AIM To determine the prevalence of left ventricular hypertrophy(LVH),left ventricular systolic dysfunction(LVSD),diastolic dysfunction(DD),pulmonary hypertension(PH),and their predictors,and to assess their impact on graft function in pre-transplant candidates.METHODS The study included all successful transplant candidates older than 14 who had a baseline echocardiogram.Binary logistic regression models were constructed to identify factors associated with LVH,LVSD,DD,and PH.RESULTS Out of 259 patients,LVH was present in 64%(166),12%(31)had LVSD,27.5%(71)had DD,and 66(25.5%)had PH.Independent predictors of LVH included male gender[odds ratio(OR):2.51;95%CI:1.17-5.41 P=0.02],PH(OR=2.07;95%CI:1.11-3.86;P=0.02),DD(OR:2.47;95%CI:1.29-4.73;P=0.006),and dyslipidemia(OR=1.94;95%CI:1.07-3.53;P=0.03).Predictors for LVSD included patients with DD(OR=3.3,95%CI:1.41-7.81;P=0.006)and a family history of coronary artery disease(OR=4.50,95%CI:1.33-15.20;P=0.015).Peritoneal dialysis was an independent predictor for DD(OR=10.03;95%CI:1.71-58.94,P=0.011).The presence of LVH(OR=3.32,95%CI:1.05-10.55,P=0.04)and mild to moderate or moderate to severe mitral regurgitation(OR=4.63,95%CI:1.45-14.78,P=0.01)were significant factors associated with PH.These abnormalities had no significant impact on estimated glomerular filtration at discharge,6 months,1 year,or 2 years post-transplant.CONCLUSION Significant echocardiographic abnormalities persist in a potential transplant candidate despite cardiac clearance,although they don’t affect future graft function.Understanding the risk factors associated with these abnormalities may help clinicians address these factors pre-and post-transplant to achieve better outcomes.展开更多
Post-kidney transplant rejection is a critical factor influencing transplant success rates and the survival of transplanted organs.With the rapid advancement of artificial intelligence technologies,machine learning(ML...Post-kidney transplant rejection is a critical factor influencing transplant success rates and the survival of transplanted organs.With the rapid advancement of artificial intelligence technologies,machine learning(ML)has emerged as a powerful data analysis tool,widely applied in the prediction,diagnosis,and mechanistic study of kidney transplant rejection.This mini-review systematically summarizes the recent applications of ML techniques in post-kidney transplant rejection,covering areas such as the construction of predictive models,identification of biomarkers,analysis of pathological images,assessment of immune cell infiltration,and formulation of personalized treatment strategies.By integrating multi-omics data and clinical information,ML has significantly enhanced the accuracy of early rejection diagnosis and the capability for prognostic evaluation,driving the development of precision medicine in the field of kidney transplantation.Furthermore,this article discusses the challenges faced in existing research and potential future directions,providing a theoretical basis and technical references for related studies.展开更多
BACKGROUND Donor-specific antibodies(DSAs)against human leukocyte antigen(HLA)-DQ are increasingly recognized as major contributors to antibody-mediated rejection(AMR)and graft failure in kidney transplantation.Howeve...BACKGROUND Donor-specific antibodies(DSAs)against human leukocyte antigen(HLA)-DQ are increasingly recognized as major contributors to antibody-mediated rejection(AMR)and graft failure in kidney transplantation.However,their clinical impact remains understudied in Morocco.AIM To evaluate the presence and implications of anti-HLA-DQ DSAs in Moroccan kidney transplant recipients.METHODS We retrospectively analyzed the immunological profiles and clinical outcomes of kidney transplant recipients screened for anti-HLA antibodies between 2015 and 2020,who developed anti-HLA-DQ DSAs either before or after transplantation.Anti-HLA antibodies were identified using Luminex®single antigen bead technology,and clinical follow-up included graft function assessment,biopsy interpretation,and evaluation of immunosuppression.RESULTS In the pre-transplant group(n=6 with confirmed donor typing),patients with low to moderate median fluorescence intensity(MFI)anti-HLA-DQ DSAs(MFI 561-1581)underwent successful transplantation and maintained stable graft function under optimized immunosuppression.In contrast,in the post-transplant group(n=6 with confirmed donor typing),the emergence of de novo anti-HLA-DQ DSAs was consistently associated with AMR,with MFI values reaching up to 19473,with biopsy-proven AMR in 5 of 6 cases and suspicion of AMR in 1 case.Two representative cases are detailed to illustrate the clinical impact of DQ DSAs:one patient developed high-level anti-DQB1*02 de novo DSA(MFI 12029)with persistent AMR after 5 years,while another developed anti-DQA1*05:01 de novo DSA after an early AMR episode but maintained stable graft function after 5 years(creatinine 1.48 mg/dL).CONCLUSION Our findings underscore the clinical significance of anti-HLA-DQ DSAs in Moroccan kidney transplant recipients.While preformed DSAs with low immunogenicity may permit successful transplantation,de novo DSAs strongly correlate with AMR.Proactive monitoring,including routine DSA screening and HLA-DQ typing,could improve graft outcomes by enabling early intervention and better donor selection.展开更多
Kidney transplantation(KT)accounts for nearly three-fourths of organ transplants in India,with living donors contributing to 82%of cases.Induction immunosuppression is essential to optimize initial immunosuppression,r...Kidney transplantation(KT)accounts for nearly three-fourths of organ transplants in India,with living donors contributing to 82%of cases.Induction immunosuppression is essential to optimize initial immunosuppression,reduce acute rejections,and enable tailored use of maintenance agents.Rabbit anti-thymocyte globulin(rATG)and interleukin-2 receptor anatagonists(IL-2RA/IL-2RBs)are the most widely used induction therapies.However,data on induction practices across India are limited.To evaluate induction immunosuppression practices across KT centers in India and establish a consensus for different subsets of KT recipients.A nationwide online survey was conducted by the Indian Society of Organ Transplantation(ISOT)among its members(400 KT centers).Responses were analyzed to assess induction practices across diverse donor types,age groups,and immunological risk profiles.Heterogeneity in practices prompted consensus building using a modified Delphi process.Literature review and expert panel discussions(April 2024)were followed by structured voting,and 16 consensus statements were finalized.Of 400 centers approached,254 participated.rATG was the most commonly used induction therapy,followed by IL-2RBs;alemtuzumab was least used.Significant heterogeneity was observed in type,dose,and duration of induction therapy.Consensus recommendations were framed:rATG for high immunological risk recipients and deceased donor KTs;IL-2RB or low-dose rATG for low immunological risk;rituximab in ABOincompatible KTs;and tailoring based on age,diabetes,donor type,infection risk,and affordability.This first ISOT consensus provides 16 India-specific statements on induction therapy in KT.It emphasizes risk-stratified,evidenceinformed,and context-appropriate induction strategies,supporting standardization of care across the country.展开更多
