Background:Information on the association between physical activity(PA)and the risk of chronic kidney disease(CKD)is limited.We aimed to explore the associations of total,domain-specific,and intensity-specific PA with...Background:Information on the association between physical activity(PA)and the risk of chronic kidney disease(CKD)is limited.We aimed to explore the associations of total,domain-specific,and intensity-specific PA with CKD and its subtypes in China.Methods:The study included 475,376 adults from the China Kadoorie Biobank aged 30-79 years during 2004-2008 at baseline.An interviewer-administered questionnaire was used to collect the information about PA,which was quantified as metabolic equivalent of task hours per day(MET-h/day)and categorized into 4 groups based on quartiles.Cox regression was used to analyze the association between PA and CKD risk.Results:During a median follow-up of 12.1 years,5415 incident CKD cases were documented,including 1159 incident diabetic kidney disease(DKD)cases and 362 incident hypertensive nephropathy(HTN)cases.Total PA was inversely associated with CKD risk,with an adjusted hazard ratio(HR,95%confidence interval(95%CI))of 0.83(0.75-0.92)for incident CKD in the highest quartile of total PA as compared with participants in the lowest quartile.Similar results were observed for risk of DKD and HTN,and the corresponding HRs(95%CIs)were 0.75(0.58-0.97)for DKD risk and 0.56(0.37-0.85)for HTN risk.Increased nonoccupational PA,low-intensity PA,and moderate-to-vigorous-intensity PA were significantly associated with a decreased risk of CKD,with HRs(95%CIs)of 0.80(0.73-0.88),0.85(0.77-0.94),and 0.85(0.76-0.95)in the highest quartile,respectively.Conclusion:PA,including nonoccupational PA,low-intensity PA,and moderate-to-vigorous-intensity PA,was inversely associated with the risk of CKD,including DKD,HTN,and other CKD,and such associations were dose dependent.展开更多
BACKGROUND Diabetic kidney disease(DKD)is a major complication of diabetes mellitus.Renal tubular epithelial cell(TEC)damage,which is strongly associated with the inflammatory response and mesenchymal trans-differenti...BACKGROUND Diabetic kidney disease(DKD)is a major complication of diabetes mellitus.Renal tubular epithelial cell(TEC)damage,which is strongly associated with the inflammatory response and mesenchymal trans-differentiation,plays a significant role in DKD;However,the precise molecular mechanism is unknown.The recently identified microRNA-630(miR-630)has been hypothesized to be closely associated with cell migration,apoptosis,and autophagy.However,the association between miR-630 and DKD and the underlying mechanism remain unknown.AIM To investigate how miR-630 affects TEC injury and the inflammatory response in DKD rats.METHODS Streptozotocin was administered to six-week-old male rats to create a hypergly cemic diabetic model.In the second week of modeling,the rats were divided into control,DKD,negative control of lentivirus,and miR-630 overexpression groups.After 8 wk,urine and blood samples were collected for the kidney injury assays,and renal tissues were removed for further molecular assays.The target gene for miR-630 was predicted using bioinformatics,and the association between miR-630 and toll-like receptor 4(TLR4)was confirmed using in vitro investigations and double luciferase reporter gene assays.Overexpression of miR-630 in DKD rats led to changes in body weight,renal weight index,basic blood parameters and histopathological changes.RESULTS The expression level of miR-630 was reduced in the kidney tissue of rats with DKD(P<0.05).The miR-630 and TLR4 expressions in rat renal TECs(NRK-52E)were measured using quantitative reverse transcription polymerase chain reaction.The mRNA expression level of miR-630 was significantly lower in the high-glucose(HG)and HG+mimic negative control(NC)groups than in the normal glucose(NG)group(P<0.05).In contrast,the mRNA expression level of TLR4 was significantly higher in these groups(P<0.05).However,miR-630 mRNA expression increased and TLR4 mRNA expression significantly decreased in the HG+miR-630 mimic group than in the HG+mimic NC group(P<0.05).Furthermore,the levels of tumor necrosis factor-alpha(TNF-α),interleukin-1β(IL-1β),and IL-6 were significantly higher in the HG and HG+mimic NC groups than in NG group(P<0.05).However,the levels of these cytokines were significantly lower in the HG+miR-630 mimic group than in the HG+mimic NC group(P<0.05).Notably,changes in protein expression were observed.The HG and HG+mimic NC groups showed a significant decrease in E-cadherin protein expression,whereas TLR4,α-smooth muscle actin(SMA),and collagen IV protein expression increased(P<0.05).Conversely,the HG+miR-630 mimic group exhibited a significant increase in E-cadherin protein expression and a notable decrease in TLR4,α-SMA,and collagen IV protein expression than in the HG+mimic NC group(P<0.05).The miR-630 targets TLR4 gene expression.In vivo experiments demonstrated that DKD rats treated with miR-630 agomir exhibited significantly higher miR-630 mRNA expression than DKD rats injected with agomir NC.Additionally,rats treated with miR-630 agomir showed significant reductions in urinary albumin,blood glucose,TLR4,and proinflammatory markers(TNF-α,IL-1β,and IL-6)expression levels(P<0.05).Moreover,these rats exhibited fewer kidney lesions and reduced infiltration of inflammatory cells.CONCLUSION MiR-630 may inhibit the inflammatory reaction of DKD by targeting TLR4,and has a protective effect on DKD.展开更多
Diabetic kidney disease(DKD)is a common complication of diabetes mellitus that contributes to the risk of end-stage kidney disease(ESKD).Wide glycemic var-iations,such as hypoglycemia and hyperglycemia,are broadly fou...Diabetic kidney disease(DKD)is a common complication of diabetes mellitus that contributes to the risk of end-stage kidney disease(ESKD).Wide glycemic var-iations,such as hypoglycemia and hyperglycemia,are broadly found in diabetic patients with DKD and especially ESKD,as a result of impaired renal metabolism.It is essential to monitor glycemia for effective management of DKD.Hemoglobin A1c(HbA1c)has long been considered as the gold standard for monitoring glycemia for>3 months.However,assessment of HbA1c has some bias as it is susceptible to factors such as anemia and liver or kidney dysfunction.Continuous glucose monitoring(CGM)has provided new insights on glycemic assessment and management.CGM directly measures glucose level in interstitial fluid,reports real-time or retrospective glucose concentration,and provides multiple glycemic metrics.It avoids the pitfalls of HbA1c in some contexts,and may serve as a precise alternative to estimation of mean glucose and glycemic variability.Emerging studies have demonstrated the merits of CGM for precise monitoring,which allows fine-tuning of glycemic management in diabetic patients.Therefore,CGM technology has the potential for better glycemic monitoring in DKD patients.More research is needed to explore its application and management in different stages of DKD,including hemodialysis,peritoneal dialysis and kidney transplantation.展开更多
BACKGROUND Diabetic kidney disease(DKD),characterized by increased urinary microalbumin levels and decreased renal function,is the primary cause of end-stage renal di-sease.Its pathological mechanisms are complicated ...BACKGROUND Diabetic kidney disease(DKD),characterized by increased urinary microalbumin levels and decreased renal function,is the primary cause of end-stage renal di-sease.Its pathological mechanisms are complicated and multifactorial;Therefore,sensitive and specific biomarkers are needed.Urinary exosome originate from diverse renal cells in nephron segments and partially mirror the pathological changes in the kidney.The microRNAs(miRNAs)in urinary exosome are remark-ably stable and highly tissue-specific for the kidney.METHODS Type 2 diabetic mellitus(T2DM)patients were recruited from the Second Hospital of Hebei Medical University and were divided into two groups:DM,diabetic pa-tients without albuminuria[urinary albumin to creatinine ratio(UACR)<30 mg/g]and DKD,diabetic patients with albuminuria(UACR≥30 mg/g).Healthy subjects were the normal control(NC)group.Urinary exosomal miR-145-5p,miR-27a-3p,and miR-29c-3p,were detected using real-time quantitative polymerase chain reaction.The correlation between exosomal miRNAs and the clinical in-dexes was evaluated.The diagnostic values of exosomal miR-145-5p and miR-27a-3p in DKD were determined using receiver operating characteristic(ROC)analysis.Biological functions of miR-145-5p were investigated by performing RESULTS Urinary exosomal expression of miR-145-5p and miR-27a-3p was more upregulated in the DKD group than in the DM group(miR-145-5p:4.54±1.45 vs 1.95±0.93,P<0.001;miR-27a-3p:2.33±0.79 vs 1.71±0.76,P<0.05)and the NC group(miR-145-5p:4.54±1.45 vs 1.55±0.83,P<0.001;miR-27a-3p:2.33±0.79 vs 1.10±0.51,P<0.001).The exosomal miR-145-5p and miR-27a-3p positively correlated with albuminuria and serum creatinine and negatively correlated with the estimated glomerular filtration rate.miR-27a-3p was also closely related to blood glucose,gly-cosylated hemoglobin A1c,and low-density lipoprotein cholesterol.ROC analysis revealed that miR-145-5p had a better area under the curve of 0.88[95%confidence interval(CI):0.784-0.985,P<0.0001]in diagnosing DKD than miR-27a-3p with 0.71(95%CI:0.547-0.871,P=0.0239).Bioinformatics analysis revealed that the target genes of miR-145-5p were located in the actin filament,cytoskeleton,and extracellular exosome and were involved in the pathological processes of DKD,including apoptosis,inflammation,and fibrosis.CONCLUSION Urinary exosomal miR-145-5p and miR-27a-3p may serve as novel noninvasive diagnostic biomarkers or promising therapeutic targets for DKD.展开更多
