Evaluation of chronic kidney disease in chronic heart failure: From biomarkers to arterial renal resistances

Chronic kidney disease and its worsening are recurring conditions in chronic heart failure(CHF) which are independently associated with poor patient outcome.The heart and kidney share many pathophysiological mechanisms which can determine dysfunction in each organ. Cardiorenal syndrome is the condition in which these two organs negatively affect each other, therefore an accurate evaluation of renal function in the clinical setting of CHF is essential. This review aims to revise the parameters currently used to evaluate renal dysfunction in CHF with particular reference to the usefulness and the limitations of biomarkers in evaluating glomerular dysfunction and tubular damage. Moreover, it is reported the possible utility of renal arterial resistance index(a parameter associated with abnormalities in renal vascular bed) for a better assesment of kidney disfunction.

Biomarkers in chronic kidney disease,from kidney function to kidney damage

Chronic kidney disease(CKD) typically evolves over many years, with a long latent period when the disease is clinically silent and therefore diagnosis, evaluation and treatment is based mainly on biomarkers that assess kidney function. Glomerular filtration rate(GFR) remains the ideal marker of kidney function. Unfortunately measuring GFR is time consuming and therefore GFR is usually estimated from equations that take into account endogenous filtration markers like serum creatinine(SCr) and cystatin C(Cys C). Other biomarkers such as albuminuria may precede kidney function decline and have demonstrated to have strong associationswith disease progression and outcomes. New potential biomarkers have arisen with the promise of detecting kidney damage prior to the currently used markers. The aim of this review is to discuss the utility of the GFR estimating equations and biomarkers in CKD and the different clinical settings where these should be applied. The CKD-Epidemiology Collaboration equation performs better than the modification of diet in renal disease equation, especially at GFR above 60 m L/min per 1.73 m2. Equations combining Cys C and SCr perform better than the equations using either Cys C or SCr alone and are recommended in situations where CKD needs to be confirmed. Combining creatinine, Cys C and urine albumin to creatinine ratio improves risk stratification for kidney disease progression and mortality. Kidney injury molecule and neutrophil gelatinase-associated lipocalin are considered reasonable biomarkers in urine and plasma to determine severity and prognosis of CKD.

Risk factors and urinary biomarkers of non-albuminuric and albuminuric chronic kidney disease in patients with type 2 diabetes

BACKGROUND A number of recent studies indicate a transformation in the natural course of chronic kidney disease(CKD)in type 2 diabetes(T2D)patients:an increasing prevalence of declined renal function without proceeding to the accompanying elevation of albuminuria.It has been suggested that albuminuric and nonalbuminuric CKD patterns could be different in their phenotypes and pathogenic mechanisms.AIM To identify the risk factors and biomarkers of albuminuric and non-albuminuric patterns of CKD in patients with T2D.METHODS Three hundred sixty patients with T2D duration≥10 years were included in this observational cross-sectional study.The associations of a panel of demographic and clinical characteristics,complications,comorbidities,and metabolic and hematology parameters with albuminuric and non-albuminuric CKD patterns were analyzed.The urinary excretion of nephrin and podocin,two podocytespecific markers,and WAP-four-disulfide core domain protein 2(WFDC-2),a marker of tubulointerstitial fibrosis,was determined by ELISA in comparison with healthy controls.RESULTS Non-albuminuric CKD was associated with age≥65 years(P=0.0001),female sex(P=0.04),diabetes duration≥15 years(P=0.0009),and the use of diuretics(P=0.0005).Male sex(P=0.01),smoking(P=0.01),waist-to-hip ratio>1.0(P=0.01)and hemoglobin A1c(HbA1c)>8.0%(P=0.005)were risk factors for elevated albuminuria not accompanied by a decrease in estimated glomerular filtration rate(eGFR).Duration of diabetes≥15 years and the use of calcium channel blockers were risk factors for albuminuria with decreased eGFR(both P=0.01).In multivariate logistic regression analysis,age,HbA1c,female sex and diuretics were significant predictors for reduced eGFR,while waist-to-hip ratio,HbA1c and male sex were associated with elevated urinary albumin-to-creatinine ratio(UACR).Excretion of nephrin and podocin was increased in patients with albuminuria,regardless of decline in renal function(P<0.001),correlating positively with UACR.The urinary excretion of WFDC-2 was markedly higher in men than in women(P<0.000001).Men with T2D demonstrated increased WFDC-2 levels independently of the CKD pattern(all P<0.05).In T2D women,WFDC-2 excretion was increased in those with reduced renal function(P≤0.01),correlating negatively with eGFR.CONCLUSION The data provide further evidence that albuminuric and non-albuminuric CKD phenotypes correspond to different pathways of diabetic kidney disease progression.