BACKGROUND With the increasing use of laparoscopic techniques in living-donor kidney transplantation,limitations in donor vessel length,particularly of the right renal vein,pose significant challenges for vascular ana...BACKGROUND With the increasing use of laparoscopic techniques in living-donor kidney transplantation,limitations in donor vessel length,particularly of the right renal vein,pose significant challenges for vascular anastomosis to the recipient’s external iliac vein.These anatomical constraints can complicate graft implantation and increase the risk of postoperative complications.CASE SUMMARY To address the issue of short right renal veins,several surgical strategies have been proposed.In this report,we describe our experience with three cases in which venous extension was successfully achieved using a venous cuff interposition technique during back-table reconstruction.This approach was used to facilitate secure vascular anastomosis and improve graft positioning in anatomically complex transplant scenarios.CONCLUSION Venous cuff interposition represents an effective technique for managing short renal veins in living-donor kidney transplantation.It provides additional length and flexibility,easing anastomotic tension and supporting successful transplantation.展开更多
BACKGROUND Post-transplant tertiary hyperparathyroidism(PT-tHPT)is a well-recognized complication following kidney transplantation,characterized by persistent excessive secretion of parathyroid hormone(PTH)despite imp...BACKGROUND Post-transplant tertiary hyperparathyroidism(PT-tHPT)is a well-recognized complication following kidney transplantation,characterized by persistent excessive secretion of parathyroid hormone(PTH)despite improved renal function.It is potentially associated with an increased risk of cardiovascular events,renal osteodystrophy,pathologic fractures,graft loss,and mortality.AIM To evaluate the incidence,risk factors,and outcomes of PT-tHPT amongst kidney transplant recipients.METHODS A total of 887 transplant recipients who underwent transplantation between 2000 and 2020 were evaluated.Univariable and multivariable logistic regression was performed to determine the predictors of tertiary hyperparathyroidism.Graft and recipient outcomes were assessed using multivariable Cox regression.A separate multivariable Cox regression was performed to determine the effect of treatment strategies on outcomes.RESULTS PT-tHPT,defined as elevated PTH(>65 ng/L)and persistent hypercalcemia(>2.60 mmol/L),was diagnosed in 14%of recipients.Risk factors for PT-tHPT included older age[odds ratio(OR)=1.36,P<0.001],Asian ethnicity(OR=0.33,P=0.006),total ischemia time(OR=1.03,P=0.048 per hour),pre-transplant serum calcium(OR=1.38,P<0.001)per decile increase,pre-transplant PTH level(OR=1.31,P<0.001)per decile increase,longer dialysis duration(OR=1.12,P=0.002)per year,history of acute rejection(OR=2.37,P=0.012),and slope of estimated glomerular filtration rate change(OR=0.91,P=0.001).There were a 3.4-fold higher risk of death-censored graft loss and a 1.9-fold greater risk of recipient death with PT-tHPT.The three treatment strategies of conservative management,calcimimetic and parathyroidectomy did not significantly change the graft or patient outcome.CONCLUSION Pretransplant elevated calcium and PTH levels,older age and dialysis duration are associated with PT-tHPT.While PT-tHPT significantly affects graft and recipient survival,the treatment strategies did not affect survival.展开更多
Background:Refined models of kidney disease are critical to better understand disease processes and study novel treatments while minimizing discomfort in research animals.The objective of this study was to report a te...Background:Refined models of kidney disease are critical to better understand disease processes and study novel treatments while minimizing discomfort in research animals.The objective of this study was to report a technique for minimally invasive partial kidney embolism in cats and describe outcomes following transcatheter administration of embolic microspheres with subsequent contralateral nephrectomy.Methods:Eleven,apparently healthy,male,purpose-bred cats underwent unilateral kidney embolism with 0.25 or 0.5 mL of embolic microparticle(40-120μm)suspension(0.2 mL microspheres/mL)delivered into the right renal artery under fluoroscopic guidance,followed 5 months later by contralateral nephrectomy.One month after nephrectomy,blood and urinary markers of kidney function were evaluated,and embolized kidneys were harvested for histopathology evaluation.Results:Renal artery embolization was possible in all cats.Two cats did not complete the study,one after experiencing congestive heart failure(n=1)and the other following evidence of complete kidney embolism precluding nephrectomy(n=1)postembolization.At study end,compared to baseline,cats had significant increases in median(range)serum creatinine(159.1μmol/L[141.4-530.4]versus 128.2μmol/L[92.8-150.3];p=0.0004),urea nitrogen(15.71 mmol/L[9.29-47.85]versus 7.50 mmol/L[6.07-8.57];p<0.0001),and symmetric dimethylarginine(0.74μmol/L[0.59-3.12]versus 0.67μmol/L[0.54-0.72];p=0.0288)concentrations.No differences in markers of kidney function were documented between dose groups.Conclusions:M inimally invasive kidney embolism is a promising technique for modeling kidney disease in cats.Understanding optimal dose,timing of nephrectomy,and longer-term consequences requires additional work.展开更多
BACKGROUND Acute kidney injury(AKI)is a common and serious complication following heart transplantation,significantly impacting patient outcomes and survival rates.AKI after transplantation can lead to prolonged hospi...BACKGROUND Acute kidney injury(AKI)is a common and serious complication following heart transplantation,significantly impacting patient outcomes and survival rates.AKI after transplantation can lead to prolonged hospital stays,increased morbidity,and even mortality.AIM To identify and quantify significant risk factors associated with AKI following heart transplantation through a systematic review and meta-analysis.This study aims to distinguish predictive variables that may inform perioperative risk stratification and clinical decision-making.METHODS Electronic searches on MEDLINE,Google Scholar,ScienceDirect,Clinical-Trials.gov,and Cochrane databases were conducted from inception up till September 1.Included studies were randomized controlled trials,clinical trials,retrospective cohort,and observational studies.Exclusion criteria encompassed studies with pediatric populations,non-English publications,case reports,and studies lacking sufficient data on AKI outcomes.Statistical analysis was performed using RevMan 5.4,reporting dichotomous outcomes as odds ratios(OR)and continuous outcomes as mean differences(MD)with 95%confidence intervals(CI).Quality assessment of the included studies was performed using the New Castle Ottawa Scale.RESULTS Out of 1345 articles,13 studies with 3330 patients were included.Significant risk factors included age[overall MD=2.27 years(95%CI:0.13 to 4.41)],body mass index(BMI)[MD=1.42(95%CI:0.60 to 2.24)],diabetes[overall OR=1.47(95%CI:1.16 to 1.85)],chronic kidney disease(CKD)[OR=2.67(95%CI:1.73 to 4.14)],chronic obstructive pulmonary disorder(COPD)[OR=0.49(95%CI:0.27 to 0.89)],previous thoracic surgery[(OR)=1.27,95%CI:(1.05 to 1.54)],cardio-pulmonary bypass time[(MD)=17.10,95%CI:(6.12 to 28.08)],mechanical ventilation duration[(MD)=30.87 hours,95%CI:(10.69 to 51.05)]and extracorporeal membrane oxygenation[(OR)=2.31,95%CI:(1.25 to 4.26)].Factors not associated with AKI after heart transplantation included Recipients’male sex(P=0.55),donor sex(P=0.11),hypertension(P=0.13),smoking(P=0.20),coronary artery disease(P=0.90),pulmonary artery disease(P=0.81),dilated cardiomyopathy(P=0.79),ventilation duration(P=0.24),ischemic time(P=0.06),use of intra-aortic balloon pump(P=0.14),LVAD transplantation(P=0.83),and Inotropes use(P=0.78).CONCLUSION Age,BMI,diabetes,CKD,COPD,previous thoracic surgery,prolonged CPB time,extended mechanical ventilation,and ECMO use are significant predictors of AKI following heart transplantation,necessitating vigilant monitoring and individualized risk assessment.Conversely,factors such as LVAD implantation and inotrope use showed no significant association,highlighting the need for further investigation into their roles.Future prospective studies are essential to validate these findings,elucidate underlying mechanisms,and develop targeted interventions to mitigate AKI risk and improve patient outcomes.展开更多