Hyperuricemia(HUA)is a vital risk factor for chronic kidney diseases(CKD)and development of functional foods capable of protecting CKD is of importance.This paper aimed to explore the amelioration effects and mechanis...Hyperuricemia(HUA)is a vital risk factor for chronic kidney diseases(CKD)and development of functional foods capable of protecting CKD is of importance.This paper aimed to explore the amelioration effects and mechanism of Andrias davidianus bone peptides(ADBP)on HUA-induced kidney damage.In the present study,we generated the standard ADBP which contained high hydrophobic amino acid and low molecular peptide contents.In vitro results found that ADBP protected uric acid(UA)-induced HK-2 cells from damage by modulating urate transporters and antioxidant defense.In vivo results indicated that ADBP effectively ameliorated renal injury in HUA-induced CKD mice,evidenced by a remarkable decrease in serum UA,creatinine and blood urea nitrogen,improving kidney UA excretion,antioxidant defense and histological kidney deterioration.Metabolomic analysis highlighted 14 metabolites that could be selected as potential biomarkers and attributed to the amelioration effects of ADBP on CKD mice kidney dysfunction.Intriguingly,ADBP restored the gut microbiome homeostasis in CKD mice,especially with respect to the elevated helpful microbial abundance,and the decreased harmful bacterial abundance.This study demonstrated that ADBP displayed great nephroprotective effects,and has great promise as a food or functional food ingredient for the prevention and treatment of HUA-induced CKD.展开更多
BACKGROUND Chronic kidney disease(CKD)patients have been found to be at risk of concurrent cognitive dysfunction in previous studies,which has now become an important public health issue of widespread concern.AIM To i...BACKGROUND Chronic kidney disease(CKD)patients have been found to be at risk of concurrent cognitive dysfunction in previous studies,which has now become an important public health issue of widespread concern.AIM To investigate the risk factors for concurrent cognitive dysfunction in patients with CKD.METHODS This is a prospective cohort study conducted among patients with CKD between October 2021 and March 2023.A questionnaire was formulated by literature review and expert consultation and included questions about age,sex,education level,per capita monthly household income,marital status,living condition,payment method,and hypertension.RESULTS Logistic regression analysis showed that patients aged 60-79 years[odds ratio(OR)=1.561,P=0.015]and≥80 years(OR=1.760,P=0.013),participants with middle to high school education(OR=0.820,P=0.027),divorced or widowed individuals(OR=1.37,P=0.032),self-funded patients(OR=2.368,P=0.008),and patients with hypertension(OR=2.011,P=0.041)had a higher risk of cognitive impairment.The risk of cognitive impairment was lower for those with a college degree(OR=0.435,P=0.034)and married individuals.CONCLUSION The risk factors affecting cognitive dysfunction are age,60-79 years and≥80 years;education,primary school education or less;marital status,divorced or widowed;payment method,selffunded;hypertension;and CKD.展开更多
Contrast-induced acute kidney injury(CI-AKI)is the third leading cause of acute kidney injury deriving from the intravascular administration of contrast media in diagnostic and therapeutic procedures and leading to lo...Contrast-induced acute kidney injury(CI-AKI)is the third leading cause of acute kidney injury deriving from the intravascular administration of contrast media in diagnostic and therapeutic procedures and leading to longer in-hospital stay and increased short and long-term mortality.Its pathophysiology,although not well-established,revolves around medullary hypoxia paired with the direct toxicity of the substance to the kidney.Critically ill patients,as well as those with pre-existing renal disease and cardiovascular comorbidities,are more susceptible to CI-AKI.Despite the continuous research in the field of CI-AKI prevention,clinical practice is based mostly on periprocedural hydration.In this review,all the investigated methods of prevention are presented,with an emphasis on the latest evidence regarding the potential of RenalGuard and contrast removal systems for CI-AKI prevention in high-risk individuals.展开更多
BACKGROUND Viral and bacterial infections may be complicated by rhabdomyolysis,which has a spectrum of clinical presentations ranging from asymptomatic laboratory abnor-malities to life-threatening conditions such as ...BACKGROUND Viral and bacterial infections may be complicated by rhabdomyolysis,which has a spectrum of clinical presentations ranging from asymptomatic laboratory abnor-malities to life-threatening conditions such as renal failure.Direct viral injury as well as inflammatory responses may cause rhabdomyolysis in the course of coronavirus disease 2019(COVID-19).When presented with acute kidney injury(AKI),rhabdomyolysis may be related to higher morbidity and mortality.AIM To compare rhabdomyolysis-related AKI with other AKIs during COVID-19.METHODS A total of 115 patients with COVID-19 who had AKI were evaluated retrospec-tively.Fifteen patients had a definite diagnosis of rhabdomyolysis(i.e.,creatine kinase levels increased to>5 times the upper normal range with a concomitant increase in transaminases and lactate dehydrogenase).These patients were aged 61.0±19.1 years and their baseline creatinine levels were 0.87±0.13 mg/dL.Patients were treated according to national COVID-19 treatment guidelines.They were compared with patients with COVID-19 who had AKI due to other reasons.RESULTS For patients with rhabdomyolysis,creatinine reached 2.47±1.17 mg/dL during follow-up in hospital.Of these patients,13.3%had AKI upon hospital admission,and 86.4%developed AKI during hospital follow-up.Their peak C-reactive protein reached as high as 253.2±80.6 mg/L and was higher than in patients with AKI due to other reasons(P<0.01).Peak ferritin and procalcitonin levels were also higher for patients with rhabdomyolysis(P=0.02 and P=0.002,respective-ly).The mortality of patients with rhabdomyolysis was calculated as 73.3%,which was higher than in other patients with AKI(18.1%)(P=0.001).CONCLUSION Rhabdomyolysis was present in 13.0%of the patients who had AKI during COVID-19 infection.Rhabdomyolysis-related AKI is more proinflammatory and has a more mortal clinical course.展开更多
Oxalate is an organic dicarboxylic acid that is a common component of plant foods.The kidneys are essential organs for oxalate excretion,but excessive oxalates may induce kidney stones.Jupiter microtubule associated h...Oxalate is an organic dicarboxylic acid that is a common component of plant foods.The kidneys are essential organs for oxalate excretion,but excessive oxalates may induce kidney stones.Jupiter microtubule associated homolog 2(JPT2)is a critical molecule in Ca^(2+)mobilization,and its intrinsic mechanism in oxalate exposure and kidney stones remains unclear.This study aimed to reveal the mechanism of JPT2 in oxalate exposure and kidney stones.Genetic approaches were used to control JPT2 expression in cells and mice,and the JPT2 mechanism of action was analyzed using transcriptomics and untargeted metabolomics.The results showed that oxalate exposure triggered the upregulation of JPT2,which is involved in nicotinic acid adenine dinucleotide phosphate(NAADP)-mediated Ca^(2+)mobilization.Transcriptomic analysis revealed that cell adhesion and macrophage inflammatory polarization were inhibited by JPT2 knockdown,and these were dominated by phosphatidylinositol 3-kinase(PI3K)/AKT signaling,respectively.Untargeted metabolomics indicated that JPT2 knockdown inhibited the production of succinic acid semialdehyde(SSA)in macrophages.Furthermore,JPT2 deficiency in mice inhibited kidney stones mineralization.In conclusion,this study demonstrates that oxalate exposure facilitates kidney stones by promoting crystal-cell adhesion,and modulating macrophage metabolism and inflammatory polarization via JPT2/PI3K/AKT signaling.展开更多
Acute kidney injury(AKI)and chronic kidney disease(CKD)are significant public health issues associated with a long-term increase in mortality risk,resulting from various etiologies including renal ischemia,sepsis,drug...Acute kidney injury(AKI)and chronic kidney disease(CKD)are significant public health issues associated with a long-term increase in mortality risk,resulting from various etiologies including renal ischemia,sepsis,drug toxicity,and diabetes mellitus.Numerous preclinical models have been developed to deepen our understanding of the pathophysiological mechanisms and therapeutic approaches for kidney diseases.Among these,rodent models have proven to be powerful tools in the discovery of novel therapeutics,while the development of kidney organoids has emerged as a promising advancement in the field.This review provides a comprehensive analysis of the construction methodologies,underlying biological mechanisms,and recent therapeutic developments across different AKI and CKD models.Additionally,this review summarizes the advantages,limitations,and challenges inherent in these preclinical models,thereby contributing robust evidence to support the development of effective therapeutic strategies.展开更多
