Link between obstructive uropathy and acute kidney injury

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

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

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

Longitudinal assessment of measured and estimated glomerular filtration-rate in autosomal dominant polycystic kidney disease:Real practice experience

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.

Exploring the mechanistic role of epidermal growth factor receptor activation in non-cancer kidney disease

The epidermal growth factor receptor(EGFR)is a transmembrane glycoprotein that plays a crucial role in signal transduction and cellular responses.This review explores the function of EGFR in kidney physiology and its implications for various kidney diseases.EGFR signaling is essential for kidney function and repair mechanisms,and its dysregulation significantly impacts both acute and chronic kidney conditions.The review discusses the normal distribution of EGFR in kidney tubular segments,the mechanism of its activation and inhibition,and the therapeutic potential of EGFR-targeting antagonists and ligands.Additionally,it explores the pathophysiological characteristics observed in rodent models of kidney diseases through pharmacological and genetic inhibition of EGFR,highlighting therapeutic challenges and limitations such as species differences,variability in disease models,and potential adverse effects.Overall,the findings underscore the multifaceted role of EGFR in kidney diseases,influencing inflammation,fibrosis,and tissue injury.This complex involvement suggests that targeting EGFR may be a beneficial therapeutic strategy for managing these conditions,potentially mitigating inflammation and fibrosis while promoting tissue repair.

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

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

Optimizing chronic kidney disease management:The potential of a multi-strain probiotic formulation

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.

Hepatorenal syndrome:Paving a pathway from a fatal condition to an opportunity to preserve kidney function

In the 19^(th)century,von Frerichs F and Flint A identified a type of acute renal impairment associated with advanced liver disease,characterized by oliguria,absence of proteinuria,and normal renal histology,which was later termed hepatorenal syndrome(HRS).HRS primarily affects cirrhotic patients with ascites and often follows severe infections,digestive hemorrhages,or high-volume paracentesis.Pathophysiologically,HRS involves low glomerular filtration rate,hypotension,renin-angiotensin axis activation,water clearance,hyponatremia,and minimal urinary sodium excretion.These conditions mimic those seen in decreased effective circulatory volume(ECV)scenarios such as septic shock or heart failure.HRS represents a specific form of prerenal acute kidney injury(AKI)in patients with baseline renal ischemia,where the kidney attempts to correct decreased ECV by retaining sodium and water.Intense renal vasoconstriction,passive hyperemia from ascites,and acute tubular necrosis(ATN)with specific urinary sediment changes are observed.Persistent oliguria may transition HRS to ATN,although this shift is less straightforward than in other prerenal AKI contexts.Notably,liver grafts from HRS patients can recover function more rapidly than those from other ischemic conditions.Experimental studies,such as those by Duailibe et al,using omega-3 fatty acids in cirrhotic rat models,have shown promising results in reducing oxidative stress and improving kidney function.These findings suggest potential therapeutic strategies and underscore the need for further research to understand the mechanisms of HRS and explore possible treatments.Future research should address the impact of omega-3 on survival and secondary outcomes,as well as consider the balance of therapeutic risks and benefits in severe liver disease.

Intravenous iron in chronic kidney disease without anaemia but iron deficiency:A scoping review