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.Althou...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.展开更多
BACKGROUND Equations for estimation glomerular filtration rate(eGFR)have been associated with poor clinical performance and their clinical accuracy and reliability have been called into question.AIM To assess the long...BACKGROUND Equations for estimation glomerular filtration rate(eGFR)have been associated with poor clinical performance and their clinical accuracy and reliability have been called into question.AIM To assess the longitudinal changes in measured glomerular filtration rate(mGFR)in patients with autosomal dominant polycystic kidney disease(ADPKD).METHODS Analysis of an ambispective data base conducted on consecutive patients diagnosed with ADPKD.The mGFR was assessed by iohexol clearance;while eGFR was calculated by three different formulas:(1)The chronic kidney disease epidemiology collaboration(CKD-EPI);(2)Modification of diet in renal disease(MDRD);and(3)The 24-hour urine creatinine clearance(CrCl).The primary end-points were the mean change in mGFR between the baseline and final visit,as well as the comparison of the mean change in mGFR with the change estimated by the different formulas.RESULTS Thirty-seven patients were included in the study.As compared to baseline,month-6 mGFR was significantly decrease by-4.4 mL/minute±10.3 mL/minute(P=0.0132).However,the CKD-EPI,MDRD,and CrCl formulas underestimated this change by 48.3%,89.0%,and 45.8%respectively,though none of these differences reached statistical significance(P=0.3647;P=0.0505;and P=0.736,respectively).The discrepancies between measured and estimated glomerular filtration rate values,as evaluated by CKD-EPI(r=0.29,P=0.086);MDRD(r=0.19,P=0.272);and CrCl(r=0.09,P=0.683),were not correlated with baseline mGFR values.CONCLUSION This study indicated that eGFR inaccurately reflects the decline in mGFR and cannot reliably track changes over time.This poses significant challenges for clinical decision-making,particularly in treatment strategies.展开更多
The endothelium modulates vascular homeostasis owing to a variety of vasoconstrictors and vasodilators.Endothelial dysfunction(ED),characterized by impaired vasodilation,inflammation,and thrombosis,triggers future car...The endothelium modulates vascular homeostasis owing to a variety of vasoconstrictors and vasodilators.Endothelial dysfunction(ED),characterized by impaired vasodilation,inflammation,and thrombosis,triggers future cardiovascular(CV)diseases.Chronic kidney disease,a state of chronic inflammation caused by oxidative stress,metabolic abnormalities,infection,and uremic toxins damages the endothelium.ED is also associated with a decline in estimated glomerular filtration rate.After kidney transplantation,endothelial functions undergo immediate but partial restoration,promising graft longevity and enhanced CV health.However,the anticipated CV outcomes do not happen due to various transplant-related and unrelated risk factors for ED,culminating in poor CV health and graft survival.ED in kidney transplant recipients is an underrecognized and poorly studied entity.CV diseases are the leading cause of death among kidney transplant candidates with functioning grafts.ED contributes to the pathogenesis of many of the CV diseases.Various biomarkers and vasoreactivity tests are available to study endothelial functions.With an increasing number of transplants happening every year,and improved graft rejection rates due to the availability of effective immunosuppressants,the focus has now shifted to endothelial protection for the prevention,early recognition,and treatment of CV diseases.展开更多
Chronic Kidney Disease (CKD) is ongoing damage of the kidneys, which affects their ability to filter the blood the way they should. Worldwide CKD is considered as the 16th leading cause of death and affects 8% - 16% o...Chronic Kidney Disease (CKD) is ongoing damage of the kidneys, which affects their ability to filter the blood the way they should. Worldwide CKD is considered as the 16th leading cause of death and affects 8% - 16% of the population. CKD often goes unnoticed and is revealed as an incidental finding. Healthcare providers diagnose the condition as CKD based on persistent abnormal kidney function tests revealing kidney damage markers > 3 months, urine albumin creatinine ratio (UACR) > or equal to 30 mg/g per 24 hours, and GFR < 60 mL/min/1.73m<sup>2</sup>. In this article, we have discussed chronic kidney disease in terms of kidney physiology, chronic kidney disease pathophysiology, etiology, diagnosis, signs and symptoms, and management.展开更多
BACKGROUND Despite the developments in the field of kidney transplantation,the already existing diagnostic techniques for patient monitoring are considered insufficient.Protein biomarkers that can be derived from mode...BACKGROUND Despite the developments in the field of kidney transplantation,the already existing diagnostic techniques for patient monitoring are considered insufficient.Protein biomarkers that can be derived from modern approaches of proteomic analysis of liquid biopsies(serum,urine)represent a promising innovation in the monitoring of kidney transplant recipients.AIM To investigate the diagnostic utility of protein biomarkers derived from proteomics approaches in renal allograft assessment.METHODS A systematic review was conducted in accordance with PRISMA guidelines,based on research results from the PubMed and Scopus databases.The primary focus was on evaluating the role of biomarkers in the non-invasive diagnosis of transplant-related com-plications.Eligibility criteria included protein biomarkers and urine and blood samples,while exclusion criteria were language other than English and the use of low resolution and sensitivity methods.The selected research articles,were categorized based on the biological sample,condition and methodology and the significantly and reproducibly differentiated proteins were manually selected and extracted.Functional and network analysis of the selected proteins was performed.RESULTS In 17 included studies,58 proteins were studied,with the cytokine CXCL10 being the most investigated.Biological pathways related to immune response and fibrosis have shown to be enriched.Applications of biomarkers for the assessment of renal damage as well as the prediction of short-term and long-term function of the graft were reported.Overall,all studies have shown satisfactory diagnostic accuracy of proteins alone or in combination with conventional methods,as far as renal graft assessment is concerned.CONCLUSION Our review suggests that protein biomarkers,evaluated in specific biological fluids,can make a significant contribution to the timely,valid and non-invasive assessment of kidney graft.展开更多