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.

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.

Risk factors for cognitive impairment in patients with chronic kidney disease

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.

Heat exposure and hospitalizations for chronic kidney disease in China: a nationwide time series study in 261 major Chinese cities

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.

Clinical features of chronic kidney disease in dogs with the serological presence of Leptospira spp.,Ehrlichia canis,and Anaplasma phagocytophilum

Chronic kidney disease is commonly diagnosed in dogs,and clinical signs may be aggravated when infected agents are involved.In this case report,33 dogs with chronic kidney disease were clinically evaluated and serologically tested for Leptospira spp.,Ehrlichia canis,and Anaplasma phagocytophilum.The seroprevalence for Leptospira spp.was 39.4%.The most frequent serovars found were Pyrogenes,Canicola,Bratislava and Australis,with serological titers between 1:100 to 1:800.Clinical signs included fever,depression,decreased body condition,vomiting and hema‑turia.Signifcant laboratory fndings were anemia,leukocytosis,thrombocytopenia,increased liver enzymes,urea and creatinine,hyperbilirubinemia and hyperphosphatemia.All leptospira seronegative dogs were positive for one or both monitored homoparasites(i.e.,E.canis and A.phagocytophilum);only three leptospira seropositive dogs were positive for one or both hemoparasites.Findings also suggest that endemic hemoparasites of dogs should be moni‑tored in dogs with a kidney condition for a better clinical picture of the patients and therapeutic approach.

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.

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.

Retinal nerve fiber layer defects and chronic kidney disease:the Kailuan Eye Study

AIM:To investigate whether retinal nerve fiber layer defects(RNFLDs)is a potential risk factor for chronic kidney disease(CKD)in Chinese adults.METHODS:The Kailuan Eye Study was a populationbased study that included 14440 participants.All participants underwent detailed assessments,RNFLDs were diagnosed using color fundus photographs.RESULTS:Overall,12507 participants[8533 males(68.23%)]had complete systemic examination data and at least one evaluable fundus photograph.RNFLDs were found in 621 participants[5.0%;95%confidence interval(CI):4.6%-5.34%],and 70 cases of multiple RNFLDs were found(11.27%).After adjusting multiple factors,RNFLDs was significantly associated with CKD severity,the ORs of CKD stage 3,stage 4 and stage 5 were 1.698,4.167,and 9.512,respectively.Multiple RNFLDs were also associated with CKD severity after adjusting multiple factors,the ORs of CKD stage 3 and stage 5 were 4.465 and 11.833 respectively.Furthermore,2294 participants had CKD(18.34%,95%CI:17.68%-18.99%).After adjusting for other factors,CKD presence was significantly correlated with the presence of RNFLDs.CONCLUSION:The strongest risk factors for RNFLDs are CKD and hypertension.Conversely,RNFLDs can be an ocular feature in patients with CKD.Fundoscopy can help detect systemic diseases,and assessment for RNFLDs should be considered in CKD patients.

Potential efficacy and mechanism of medicinal plants on chronic kidney disease-associated vascular calcification:a review

Vascular calcification is a crucial risk factor that affects the incidence and mortality of cardiovascular disease in chronic kidney disease patients.Modern medicine relies on calcium-phosphorus binding agents,calcium mimetics,active vitamin D,and hemodialysis to prevent and treat vascular calcification,however,their efficacy is unsatisfactory and adverse reactions often occur.Medical plant therapy can act as an integrative regulator in patients with chronic kidney disease-associated vascular calcification,which can significantly improve patients’symptoms,but its specific mechanism has not been fully elucidated yet.In this paper,we reviewed the domestic and international theoretical studies on the pathogenesis mechanism of chronic kidney disease-associated vascular calcification in recent years,summarized eight active ingredients of medicinal plants as well as four compound formulas for improving chronic kidney disease-associated vascular calcification,and explored the mechanism of action of herbal medicine,which will provide a new strategy for promoting the prevention and treatment of vascular calcification.

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.