Background:Climate change profoundly shapes the population health at the global scale.However,there was still insufficient and inconsistent evidence for the association between heat exposure and chronic kidney disease...Background:Climate change profoundly shapes the population health at the global scale.However,there was still insufficient and inconsistent evidence for the association between heat exposure and chronic kidney disease(CKD).Methods:In the present study,we studied the association of heat exposure with hospitalizations for cause-specific CKD using a national inpatient database in China during the study period of hot season from 2015 to 2018.Standard time-series regression models and random-effects Meta-analysis were developed to estimate the city-specific and national averaged associations at a 7 lag-day span,respectively.Results:A total of 768,129 hospitalizations for CKD was recorded during the study period.The results showed that higher temperature was associated with elevated risk of hospitalizations for CKD,especially in sub-tropical cities.With a 1℃ increase in daily mean temperature,the cumulative relative risks(RR)over lag 0-7 d were 1.008[95% confidence interval(CI)1.003-1.012]for nationwide.The attributable fraction of CKD hospitalizations due to high temperatures was 5.50%.Stronger associations were observed among younger patients and those with obstructive nephropathy.Our study also found that exposure to heatwaves was associated with added risk of hospitalizations for CKD compared to non-heatwave days(RR=1.116,95%CI 1.069-1.166)above the effect of daily mean temperature.Conclusions:Short-term heat exposure may increase the risk of hospitalization for CKD.Our findings provide insights into the health effects of climate change and suggest the necessity of guided protection strategies against the adverse effects of high temperatures.展开更多
Chronic kidney disease(CKD)is a major health concern today,requiring early and accurate diagnosis.Machine learning has emerged as a powerful tool for disease detection,and medical professionals are increasingly using ...Chronic kidney disease(CKD)is a major health concern today,requiring early and accurate diagnosis.Machine learning has emerged as a powerful tool for disease detection,and medical professionals are increasingly using ML classifier algorithms to identify CKD early.This study explores the application of advanced machine learning techniques on a CKD dataset obtained from the University of California,UC Irvine Machine Learning repository.The research introduces TrioNet,an ensemble model combining extreme gradient boosting,random forest,and extra tree classifier,which excels in providing highly accurate predictions for CKD.Furthermore,K nearest neighbor(KNN)imputer is utilized to deal withmissing values while synthetic minority oversampling(SMOTE)is used for class-imbalance problems.To ascertain the efficacy of the proposed model,a comprehensive comparative analysis is conducted with various machine learning models.The proposed TrioNet using KNN imputer and SMOTE outperformed other models with 98.97%accuracy for detectingCKD.This in-depth analysis demonstrates the model’s capabilities and underscores its potential as a valuable tool in the diagnosis of CKD.展开更多
BACKGROUND:The molecular mechanism of sepsis-associated acute kidney injury(SA-AKI)is unclear.We analyzed co-differentially expressed genes(co-DEGs)to elucidate the underlying mechanism and intervention targets of SA-...BACKGROUND:The molecular mechanism of sepsis-associated acute kidney injury(SA-AKI)is unclear.We analyzed co-differentially expressed genes(co-DEGs)to elucidate the underlying mechanism and intervention targets of SA-AKI.METHODS:The microarray datasets GSE65682,GSE30718,and GSE174220 were downloaded from the Gene Expression Omnibus(GEO)database.We identified the co-DEGs and constructed a gene co-expression network to screen the hub genes.We analyzed immune correlations and disease correlations and performed functional annotation of the hub genes.We also performed single-cell and microenvironment analyses and investigated the enrichment pathways and the main transcription factors.Finally,we conducted a correlation analysis to evaluate the role of the hub genes.RESULTS:Interleukin 32(IL32)was identified as the hub gene in SA-AKI,and the main enriched signaling pathways were associated with hemopoiesis,cellular response to cytokine stimulus,inflammatory response,and regulation of kidney development.Additionally,IL32 was significantly associated with mortality in SA-AKI patients.Monocytes,macrophages,T cells,and NK cells were closely related to IL32 and were involved in the immune microenvironment in SA-AKI patients.IL32 expression increased significantly in the kidney of septic mouse.Toll-like receptor 2(TLR2)was significantly and negatively correlated with IL32.CONCLUSION:IL32 is the key gene involved in SA-AKI and is significantly associated with prognosis.TLR2 and relevant immune cells are closely related to key genes.展开更多
Diabetic kidney disease is one of the most severe chronic microvascular complications of diabetes and a primary cause of end-stage renal disease.Clinical studies have shown that renal inflammation is a key factor dete...Diabetic kidney disease is one of the most severe chronic microvascular complications of diabetes and a primary cause of end-stage renal disease.Clinical studies have shown that renal inflammation is a key factor determining kidney damage during diabetes.With the development of immunological technology,many studies have shown that diabetic nephropathy is an immune complex disease,and that most patients have immune dysfunction.However,the immune response associated with diabetic nephropathy and autoimmune kidney disease,or caused by ischemia or infection with acute renal injury,is different,and has a complicated pathological mechanism.In this review,we discuss the pathogenesis of diabetic nephropathy in immune disorders and the intervention mechanism,to provide guidance and advice for early intervention and treatment of diabetic nephropathy.展开更多
The angiotensin-converting enzyme(ACE)inhibitory peptide NCW derived from Mizuhopecten yessoensis has been demonstrated to have significant in vivo anti-hypertensive effects,however,its anti-hypertensive mechanism is ...The angiotensin-converting enzyme(ACE)inhibitory peptide NCW derived from Mizuhopecten yessoensis has been demonstrated to have significant in vivo anti-hypertensive effects,however,its anti-hypertensive mechanism is still not fully clarified.This study established a UPLC-Q-TRAP-MS/MS-based widely targeted kidney metabolomics approach to explore the changes of kidney metabolic profiles and to clarify the antihypertensive mechanism of peptide NCW in spontaneously hypertensive rats(SHRs).Multivariate statistical analysis indicated that the kidney metabolic profiles were clearly separated between the SHR-NCW and SHRUntreated groups.A total of 85 metabolites were differentially regulated,and 16 metabolites were identified as potential kidney biomarkers,e.g.,3-hydroxybutyrate,malonic acid,deoxycytidine,and L-aspartic acid.The peptide NCW might regulate kidney metabolic disorder of SHRs to alleviate hypertension by suppressing inflammation and improving nitric oxide production under the regulation of linoleic acid metabolism,folate related pathways,synthesis and degradation of ketone bodies,pyrimidine metabolism,β-alanine metabolism,and retinal metabolism.展开更多
Objective:Compared with long-term renal replacement therapy,kidney transplantation is the ideal treatment for end-stage renal disease(ESRD),significantly extending patient life and improving quality of life.Kidney tra...Objective:Compared with long-term renal replacement therapy,kidney transplantation is the ideal treatment for end-stage renal disease(ESRD),significantly extending patient life and improving quality of life.Kidney transplant patients need to adhere to lifelong immunosuppressive medication regimens,but their medication adherence is generally poor compared with other organ transplant recipients.Medication adherence is closely related to medication literacy and psychological status,yet related studies are limited.This study aims to investigate the current status of medication adherence,inner strength,and medication literacy in kidney transplant patients,analyze the relationships among these 3 factors,and explore the mediating role of inner strength in the relationship between medication literacy and medication adherence.Methods:A cross-sectional survey was conducted from March to October 2023 involving 421 patients aged≥18 years who visited kidney transplantation outpatient clinics at 4 tertiary hospitals in Hunan Province.The inner strength,medication literacy,and medication adherence of kidney transplant patients were investigated using the Inner Strength Scale(ISS),the Chinese version of the Medication Literacy Assessment in Spanish and English(MedLitRxSE),and the Chinese version of the Morisky Medication Adherence Scale-8(C-MMAS-8),respectively.Univariate analysis was performed to examine the effects of demographic and clinical data on medication adherence.Correlation analysis was conducted to explore the relationships among medication literacy,medication adherence,and inner strength.Significant variables from univariate and correlation analyses were further analyzed using multiple linear regression,and the mediating effect of inner strength was explored.Results:Among the 421 questionnaires collected,408 were valid,with an effective rate of 96.91%.The scores of C-MMAS-8,MedLitRxSE,and ISS were 6.64±1.16,100.63±14.67,and 8.47±4.03,respectively.Among the 408 patients,only 86(21.08%)patients had a high level of medication adherence,whereas 230(56.37%)patients had a medium level of medication adherence,and 92(22.55%)patients had poor medication adherence.Univariate analysis indicated that the kidney transplant patients’age,marital status,education levels,years since their kidney transplant operation,number of hospitalizations after the kidney transplant,and adverse drug reactions showed significant differences in medication adherence(all P<0.05).Correlation analysis showed that inner strength positively correlated with both medication literacy(r=0.183,P<0.001)and medication adherence(r=0.201,P<0.001).Additionally,there was a positive correlation between medication adherence and medication literacy(r=0.236,P<0.001).Inner strength accounted for 13.22%of the total effect in the mediating role between medication literacy and medication adherence.Conclusion:The level of medication adherence among kidney transplant patients needs improvement,and targeted intervention measures are essential.Inner strength mediates the relationship between medication literacy and medication adherence in these patients.Healthcare professionals should focus on enhancing medication literacy and supporting patients’inner strength to improve medication adherence.展开更多