BACKGROUND Diabetic patients with atypical presentation are often challenging in terms of diagnosis and management.Kidney biopsy is not routinely done in diabetics,and clinicians are always in a dilemma in such a scen...BACKGROUND Diabetic patients with atypical presentation are often challenging in terms of diagnosis and management.Kidney biopsy is not routinely done in diabetics,and clinicians are always in a dilemma in such a scenario to decide whether to do a biopsy or not.Since non-diabetic kidney diseases(NDKD)are common,and some patients may have NDKD superimposed on diabetic kidney diseases(DKD),therefore,kidney biopsy may be warranted to rule out NDKD.AIM To determine the prevalence of NDKD,DKD,or mixed lesions,identify predictors of NDKD,and investigate renal and patient survival,as well as factors associated with these outcomes.METHODS This retrospective observational study was conducted on patients with biopsyproven NDKD,DKD,and mixed lesions(having both NDKD and DKD).Binary logistic regression models were constructed to identify predictors of NDKD.Kaplan-Meier survival analysis was performed to compare time to kidney failure and patient survival across the three histological groups.Multivariable Cox proportional hazards regression was used to identify clinical and pathological factors associated with kidney failure and all-cause mortality.RESULTS A total of 103 biopsies were analyzed.Sixty-four(62.1%)had NDKD alone or mixed lesions.The most common NDKD pathologies were interstitial nephritis in 12(29.2%),focal segmental glomerulosclerosis in 10(24.4%),and immune complex–mediated glomerulonephritis in five(12.2%)patients.Compared to DKD,NDKD was associated with significantly lower odds of proteinuria>3.5 g/day[odds ratio(OR),0.02;P=0.0015],retinopathy(OR=0.04;P=0.0067),and diabetes duration≥10 years(OR=0.01;P=0.0002).However,NDKD had higher odds of anemia(Hemoglobin<12 g/dL;OR=9.56;P=0.0107)and creatinine levels>180μmol/L(OR=18.68;P=0.0063).Kaplan-Meier analysis showed significant differences in renal survival(log-rank P=0.0033).Patients with NDKD have the best outcomes,while those with DKD have the worst.In a multivariable Cox regression analysis,increasing age,creatinine,arteriosclerosis,and severe interstitial fibrosis and tubular atrophy were independently associated with kidney failure.At the same time,the use of renin angiotensin system blockers was protective(hazard ratio=0.43,P=0.02).Kaplan-Meier curves for patient survival also differed significantly(log-rank P=0.018);patients in the mixed group showed the highest mortality,while those with NDKD showed the lowest.Mortality was independently associated with older age,hypoalbuminemia,diabetic retinopathy,arteriosclerosis,and higher creatinine.CONCLUSION NDKD and mixed lesions are frequent in diabetic patients.These histological lesions carry distinct prognostic implications.Clinical features such as a shorter diabetes duration,absence of retinopathy,anemia,and elevated creatinine levels suggest NDKD and warrant biopsy.NDKD had better renal and patient survival rates,while mixed lesions had the worst outcomes.Older age,hypoalbuminemia,retinopathy,arteriosclerosis,and elevated creatinine were key predictors of mortality.展开更多
文摘With advances in solid organ transplantation,the option of combined kidney with other solid organ transplantation is an enticing option for patients with advanced kidney disease and concomitant other solid organ failure.Kidney allograft dysfunction is well known to be associated with increased adverse outcomes post solitary kidney transplant however,outcomes for patients and the kidney allograft are somewhat understudied in the setting of kidney transplantation when combined with other solid organ transplantation such as in a simultaneous liverkidney transplant.We will provide an overview of the current literature available on kidney allograft clinical outcome measures in combined solid organ transplant recipients such as delayed kidney allograft function,kidney allograft rejection,kidney allograft and patient survival metrics and how they compare to patients with kidney transplants alone.Worse kidney allograft survival outcomes were noted in most combined other organ with kidney transplantation(liver-kidney,heart-kidney,and lung-kidney)due to comorbidities attributed to non-renal organ dysfunction whereas improved kidney allograft survival outcomes were noted for pancreas-kidney transplantation.
基金supported by the Natural Science Foundation of Beijing Municipality(Grant No.7234401)the Postdoctoral Research Foundation of China(Grant No.88014Y0226)。
文摘Cardiovascular disease(CVD)is often accompanied by chronic kidney disease(CKD)and metabolic disorders such as obesity and type 2 diabetes^([1]).The coexistence of these conditions can lead to systemic dysfunction and substantially increase adverse cardiovascular outcomes.To describe this interplay,the American Heart Association(AHA)recently proposed the concept of cardiovascular-kidney-metabolic(CKM)syndrome^([1]).However,its risk-enhancing factors and underlying mechanisms remain unclear.
基金funded by the National Natural Science Foundation of China(Grant No.82470766 to H.M.)the Jiangsu Provincial Medical Key Discipline(Laboratory)Cultivation Unit(Grant No.JSDW202206 to C.X.)the First Affiliated Hospital of Nanjing Medical University Clinical Capacity Enhancement Project(Grant No.JSPH-MC-2022-18 to C.X.).
文摘Acute kidney injury(AKI)is a critical condition with limited effective therapies.Akkermansia muciniphila(A.muciniphila)is a probiotic with multiple beneficial effects,including the regulation of epithelial cell tight junctions.Since renal pathophysiology is associated with gut barrier integrity,we hypothesized that A.muciniphila may have preventive effects on AKI.We established a lipopolysaccharide(LPS)-induced AKI mouse model to evaluate the effects of A.muciniphila.Our findings showed that pretreatment with A.muciniphila significantly attenuated kidney injury,as evidenced by reduced serum creatinine and urea nitrogen levels,alongside decreased tubular necrosis and apoptosis.A.muciniphila preserved intestinal barrier integrity and induced marked shifts in gut microbial ecology and the metabolome.A.muciniphila notably induced an increase in the relative abundance of the phylum Proteobacteria while decreasing in that of the phylum Bacteroidetes.At the genus level,Prevotella,Faecalibaculum,Moraxella,and Lactobacillus were more abundant in A.muciniphilapretreated mice.Metabolomic analysis revealed that A.muciniphila altered the gut metabolome,with changes involving pathways such as tyrosine metabolism,alanine/aspartate/glutamate homeostasis,cancer-related carbon flux,and GABAergic synaptic signaling.In conclusion,our findings indicate that A.muciniphila exerts renoprotective effects by modulating the gut-kidney axis,thereby establishing a foundation for future studies to explore the connection between gut microbiota and AKI.
文摘Antibody-mediated rejection(AMR)remains a leading cause of kidney allograft failure,posing significant clinical and economic challenges.Donor-specific antibodies against human leukocyte antigens or non-human leukocyte antigens are critical risk factors for AMR and graft loss.The diagnostic criteria and classification of AMR have evolved considerably over the past three decades,driven largely by the Banff classification.The latest Banff 2022 classification introduced two additional subcategories of“microvascular inflammation,donor-specific antibody-negative,C4d-negative”and“probable AMR”.Traditionally,graft monitoring has relied on non-specific markers such as serum creatinine and proteinuria,and the invasive biopsies.Noninvasive tools using blood and urine biomarkers,including cellular assays and molecular profiling,are increasingly being investigated.Technologies such as the Molecular Microscope Diagnostic System show promise,with studies reporting 80%sensitivity and 90%specificity in detecting AMR.Treatment of AMR remains inconsistent.Recent advances,including CD38 antibodies,have demonstrated up to 60%efficacy in reversing AMR,while complement inhibition shows potential in severe early cases.Ongoing clinical trials evaluating high-dose intravenous immunoglobulin,efgartigimod,fostamatinib,and other novel therapies aim to expand treatment options.These developments highlight the need for well-designed clinical trials to validate biomarkers and therapies and to improve long-term outcomes for kidney transplant recipients.
