Changes in renal function and morphological variations of kidney diseases in rheumatoid arthritis patients

Objective:Rheumatoid nephropathy is one of the most severe extra-articular manifestations of rheumatoid arthritis(RA)associated with a very unfavorable prognosis.This study aimed to identify changes in renal function and morphological variations of kidney diseases in RA patients.Methods:The study enrolled patients(126 patients)between 18 and 55 years of age with a confirmed active RA of more than 12 months.Each patient underwent the following range of laboratory and instrumental research methods:general clinical analysis of blood and urine,performing urinalysis according to Nechiporenko method;determining daily proteinuria;determining the blood content of glucose,urea,creatinine,uric acid,total bilirubin,liver transaminase level,ionogram,lipidogram,and coagulogram;determining the blood content of rheumatoid factor,anti-streptolysin O,and C-reactive protein;and X-ray of the joints of hands and feet.Renal function was examined by estimating glomerular filtration rate,tubular reabsorption index,and renal functional reserve.For studying the morphological changes in the kidneys under ultrasound examination,renal biopsy was performed in 31 patients with RA with urinary syndrome(proteinuria more than 0.3 g per day and hematuria).Results:Nephropathy in RA is characterized by impaired renal function and manifested by an increased blood creatinine and a decrease in glomerular filtration rate and renal functional reserve.Among morphological variations of nephropathy at RA,mesangial proliferative glomerulonephritis prevails,accounting for 48.4%of patients.Other disorders include the secondary amyloidosis(29.0%of patients),tubulointerstitial nephritis(16.1%),membranous glomerulonephritis(3.2%),and focal-segmental glomerulosclerosis(3.2%).Conclusion:Kidney damage is a common systemic manifestation of RA with a long and active course,a major nephropathy trigger.

Renal resistive index measurements by ultrasound in patients with liver cirrhosis:Magnitude and associations with renal dysfunction

BACKGROUND The hemodynamic alterations seen in liver cirrhosis lead to renal vasoconstriction,ultimately causing acute kidney injury(AKI).The renal resistive index(RRI)is the most common Doppler ultrasound variable for measuring intrarenal vascular resistance.AIM To evaluate the association of the RRI with AKI in patients with liver cirrhosis and to identify risk factors for high RRI.METHODS This was a prospective observational study,where RRI was measured using Doppler ultrasound in 200 consecutive hospitalized patients with cirrhosis.The association of RRI with AKI was studied.The receiver operating characteristic(ROC)curve analysis was utilized to determine discriminatory cut-offs of RRI for various AKI phenotypes.Multivariate analysis was conducted to determine the predictors of high RRI.RESULTS The mean patient age was 49.08±11.68 years,with the majority(79.5%)being male;the predominant etiology of cirrhosis was alcohol(39%).The mean RRI for the study cohort was 0.68±0.09,showing a progressive increase with higher Child-Pugh class of cirrhosis.Overall,AKI was present in 129(64.5%)patients.The mean RRI was significantly higher in patients with AKI compared to those without it(0.72±0.06 vs 0.60±0.08;P<0.001).A total of 82 patients(41%)had hepatorenal syndrome(HRS)-AKI,29(22.4%)had prerenal AKI(PRA),and 18(13.9%)had acute tubular necrosis(ATN)-AKI.The mean RRI was significantly higher in the ATN-AKI(0.80±0.02)and HRS-AKI(0.73±0.03)groups than in the PRA(0.63±0.07)and non-AKI(0.60±0.07)groups.RRI demonstrated excellent discriminatory ability in distinguishing ATN-AKI from non-ATN-AKI(area under ROC curve:93.9%).AKI emerged as an independent predictor of high RRI(adjusted odds ratio[OR]:11.52),and high RRI independently predicted mortality among AKI patients(adjusted OR:3.18).CONCLUSION In cirrhosis patients,RRI exhibited a significant association with AKI,effectively differentiated between AKI phenotypes,and predicted AKI mortality.