Iron deficiency(ID)is a prevalent complication of chronic kidney disease(CKD),often managed reactively when associated with anaemia.This scoping review evaluates the evidence supporting intravenous(IV)iron therapy in non-anaemic individuals with CKD and ID,focusing on safety,efficacy,and emerging therapeutic implications.Current diagnostic markers,including serum ferritin,transferrin saturation,and reticulocyte haemoglobin content,are reviewed alongside their limitations in the context of inflammation and variability.The pathophysiology of ID in CKD is explored,highlighting the roles of hepcidin,hypoxia-inducible factor pathways,and uraemic toxins.Comparative studies reveal that IV iron offers a more rapid correction of iron stores,improved com-pliance,and fewer gastrointestinal side effects compared to oral iron.Evidence from trials such as“iron and heart”and“iron and muscle”suggests potential benefits of IV iron on functional capacity and fatigue,though findings were sta-tistically non-significant.Insights from heart failure trials support the safety and efficacy of IV iron in improving quality of life and reducing hospitalizations,with newer formulations like ferric derisomaltose demonstrating favourable safety profiles.This review underscores the need for standardized screening protocols for ID in CKD,even in the absence of anaemia,to facilitate earlier intervention.Future research should prioritise robust outcome measures,larger sample sizes,and person-specific treatment strategies to optimise dosing and administration frequency.Tailored approaches to IV iron therapy have the potential to significantly improve functional outcomes,quality of life,and long-term health in people with CKD.

Safety and efficacy of sodium bicarbonate for treating metabolic acidosis in chronic kidney disease:A systematic review and metaanalysis

BACKGROUND Kidney dysfunction and reduced filtration capacity due to chronic kidney disease(CKD)lead to a shift in the body's acid-base balance,ultimately causing metabolic acidosis(MA).Sodium bicarbonate has been used as a supplement to alleviate the symptoms and reverse the acidosis,and it may even slow the progression of CKD.However,its safety profile and overall effectiveness are uncertain.AIM To conduct a systematic review and meta-analysis of clinical trials assessing sodium bicarbonate's safety and efficacy for treating CKD-induced MA.METHODS Medline,Scopus,EMBASE,and Cochrane Central were systematically searched from inception until May 2024 to select all relevant randomized control trials(RCTs)and non-RCT(NRCTs)evaluating the effectiveness of sodium bicarbonate in correcting MA in end-stage renal disease patients.In addition,ClinicalTrials.gov,Medrxiv.org,and Google Scholar were searched for other literature.A random-effects meta-analysis was performed to derive mean differences(MD)and risk ratios(RR)with their 95%CI for continuous and dichotomous outcomes respectively.RESULTS Following a systematic search of the databases,20 RCTs and 2 and NRCTs comprising 2932 patients were included in our study.The results revealed that sodium bicarbonate significantly increased serum bicarbonate in CKD patients(MD:2.59,95%CI:0.95-4.22;P=0.02;I2=95%).However,there was a non-significant increase in estimated glomerular filtration rate(eGFR)in patients on sodium bicarbonate therapy(MD:0.93,95%CI:-1.88-3.75;P=0.52;I2=93%).Upon assessment of the safety profile of sodium bicarbonate,no significant association was found in the outcomes of death/prolonged hospitalization(RR:1.05,95%CI:0.84-1.32;P=0.66;I2=0%),or gastrointestinal disorders(RR:1.64,95%CI:0.35-7.66;P=0.53;I2=76%),or worsening edema(RR:1.26,95%CI:0.94-1.68;P=0.12;I2=37%)when compared to control.CONCLUSION Sodium bicarbonate therapy may halt worsening kidney function by correcting serum bicarbonate levels and treating MA.Although sodium bicarbonate does not significantly improve the eGFR,it may potentially prevent CKD progression while maintaining an overall favorable safety profile.

Exploring the links between gallstone disease, non-alcoholic fattyliver disease, and kidney stones: A path to comprehensiveprevention

The recent study exploring the bidirectional associations between gallstone disease,non-alcoholic fatty liver disease,and kidney stone disease highlights a critical concern in chronic disease management.Given the rising global prevalence of these conditions,understanding their interconnections is essential.The study emphasizes the importance of shared risk factors,such as obesity,type 2 diabetes,dyslipidemia,and oxidative stress,and calls for multidisciplinary screening strategies.This approach would improve patient outcomes and reduce the socio-economic burden.While the study contributes valuable insights from a Chinese population,further research across diverse populations is necessary to validate and extend these findings globally.Ultimately,the research underscores the need for integrated prevention programs to better manage these interconnected diseases and improve health outcomes.