文摘BACKGROUND The use of induction immunosuppression agents has improved kidney transplant outcomes,but selecting the optimal agent remains a point of debate.AIM To compare the long-term outcomes of kidney transplant recipients receiving alemtuzumab vs basiliximab induction,focusing on graft function,acute rejection,infection,malignancy,post-transplant glomerulonephritis,and survival,using a propensity score matched cohort design.METHODS Kidney transplant recipients who received alemtuzumab or basiliximab induction from 2014 to 2019 across two nephrology centres in Northwest England were evaluated.Propensity score matching at a 1:1.5 ratio ensured comparability between cohorts.Baseline characteristics,immunosuppression regimens,and outcomes were analyzed.Linear,binary logistic and Cox proportional hazard regression models.RESULTS A total of 436 recipients were included,with a median follow-up of 5.2 years.The matched cohort(n=262)had a mean age of 51.1±13.5 years;39%were female and 92%were white.There was no significant difference in the cumulative incidence of acute rejection[odds ratio(OR)=2.10;95%CI:0.9-4.9;P=0.110].Compared with basiliximab,alemtuzumab was associated with lower estimated glomerular filtration rate at 12 months(-6.6 mL/minute/1.73 m2;95%CI:-10.5 to-2.7;P<0.001)and higher risks of cytomegalovirus viremia(OR=3.2;95%CI:1.6-6.5;P<0.001),BK viremia(OR=2.4;95%CI:1.1-5.5;P=0.02),post-transplant malignancy(OR=6.2;95%CI:1.6-29.9;P=0.013),and death-censored graft loss(hazard ratio=3.6;95%CI:1.2-11.4;P=0.03).No significant differences were observed in post-transplant glomerulonephritis or recipient mortality.CONCLUSION In this propensity score-matched analysis,alemtuzumab induction was associated with lower graft function at 12 months and higher risks of viral infection,post-transplant malignancy,and graft loss compared with basiliximab.These findings highlight the need for further studies to confirm the long-term safety and effectiveness of alemtuzumab in kidney transplantation.
基金supported by Hebei Province Natural Science Foundation(H2023423037)The Government Funded Clinical Program of Hebei Province(No.ZF2025287)+1 种基金Special Project of Hebei Industrial Technology Institute for Traditional Chinese Medicine Preparation(No.YJY2024001)Chinese Medicine Scientific Research Program of Hebei Province(No.2025222).
文摘Background:Acute kidney injury(AKI),characterized by rapid renal dysfunction(KDIGO 2022 criteria:48-hour doubling of serum creatinine or<0.5 mL/kg/h urine output for>6 h),affects 13.3 million people annually with>20%mortality.Its progression involves metabolic imbalances,toxin accumulation,and multiorgan failure,often culminating in chronic kidney disease.Current therapies(fluid resuscitation,diuretics,renal replacement therapy)remain limited.Inflammation drives AKI pathogenesis:renal insults(ischemia,toxins)trigger tubular cell release of pro-inflammatory mediators(TNF-α,IL-1β,IL-6),activating neutrophil gelatinase-associated lipocalin(NGAL)and dysregulating P38 MAPK/ERK pathways.This cascade promotes leukocyte infiltration,oxidative stress,and apoptosis,exacerbating renal damage.Ononin,a flavonoid from Astragali Radix,shows multi-target potential by suppressing pro-inflammatory cytokines,modulating signaling,and mitigating oxidative stress.Its dual anti-inflammatory/antioxidant properties position it as a promising candidate for AKI intervention.Exploring the ameliorative effect of ononin on the inflammatory response Ameliorative effect of ononin on the inflammatory response in doxorubicin-induced AKI mice.Methods:We used network pharmacology to explore ononin’s target molecules and AKI-related disease molecules,identified their intersections,and predicted potential mechanisms via enrichment analysis,followed by molecular docking verification.For in-vivo validation,50 mice were randomly divided into five groups(n=10/group):Control,Model,Ononin-L(15 mg/kg),Ononin-H(60 mg/kg),and Dexamethasone(2.6 mg/kg).An AKI model was established by intravenous tail-vein injection of Doxorubicin(15 mg/kg).Samples were collected 12 h post-induction.We calculated the renal coefficient,examined renal histopathology using hematoxylin and eosin(HE),periodic acid-Schiff(PAS),and Masson’s trichrome(MASSON)staining,and observed mitochondrial morphology by electron microscopy(EM).ELISA was used to measure NGAL,serum creatinine(Scr),and blood urea nitrogen(BUN)levels in serum.Immunofluorescence(IF)evaluated the expression of P-P38,P-ERK,NGAL,and KIM-1 in renal tissues.RT-qPCR assessed the gene expression of pro-inflammatory cytokines,MAPK pathway components,and renal injury markers in kidney tissues.Western Blot(WB)quantified P-P38,P38 MAPK,P-ERK,ERK,NGAL,and KIM-1 in renal tissues.Results:Network pharmacology analysis suggested that ononin could attenuate AKI through its anti-inflammatory properties and regulation of the MAPK signaling pathway.The Model group exhibited a significantly elevated renal coefficient(P<0.05),severe histopathological damage,and mitochondrial dysfunction compared to controls.Serum levels of NGAL,Scr,and BUN were markedly increased(P<0.05),indicating impaired renal function.Enhanced fluorescence signals of P-P38 MAPK,P-ERK,NGAL,and KIM-1 suggested activation of MAPK pathways and renal injury.Upregulation of pro-inflammatory cytokines(IL-1β,IL-6,TNF-α)and MAPK-related genes(P38 MAPK,ERK)alongside injury markers(NGAL,KIM-1)(P<0.05).Increased ratios of phosphorylated-to-total proteins(P-P38/P38,P-ERK/ERK)and elevated NGAL/KIM-1 protein levels confirmed pathway dysregulation.Treatment significantly reduced the renal coefficient(P<0.05),attenuated histological damage,and restored mitochondrial integrity.NGAL,Scr,and BUN levels were lowered,reflecting functional recovery.Diminished fluorescence intensities of P-P38,P-ERK,NGAL,and KIM-1 indicated suppression of injury pathways.Downregulation of inflammatory cytokines(IL-1β,IL-6,TNF-α),MAPK components(P38 MAPK,ERK),and injury markers(NGAL,KIM-1)(P<0.05).Reduced phosphorylation ratios(P-P38/P38,P-ERK/ERK)and decreased NGAL/KIM-1 protein expression demonstrated therapeutic efficacy.Conclusion:Ononin ameliorates inflammatory responses in AKI mice via the P38 MAPK/ERK pathway.
