Potential application of Nardostachyos Radix et Rhizoma-Rhubarb for the treatment of diabetic kidney disease based on network pharmacology and cell culture experimental verification

BACKGROUND Diabetic kidney disease(DKD)is one of the serious complications of diabetes mellitus,and the existing treatments cannot meet the needs of today's patients.Traditional Chinese medicine has been validated for its efficacy in DKD after many years of clinical application.However,the specific mechanism by which it works is still unclear.Elucidating the molecular mechanism of the Nardostachyos Radix et Rhizoma-rhubarb drug pair(NRDP)for the treatment of DKD will provide a new way of thinking for the research and development of new drugs.AIM To investigate the mechanism of the NRDP in DKD by network pharmacology combined with molecular docking,and then verify the initial findings by in vitro experiments.METHODS The Traditional Chinese Medicine Systems Pharmacology(TCMSP)database was used to screen active ingredient targets of NRDP.Targets for DKD were obtained based on the Genecards,OMIM,and TTD databases.The VENNY 2.1 database was used to obtain DKD and NRDP intersection targets and their Venn diagram,and Cytoscape 3.9.0 was used to build a"drug-component-target-disease"network.The String database was used to construct protein interaction networks.Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis and Gene Ontology analysis were performed based on the DAVID database.After selecting the targets and the active ingredients,Autodock software was used to perform molecular docking.In experimental validation using renal tubular epithelial cells(TCMK-1),we used the Cell Counting Kit-8 assay to detect the effect of NRDP on cell viability,with glucose solution used to mimic a hyperglycemic environment.Flow cytometry was used to detect the cell cycle progression and apoptosis.Western blot was used to detect the protein expression of STAT3,p-STAT3,BAX,BCL-2,Caspase9,and Caspase3.RESULTS A total of 10 active ingredients and 85 targets with 111 disease-related signaling pathways were obtained for NRDP.Enrichment analysis of KEGG pathways was performed to determine advanced glycation end products(AGEs)-receptor for AGEs(RAGE)signaling as the core pathway.Molecular docking showed good binding between each active ingredient and its core targets.In vitro experiments showed that NRDP inhibited the viability of TCMK-1 cells,blocked cell cycle progression in the G0/G1 phase,and reduced apoptosis in a concentrationdependent manner.Based on the results of Western blot analysis,NRDP differentially downregulated p-STAT3,BAX,Caspase3,and Caspase9 protein levels(P<0.01 or P<0.05).In addition,BAX/BCL-2 and p-STAT3/STAT3 ratios were reduced,while BCL-2 and STAT3 protein expression was upregulated(P<0.01).CONCLUSION NRDP may upregulate BCL-2 and STAT3 protein expression,and downregulate BAX,Caspase3,and Caspase9 protein expression,thus activating the AGE-RAGE signaling pathway,inhibiting the vitality of TCMK-1 cells,reducing their apoptosis.and arresting them in the G0/G1 phase to protect them from damage by high glucose.

Improving Prediction of Chronic Kidney Disease Using KNN Imputed SMOTE Features and TrioNet Model

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.

Application and management of continuous glucose monitoring in diabetic kidney disease

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.

Pathological mechanism of immune disorders in diabetic kidney disease and intervention strategies

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.

Meta-analysis of the association between chronic periodontitis and chronic kidney disease

BACKGROUND Many scholars have performed several clinical studies have investigated the association between chronic periodontitis(CP)and chronic kidney disease(CKD).However,there are still differences between these research results,and there is no unified conclusion.Therefore,a systematic review is required to understand this issue fully.AIM To explore the correlation between CP and CKD.METHODS Literature on the correlation between CP and CKD,as well as the clinical attachment level(CAL)and pocket probing depth(PPD)of CKD and non-CKD,were retrieved from PubMed,Embase,the Cochrane Library,and Web of Science repositories until January 2024.After the effective data were extracted,data processing and statistics were performed using Stata 12.0.RESULTS Of the 22 studies,13 were related to CP and CKD,and 9 reported CAL and PPD in patients with CKD and healthy controls.Meta-analysis of the correlation between CP and CKD revealed that CKD probability in people with CP was 1.54 times that of healthy individuals[relative risk=1.54,95%confidence interval(CI):1.40-1.70],and CP incidence in patients with CKD was 1.98 times that of healthy individuals[overall risk(OR)=1.98,95%CI:1.53-2.57].Meta-analysis of CAL and PPD evaluations between CKD patients and healthy individuals showed that CAL and PPD levels were higher in CKD patients[standard mean difference(SMD)of CAL=0.65,95%CI:0.29-1.01;SMD of PPD=0.33,95%CI:0.02-0.63].CONCLUSION A bidirectional association exists between CP and CKD.CKD risk is increased in CP patients and vice versa.Periodontal tissue or tooth loss risks increase over time in CKD patients.