Critical assessment of the reported bidirectional associations between gallstone, non-alcoholic fatty liver, and kidney stone diseases

The recent article by Jiang et al published in World Journal of Gastroenterology reports substantial bidirectional associations between gallstone disease(GSD),non-alcoholic fatty liver disease(NAFLD),and kidney stone disease(KSD),based on multicenter cross-sectional studies and a systematic review with meta-analysis.While the findings have the potential to significantly impact clinical and pre-ventive strategies,several methodological issues merit closer examination.This letter critiques key aspects of the study,including sample population hetero-geneity,potential confounding variables,and the reliance on cross-sectional data that may limit causal inferences.We also discuss the generalizability of these results to broader populations given the study's focus on the Chinese demogra-phic.By addressing these concerns,we suggest a more nuanced interpretation of the associations between GSD,NAFLD,and KSD,advocating for longitudinal studies to validate these findings and enhance their applicability in global health contexts.

Providing care for kidney transplant recipients:An overview for generalists

Kidney transplantation is the preferred treatment for patients with advanced chronic kidney disease and end-stage kidney disease,offering superior quality of life and survival compared to dialysis.This manuscript provides an updated overview of post-transplant care,highlighting recent advancements and current practices to assist generalists in managing these patients.It covers key areas such as immunosuppression strategies,drug interactions,and the management of transplant-specific acute kidney injury.The focus includes the use of sodium-glucose cotransporter-2 inhibitors and cell-free DNA monitoring for evaluating allograft health and immune-mediated injury.The manuscript reviews the fundamentals of immunosuppression,including both induction and maintenance therapies,and underscores the importance of monitoring kidney function,as well as addressing hypertension,diabetes,and infections.It also provides recommen-dations for vaccinations and cancer screening tailored to kidney transplant reci-pients and emphasizes lifestyle management strategies,such as exercise and so-dium intake,to reduce post-transplant complications.

Alpiniae oxyphyllae Fructus ameliorates renal lipid accumulation in diabetic kidney disease via activating PPARα

Objective:To investigate the effects of Alpiniae oxyphyllae Fructus(AOF)on renal lipid deposition in diabetic kidney disease(DKD)and elucidate its molecular mechanisms.Methods:The mechanism of AOF in treating DKD was explored by network pharmacological enrichment analysis,molecular docking,and molecular dynamics simulation.The effects of AOF on renal function and lipid deposition were assessed in a mouse model of DKD and high glucose-stressed HK-2 cells.Cell viability and lipid accumulation were detected by CCK8 and oil red O staining.The expressions of PPARαand fatty acid oxidation-related genes(ACOX1 and CPT1A)were detected by quantitative RT-PCR,Western blot,and immunofluorescence.Furthermore,PPARαknockdown was performed to examine the molecular mechanism of AOF in treating DKD.Results:Network pharmacological enrichment analysis,molecular docking,and molecular dynamics simulation showed that the active compounds in AOF targeted PPARαand thus transcriptionally regulated ACOX1 and CPT1A.AOF lowered blood glucose,improved dyslipidemia,and attenuated renal injury in DKD mice.AOF-containing serum accentuated high glucose-induced decrease in cell viability and ameliorated lipid accumulation.Additionally,it significantly upregulated the expression of PPARα,ACOX1,and CPT1A in both in vivo and in vitro experiments,which was reversed by PPARαknockdown.Conclusions:AOF may promote fatty acid oxidation via PPARαto ameliorate renal lipid deposition in DKD.