文摘BACKGROUND An echocardiogram is an essential tool in the evaluation of potential kidney transplant recipients(KTRs).Despite cardiac clearance,potential KTRs still have structural and functional abnormalities.Identifying the prevalence of these abnormalities and understanding their predictors is vital for optimizing pretransplant risk stratification and improving post-transplant outcomes.AIM To determine the prevalence of left ventricular hypertrophy(LVH),left ventricular systolic dysfunction(LVSD),diastolic dysfunction(DD),pulmonary hypertension(PH),and their predictors,and to assess their impact on graft function in pre-transplant candidates.METHODS The study included all successful transplant candidates older than 14 who had a baseline echocardiogram.Binary logistic regression models were constructed to identify factors associated with LVH,LVSD,DD,and PH.RESULTS Out of 259 patients,LVH was present in 64%(166),12%(31)had LVSD,27.5%(71)had DD,and 66(25.5%)had PH.Independent predictors of LVH included male gender[odds ratio(OR):2.51;95%CI:1.17-5.41 P=0.02],PH(OR=2.07;95%CI:1.11-3.86;P=0.02),DD(OR:2.47;95%CI:1.29-4.73;P=0.006),and dyslipidemia(OR=1.94;95%CI:1.07-3.53;P=0.03).Predictors for LVSD included patients with DD(OR=3.3,95%CI:1.41-7.81;P=0.006)and a family history of coronary artery disease(OR=4.50,95%CI:1.33-15.20;P=0.015).Peritoneal dialysis was an independent predictor for DD(OR=10.03;95%CI:1.71-58.94,P=0.011).The presence of LVH(OR=3.32,95%CI:1.05-10.55,P=0.04)and mild to moderate or moderate to severe mitral regurgitation(OR=4.63,95%CI:1.45-14.78,P=0.01)were significant factors associated with PH.These abnormalities had no significant impact on estimated glomerular filtration at discharge,6 months,1 year,or 2 years post-transplant.CONCLUSION Significant echocardiographic abnormalities persist in a potential transplant candidate despite cardiac clearance,although they don’t affect future graft function.Understanding the risk factors associated with these abnormalities may help clinicians address these factors pre-and post-transplant to achieve better outcomes.
文摘Post-kidney transplant rejection is a critical factor influencing transplant success rates and the survival of transplanted organs.With the rapid advancement of artificial intelligence technologies,machine learning(ML)has emerged as a powerful data analysis tool,widely applied in the prediction,diagnosis,and mechanistic study of kidney transplant rejection.This mini-review systematically summarizes the recent applications of ML techniques in post-kidney transplant rejection,covering areas such as the construction of predictive models,identification of biomarkers,analysis of pathological images,assessment of immune cell infiltration,and formulation of personalized treatment strategies.By integrating multi-omics data and clinical information,ML has significantly enhanced the accuracy of early rejection diagnosis and the capability for prognostic evaluation,driving the development of precision medicine in the field of kidney transplantation.Furthermore,this article discusses the challenges faced in existing research and potential future directions,providing a theoretical basis and technical references for related studies.
基金Supported by the National Science and Technology Research Center(Morocco)“PhD-Associate Scholarship-PASS”Program,No.88UH2C2023.
文摘BACKGROUND Donor-specific antibodies(DSAs)against human leukocyte antigen(HLA)-DQ are increasingly recognized as major contributors to antibody-mediated rejection(AMR)and graft failure in kidney transplantation.However,their clinical impact remains understudied in Morocco.AIM To evaluate the presence and implications of anti-HLA-DQ DSAs in Moroccan kidney transplant recipients.METHODS We retrospectively analyzed the immunological profiles and clinical outcomes of kidney transplant recipients screened for anti-HLA antibodies between 2015 and 2020,who developed anti-HLA-DQ DSAs either before or after transplantation.Anti-HLA antibodies were identified using Luminex®single antigen bead technology,and clinical follow-up included graft function assessment,biopsy interpretation,and evaluation of immunosuppression.RESULTS In the pre-transplant group(n=6 with confirmed donor typing),patients with low to moderate median fluorescence intensity(MFI)anti-HLA-DQ DSAs(MFI 561-1581)underwent successful transplantation and maintained stable graft function under optimized immunosuppression.In contrast,in the post-transplant group(n=6 with confirmed donor typing),the emergence of de novo anti-HLA-DQ DSAs was consistently associated with AMR,with MFI values reaching up to 19473,with biopsy-proven AMR in 5 of 6 cases and suspicion of AMR in 1 case.Two representative cases are detailed to illustrate the clinical impact of DQ DSAs:one patient developed high-level anti-DQB1*02 de novo DSA(MFI 12029)with persistent AMR after 5 years,while another developed anti-DQA1*05:01 de novo DSA after an early AMR episode but maintained stable graft function after 5 years(creatinine 1.48 mg/dL).CONCLUSION Our findings underscore the clinical significance of anti-HLA-DQ DSAs in Moroccan kidney transplant recipients.While preformed DSAs with low immunogenicity may permit successful transplantation,de novo DSAs strongly correlate with AMR.Proactive monitoring,including routine DSA screening and HLA-DQ typing,could improve graft outcomes by enabling early intervention and better donor selection.
文摘Kidney transplantation(KT)accounts for nearly three-fourths of organ transplants in India,with living donors contributing to 82%of cases.Induction immunosuppression is essential to optimize initial immunosuppression,reduce acute rejections,and enable tailored use of maintenance agents.Rabbit anti-thymocyte globulin(rATG)and interleukin-2 receptor anatagonists(IL-2RA/IL-2RBs)are the most widely used induction therapies.However,data on induction practices across India are limited.To evaluate induction immunosuppression practices across KT centers in India and establish a consensus for different subsets of KT recipients.A nationwide online survey was conducted by the Indian Society of Organ Transplantation(ISOT)among its members(400 KT centers).Responses were analyzed to assess induction practices across diverse donor types,age groups,and immunological risk profiles.Heterogeneity in practices prompted consensus building using a modified Delphi process.Literature review and expert panel discussions(April 2024)were followed by structured voting,and 16 consensus statements were finalized.Of 400 centers approached,254 participated.rATG was the most commonly used induction therapy,followed by IL-2RBs;alemtuzumab was least used.Significant heterogeneity was observed in type,dose,and duration of induction therapy.Consensus recommendations were framed:rATG for high immunological risk recipients and deceased donor KTs;IL-2RB or low-dose rATG for low immunological risk;rituximab in ABOincompatible KTs;and tailoring based on age,diabetes,donor type,infection risk,and affordability.This first ISOT consensus provides 16 India-specific statements on induction therapy in KT.It emphasizes risk-stratified,evidenceinformed,and context-appropriate induction strategies,supporting standardization of care across the country.
文摘BACKGROUND With the increasing use of laparoscopic techniques in living-donor kidney transplantation,limitations in donor vessel length,particularly of the right renal vein,pose significant challenges for vascular anastomosis to the recipient’s external iliac vein.These anatomical constraints can complicate graft implantation and increase the risk of postoperative complications.CASE SUMMARY To address the issue of short right renal veins,several surgical strategies have been proposed.In this report,we describe our experience with three cases in which venous extension was successfully achieved using a venous cuff interposition technique during back-table reconstruction.This approach was used to facilitate secure vascular anastomosis and improve graft positioning in anatomically complex transplant scenarios.CONCLUSION Venous cuff interposition represents an effective technique for managing short renal veins in living-donor kidney transplantation.It provides additional length and flexibility,easing anastomotic tension and supporting successful transplantation.