Metallothionein 1E Alleviates Cadmium-induced Renal Cytotoxicity through Promoting Mitochondrial Functional Recovery

The pervasive utilization of industrial substances has escalated human exposure to cadmium(Cd),a metal associated with long-term negative health outcomes such as renal dysfunction,neurological disorders,and various cancers^([1]).Once ingested by humans,Cd interacts with cysteine-rich metallothioneins(MTs)which have metal-binding and antioxidant properties and is subsequently transported to the kidney^([2]).

Therapeutic potential of urine-derived stem cells in renal regeneration following acute kidney injury:A comparative analysis with mesenchymal stem cells

BACKGROUND Acute kidney injury(AKI)is a common clinical syndrome with high morbidity and mortality rates.The use of pluripotent stem cells holds great promise for the treatment of AKI.Urine-derived stem cells(USCs)are a novel and versatile cell source in cell-based therapy and regenerative medicine that provide advantages of a noninvasive,simple,and low-cost approach and are induced with high multidifferentiation potential.Whether these cells could serve as a potential stem cell source for the treatment of AKI has not been determined.METHODS Stem cell markers with multidifferentiation potential were isolated from human amniotic fluid.AKI severe combined immune deficiency(SCID)mice models were induced by means of an intramuscular injection with glycerol.USCs isolated from human-voided urine were administered via tail veins.The functional changes in the kidney were assessed by the levels of blood urea nitrogen and serum creatinine.The histologic changes were evaluated by hematoxylin and eosin staining and transferase dUTP nick-end labeling staining.Meanwhile,we compared the regenerative potential of USCs with bone marrow-derived mesenchymal stem cells(MSCs).RESULTS Treatment with USCs significantly alleviated histological destruction and functional decline.The renal function was rapidly restored after intravenous injection of 5×105 human USCs into SCID mice with glycerol-induced AKI compared with injection of saline.Results from secretion assays conducted in vitro demonstrated that both stem cell varieties released a wide array of cytokines and growth factors.This suggests that a mixture of various mediators closely interacts with their biochemical functions.Two types of stem cells showed enhanced tubular cell prolif-eration and decreased tubular cell apoptosis,although USC treatment was not more effective than MSC treatment.We found that USC therapy significantly improved renal function and histological damage,inhibited inflammation and apoptosis processes in the kidney,and promoted tubular epithelial proliferation.CONCLUSION Our study demonstrated the potential of USCs for the treatment of AKI,representing a new clinical therapeutic strategy.

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.

Primary Ewing sarcoma of the kidney mimicking cystic papillary renal cell carcinoma in an older patient:A case repor

BACKGROUND Ewing’s sarcoma(ES)is a neuroectodermal tumor that typically occurs in the bones and soft tissues of children and young adults.Primary renal ES is rare;only a few cases and a small case series have been documented,and only four cases involved primary renal ES in older people(>65 years old).CASE SUMMARY Herein,we describe the radiological and pathological features of primary renal ES in an older person.A 76-year-old man complained of poor oral intake and was found to have a large cystic renal mass with indistinct margins on computed tomography.Ultrasound-guided biopsy revealed that the tumor contained small round blue cells.The patient underwent a right radical nephrectomy.The tumor cells showed diffuse membranous CD99,and nuclear friend leukemia integration 1 transcription factor and NK2 Homeobox 2.Fluorescence in situ hybridization revealed EWSR1 translocation.Postoperatively,18F-fluorodeoxyglucose positron emission tomography revealed no evidence of metastasis.The patient was diagnosed with primary renal ES.Six months following the surgery,local recurrence and distant metastasis were observed.Primary renal ES is rare and often lethal in older individuals.The specific imaging findings are unknown,and treatment protocols have not been standardized.CONCLUSION This case report describes the radiological and pathological features of primary renal ES in an older person.