Distressing symptoms and health-related quality of life in patients with chronic kidney disease

BACKGROUND Chronic kidney disease(CKD)is an incapacitating illness associated with distressing symptoms(DS)that have negative impact on patients’health-related quality of life(HRQOL).AIM To assess the severity of DS and their relationships with HRQOL among patients with CKD in Jordan.METHODS A descriptive cross-sectional design was used.A convenience sampling approach was used to recruit the participants.Patients with CKD(n=140)who visited the outpatient clinics in four hospitals in Amman between November 2021 and December 2021 were included.RESULTS The Edmonton Symptom Assessment System was used to measure the severity of the DS while the Short Form-36 tool was used to measure the HRQOL.Participants’mean age was 50.9(SD=15.14).Most of them were males(n=92,65.7%),married(n=95,67.9%),and unemployed(n=93,66.4%).The highest DS were tiredness(mean=4.68,SD=2.98)and worse well-being(mean=3.69,SD=2.43).The highest HRQOL mean score was for the bodily pain scale with a mean score of 68.50 out of 100(SD=32.02)followed by the emotional well-being scale with mean score of 67.60(SD=18.57).CONCLUSION Patients with CKD had suboptimal HRQOL,physically and mentally.They suffer from multiple DS that have a strong association with diminished HRQOL such as tiredness and depression.Therefore,healthcare providers should be equipped with the essential knowledge and skills to promote individualized strategies that focusing on symptom management.

Effect of kidney transplantation on sexual dysfunction in patients with end stage renal disease:A systematic review

BACKGROUND End-stage renal disease(ESRD)is associated with a multitude of physical,psychological,and social health challenges,including a profound impact on sexual and reproductive health.Among males with ESRD,erectile dysfunction(ED)is highly prevalent due to factors such as underlying comorbidities,including diabetes and hypertension,and the physiological effects of long-term dialysis.Kidney transplantation(KTx)has been proposed as a potential intervention to mitigate the effects of ED by restoring renal function and improving hormonal balance.However,the evidence surrounding the effectiveness of KTx in improving sexual function,specifically erectile function(EF),remains inconclusive.This systematic review and meta-analysis aim to evaluate the effects of KTx on sexual dysfunction(SexDys),particularly ED,in male ESRD patients.AIM To evaluate the benefits and potential harms of KTx compared to other forms of renal replacement therapy in improving EF in adult males with ESRD,assessed using the international index of EF(IIEF),to survey the prevalence of SexDys in this population,and to assess the correlation between various factors and SexDys through regression analysis.METHODS A systematic search of PubMed,EMBASE,Cochrane Library,Scopus,Clinical-Trials.gov,and Google Scholar was conducted,following the PRISMA 2020 guidelines.Prospective and retrospective cohort studies,as well as cross-sectional studies assessing EF pre-and post-transplantation,were included.These studies used validated tools such as the IIEF to measure EF.Meta-analyses were performed using a random-effects model to estimate standardized mean differences(SMD)and hazard ratios(HR)with 95%confidence intervals(CI).Heterogeneity was assessed using the I²statistic,and publication bias was evaluated with a funnel plot and the Egger’s test.RESULTS A total of 2419 studies were identified,with 362 abstracts screened and 193 full-text articles reviewed.Ultimately,11 studies were included for qualitative analysis and 7 for quantitative synthesis.The random effects model for SMD yielded a combined estimate of 0.43(95%CI:-0.20-1.07),indicating a small but non-significant improvement in EF post-transplantation.The heterogeneity across studies was substantial(I²=90%),reflecting significant variability in outcomes.Subgroup analysis showed greater improvements in EF among living-donor transplant recipients compared to those receiving organs from deceased donors.Despite this trend,the overall result for changes in EF was not statistically significant(P=0.15).Additionally,the combined HR from the meta-analysis was 2.87(95%CI:1.76-4.69),suggesting that KTx significantly increases the likelihood of improved EF,though variability between studies persisted(I²=63%).CONCLUSION While KTx offers some promise for improving EF in male ESRD patients,the overall evidence remains inconclusive due to high heterogeneity between studies and a lack of statistical significance in the combined results.Despite this,individual studies suggest that KTx may lead to significant improvements in EF for certain subgroups,particularly living-donor recipients.Future research should focus on larger,well-designed cohort studies with standardized outcome measures to provide more definitive conclusions.Addressing SexDys as part of routine care for ESRD patients undergoing KTx is crucial to improving their overall quality of life.However,adjunct therapies such as phosphodiesterase type 5 inhibitors may be necessary for those who do not experience adequate improvements post-transplantation.