Experience of humanistic nursing in hemodialysis nursing for patients with diabetic kidney disease

BACKGROUND Diabetic kidney disease(DKD)is a prevalent complication of diabetes that often requires hemodialysis for treatment.In the field of nursing,there is a growing recognition of the importance of humanistic care,which focuses on the holistic needs of patients,including their emotional,psychological,and social well-being.However,the application of humanistic nursing in the context of hemodialysis for DKD patients remains relatively unexplored.AIM To explore the experience of humanistic nursing in hemodialysis nursing for DKD patients.METHODS Ninety-six DKD patients treated with hemodialysis from March 2020 to June 2022 were included in the study and divided into the control cluster(48 cases)and the study cluster(48 cases)according to different nursing methods;the control cluster was given routine nursing and the study cluster was given humanized nursing.The variances of negative emotion mark,blood glucose,renal function,the incidence of complications,life mark and nursing satisfaction before and after nur-sing were contrasted between the two clusters.RESULTS No significant difference in negative emotion markers between the two clusters were observed before nursing(P>0.05),and the negative emotion markers of the two clusters decreased after nursing.The Hamilton Anxiety Rating Scale and Hamilton Depression Rating Scale markers were lower in the study cluster than the control cluster.The healing rate of patients in the study cluster was significantly higher than the control cluster(97.92%vs 85.42%,P<0.05).Blood glucose parameters were not significantly different between the groups prior to nursing(P>0.05).However,after nursing,blood urea nitrogen and serum creatinine(SCr)levels in the study cluster were lower than those in the control cluster(P<0.05).The incidence rate of complications was significantly lower in the study group compared to the control cluster(6.25%vs 20.83%,P<0.05).There was no significant difference in the life markers between the two clusters before nursing.While the life markers increased after nursing for both groups,the 36-item health scale markers in the study cluster were higher than those within the control cluster(P<0.05).Finally,the nursing satisfaction rate was 93.75% in the study cluster,compared to 75% in the control cluster(P<0.05).CONCLUSION In hemodialysis for DKD patients,the implementation of humanistic nursing achieved ideal results,effectively reducing patients’psychological negative emotion markers so that they can actively cooperate with the diagnosis and nursing,facilitate the control of blood glucose and the maintenance of residual renal function,reduce the occurrence of complications,and finally enhance the life quality and nursing satisfaction of patients.It is worthy of being widely popularized and applied.

MicroRNA-630:A promising avenue for alleviating inflammation in diabetic kidney disease

Diabetic kidney disease(DKD)is one of the complications of diabetes,affecting millions of people worldwide.The relentless progression of this condition can lead to kidney failure,requiring life-altering interventions such as dialysis or transplants.Accumulating evidence suggests that immunologic and inflammatory elements play an important role in initiating and perpetuating the damage inflicted on renal tissues,exacerbating the decline in organ function.Toll-like receptors(TLRs)are a family of receptors that play a role in the activation of the innate immune system by the recognition of pathogen-associated molecular patterns.Recent data from in vitro and in vivo studies have highlighted the critical role of TLRs,mainly TLR2 and TLR4,in the pathogenesis of DKD.In the diabetic milieu,these TLRs recognize diabetic-associated molecular signals,triggering a proinflammatory cascade that initiates and perpetuates inflammation and fibrogenesis in the diabetic kidney.Emerging non-traditional strategies targeting TLR signaling with potential therapeutic implications in DKD have been proposed.One of these approaches is the use of microRNAs,small non-coding RNAs that can regulate gene expression.This editorial comments on the results of this approach carried out in a rat model of diabetes by Wu et al,published in this issue of the World Journal of Diabetes.The results of the experimental study by Wu et al shows that microRNA-630 decreased levels compared to non-diabetic rats.Additionally,microRNA-630 exerted anti-inflammatory effects in the kidneys of diabetic rats through the modulation of TLR4.These findings indicate that the microRNA-630/TLR4 axis might represent a pathological mechanism of DKD and a potential therapeutic target capable of curbing the destructive inflammation characteristic of DKD.