Renin-angiotensin system inhibitors prescriptions in Chinese hospitalized chronic kidney disease patients

BACKGROUND Many guidelines have recommended renin-angiotensin system inhibitors(RASI)as the first-line treatment for patients with chronic kidney disease(CKD).We studied RASI prescription trends from 2010 to 2019,and analyzed the characteristics associated with RASI prescription in Chinese hospitalized CKD patients.AIM To study the prescription of renin angiotensin system inhibitors in hospitalized patients with CKD in China.METHODS It was retrospectively,cross-sectional reviewed RASI prescriptions in hospitalized CKD patients in China from 2010 to 2019.RASI prescribing trends were analyzed from 2010 to 2019,and bivariate and multivariate logistic regression analyses were conducted to identify characteristics associated with RASI prescription.RESULTS A total of 35090 CKD patients were included,with 10043(28.6%)RASI prescriptions.Among these patients,18919(53.9%)met the criteria for RASI treatments based on the 2012 kidney disease:Improving global outcomes guidelines.Of these,7246(38.3%)patients received RASI prescriptions.RASI prescriptions showed an initial rapid increase from 2011 to 2012,reached its peak around 2015 and 2016,and then exhibited a subsequent slight decreasing trend.Both bivariate and multivariate analyses showed that several characteristics,including the male gender,age less than 60-year-old,nephrology department admission,lower CKD stage,history of hypertension or diabetes,proteinuria,glomerulonephritis as the CKD etiology,and non-acute kidney injury were associated with RASI prescriptions.CONCLUSION The frequency of RASI prescriptions showed an initial increase but a slight decreasing trend in more recent years.CKD patients with certain characteristics such as elderly age,advanced disease stage,surgery department admission,or acute kidney injury were less likely to receive RASI prescriptions.In the application of RASI in hospitalized CKD patients is insufficient.The actual clinical practice needs to be improved.The development of related research is helpful to guide the correct choice of clinical treatment strategy.

Hematological Alterations in an Eastern Sudanese Chronic Kidney Disease Patient Population

Background: Chronic Kidney Disease (CKD), associated with a slow and progressive loss of kidney function over a period of several years, is an important clinical disaster with an increasing rate of morbidity and mortality especially in the least developed countries. Many hematological parameters are thought to alter dramatically during the course of the disease. These include white blood cells, red blood cells, and platelets. Methods: We tried, retrospectively, to evaluate the peripheral blood hematological alterations in a group of patients undergoing hemodialysis in an eastern Sudan dialysis center to add local medical information. Results: Anemia (Low hemoglobin and hematocrit) was detected in 94% of the patients’ group. Mean Erythrocyte count (3.32vs.4.76 (×109/L)), Hemoglobin concentration (9.4vs.13 (g/dl)), Hematocrit (28.7vs.38.7 (L/L)) and platelet count (296 vs. 238 (×109/L)) were significantly lower in the patients’ group than in the control group (P-values Conclusion: Five out of eight studied parameters (Red cell count, hemoglobin, hematocrit, mean cell hemoglobin concentration, and platelets count) have shown a significant alteration in CKD patients. As the complete blood count (CBC) test is the most utilized test in clinical laboratory practice, these alterations may be considered as early indicators for CKD. Furthermore, all patients with CKD must be routinely checked for these alterations.

Complexity and Management of Chronic Kidney Disease

Chronic Kidney Disease (CKD) is ongoing damage of the kidneys, which affects their ability to filter the blood the way they should. Worldwide CKD is considered as the 16th leading cause of death and affects 8% - 16% of the population. CKD often goes unnoticed and is revealed as an incidental finding. Healthcare providers diagnose the condition as CKD based on persistent abnormal kidney function tests revealing kidney damage markers > 3 months, urine albumin creatinine ratio (UACR) > or equal to 30 mg/g per 24 hours, and GFR < 60 mL/min/1.73m2. In this article, we have discussed chronic kidney disease in terms of kidney physiology, chronic kidney disease pathophysiology, etiology, diagnosis, signs and symptoms, and management.

Impact of Sarcopenia on Prognosis in Frail Elderly Patients with Chronic Kidney Disease

Objective:To investigate the impact of sarcopenia on the prognosis of frail elderly patients with chronic kidney disease.Methods:A total of 98 elderly frail patients with chronic kidney disease were included in this study from June 2020 to July 2022.The patients were randomly divided into a study group of 48 cases and a control group of 50 cases.The control group only received conventional treatment for chronic kidney disease.On the basis of conventional treatment for chronic kidney disease,the study group added sarcopenia intervention treatment.The quality-of-life scores,muscle mass and muscle strength,renal function,and incidence of complications of the two groups were observed and analyzed.Results:The quality-of-life score,muscle mass and muscle strength,and renal function of the study group were significantly better than those of the control group(P<0.05);the incidence of complications in the study group was 12.5%,which was significantly lower than that of the control group 36%of the group(P<0.05).Conclusion:There is a close relationship between sarcopenia and frail elderly patients with chronic kidney disease.Sarcopenia will further aggravate the frailty symptoms and increase the risk of complications in elderly patients with chronic kidney disease.For elderly patients with chronic kidney disease,sarcopenia should be screened and intervened as early as possible to improve the prognosis and quality of life of the patients.