文摘BACKGROUND Post-transplant tertiary hyperparathyroidism(PT-tHPT)is a well-recognized complication following kidney transplantation,characterized by persistent excessive secretion of parathyroid hormone(PTH)despite improved renal function.It is potentially associated with an increased risk of cardiovascular events,renal osteodystrophy,pathologic fractures,graft loss,and mortality.AIM To evaluate the incidence,risk factors,and outcomes of PT-tHPT amongst kidney transplant recipients.METHODS A total of 887 transplant recipients who underwent transplantation between 2000 and 2020 were evaluated.Univariable and multivariable logistic regression was performed to determine the predictors of tertiary hyperparathyroidism.Graft and recipient outcomes were assessed using multivariable Cox regression.A separate multivariable Cox regression was performed to determine the effect of treatment strategies on outcomes.RESULTS PT-tHPT,defined as elevated PTH(>65 ng/L)and persistent hypercalcemia(>2.60 mmol/L),was diagnosed in 14%of recipients.Risk factors for PT-tHPT included older age[odds ratio(OR)=1.36,P<0.001],Asian ethnicity(OR=0.33,P=0.006),total ischemia time(OR=1.03,P=0.048 per hour),pre-transplant serum calcium(OR=1.38,P<0.001)per decile increase,pre-transplant PTH level(OR=1.31,P<0.001)per decile increase,longer dialysis duration(OR=1.12,P=0.002)per year,history of acute rejection(OR=2.37,P=0.012),and slope of estimated glomerular filtration rate change(OR=0.91,P=0.001).There were a 3.4-fold higher risk of death-censored graft loss and a 1.9-fold greater risk of recipient death with PT-tHPT.The three treatment strategies of conservative management,calcimimetic and parathyroidectomy did not significantly change the graft or patient outcome.CONCLUSION Pretransplant elevated calcium and PTH levels,older age and dialysis duration are associated with PT-tHPT.While PT-tHPT significantly affects graft and recipient survival,the treatment strategies did not affect survival.
文摘Background:Refined models of kidney disease are critical to better understand disease processes and study novel treatments while minimizing discomfort in research animals.The objective of this study was to report a technique for minimally invasive partial kidney embolism in cats and describe outcomes following transcatheter administration of embolic microspheres with subsequent contralateral nephrectomy.Methods:Eleven,apparently healthy,male,purpose-bred cats underwent unilateral kidney embolism with 0.25 or 0.5 mL of embolic microparticle(40-120μm)suspension(0.2 mL microspheres/mL)delivered into the right renal artery under fluoroscopic guidance,followed 5 months later by contralateral nephrectomy.One month after nephrectomy,blood and urinary markers of kidney function were evaluated,and embolized kidneys were harvested for histopathology evaluation.Results:Renal artery embolization was possible in all cats.Two cats did not complete the study,one after experiencing congestive heart failure(n=1)and the other following evidence of complete kidney embolism precluding nephrectomy(n=1)postembolization.At study end,compared to baseline,cats had significant increases in median(range)serum creatinine(159.1μmol/L[141.4-530.4]versus 128.2μmol/L[92.8-150.3];p=0.0004),urea nitrogen(15.71 mmol/L[9.29-47.85]versus 7.50 mmol/L[6.07-8.57];p<0.0001),and symmetric dimethylarginine(0.74μmol/L[0.59-3.12]versus 0.67μmol/L[0.54-0.72];p=0.0288)concentrations.No differences in markers of kidney function were documented between dose groups.Conclusions:M inimally invasive kidney embolism is a promising technique for modeling kidney disease in cats.Understanding optimal dose,timing of nephrectomy,and longer-term consequences requires additional work.
文摘BACKGROUND Acute kidney injury(AKI)is a common and serious complication following heart transplantation,significantly impacting patient outcomes and survival rates.AKI after transplantation can lead to prolonged hospital stays,increased morbidity,and even mortality.AIM To identify and quantify significant risk factors associated with AKI following heart transplantation through a systematic review and meta-analysis.This study aims to distinguish predictive variables that may inform perioperative risk stratification and clinical decision-making.METHODS Electronic searches on MEDLINE,Google Scholar,ScienceDirect,Clinical-Trials.gov,and Cochrane databases were conducted from inception up till September 1.Included studies were randomized controlled trials,clinical trials,retrospective cohort,and observational studies.Exclusion criteria encompassed studies with pediatric populations,non-English publications,case reports,and studies lacking sufficient data on AKI outcomes.Statistical analysis was performed using RevMan 5.4,reporting dichotomous outcomes as odds ratios(OR)and continuous outcomes as mean differences(MD)with 95%confidence intervals(CI).Quality assessment of the included studies was performed using the New Castle Ottawa Scale.RESULTS Out of 1345 articles,13 studies with 3330 patients were included.Significant risk factors included age[overall MD=2.27 years(95%CI:0.13 to 4.41)],body mass index(BMI)[MD=1.42(95%CI:0.60 to 2.24)],diabetes[overall OR=1.47(95%CI:1.16 to 1.85)],chronic kidney disease(CKD)[OR=2.67(95%CI:1.73 to 4.14)],chronic obstructive pulmonary disorder(COPD)[OR=0.49(95%CI:0.27 to 0.89)],previous thoracic surgery[(OR)=1.27,95%CI:(1.05 to 1.54)],cardio-pulmonary bypass time[(MD)=17.10,95%CI:(6.12 to 28.08)],mechanical ventilation duration[(MD)=30.87 hours,95%CI:(10.69 to 51.05)]and extracorporeal membrane oxygenation[(OR)=2.31,95%CI:(1.25 to 4.26)].Factors not associated with AKI after heart transplantation included Recipients’male sex(P=0.55),donor sex(P=0.11),hypertension(P=0.13),smoking(P=0.20),coronary artery disease(P=0.90),pulmonary artery disease(P=0.81),dilated cardiomyopathy(P=0.79),ventilation duration(P=0.24),ischemic time(P=0.06),use of intra-aortic balloon pump(P=0.14),LVAD transplantation(P=0.83),and Inotropes use(P=0.78).CONCLUSION Age,BMI,diabetes,CKD,COPD,previous thoracic surgery,prolonged CPB time,extended mechanical ventilation,and ECMO use are significant predictors of AKI following heart transplantation,necessitating vigilant monitoring and individualized risk assessment.Conversely,factors such as LVAD implantation and inotrope use showed no significant association,highlighting the need for further investigation into their roles.Future prospective studies are essential to validate these findings,elucidate underlying mechanisms,and develop targeted interventions to mitigate AKI risk and improve patient outcomes.
文摘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.