Rates, predictors, and causes of readmission after transcatheter aortic valve replacement in patients with chronic kidney disease

BACKGROUND Transcatheter aortic valve replacement(TAVR)is a revolutionary procedure for severe aortic stenosis.The coexistence of chronic kidney disease(CKD)and TAVR introduces a challenge that significantly impacts patient outcomes.AIM To define readmission rates,predictors,and causes after TAVR procedure in CKD stage 1-4 patients.METHODS We used the national readmission database 2018 and 2020 to look into readmission rates,causes and predictors after TAVR procedure in patients with CKD stage 1-4.RESULTS Out of 24758 who underwent TAVR and had CKD,7892(32.4%)patients were readmitted within 90 days,and had higher adjusted odds of being females(adjusted odds ratio:1.17,95%CI:1.02-1.31,P=0.02)with longer length of hospital stay>6 days,and more comorbidities including but not limited to diabetes mellitus,anemia,and congestive heart failure(CHF).CONCLUSION Most common causes of readmission included CHF(18.0%),sepsis,and complete atrioventricular block.Controlling readmission predictors with very close followup is warranted to prevent such high rate of readmission.

Clinical Observation on the Treatment of Diabetic Kidney Disease with Damp-heat Stasis Syndrome in Clinical Proteinuria Stage by Kunkui Kidney Preserving Paste

[Objectives]To evaluate the clinical efficacy and safety of Kunkui Kidney Preserving Paste in the treatment of diabetic kidney disease(DKD)patients with damp-heat stasis syndrome in the clinical proteinuria stage.[Methods]Retrospective analysis was made on 30 patients with DKD who were diagnosed with damp-heat stasis syndrome in the clinical proteinuria stage from March 2021 to March 2023 in Jiangsu Province Hospital of Chinese Medicine,and who took Kunkui Kidney Preserving Paste continuously for six months.The urinary albumin/creatinine ratio(UACR),urinary complement C3,and urea nitrogen(BUN)of DKD patients before and after treatment were compared,and estimated glomerular filtration rate(eGFR),blood creatinine(Scr),and cystatin C(CysC)were estimated,and the therapeutic effects on renal function and urinary protein were evaluated.[Results]After treatment,UACR significantly decreased(P<0.01),and urinary complement C3 and Scr decreased(P<0.05),while other indicators showed no significant statistical difference(P>0.05).In terms of evaluating the efficacy of urinary protein therapy,8 cases showed recent relief;8 cases showed significant effect;9 cases were effective,and 5 cases were invalid after treatment,with a total effective rate of 83.33%.In terms of renal function efficacy evaluation,8 cases showed significant effect;4 cases were effective;11 cases were stable,and 7 cases were invalid,with a total effective rate of 76.67%.In the safety evaluation,there were no obvious adverse reactions.[Conclusions]The Kunkui Kidney Preserving Past has significant clinical efficacy and safety in treating DKD patients with damp-heat stasis syndrome in the clinical proteinuria period.It has significant advantages in reducing urinary protein and protecting renal function,which is worthy of clinical promotion.

Mechanistic study of lipid metabolism disorders in diabetic kidney disease treated with GLQMP based on network pharmacology,molecular docking and in vitro experiments