Association between high-sensitivity troponin T levels below the ninety-ninth percentile and diabetic kidney disease: A crosssectional study

BACKGROUND Identification of myocardial injury has traditionally relied on high-sensitivity troponin T(hs-TnT)levels exceeding the 99th percentile threshold.However,patients with detectable hs-TnT levels below this threshold represent a heterogeneous group with an inadequately characterized risk profile.AIM To investigate the association between hs-TnT levels below the 99th percentile and the presence of diabetic kidney disease(DKD)in patients with diabetes mellitus.METHODS This study analyzed data from the National Health and Nutrition Examination Survey obtained between 1999 and 2004,focusing on adults with type 2 diabetes mellitus.Serum hs-TnT concentrations were evaluated.DKD was defined as impaired glomerular filtration rate(<60 mL/minute/1.73 m^(2)),proteinuria(urinary albumin-to-creatinine ratio of≥30 mg/g),or both conditions in patients with diabetes mellitus.Weighted multivariable logistic regression analysis and restricted cubic spline analyses were employed to examine the independent association between hs-TnT and DKD,with the likelihood ratio test being used to evaluate nonlinearity.RESULTS The study included 2505 patients with a mean age of 55.02(standard error:0.72)years,of whom 44.87%were females.Among the participants,909(32.34%)were diagnosed with DKD.Multivariable logistic regression analysis indicated that,compared to the lowest tertile of hs-TnT(<5.93 ng/L),tertile 2(5.94-9.79 ng/L)had an odds ratio of 1.25(95%confidence interval:0.77-2.02,P=0.350),while tertile 3(9.80-21.88 ng/L)had an odds ratio of 2.07(95%confidence interval:1.13-3.80,P=0.022),with a significant trend(P for trend=0.022).Smoothed curve fitting demonstrated a linear association between hs-TnT levels and DKD in the overall population(P=0.061 for nonlinearity)and in male(P=0.136 for nonlinearity)and female(P=0.067 for nonlinearity)subgroups.Further stratification and sensitivity analyses yielded consistent conclusions.CONCLUSION Our study findings suggest that in individuals with type 2 diabetes,detectable hs-TnT levels below the 99th percentile are associated with DKD.

Prevalence and clinical characteristics of chronic kidney disease among patients with newly diagnosed ketosis-onset diabetes

BACKGROUND The prevalence and clinical characteristics of chronic kidney disease(CKD)among patients with ketosis-onset diabetes(also known as ketosis-prone diabetes)remain unclear.Furthermore,the classification of ketosis-onset diabetes remains controversial and requires further investigation.AIM To investigate the prevalence and clinical features of CKD in patients with newly diagnosed ketosis-onset diabetes.METHODS This real-world study included 217 patients with type 1 diabetes mellitus(T1DM),698 with ketosis-onset diabetes,and 993 with non-ketotic T2DM.The prevalence and clinical characteristics of CKD were compared among the three groups.Risk factors associated with CKD were evaluated using binary logistic regression for each group.RESULTS After adjusting for age and sex,the prevalence of CKD among patients with ketosis-onset diabetes(17.8%)was significantly higher than that in those with T1DM(8.3%,P=0.007),but was not statistically different compared to those with non-ketotic T2DM(21.7%,P=0.214).Furthermore,some risk factors for CKD,including age,and serum uric acid and C-reactive protein levels,in patients with ketosis-onset diabetes were similar to those with T2DM,but significantly different from those with T1DM.CONCLUSION The prevalence,clinical characteristics,and risk factors for CKD among patients with ketosis-onset diabetes were more similar to those with non-ketotic T2DM but considerably different from those with T1DM.These findings further support the classification of ketosis-onset diabetes as a subtype of T2DM rather than idiopathic T1DM.