Integrative bioinformatics and in vitro exploration of EVI2A expression:unraveling its immunological and prognostic implications in kidney renal clear cell carcinoma

EVI2A has emerged as a significant biomarker in various diseases;however,its biological role and mechanism in kidney renal clear cell carcinoma(KIRC)remains unexplored.We used TCGA and GEO databases to analyze EVI2A gene expression comprehensively and performed pan-cancer assessments.Clinical relevance was evaluated through Kaplan-Meier analysis and ROC curves.The gene’s immune relevance was explored through analyses of the tumor microenvironment(TME),Tumor Immune Single-cell Hub(TISCH),immune checkpoints,and immunotherapy sensitivity.Our results indicate that EVI2A expression is upregulated in KIRC,showing correlations with tumor grade and T/N/M stage.EVI2A demonstrates high diagnostic accuracy(AUC=0.906)and predicts poor overall and progression-free survival in KIRC patients.Furthermore,EVI2A expression exhibits significant associations with immunity,including TME scores and specific immune cell types such as Tfh cells,CD4 memory T cells,and CD8+T cells.Elevated EVI2A expression suggests increased sensitivity to PD-1/CTLA-4 and tyrosine kinase inhibitors.In vitro assays confirmed the impact of EVI2A on KIRC behavior,with its knockdown resulting in reduced cell proliferation and migration.In conclusion,our comprehensive analysis identifies EVI2A as a promising biomarker and a novel therapeutic target for intervening in KIRC.These findings hold significant implications for further research and potential clinical applications.

Prevalence and risk factors for impaired renal function among Asian patients with nonalcoholic fatty liver disease

Background:Nonalcoholic fatty liver disease(NAFLD)is associated with impaired renal function,and both diseases often occur alongside other metabolic disorders.However,the prevalence and risk factors for impaired renal function in patients with NAFLD remain unclear.The objective of this study was to identify the prevalence and risk factors for renal impairment in NAFLD patients.Methods:All adults aged 18-70 years with ultrasound-diagnosed NAFLD and transient elastography examination from eight Asian centers were enrolled in this prospective study.Liver fibrosis and cirrhosis were assessed by FibroScan-aspartate aminotransferase(FAST),Agile 3+and Agile 4 scores.Impaired renal function and chronic kidney disease(CKD)were defined by an estimated glomerular filtration rate(eGFR)with value of<90 mL/min/1.73 m^(2) and<60 mL/min/1.73 m^(2),respectively,as estimated by the CKD-Epidemiology Collaboration(CKD-EPI)equation.Results:Among 529 included NAFLD patients,the prevalence rates of impaired renal function and CKD were 37.4%and 4.9%,respectively.In multivariate analysis,a moderate-high risk of advanced liver fibrosis and cirrhosis according to Agile 3+and Agile 4 scores were independent risk factors for CKD(P<0.05).Furthermore,increased fasting plasma glucose(FPG)and blood pressure were significantly associated with impaired renal function after controlling for the other components of metabolic syndrome(P<0.05).Compared with patients with normoglycemia,those with prediabetes[FPG≥5.6 mmol/L or hemoglobin A1c(HbA1c)≥5.7%]were more likely to have impaired renal function(P<0.05).Conclusions:Agile 3+and Agile 4 are reliable for identifying NAFLD patients with high risk of CKD.Early glycemic control in the prediabetic stage might have a potential renoprotective role in these patients.

Interplay between metabolic dysfunction-associated fatty liver disease and renal function: An intriguing pediatric perspective

Over recent years,the nomenclature of non-alcoholic fatty liver disease has undergone significant changes.Indeed,in 2020,an expert consensus panel proposed the term“Metabolic(dysfunction)associated fatty liver disease”(MAFLD)to underscore the close association of fatty liver with metabolic abnormalities,thereby highlighting the cardiometabolic risks(such as metabolic syndrome,type 2 diabetes,insulin resistance,and cardiovascular disease)faced by these patients since childhood.More recently,this term has been further replaced with metabolic associated steatotic liver disease.It is worth noting that emerging evidence not only supports a close and independent association of MAFLD with chronic kidney disease in adults but also indicates its interplay with metabolic impairments.However,comparable pediatric data remain limited.Given the progressive and chronic nature of both diseases and their prognostic cardiometabolic implications,this editorial aims to provide a pediatric perspective on the intriguing relationship between MAFLD and renal function in childhood.