Background:In this study,we used network pharmacology and molecular docking combined with vitro experiments to explore the potential mechanism of action of Gualou Qumai pill(GLQMP)against DKD.Methods:We screened effective compounds and drug targets using Chinese medicine systemic pharmacology database and analysis platform and Chinese medicine molecular mechanism bioinformatics analysis tools;and searched for DKD targets using human online Mendelian genetics and gene cards.The potential targets of GLQMP for DKD were obtained through the intersection of drug targets and disease targets.Cytoscape software was applied to build herbal medicine-active compound-target-disease networks and analyze them;protein-protein interaction networks were analyzed using the STRING database platform;gene ontology and Kyoto Encyclopedia of Genes and Genomes were used for gene ontology and gene and genome encyclopedia to enrich potential targets using the DAVID database;and the AutoDock Vina 1.1.2 software for molecular docking of key targets with corresponding key components.In vitro experiments were validated by CCK8,oil red O staining,TC,TG,RT-qPCR,and Western blot.Results:Through network pharmacology analysis,a total of 99 potential therapeutic targets of GLQMP for DKD and the corresponding 38 active compounds were obtained,and 5 core compounds were identified.By constructing the protein-protein interaction network and performing network topology analysis,we found that PPARA and PPARG were the key targets,and then we molecularly docked these two key targets with the 38 active compounds,especially the 5 core compounds,and found that PPARA and PPARG had good binding ability with a variety of compounds.In vitro experiments showed that GLQMP was able to ameliorate HK-2 cell injury under high glucose stress,improve cell viability,reduce TC and TG levels as well as decrease the accumulation of lipid droplets,and RT-qPCR and Western blot confirmed that GLQMP was able to promote the expression levels of PPARA and PPARG.Conclusion:Overall,this study revealed the active compounds,important targets and possible mechanisms of GLQMP treatment for DKD,and conducted preliminary verification experiments on its correctness,provided novel insights into the treatment of DKD by GLQMP.

Research progress of TCM monomer in treating diabetic kidney disease based on inflammatory mechanism

With the increasing morbidity of diabetes mellitus (DM), diabetic kidney disease (DKD) has become the major reason causing chronic kidney disease (CKD) and end-stage renal disease (ESRD) over the world. However, current treating strategy is aiming at blood glucose controlling and renin-angiotensin system (RAS) restricting which can’t effectively preventing the development of DKD. Recent research indicating that low level of inflammatory and activation of immune system play a significant role in occurrence and progression of DKD. Understanding of inflammatory cascade and its mechanism is conducive to discern novel target of DKD and contributing to design new treating strategy based on anti-inflammatory. For the past few years, an increasing number of evidences proved that Tradit Chin Med (TCM) could delay the progression of ESRD on the basis of inflammatory. In this review, we overview the protective effect against DKD-based renal injury of TCM monomer, offering novel ideas in drug discovery and in mechanism-related research.sd.

Network pharmacology and molecular dynamics study of the effect of the Astragalus-Coptis drug pair on diabetic kidney disease

BACKGROUND Diabetic kidney disease(DKD)is the primary cause of end-stage renal disease.The Astragalus-Coptis drug pair is frequently employed in the management of DKD.However,the precise molecular mechanism underlying its therapeutic effect remains elusive.AIM To investigate the synergistic effects of multiple active ingredients in the Astragalus-Coptis drug pair on DKD through multiple targets and pathways.METHODS The ingredients of the Astragalus-Coptis drug pair were collected and screened using the TCMSP database and the SwissADME platform.The targets were predicted using the SwissTargetPrediction database,while the DKD differential gene expression analysis was obtained from the Gene Expression Omnibus database.DKD targets were acquired from the GeneCards,Online Mendelian Inheritance in Man database,and DisGeNET databases,with common targets identified through the Venny platform.The protein-protein interaction network and the“disease-active ingredient-target”network of the common targets were constructed utilizing the STRING database and Cytoscape software,followed by the analysis of the interaction relationships and further screening of key targets and core active ingredients.Gene Ontology(GO)function and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichments were performed using the DAVID database.The tissue and organ distributions of key targets were evaluated.PyMOL and AutoDock software validate the molecular docking between the core ingredients and key targets.Finally,molecular dynamics(MD)simulations were conducted to simulate the optimal complex formed by interactions between core ingredients and key target proteins.RESULTS A total of 27 active ingredients and 512 potential targets of the Astragalus-Coptis drug pair were identified.There were 273 common targets between DKD and the Astragalus-Coptis drug pair.Through protein-protein interaction network topology analysis,we identified 9 core active ingredients and 10 key targets.GO and KEGG pathway enrichment analyses revealed that Astragalus-Coptis drug pair treatment for DKD involves various biological processes,including protein phosphorylation,negative regulation of apoptosis,inflammatory response,and endoplasmic reticulum unfolded protein response.These pathways are mainly associated with the advanced glycation end products(AGE)-receptor for AGE products signaling pathway in diabetic complications,as well as the Lipid and atherosclerosis.Molecular docking and MD simulations demonstrated high affinity and stability between the core active ingredients and key targets.Notably,the quercetin-AKT serine/threonine kinase 1(AKT1)and quercetin-tumor necrosis factor(TNF)protein complexes exhibited exceptional stability.CONCLUSION This study demonstrated that DKD treatment with the Astragalus-Coptis drug pair involves multiple ingredients,targets,and signaling pathways.We propose a novel approach for investigating the molecular mechanism underlying the therapeutic effects of the Astragalus-Coptis drug pair on DKD.Furthermore,we suggest that quercetin is the most potent active ingredient and specifically targets AKT1 and TNF,providing a theoretical foundation for further exploration of pharmacologically active ingredients and elucidating their molecular mechanisms in DKD treatment.