Objective Variations are present in common clinical practices regarding best practice in managing hyperkalaemia(HK),there is therefore a need to establish a multi-specialty approach to optimal renin angiotension-aldos...Objective Variations are present in common clinical practices regarding best practice in managing hyperkalaemia(HK),there is therefore a need to establish a multi-specialty approach to optimal renin angiotension-aldosterone system inhibitors(RAASi)usage and HK management in patients with chronic kidney disease(CKD)&heart failure(HF).This study aimed to establish a multi-speciality approach to the optimal use of RAASi and the management of HK in patients with CKD and HF.Methods A steering expert group of cardiology and nephrology experts across China were convened to discuss challenges to HK management through a nominal group technique.The group then created a list of 41 statements for a consensus questionnaire,which was distributed for a further survey in extended panel group of cardiologists and nephrologists across China.Consensus was assessed using a modified Delphi technique,with agreement defined as"strong"(≥75%and<90%)and"very strong"(≥90%).The steering group,data collection,and analysis were aided by an independent facilitator.Results A total of 150 responses from 21 provinces across China were recruited in the survey.Respondents were comprised of an even split(n=75,50%)between cardiologists and nephrologists.All 41 statements achieved the 75%consensus agreement threshold,of which 27 statements attained very strong consensus(≥90%agreement)and 14 attained strong consensus(agreement between 75%and 90%).Conclusion Based on the agreement levels from respondents,the steering group agreed a set of recommendations intended to improve patient outcomes in the use of RAASi therapy and HK management in China.展开更多
Clinical practice has shown that kidney transplant recipients infected with COVID-19 are prone to developing critical illness and have a higher mortality rate.[1]Kidney transplant recipients require long-term oral ant...Clinical practice has shown that kidney transplant recipients infected with COVID-19 are prone to developing critical illness and have a higher mortality rate.[1]Kidney transplant recipients require long-term oral anti-rejection drugs to suppress the immune response.This result may be related to the strong immunosuppression in kidney transplant recipients compared to the general population.[2]Therefore,the treatment of kidney transplant recipients infected with severe COVID-19 is a difficult problem.Here,we report the use of extracorporeal membrane oxygenation(ECMO)-assisted treatment for a kidney transplant recipient who was infected with severe COVID-19.展开更多
Background Individuals with diabetes have a significantly higher risk of developing chronic kidney disease(CKD)and higher levels of social isolation and loneliness compared with those without diabetes.Recently,the Ame...Background Individuals with diabetes have a significantly higher risk of developing chronic kidney disease(CKD)and higher levels of social isolation and loneliness compared with those without diabetes.Recently,the American Heart Association highlighted the importance of considering social determinants of health(SDOH)in conjunction with traditional risk factors in patients with diabetes.Aims To investigate the associations of loneliness and social isolation with incident CKD risk in patients with diabetes in the UK Biobank.Methods A total of 18972 patients with diabetes were included in this prospective study.Loneliness and Social Isolation Scales were created based on self-reported factors.An adjusted Cox proportional hazard model was used to investigate the associations of loneliness and social isolation with CKD risk among patients with diabetes.The relative importance in predicting CKD was also calculated alongside traditional risk factors.Results During a median follow-up of 10.8 years,1127 incident CKD cases were reported.A higher loneliness scale,but not social isolation,was significantly associated with a 25%higher risk of CKD,independent of traditional risk factors,among patients with diabetes.Among the individual loneliness factors,the sense of feeling lonely emerged as the primary contributing factor to the elevated risk of CKD.Compared with individuals not experiencing feelings of loneliness,those who felt lonely exhibited a 22%increased likelihood of developing CKD.In addition,feeling lonely demonstrated greater relative importance of predicting CKD compared with traditional risk factors such as body mass index,smoking,physical activity and diet.Conclusions This study indicates the significant relationship between loneliness and CKD risk among patients with diabetes,highlighting the need to address SDOH in preventing CKD in this population.展开更多
Objective Previous studies on the association between lipid profiles and chronic kidney disease(CKD)have yielded inconsistent results and no defined thresholds for blood lipids.Methods A prospective cohort study inclu...Objective Previous studies on the association between lipid profiles and chronic kidney disease(CKD)have yielded inconsistent results and no defined thresholds for blood lipids.Methods A prospective cohort study including 32,351 subjects who completed baseline and follow-up surveys over 5 years was conducted.Restricted cubic splines and Cox models were used to examine the association between the lipid profiles and CKD.A regression discontinuity design was used to determine the cutoff value of lipid profiles that was significantly associated with increased the risk of CKD.Results Over a median follow-up time of 2.2(0.5,4.2)years,648(2.00%)subjects developed CKD.The lipid profiles that were significantly and linearly related to CKD included total cholesterol(TC),triglycerides(TG),high-density lipoprotein cholesterol(HDL-C),TC/HDL-C,and TG/HDL-C,whereas lowdensity lipoprotein cholesterol(LDL-C)and LDL-C/HDL-C were nonlinearly correlated with CKD.TC,TG,TC/HDL-C,and TG/HDL-C showed an upward jump at the cutoff value,increasing the risk of CKD by 0.90%,1.50%,2.30%,and 1.60%,respectively,whereas HDL-C showed a downward jump at the cutoff value,reducing this risk by 1.0%.Female and participants with dyslipidemia had a higher risk of CKD,while the cutoff values for the different characteristics of the population were different.Conclusion There was a significant association between lipid profiles and CKD in a prospective cohort from Northwest China,while TG,TC/HDL-C,and TG/HDL-C showed a stronger risk association.The specific cutoff values of lipid profiles may provide a clinical reference for screening or diagnosing CKD risk.展开更多
基金supported by National Natural Science Foundation of China(82192900,82192901,82192904,81941018,and 91846303)Peking University Medicine Seed Fund for Interdisciplinary Research(BMU2022MX025)+5 种基金the Fundamental Research Funds for the Central Universitiessupported by a grant from the Kadoorie Charitable Foundation in Hong Kongsupported by grants from the UK Wellcome Trust(212946/Z/18/Z,202922/Z/16/Z,104085/Z/14/Z,and 088158/Z/09/Z)the National Key R&D Program of China(2016YFC0900500)National Natural Science Foundation of China(81390540)Chinese Ministry of Science and Technology(2011BAI09B01)。
文摘Background:Information on the association between physical activity(PA)and the risk of chronic kidney disease(CKD)is limited.We aimed to explore the associations of total,domain-specific,and intensity-specific PA with CKD and its subtypes in China.Methods:The study included 475,376 adults from the China Kadoorie Biobank aged 30-79 years during 2004-2008 at baseline.An interviewer-administered questionnaire was used to collect the information about PA,which was quantified as metabolic equivalent of task hours per day(MET-h/day)and categorized into 4 groups based on quartiles.Cox regression was used to analyze the association between PA and CKD risk.Results:During a median follow-up of 12.1 years,5415 incident CKD cases were documented,including 1159 incident diabetic kidney disease(DKD)cases and 362 incident hypertensive nephropathy(HTN)cases.Total PA was inversely associated with CKD risk,with an adjusted hazard ratio(HR,95%confidence interval(95%CI))of 0.83(0.75-0.92)for incident CKD in the highest quartile of total PA as compared with participants in the lowest quartile.Similar results were observed for risk of DKD and HTN,and the corresponding HRs(95%CIs)were 0.75(0.58-0.97)for DKD risk and 0.56(0.37-0.85)for HTN risk.Increased nonoccupational PA,low-intensity PA,and moderate-to-vigorous-intensity PA were significantly associated with a decreased risk of CKD,with HRs(95%CIs)of 0.80(0.73-0.88),0.85(0.77-0.94),and 0.85(0.76-0.95)in the highest quartile,respectively.Conclusion:PA,including nonoccupational PA,low-intensity PA,and moderate-to-vigorous-intensity PA,was inversely associated with the risk of CKD,including DKD,HTN,and other CKD,and such associations were dose dependent.