Transcriptome and single-cell profiling of the mechanism of diabetic kidney disease

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.

Radiotherapy in Non-Functioning Pituitary Macroadenoma： Mansoura Experience

OBJECTIVE The current retrospective study aims to evaluate the management of non-functioning the assessment of experience on pituitary macroadenoma through clinical, biochemical, radiological features, and treatment outcome of patients, and to identify prognostic factors affecting progression-free survival （PFS）. METHODS Data of 55 patients macroadenoma presented to the with non-functioning pituitary Clinical Oncology and Nuclear Medicine department between 1998 and 2009 were investigated. RESULTS The most common symptom was visual disturbance （38.2%） followed by headache （27.3%）. The presence of male predominance was observed （1.4：1）. Ten patients received radio-therapy （RT） only. Extrasellar extension was the more common treatment. The overall response rate was 72.8% with completed response at 16.4%. Memory and intellectual sequelae were the most common late complications of treatment （14%）. The ten-year PFS was at 84.6%. PFS was found to be significantly better with higher dose of RT （up to 54 Gy）, treatment by both surgery and RT, absence of visual field defect, and tumor localized to sella, whereas it was not significantly affected by age and sex. CONCLUSION The data confirmed that the prevalence of mass effect and hypopituitarism in patients with non-functioning pituitary macroadenoma is elevated. Conventional external RT up to 54 Gy is safe and effective in controlling non-functioning pituitary macro- adenoma with tolerable and acceptable morbidity.

Validation and performance of three scoring systems for predicting primary non-function and early allograft failure after liver transplantation

Background: Primary non-function(PNF) and early allograft failure(EAF) after liver transplantation(LT) seriously affect patient outcomes. In clinical practice, effective prognostic tools for early identifying recipients at high risk of PNF and EAF were urgently needed. Recently, the Model for Early Allograft Function(MEAF), PNF score by King's College(King-PNF) and Balance-and-Risk-Lactate(BAR-Lac) score were developed to assess the risks of PNF and EAF. This study aimed to externally validate and compare the prognostic performance of these three scores for predicting PNF and EAF. Methods: A retrospective study included 720 patients with primary LT between January 2015 and December 2020. MEAF, King-PNF and BAR-Lac scores were compared using receiver operating characteristic(ROC) and the net reclassification improvement(NRI) and integrated discrimination improvement(IDI) analyses. Results: Of all 720 patients, 28(3.9%) developed PNF and 67(9.3%) developed EAF in 3 months. The overall early allograft dysfunction(EAD) rate was 39.0%. The 3-month patient mortality was 8.6% while 1-year graft-failure-free survival was 89.2%. The median MEAF, King-PNF and BAR-Lac scores were 5.0(3.5–6.3),-2.1(-2.6 to-1.2), and 5.0(2.0–11.0), respectively. For predicting PNF, MEAF and King-PNF scores had excellent area under curves(AUCs) of 0.872 and 0.891, superior to BAR-Lac(AUC = 0.830). The NRI and IDI analyses confirmed that King-PNF score had the best performance in predicting PNF while MEAF served as a better predictor of EAD. The EAF risk curve and 1-year graft-failure-free survival curve showed that King-PNF was superior to MEAF and BAR-Lac scores for stratifying the risk of EAF. Conclusions: MEAF, King-PNF and BAR-Lac were validated as practical and effective risk assessment tools of PNF. King-PNF score outperformed MEAF and BAR-Lac in predicting PNF and EAF within 6 months. BAR-Lac score had a huge advantage in the prediction for PNF without post-transplant variables. Proper use of these scores will help early identify PNF, standardize grading of EAF and reasonably select clinical endpoints in relative studies.