Exploring kidney biopsy findings in congenital heart diseases:Insights beyond cyanotic nephropathy

BACKGROUND The association between congenital heart disease and chronic kidney disease is well known.Various mechanisms of kidney damage associated with congenital heart disease have been established.The etiology of kidneydisease has commonly been considered to be secondary to focal segmental glomerulosclerosis(FSGS),however,this has only been demonstrated in case reports and not in observational or clinical trials.AIM To identify baseline and clinical characteristics,as well as the findings in kidney biopsies of patients with congenital heart disease in our hospital.METHODS This is a retrospective observational study conducted at the Nephrology Depart-ment of the National Institute of Cardiology“Ignacio Chávez”.All patients over 16 years old who underwent percutaneous kidney biopsy from January 2000 to January 2023 with congenital heart disease were included in the study.RESULTS Ten patients with congenital heart disease and kidney biopsy were found.The average age was 29.00 years±15.87 years with pre-biopsy proteinuria of 6193 mg/24 h±6165 mg/24 h.The most common congenital heart disease was Fallot’s tetralogy with 2 cases(20%)and ventricular septal defect with 2(20%)cases.Among the 10 cases,one case of IgA nephropathy and one case of membranoproliferative glomerulonephritis associated with immune complexes were found,receiving specific treatment after histopathological diagnosis,delaying the initiation of kidney replacement therapy.Among remaining 8 cases(80%),one case of FSGS with perihilar variety was found,while the other 7 cases were non-specific FSGS.CONCLUSION Determining the cause of chronic kidney disease can help in delaying the need for kidney replacement therapy.In 2 out of 10 patients in our study,interventions were performed,and initiation of kidney replacement therapy was delayed.Prospective studies are needed to determine the usefulness of kidney biopsy in patients with congenital heart disease.

MicroRNA-630 alleviates inflammatory reactions in rats with diabetic kidney disease by targeting toll-like receptor 4

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.

Dietary fiber intake and its association with diabetic kidney disease in American adults with diabetes:A cross-sectional study

BACKGROUND Dietary fiber(DF)intake may have a protective effect against type 2 diabetes(T2D);however,its relationship with diabetic kidney disease(DKD)remains unclear.AIM To investigate the potential association between DF intake and the prevalence of DKD in individuals diagnosed with T2D.METHODS This cross-sectional study used data from the National Health and Nutrition Examination Survey collected between 2005 and 2018.DF intake was assessed through 24-h dietary recall interviews,and DKD diagnosis in individuals with T2D was based on predefined criteria,including albuminuria,impaired glomerular filtration rate,or a combination of both.Logistic regression analysis was used to assess the association between DF intake and DKD,and comprehensive subgroup and sensitivity analyses were performed.RESULTS Among the 6032 participants,38.4%had DKD.With lower DF intake-T1(≤6.4 g/1000 kcal/day)-as a reference,the adjusted odds ratio for DF and DKD for levels T2(6.5-10.0 g/1000 kcal/day)and T3(≥10.1 g/1000 kcal/day)were 0.97(95%CI:0.84-1.12,P=0.674)and 0.79(95%CI:0.68-0.92,P=0.002),respectively.The subgroup analysis yielded consistent results across various demographic and health-related subgroups,with no statistically significant interactions(all P>0.05).CONCLUSION In United States adults with T2D,increased DF intake may be related to reduced DKD incidence.Further research is required to confirm these findings.