基金Supported by the Huadong Medicine Joint Funds of the Zhejiang Provincial Natural Science Foundation of China,No.LHDMZ22H050001the Construction of Key Projects by Zhejiang Provincial Ministry,No.WKJ-ZJ-2302+3 种基金the Zhejiang Province Chinese Medicine Modernization Program,No.2020ZX001the Key Project of Scientific Research Foundation of Chinese Medicine,No.2022ZZ002the“Pioneer”and“LeadingGoose”R&D Program of Zhejiang,No.2022C03118 and 2023C03075the Key Project of Basic Scientific Research Operating Funds of Hangzhou Medical College,No.KYZD202002.
文摘BACKGROUND Diabetic kidney disease(DKD)is a major complication of diabetes mellitus.Renal tubular epithelial cell(TEC)damage,which is strongly associated with the inflammatory response and mesenchymal trans-differentiation,plays a significant role in DKD;However,the precise molecular mechanism is unknown.The recently identified microRNA-630(miR-630)has been hypothesized to be closely associated with cell migration,apoptosis,and autophagy.However,the association between miR-630 and DKD and the underlying mechanism remain unknown.AIM To investigate how miR-630 affects TEC injury and the inflammatory response in DKD rats.METHODS Streptozotocin was administered to six-week-old male rats to create a hypergly cemic diabetic model.In the second week of modeling,the rats were divided into control,DKD,negative control of lentivirus,and miR-630 overexpression groups.After 8 wk,urine and blood samples were collected for the kidney injury assays,and renal tissues were removed for further molecular assays.The target gene for miR-630 was predicted using bioinformatics,and the association between miR-630 and toll-like receptor 4(TLR4)was confirmed using in vitro investigations and double luciferase reporter gene assays.Overexpression of miR-630 in DKD rats led to changes in body weight,renal weight index,basic blood parameters and histopathological changes.RESULTS The expression level of miR-630 was reduced in the kidney tissue of rats with DKD(P<0.05).The miR-630 and TLR4 expressions in rat renal TECs(NRK-52E)were measured using quantitative reverse transcription polymerase chain reaction.The mRNA expression level of miR-630 was significantly lower in the high-glucose(HG)and HG+mimic negative control(NC)groups than in the normal glucose(NG)group(P<0.05).In contrast,the mRNA expression level of TLR4 was significantly higher in these groups(P<0.05).However,miR-630 mRNA expression increased and TLR4 mRNA expression significantly decreased in the HG+miR-630 mimic group than in the HG+mimic NC group(P<0.05).Furthermore,the levels of tumor necrosis factor-alpha(TNF-α),interleukin-1β(IL-1β),and IL-6 were significantly higher in the HG and HG+mimic NC groups than in NG group(P<0.05).However,the levels of these cytokines were significantly lower in the HG+miR-630 mimic group than in the HG+mimic NC group(P<0.05).Notably,changes in protein expression were observed.The HG and HG+mimic NC groups showed a significant decrease in E-cadherin protein expression,whereas TLR4,α-smooth muscle actin(SMA),and collagen IV protein expression increased(P<0.05).Conversely,the HG+miR-630 mimic group exhibited a significant increase in E-cadherin protein expression and a notable decrease in TLR4,α-SMA,and collagen IV protein expression than in the HG+mimic NC group(P<0.05).The miR-630 targets TLR4 gene expression.In vivo experiments demonstrated that DKD rats treated with miR-630 agomir exhibited significantly higher miR-630 mRNA expression than DKD rats injected with agomir NC.Additionally,rats treated with miR-630 agomir showed significant reductions in urinary albumin,blood glucose,TLR4,and proinflammatory markers(TNF-α,IL-1β,and IL-6)expression levels(P<0.05).Moreover,these rats exhibited fewer kidney lesions and reduced infiltration of inflammatory cells.CONCLUSION MiR-630 may inhibit the inflammatory reaction of DKD by targeting TLR4,and has a protective effect on DKD.
基金Supported by Natural Science Foundation of Zhejiang Province,No.LY23H050005and Zhejiang Medical Technology Project,No.2022RC009.
文摘Diabetic kidney disease(DKD)is a common complication of diabetes mellitus that contributes to the risk of end-stage kidney disease(ESKD).Wide glycemic var-iations,such as hypoglycemia and hyperglycemia,are broadly found in diabetic patients with DKD and especially ESKD,as a result of impaired renal metabolism.It is essential to monitor glycemia for effective management of DKD.Hemoglobin A1c(HbA1c)has long been considered as the gold standard for monitoring glycemia for>3 months.However,assessment of HbA1c has some bias as it is susceptible to factors such as anemia and liver or kidney dysfunction.Continuous glucose monitoring(CGM)has provided new insights on glycemic assessment and management.CGM directly measures glucose level in interstitial fluid,reports real-time or retrospective glucose concentration,and provides multiple glycemic metrics.It avoids the pitfalls of HbA1c in some contexts,and may serve as a precise alternative to estimation of mean glucose and glycemic variability.Emerging studies have demonstrated the merits of CGM for precise monitoring,which allows fine-tuning of glycemic management in diabetic patients.Therefore,CGM technology has the potential for better glycemic monitoring in DKD patients.More research is needed to explore its application and management in different stages of DKD,including hemodialysis,peritoneal dialysis and kidney transplantation.
基金Supported by the Nature Science Foundation of Hebei Province,No.H2023104011.