Anti-fibrotic and anti-inflammatory effect of mesenchymal stromal cell-derived extracellular vesicles in chronic kidney disease

Renal fibrosis and inflammation are common pathological features of chronic kidney disease(CKD).Since currently available treatments can only delay the progression of CKD,the outcome of patients with CKD is still poor.One therapeutic option for the prevention of CKD-related complications could be the use of mesenchymal stromal cells(MSCs),which have shown beneficial effects in tissue fibrosis and regeneration after damage.However,safety issues,such as cellular rejection and carcinogenicity,limit their clinical application.Among the bioactive factors secreted by MSCs,extracellular vesicles(EVs)have shown the same beneficial effect of MSCs,without any notable side effects.This heterogeneous population of membranous nano-sized particles can deliver genetic material and functional proteins to injured cells,prompting tissue regeneration.Here we describe the anti-fibrotic and antiinflammatory properties of MSC-derived EVs in CKD preclinical models and summarize the potential molecular mechanisms involved in the regulation of renal fibrosis and inflammation.

Transcriptomic and metabolomic analysis of the effects of Zhenwu decoction on kidney yang deficiency pattern in chronic kidney disease

Objective:To explore the kidney yang deficiency pattern(KYDP)in a chronic kidney disease(CKD)rat model and the mechanisms underlying the effects of Zhenwu decoction(ZWD)by conducting tran-scriptomic and metabolomic analyses.Methods:Adriamycin(ADR)combined with hydrocortisone(HC)was used to induce CKD with KYDP in rats.ADR was injected into the tail vein twice.HC was injected intramuscularly for 8 weeks.ZWD was administered by gavage for 8 weeks.The general condition was observed,24-h urine protein was detected,serum corticosterone,triiodothyronine,thyroxine,TSH,testosterone,cAMP,and cGMP levels were determined,and pathological analysis was conducted.Transcriptomic and metabolomic analyses were conducted to screen differentially expressed genes(DEGs),differentially expressed metabolites(DEMs),and differentially expressed pathways(DEPs).The core DEMs and DEGs were input to Metab-oanalyst 5.0 to identify the pathways affected by ZWD.Results:In the HC group,KYDP symptoms were observed.Compared with control group,the levels of 24-h urine protein,TSH,and cGMP significantly increased(all P<0.01),and corticosterone,triiodothyronine,thyroxine,and cAMP significantly decreased(all P<0.01)in the HC group.After ZWD intervention,the levels of above-mentioned indicators could be reversed to some extent.Pathological analysis in the HC group revealed kidney lesions.DEGs in the ZWD group were mainly associated with pathways such as nucleotide synthesis and endocrine pathways.In the ZWD group,differences in biosynthesis of unsat-urated fatty acids and butanoate metabolism were observed.The following pathways were significantly affected by ZWD:arachidonic acid metabolism,valine,leucine,and isoleucine biosynthesis,linoleic acid metabolism,and alpha-linolenic acid metabolism.Conclusion:ZWD can be used to treat KYDP in CKD through regulating arachidonic acid metabolism,valine,leucine,and isoleucine biosynthesis,linoleic acid metabolism,and alpha-linolenic acid metabolism.

Risk estimation of chronic kidney disease in a leptospirosis endemic area: A case-control study from south Andaman Islands of India

Objective:To estimate the risk of chronic kidney disease in patients with leptospirosis.Methods:All reported(41890)and later confirmed leptospirosis(1990)cases from 2010-2020 were traced by universal sampling.386 Laboratory-confirmed leptospirosis cases were enrolled and 413 age,gender,area,and occupation matched healthy persons were included as controls.Variables including socio-demographic characteristics,medical history,and health-related behaviours were compared between the two groups and association between these variables and reduced estimated glomerular filtration rate(eGFR)was analyzed with multiple linear regression.Results:The median of eGFR was 49.0(27.0,75.0)mL/min/1.73 m^(2) in the cases and 96.0(72.0,121.0)mL/min/1.73 m^(2) in the controls,showing significant differences(P<0.001).Bivariate analysis showed that leptospirosis seropositivitiy,repeat leptospirosis infection,diabetes,male gender,working in field(sun exposure),COVID-19 infection and smoking had statistically significant association with reduced eGFR.Leptospirosis seropositivity had negative effects on eGFR.Multiple linear regression confirmed that leptospirosis seropositivity had negative effects on eGFR(unstandardised β coefficients=−30.86,95%CI−49.7 to−11.9,P<0.001).Conclusions:Chronic kidney disease is a complex disease with multiple risk factors involved.Exposure to leptospirosis is one of the essential factors in accelerating its progression.