Urinary exosomal microRNA-145-5p and microRNA-27a-3p act as noninvasive diagnostic biomarkers for diabetic kidney disease

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.

The research progress of epigenetics and metabolic memory in diabetic kidney disease

Diabetic kidney disease(DKD)is a clinical syndrome that is one of the major causes of end-stage renal disease(ESRD).The pathogenesis of DKD is complex and multifaceted,with most studies indicating its association with genetics,advanced glycosylation end-product deposition,polyol pathway and protein C activation,lipid metabolism abnormalities,microcirculatory dysfunction,oxidative stress,inflammatory factors,and the kallikrein-kinin system.Epigenetics is the science studying gene expression regulation without changes in the DNA sequence.In recent years,increasing evidence has shown that epigenetic mechanisms play a crucial role in the initiation and progression of DKD.For instance,epigenetic modifications such as DNA methylation,histone modifications,and non-coding RNAs can influence the expression of DKD-related genes,thereby regulating the development and progression of DKD.On the other hand,metabolic memory is an important concept in DKD research.Metabolic memory refers to the phenomenon where cells maintain a certain metabolic state even after the disappearance of metabolic stress factors.This state can influence cell function and fate.In DKD,metabolic stress factors such as hyperglycemia can lead to metabolic memory in renal cells,affecting their function and fate,ultimately leading to the development and progression of DKD.Therefore,to further explore the pathogenesis of DKD,research on epigenetics should be strengthened,aiming to provide new ideas and methods for the prevention and treatment of DKD.

Multifaceted relationship between diabetes and kidney diseases:Beyond diabete

Diabetes mellitus is one of the most common causes of chronic kidney disease.Kidney involvement in patients with diabetes has a wide spectrum of clinical presentations ranging from asymptomatic to overt proteinuria and kidney failure.The development of kidney disease in diabetes is associated with structural changes in multiple kidney compartments,such as the vascular system and glomeruli.Glomerular alterations include thickening of the glomerular basement membrane,loss of podocytes,and segmental mesangiolysis,which may lead to microaneurysms and the development of pathognomonic Kimmelstiel-Wilson nodules.Beyond lesions directly related to diabetes,awareness of the possible coexistence of nondiabetic kidney disease in patients with diabetes is increasing.These nondiabetic lesions include focal segmental glomerulosclerosis,IgA nephropathy,and other primary or secondary renal disorders.Differential diagnosis of these conditions is crucial in guiding clinical management and therapeutic approaches.However,the relationship between diabetes and the kidney is bidirectional;thus,new-onset diabetes may also occur as a complication of the treatment in patients with renal diseases.Here,we review the complex and multifaceted correlation between diabetes and kidney diseases and discuss clinical presentation and course,differential diagnosis,and therapeutic opportunities offered by novel drugs.

Association of physical activity with risk of chronic kidney disease in China:A population-based cohort study

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.

Incidental renal cell carcinoma post bilateral nephrectomy in autosomal dominant polycystic kidney disease

BACKGROUND Renal cell carcinoma(RCC)is more common in patients with autosomal dominant polycystic kidney disease(ADPKD)than in the general population.Diagnosing RCC in ADPKD is challenging due to the presence of multiple renal cysts,often leading to delays and difficulties in distinguishing RCC from cyst infection or hemorrhage.A total of 38 kidneys were excised from 19 patients,with a mean age of 56.8 years and an average hemodialysis duration of 84.2 months.Eight patients underwent open nephrectomies,and 11 underwent hand-assisted laparoscopic nephrec-tomies.RCC was detected in 15.8%of kidneys,affecting 21.1%of patients.Two patients had multifocal RCC in both kidneys.All RCC cases were pT1 stage,with the largest lesion averaging 16.5 mm in diameter.The average operative duration was 120 minutes,with intraoperative blood loss averaging 184.2 mL.Five patients required blood transfusions.Postoperative complications occurred in five patients,with a mean hospital stay of 17.1 days.The mean follow-up period was 28.1 months.CONCLUSION The prevalence of RCC is higher in patients with ADPKD with ESRD than in those with ESRD alone.Thus,clinicians should be cautious and implement surveillance programs to monitor the development of RCC in patients with ADPKD,particularly those on dialysis.