文摘BACKGROUND Diabetic kidney disease(DKD),characterized by increased urinary microalbumin levels and decreased renal function,is the primary cause of end-stage renal di-sease.Its pathological mechanisms are complicated and multifactorial;Therefore,sensitive and specific biomarkers are needed.Urinary exosome originate from diverse renal cells in nephron segments and partially mirror the pathological changes in the kidney.The microRNAs(miRNAs)in urinary exosome are remark-ably stable and highly tissue-specific for the kidney.METHODS Type 2 diabetic mellitus(T2DM)patients were recruited from the Second Hospital of Hebei Medical University and were divided into two groups:DM,diabetic pa-tients without albuminuria[urinary albumin to creatinine ratio(UACR)<30 mg/g]and DKD,diabetic patients with albuminuria(UACR≥30 mg/g).Healthy subjects were the normal control(NC)group.Urinary exosomal miR-145-5p,miR-27a-3p,and miR-29c-3p,were detected using real-time quantitative polymerase chain reaction.The correlation between exosomal miRNAs and the clinical in-dexes was evaluated.The diagnostic values of exosomal miR-145-5p and miR-27a-3p in DKD were determined using receiver operating characteristic(ROC)analysis.Biological functions of miR-145-5p were investigated by performing RESULTS Urinary exosomal expression of miR-145-5p and miR-27a-3p was more upregulated in the DKD group than in the DM group(miR-145-5p:4.54±1.45 vs 1.95±0.93,P<0.001;miR-27a-3p:2.33±0.79 vs 1.71±0.76,P<0.05)and the NC group(miR-145-5p:4.54±1.45 vs 1.55±0.83,P<0.001;miR-27a-3p:2.33±0.79 vs 1.10±0.51,P<0.001).The exosomal miR-145-5p and miR-27a-3p positively correlated with albuminuria and serum creatinine and negatively correlated with the estimated glomerular filtration rate.miR-27a-3p was also closely related to blood glucose,gly-cosylated hemoglobin A1c,and low-density lipoprotein cholesterol.ROC analysis revealed that miR-145-5p had a better area under the curve of 0.88[95%confidence interval(CI):0.784-0.985,P<0.0001]in diagnosing DKD than miR-27a-3p with 0.71(95%CI:0.547-0.871,P=0.0239).Bioinformatics analysis revealed that the target genes of miR-145-5p were located in the actin filament,cytoskeleton,and extracellular exosome and were involved in the pathological processes of DKD,including apoptosis,inflammation,and fibrosis.CONCLUSION Urinary exosomal miR-145-5p and miR-27a-3p may serve as novel noninvasive diagnostic biomarkers or promising therapeutic targets for DKD.
基金financially supported by Shenzhen Agricultural Development Special Fund(Fishery)Agricultural High-Tech Project([2021]735)the Shenzhen Science and Technology Innovation Commission(KCXFZ20201221173207022)Youth Science Foundation Project(32101936)。
文摘Hyperuricemia(HUA)is a vital risk factor for chronic kidney diseases(CKD)and development of functional foods capable of protecting CKD is of importance.This paper aimed to explore the amelioration effects and mechanism of Andrias davidianus bone peptides(ADBP)on HUA-induced kidney damage.In the present study,we generated the standard ADBP which contained high hydrophobic amino acid and low molecular peptide contents.In vitro results found that ADBP protected uric acid(UA)-induced HK-2 cells from damage by modulating urate transporters and antioxidant defense.In vivo results indicated that ADBP effectively ameliorated renal injury in HUA-induced CKD mice,evidenced by a remarkable decrease in serum UA,creatinine and blood urea nitrogen,improving kidney UA excretion,antioxidant defense and histological kidney deterioration.Metabolomic analysis highlighted 14 metabolites that could be selected as potential biomarkers and attributed to the amelioration effects of ADBP on CKD mice kidney dysfunction.Intriguingly,ADBP restored the gut microbiome homeostasis in CKD mice,especially with respect to the elevated helpful microbial abundance,and the decreased harmful bacterial abundance.This study demonstrated that ADBP displayed great nephroprotective effects,and has great promise as a food or functional food ingredient for the prevention and treatment of HUA-induced CKD.
文摘BACKGROUND Chronic kidney disease(CKD)patients have been found to be at risk of concurrent cognitive dysfunction in previous studies,which has now become an important public health issue of widespread concern.AIM To investigate the risk factors for concurrent cognitive dysfunction in patients with CKD.METHODS This is a prospective cohort study conducted among patients with CKD between October 2021 and March 2023.A questionnaire was formulated by literature review and expert consultation and included questions about age,sex,education level,per capita monthly household income,marital status,living condition,payment method,and hypertension.RESULTS Logistic regression analysis showed that patients aged 60-79 years[odds ratio(OR)=1.561,P=0.015]and≥80 years(OR=1.760,P=0.013),participants with middle to high school education(OR=0.820,P=0.027),divorced or widowed individuals(OR=1.37,P=0.032),self-funded patients(OR=2.368,P=0.008),and patients with hypertension(OR=2.011,P=0.041)had a higher risk of cognitive impairment.The risk of cognitive impairment was lower for those with a college degree(OR=0.435,P=0.034)and married individuals.CONCLUSION The risk factors affecting cognitive dysfunction are age,60-79 years and≥80 years;education,primary school education or less;marital status,divorced or widowed;payment method,selffunded;hypertension;and CKD.
文摘Contrast-induced acute kidney injury(CI-AKI)is the third leading cause of acute kidney injury deriving from the intravascular administration of contrast media in diagnostic and therapeutic procedures and leading to longer in-hospital stay and increased short and long-term mortality.Its pathophysiology,although not well-established,revolves around medullary hypoxia paired with the direct toxicity of the substance to the kidney.Critically ill patients,as well as those with pre-existing renal disease and cardiovascular comorbidities,are more susceptible to CI-AKI.Despite the continuous research in the field of CI-AKI prevention,clinical practice is based mostly on periprocedural hydration.In this review,all the investigated methods of prevention are presented,with an emphasis on the latest evidence regarding the potential of RenalGuard and contrast removal systems for CI-AKI prevention in high-risk individuals.
文摘BACKGROUND Viral and bacterial infections may be complicated by rhabdomyolysis,which has a spectrum of clinical presentations ranging from asymptomatic laboratory abnor-malities to life-threatening conditions such as renal failure.Direct viral injury as well as inflammatory responses may cause rhabdomyolysis in the course of coronavirus disease 2019(COVID-19).When presented with acute kidney injury(AKI),rhabdomyolysis may be related to higher morbidity and mortality.AIM To compare rhabdomyolysis-related AKI with other AKIs during COVID-19.METHODS A total of 115 patients with COVID-19 who had AKI were evaluated retrospec-tively.Fifteen patients had a definite diagnosis of rhabdomyolysis(i.e.,creatine kinase levels increased to>5 times the upper normal range with a concomitant increase in transaminases and lactate dehydrogenase).These patients were aged 61.0±19.1 years and their baseline creatinine levels were 0.87±0.13 mg/dL.Patients were treated according to national COVID-19 treatment guidelines.They were compared with patients with COVID-19 who had AKI due to other reasons.RESULTS For patients with rhabdomyolysis,creatinine reached 2.47±1.17 mg/dL during follow-up in hospital.Of these patients,13.3%had AKI upon hospital admission,and 86.4%developed AKI during hospital follow-up.Their peak C-reactive protein reached as high as 253.2±80.6 mg/L and was higher than in patients with AKI due to other reasons(P<0.01).Peak ferritin and procalcitonin levels were also higher for patients with rhabdomyolysis(P=0.02 and P=0.002,respective-ly).The mortality of patients with rhabdomyolysis was calculated as 73.3%,which was higher than in other patients with AKI(18.1%)(P=0.001).CONCLUSION Rhabdomyolysis was present in 13.0%of the patients who had AKI during COVID-19 infection.Rhabdomyolysis-related AKI is more proinflammatory and has a more mortal clinical course.
基金supported by the National Natural Science Foundation of China(Grant Nos.:82070723,82270797)Nature Science Foundation of Hubei Province,China(Grant No.:2022CFC020).
文摘Oxalate is an organic dicarboxylic acid that is a common component of plant foods.The kidneys are essential organs for oxalate excretion,but excessive oxalates may induce kidney stones.Jupiter microtubule associated homolog 2(JPT2)is a critical molecule in Ca^(2+)mobilization,and its intrinsic mechanism in oxalate exposure and kidney stones remains unclear.This study aimed to reveal the mechanism of JPT2 in oxalate exposure and kidney stones.Genetic approaches were used to control JPT2 expression in cells and mice,and the JPT2 mechanism of action was analyzed using transcriptomics and untargeted metabolomics.The results showed that oxalate exposure triggered the upregulation of JPT2,which is involved in nicotinic acid adenine dinucleotide phosphate(NAADP)-mediated Ca^(2+)mobilization.Transcriptomic analysis revealed that cell adhesion and macrophage inflammatory polarization were inhibited by JPT2 knockdown,and these were dominated by phosphatidylinositol 3-kinase(PI3K)/AKT signaling,respectively.Untargeted metabolomics indicated that JPT2 knockdown inhibited the production of succinic acid semialdehyde(SSA)in macrophages.Furthermore,JPT2 deficiency in mice inhibited kidney stones mineralization.In conclusion,this study demonstrates that oxalate exposure facilitates kidney stones by promoting crystal-cell adhesion,and modulating macrophage metabolism and inflammatory polarization via JPT2/PI3K/AKT signaling.