文摘BACKGROUND Equations for estimation glomerular filtration rate(eGFR)have been associated with poor clinical performance and their clinical accuracy and reliability have been called into question.AIM To assess the longitudinal changes in measured glomerular filtration rate(mGFR)in patients with autosomal dominant polycystic kidney disease(ADPKD).METHODS Analysis of an ambispective data base conducted on consecutive patients diagnosed with ADPKD.The mGFR was assessed by iohexol clearance;while eGFR was calculated by three different formulas:(1)The chronic kidney disease epidemiology collaboration(CKD-EPI);(2)Modification of diet in renal disease(MDRD);and(3)The 24-hour urine creatinine clearance(CrCl).The primary end-points were the mean change in mGFR between the baseline and final visit,as well as the comparison of the mean change in mGFR with the change estimated by the different formulas.RESULTS Thirty-seven patients were included in the study.As compared to baseline,month-6 mGFR was significantly decrease by-4.4 mL/minute±10.3 mL/minute(P=0.0132).However,the CKD-EPI,MDRD,and CrCl formulas underestimated this change by 48.3%,89.0%,and 45.8%respectively,though none of these differences reached statistical significance(P=0.3647;P=0.0505;and P=0.736,respectively).The discrepancies between measured and estimated glomerular filtration rate values,as evaluated by CKD-EPI(r=0.29,P=0.086);MDRD(r=0.19,P=0.272);and CrCl(r=0.09,P=0.683),were not correlated with baseline mGFR values.CONCLUSION This study indicated that eGFR inaccurately reflects the decline in mGFR and cannot reliably track changes over time.This poses significant challenges for clinical decision-making,particularly in treatment strategies.
文摘The endothelium modulates vascular homeostasis owing to a variety of vasoconstrictors and vasodilators.Endothelial dysfunction(ED),characterized by impaired vasodilation,inflammation,and thrombosis,triggers future cardiovascular(CV)diseases.Chronic kidney disease,a state of chronic inflammation caused by oxidative stress,metabolic abnormalities,infection,and uremic toxins damages the endothelium.ED is also associated with a decline in estimated glomerular filtration rate.After kidney transplantation,endothelial functions undergo immediate but partial restoration,promising graft longevity and enhanced CV health.However,the anticipated CV outcomes do not happen due to various transplant-related and unrelated risk factors for ED,culminating in poor CV health and graft survival.ED in kidney transplant recipients is an underrecognized and poorly studied entity.CV diseases are the leading cause of death among kidney transplant candidates with functioning grafts.ED contributes to the pathogenesis of many of the CV diseases.Various biomarkers and vasoreactivity tests are available to study endothelial functions.With an increasing number of transplants happening every year,and improved graft rejection rates due to the availability of effective immunosuppressants,the focus has now shifted to endothelial protection for the prevention,early recognition,and treatment of CV diseases.
文摘Chronic Kidney Disease (CKD) is ongoing damage of the kidneys, which affects their ability to filter the blood the way they should. Worldwide CKD is considered as the 16th leading cause of death and affects 8% - 16% of the population. CKD often goes unnoticed and is revealed as an incidental finding. Healthcare providers diagnose the condition as CKD based on persistent abnormal kidney function tests revealing kidney damage markers > 3 months, urine albumin creatinine ratio (UACR) > or equal to 30 mg/g per 24 hours, and GFR < 60 mL/min/1.73m<sup>2</sup>. In this article, we have discussed chronic kidney disease in terms of kidney physiology, chronic kidney disease pathophysiology, etiology, diagnosis, signs and symptoms, and management.
文摘BACKGROUND Despite the developments in the field of kidney transplantation,the already existing diagnostic techniques for patient monitoring are considered insufficient.Protein biomarkers that can be derived from modern approaches of proteomic analysis of liquid biopsies(serum,urine)represent a promising innovation in the monitoring of kidney transplant recipients.AIM To investigate the diagnostic utility of protein biomarkers derived from proteomics approaches in renal allograft assessment.METHODS A systematic review was conducted in accordance with PRISMA guidelines,based on research results from the PubMed and Scopus databases.The primary focus was on evaluating the role of biomarkers in the non-invasive diagnosis of transplant-related com-plications.Eligibility criteria included protein biomarkers and urine and blood samples,while exclusion criteria were language other than English and the use of low resolution and sensitivity methods.The selected research articles,were categorized based on the biological sample,condition and methodology and the significantly and reproducibly differentiated proteins were manually selected and extracted.Functional and network analysis of the selected proteins was performed.RESULTS In 17 included studies,58 proteins were studied,with the cytokine CXCL10 being the most investigated.Biological pathways related to immune response and fibrosis have shown to be enriched.Applications of biomarkers for the assessment of renal damage as well as the prediction of short-term and long-term function of the graft were reported.Overall,all studies have shown satisfactory diagnostic accuracy of proteins alone or in combination with conventional methods,as far as renal graft assessment is concerned.CONCLUSION Our review suggests that protein biomarkers,evaluated in specific biological fluids,can make a significant contribution to the timely,valid and non-invasive assessment of kidney graft.
文摘BACKGROUND Diabetic patients with atypical presentation are often challenging in terms of diagnosis and management.Kidney biopsy is not routinely done in diabetics,and clinicians are always in a dilemma in such a scenario to decide whether to do a biopsy or not.Since non-diabetic kidney diseases(NDKD)are common,and some patients may have NDKD superimposed on diabetic kidney diseases(DKD),therefore,kidney biopsy may be warranted to rule out NDKD.AIM To determine the prevalence of NDKD,DKD,or mixed lesions,identify predictors of NDKD,and investigate renal and patient survival,as well as factors associated with these outcomes.METHODS This retrospective observational study was conducted on patients with biopsyproven NDKD,DKD,and mixed lesions(having both NDKD and DKD).Binary logistic regression models were constructed to identify predictors of NDKD.Kaplan-Meier survival analysis was performed to compare time to kidney failure and patient survival across the three histological groups.Multivariable Cox proportional hazards regression was used to identify clinical and pathological factors associated with kidney failure and all-cause mortality.RESULTS A total of 103 biopsies were analyzed.Sixty-four(62.1%)had NDKD alone or mixed lesions.The most common NDKD pathologies were interstitial nephritis in 12(29.2%),focal segmental glomerulosclerosis in 10(24.4%),and immune complex–mediated glomerulonephritis in five(12.2%)patients.Compared to DKD,NDKD was associated with significantly lower odds of proteinuria>3.5 g/day[odds ratio(OR),0.02;P=0.0015],retinopathy(OR=0.04;P=0.0067),and diabetes duration≥10 years(OR=0.01;P=0.0002).However,NDKD had higher odds of anemia(Hemoglobin<12 g/dL;OR=9.56;P=0.0107)and creatinine levels>180μmol/L(OR=18.68;P=0.0063).Kaplan-Meier analysis showed significant differences in renal survival(log-rank P=0.0033).Patients with NDKD have the best outcomes,while those with DKD have the worst.In a multivariable Cox regression analysis,increasing age,creatinine,arteriosclerosis,and severe interstitial fibrosis and tubular atrophy were independently associated with kidney failure.At the same time,the use of renin angiotensin system blockers was protective(hazard ratio=0.43,P=0.02).Kaplan-Meier curves for patient survival also differed significantly(log-rank P=0.018);patients in the mixed group showed the highest mortality,while those with NDKD showed the lowest.Mortality was independently associated with older age,hypoalbuminemia,diabetic retinopathy,arteriosclerosis,and higher creatinine.CONCLUSION NDKD and mixed lesions are frequent in diabetic patients.These histological lesions carry distinct prognostic implications.Clinical features such as a shorter diabetes duration,absence of retinopathy,anemia,and elevated creatinine levels suggest NDKD and warrant biopsy.NDKD had better renal and patient survival rates,while mixed lesions had the worst outcomes.Older age,hypoalbuminemia,retinopathy,arteriosclerosis,and elevated creatinine were key predictors of mortality.