基金supported by the Zhejiang Provincial Natural Science Foundation of China(LZ22H050001)National Natural Science Foundation of China(82270704,81970573)+1 种基金“Lingyan”R&D Research and Development Project(2024C03165)Zhejiang Provincial Program for the Cultivation of High-level Innovative Health Talents。
文摘Acute kidney injury(AKI)and chronic kidney disease(CKD)are significant public health issues associated with a long-term increase in mortality risk,resulting from various etiologies including renal ischemia,sepsis,drug toxicity,and diabetes mellitus.Numerous preclinical models have been developed to deepen our understanding of the pathophysiological mechanisms and therapeutic approaches for kidney diseases.Among these,rodent models have proven to be powerful tools in the discovery of novel therapeutics,while the development of kidney organoids has emerged as a promising advancement in the field.This review provides a comprehensive analysis of the construction methodologies,underlying biological mechanisms,and recent therapeutic developments across different AKI and CKD models.Additionally,this review summarizes the advantages,limitations,and challenges inherent in these preclinical models,thereby contributing robust evidence to support the development of effective therapeutic strategies.
基金This study was supported by the National Natural Science Foundation of China(82003529,72125009)the National Key Research and Development Program of the Ministry of Science and Technology of China(2019YFC2005000)+4 种基金the Chinese Scientific and Technical Innovation Project 2030(2018AAA0102100)the National High Level Hospital Clinical Research Funding(“Star of Outlook”Scientific Research Project of Peking University First Hospital,2022XW06)the CAMS Innovation Fund for Medical Sciences(2019-I2M-5-046)the Young Elite Scientists Sponsorship Program by CAST(2022QNRC001)the PKU-Baidu Fund(2020BD004,2020BD005 and 2020BD032).
文摘Background:Climate change profoundly shapes the population health at the global scale.However,there was still insufficient and inconsistent evidence for the association between heat exposure and chronic kidney disease(CKD).Methods:In the present study,we studied the association of heat exposure with hospitalizations for cause-specific CKD using a national inpatient database in China during the study period of hot season from 2015 to 2018.Standard time-series regression models and random-effects Meta-analysis were developed to estimate the city-specific and national averaged associations at a 7 lag-day span,respectively.Results:A total of 768,129 hospitalizations for CKD was recorded during the study period.The results showed that higher temperature was associated with elevated risk of hospitalizations for CKD,especially in sub-tropical cities.With a 1℃ increase in daily mean temperature,the cumulative relative risks(RR)over lag 0-7 d were 1.008[95% confidence interval(CI)1.003-1.012]for nationwide.The attributable fraction of CKD hospitalizations due to high temperatures was 5.50%.Stronger associations were observed among younger patients and those with obstructive nephropathy.Our study also found that exposure to heatwaves was associated with added risk of hospitalizations for CKD compared to non-heatwave days(RR=1.116,95%CI 1.069-1.166)above the effect of daily mean temperature.Conclusions:Short-term heat exposure may increase the risk of hospitalization for CKD.Our findings provide insights into the health effects of climate change and suggest the necessity of guided protection strategies against the adverse effects of high temperatures.
基金funded by Princess Nourah bint Abdulrahman University Researchers Supporting Project Number PNURSP2024R333,Princess Nourah bint Abdulrahman University,Riyadh,Saudi Arabia.
文摘Chronic kidney disease(CKD)is a major health concern today,requiring early and accurate diagnosis.Machine learning has emerged as a powerful tool for disease detection,and medical professionals are increasingly using ML classifier algorithms to identify CKD early.This study explores the application of advanced machine learning techniques on a CKD dataset obtained from the University of California,UC Irvine Machine Learning repository.The research introduces TrioNet,an ensemble model combining extreme gradient boosting,random forest,and extra tree classifier,which excels in providing highly accurate predictions for CKD.Furthermore,K nearest neighbor(KNN)imputer is utilized to deal withmissing values while synthetic minority oversampling(SMOTE)is used for class-imbalance problems.To ascertain the efficacy of the proposed model,a comprehensive comparative analysis is conducted with various machine learning models.The proposed TrioNet using KNN imputer and SMOTE outperformed other models with 98.97%accuracy for detectingCKD.This in-depth analysis demonstrates the model’s capabilities and underscores its potential as a valuable tool in the diagnosis of CKD.
基金supported by Beijing Natural Science Foundation(No.7222162 to Dr.Hui Liu)。
文摘BACKGROUND:The molecular mechanism of sepsis-associated acute kidney injury(SA-AKI)is unclear.We analyzed co-differentially expressed genes(co-DEGs)to elucidate the underlying mechanism and intervention targets of SA-AKI.METHODS:The microarray datasets GSE65682,GSE30718,and GSE174220 were downloaded from the Gene Expression Omnibus(GEO)database.We identified the co-DEGs and constructed a gene co-expression network to screen the hub genes.We analyzed immune correlations and disease correlations and performed functional annotation of the hub genes.We also performed single-cell and microenvironment analyses and investigated the enrichment pathways and the main transcription factors.Finally,we conducted a correlation analysis to evaluate the role of the hub genes.RESULTS:Interleukin 32(IL32)was identified as the hub gene in SA-AKI,and the main enriched signaling pathways were associated with hemopoiesis,cellular response to cytokine stimulus,inflammatory response,and regulation of kidney development.Additionally,IL32 was significantly associated with mortality in SA-AKI patients.Monocytes,macrophages,T cells,and NK cells were closely related to IL32 and were involved in the immune microenvironment in SA-AKI patients.IL32 expression increased significantly in the kidney of septic mouse.Toll-like receptor 2(TLR2)was significantly and negatively correlated with IL32.CONCLUSION:IL32 is the key gene involved in SA-AKI and is significantly associated with prognosis.TLR2 and relevant immune cells are closely related to key genes.
基金Supported by the National Natural Science Foundation of China,No.82100883the Research Project of Educational Commission of Jilin Province of China,No.JJKH20231214KJ.
文摘Diabetic kidney disease is one of the most severe chronic microvascular complications of diabetes and a primary cause of end-stage renal disease.Clinical studies have shown that renal inflammation is a key factor determining kidney damage during diabetes.With the development of immunological technology,many studies have shown that diabetic nephropathy is an immune complex disease,and that most patients have immune dysfunction.However,the immune response associated with diabetic nephropathy and autoimmune kidney disease,or caused by ischemia or infection with acute renal injury,is different,and has a complicated pathological mechanism.In this review,we discuss the pathogenesis of diabetic nephropathy in immune disorders and the intervention mechanism,to provide guidance and advice for early intervention and treatment of diabetic nephropathy.
基金supported by the National Natural Science Foundation of China(No.31901635)。
文摘The angiotensin-converting enzyme(ACE)inhibitory peptide NCW derived from Mizuhopecten yessoensis has been demonstrated to have significant in vivo anti-hypertensive effects,however,its anti-hypertensive mechanism is still not fully clarified.This study established a UPLC-Q-TRAP-MS/MS-based widely targeted kidney metabolomics approach to explore the changes of kidney metabolic profiles and to clarify the antihypertensive mechanism of peptide NCW in spontaneously hypertensive rats(SHRs).Multivariate statistical analysis indicated that the kidney metabolic profiles were clearly separated between the SHR-NCW and SHRUntreated groups.A total of 85 metabolites were differentially regulated,and 16 metabolites were identified as potential kidney biomarkers,e.g.,3-hydroxybutyrate,malonic acid,deoxycytidine,and L-aspartic acid.The peptide NCW might regulate kidney metabolic disorder of SHRs to alleviate hypertension by suppressing inflammation and improving nitric oxide production under the regulation of linoleic acid metabolism,folate related pathways,synthesis and degradation of ketone bodies,pyrimidine metabolism,β-alanine metabolism,and retinal metabolism.
基金This work was supported by the Natural Science Foundation of Hunan Province,China (2024JJ9201)。
文摘Objective:Compared with long-term renal replacement therapy,kidney transplantation is the ideal treatment for end-stage renal disease(ESRD),significantly extending patient life and improving quality of life.Kidney transplant patients need to adhere to lifelong immunosuppressive medication regimens,but their medication adherence is generally poor compared with other organ transplant recipients.Medication adherence is closely related to medication literacy and psychological status,yet related studies are limited.This study aims to investigate the current status of medication adherence,inner strength,and medication literacy in kidney transplant patients,analyze the relationships among these 3 factors,and explore the mediating role of inner strength in the relationship between medication literacy and medication adherence.Methods:A cross-sectional survey was conducted from March to October 2023 involving 421 patients aged≥18 years who visited kidney transplantation outpatient clinics at 4 tertiary hospitals in Hunan Province.The inner strength,medication literacy,and medication adherence of kidney transplant patients were investigated using the Inner Strength Scale(ISS),the Chinese version of the Medication Literacy Assessment in Spanish and English(MedLitRxSE),and the Chinese version of the Morisky Medication Adherence Scale-8(C-MMAS-8),respectively.Univariate analysis was performed to examine the effects of demographic and clinical data on medication adherence.Correlation analysis was conducted to explore the relationships among medication literacy,medication adherence,and inner strength.Significant variables from univariate and correlation analyses were further analyzed using multiple linear regression,and the mediating effect of inner strength was explored.Results:Among the 421 questionnaires collected,408 were valid,with an effective rate of 96.91%.The scores of C-MMAS-8,MedLitRxSE,and ISS were 6.64±1.16,100.63±14.67,and 8.47±4.03,respectively.Among the 408 patients,only 86(21.08%)patients had a high level of medication adherence,whereas 230(56.37%)patients had a medium level of medication adherence,and 92(22.55%)patients had poor medication adherence.Univariate analysis indicated that the kidney transplant patients’age,marital status,education levels,years since their kidney transplant operation,number of hospitalizations after the kidney transplant,and adverse drug reactions showed significant differences in medication adherence(all P<0.05).Correlation analysis showed that inner strength positively correlated with both medication literacy(r=0.183,P<0.001)and medication adherence(r=0.201,P<0.001).Additionally,there was a positive correlation between medication adherence and medication literacy(r=0.236,P<0.001).Inner strength accounted for 13.22%of the total effect in the mediating role between medication literacy and medication adherence.Conclusion:The level of medication adherence among kidney transplant patients needs improvement,and targeted intervention measures are essential.Inner strength mediates the relationship between medication literacy and medication adherence in these patients.Healthcare professionals should focus on enhancing medication literacy and supporting patients’inner strength to improve medication adherence.
文摘Objective Variations are present in common clinical practices regarding best practice in managing hyperkalaemia(HK),there is therefore a need to establish a multi-specialty approach to optimal renin angiotension-aldosterone system inhibitors(RAASi)usage and HK management in patients with chronic kidney disease(CKD)&heart failure(HF).This study aimed to establish a multi-speciality approach to the optimal use of RAASi and the management of HK in patients with CKD and HF.Methods A steering expert group of cardiology and nephrology experts across China were convened to discuss challenges to HK management through a nominal group technique.The group then created a list of 41 statements for a consensus questionnaire,which was distributed for a further survey in extended panel group of cardiologists and nephrologists across China.Consensus was assessed using a modified Delphi technique,with agreement defined as"strong"(≥75%and<90%)and"very strong"(≥90%).The steering group,data collection,and analysis were aided by an independent facilitator.Results A total of 150 responses from 21 provinces across China were recruited in the survey.Respondents were comprised of an even split(n=75,50%)between cardiologists and nephrologists.All 41 statements achieved the 75%consensus agreement threshold,of which 27 statements attained very strong consensus(≥90%agreement)and 14 attained strong consensus(agreement between 75%and 90%).Conclusion Based on the agreement levels from respondents,the steering group agreed a set of recommendations intended to improve patient outcomes in the use of RAASi therapy and HK management in China.
文摘Clinical practice has shown that kidney transplant recipients infected with COVID-19 are prone to developing critical illness and have a higher mortality rate.[1]Kidney transplant recipients require long-term oral anti-rejection drugs to suppress the immune response.This result may be related to the strong immunosuppression in kidney transplant recipients compared to the general population.[2]Therefore,the treatment of kidney transplant recipients infected with severe COVID-19 is a difficult problem.Here,we report the use of extracorporeal membrane oxygenation(ECMO)-assisted treatment for a kidney transplant recipient who was infected with severe COVID-19.
基金supported by grants from the National Heart,Lung,and Blood Institute(HL071981,HL034594,HL126024)the National Institute of Diabetes and Digestive and Kidney Diseases(DK115679,DK091718,DK100383,DK078616).
文摘Background Individuals with diabetes have a significantly higher risk of developing chronic kidney disease(CKD)and higher levels of social isolation and loneliness compared with those without diabetes.Recently,the American Heart Association highlighted the importance of considering social determinants of health(SDOH)in conjunction with traditional risk factors in patients with diabetes.Aims To investigate the associations of loneliness and social isolation with incident CKD risk in patients with diabetes in the UK Biobank.Methods A total of 18972 patients with diabetes were included in this prospective study.Loneliness and Social Isolation Scales were created based on self-reported factors.An adjusted Cox proportional hazard model was used to investigate the associations of loneliness and social isolation with CKD risk among patients with diabetes.The relative importance in predicting CKD was also calculated alongside traditional risk factors.Results During a median follow-up of 10.8 years,1127 incident CKD cases were reported.A higher loneliness scale,but not social isolation,was significantly associated with a 25%higher risk of CKD,independent of traditional risk factors,among patients with diabetes.Among the individual loneliness factors,the sense of feeling lonely emerged as the primary contributing factor to the elevated risk of CKD.Compared with individuals not experiencing feelings of loneliness,those who felt lonely exhibited a 22%increased likelihood of developing CKD.In addition,feeling lonely demonstrated greater relative importance of predicting CKD compared with traditional risk factors such as body mass index,smoking,physical activity and diet.Conclusions This study indicates the significant relationship between loneliness and CKD risk among patients with diabetes,highlighting the need to address SDOH in preventing CKD in this population.
基金supported by the Municipal Science and Technology Program of Wuwei City,China(WW2202RPZ037)the Fundamental Research Funds for the Central Universities in China(Grant No.lzujbky-2018-69).
文摘Objective Previous studies on the association between lipid profiles and chronic kidney disease(CKD)have yielded inconsistent results and no defined thresholds for blood lipids.Methods A prospective cohort study including 32,351 subjects who completed baseline and follow-up surveys over 5 years was conducted.Restricted cubic splines and Cox models were used to examine the association between the lipid profiles and CKD.A regression discontinuity design was used to determine the cutoff value of lipid profiles that was significantly associated with increased the risk of CKD.Results Over a median follow-up time of 2.2(0.5,4.2)years,648(2.00%)subjects developed CKD.The lipid profiles that were significantly and linearly related to CKD included total cholesterol(TC),triglycerides(TG),high-density lipoprotein cholesterol(HDL-C),TC/HDL-C,and TG/HDL-C,whereas lowdensity lipoprotein cholesterol(LDL-C)and LDL-C/HDL-C were nonlinearly correlated with CKD.TC,TG,TC/HDL-C,and TG/HDL-C showed an upward jump at the cutoff value,increasing the risk of CKD by 0.90%,1.50%,2.30%,and 1.60%,respectively,whereas HDL-C showed a downward jump at the cutoff value,reducing this risk by 1.0%.Female and participants with dyslipidemia had a higher risk of CKD,while the cutoff values for the different characteristics of the population were different.Conclusion There was a significant association between lipid profiles and CKD in a prospective cohort from Northwest China,while TG,TC/HDL-C,and TG/HDL-C showed a stronger risk association.The specific cutoff values of lipid profiles may provide a clinical reference for screening or diagnosing CKD risk.