Indications for Renal Needle Biopsy and Histological Spectrum of Kidney Disease in Togo

Introduction: The frequent late-stage diagnosis of chronic kidney disease (CKD) constrains the treatment choices for nephrologists. Renal biopsy (RB) is crucial for accurately identifying renal lesions. This key nephrological procedure, however, is invasive and not without potential complications. The purpose of this study was to evaluate the indications, frequency, and histological lesion profiles of renal biopsies in Togo. Materials and Methods: We conducted a descriptive cross-sectional study encompassing all renal biopsies performed in Togo from the inception of nephrology services to the present. Data were compiled from the medical records of the patients. Results: From 2015 to 2023, 68 high-quality renal biopsies were executed in Togo. The patients had an average age of 30.6 years, with a predominance of males (69.1%). The most common indication was nephrotic syndrome, accounting for 66.2% of cases. Histologically, glomerulopathies were predominant, representing 61.8% of lesions, followed by vascular nephropathies (25%) and tubulointerstitial nephropathies (13.2%). The most frequently observed primary glomerulopathy was focal segmental glomerulosclerosis (FSGS). Gross hematuria was the sole complication, occurring in 1.4% of the cases. Conclusion: RB is an evolving practice in Togo. Glomerulopathies are the most commonly observed lesions. The histological categorization of renal lesions is vital for clinicians in their diagnostic reasoning and approach.

Risk Factors of the Progression of Renal Function Deterioration Among Patients with Diabetic Nephropathy

Objective:To explore the risk factors for the progression of renal function deterioration in patients with diabetic nephropathy(DN).Methods:The clinical data and biochemical indexes of 100 diabetic patients admitted to our hospital from October 2021 to October 2022 were retrospectively analyzed.The patients were divided into a DN group,which consisted of 55 cases,and a nondiabetic nephropathy group(NDN),which consisted of 45 cases.The urinary microalbumin to creatinine ratio,the clinical data(gender,age,duration of the disease,and BMI),and the biochemical indexes(triglycerides[TG],low-density lipoprotein cholesterol[LDL-C],high-density lipoprotein cholesterol[HDL-C],total cholesterol[TC],glycated hemoglobin A1c[HbA1c],systolic blood pressure[SBP],diastolic blood pressure[DBP])of the two groups were compared.Subsequently,the risk factors related to the progression of renal function deterioration in DN were analyzed through multifactorial logistic regression analysis.Results:No statistically significant difference was observed in the comparison of gender,age,BMI,LDL-C,and DBP between the two groups(P>0.05).The DN group demonstrated a longer disease duration and higher SBP,TC,HDL-C,HbA1c,and TG compared to the NDN group(P<0.05).Through multifactorial logistic regression analysis,it was found that the duration of the disease,the TC,the HDL-C,the HbA1c,the TG,and the SBP were independent risk factors of the deterioration of renal function in DN patients.Conclusion:Other than conventional indicators,TC,HDL-C,HbA1c,TG,and SBP are also crucial indicators in determining the progression of renal function deterioration in DN patients.

Timing of Continuous Renal Replacement Therapy Initiation in Sepsis-Associated Acute Kidney Injury: A Comprehensive Review and Future Directions

This review examines the application of continuous renal replacement therapy(CRRT)in patients with sepsis-associated acute kidney injury(S-AKI),with a particular focus on the timing of CRRT initiation.This review addresses the controversy surrounding initiation timing and proposes future research directions.Through a systematic review of recent literature on CRRT for S-AKI,working principles,therapeutic mechanisms,initiation timing of CRRT,and related meta-analyses were summarized.Current studies indicate that the optimal timing for CRRT initiation in S-AKI patients remains inconclusive,with ongoing debate regarding whether early initiation significantly improves patient survival and renal function.This lack of consensus reflects the heterogeneity of the S-AKI patient population and the limitations of existing research methodologies.Future studies should focus on advancing the application of precision medicine in S-AKI and developing individualized treatment strategies by integrating multidimensional information to optimize CRRT utilization and improve patient outcomes.

Efficacy of prednisone combined with mycophenolate mofetil for immunoglobulin A nephropathy with moderate-to-severe renal dysfunction

BACKGROUND Immunoglobulin A nephropathy(IgAN)is a common form of chronic glomer-ulonephritis.Currently,IgAN is one of the main causes of chronic renal failure in China;its prognosis varies greatly between patients,with renal function at the time of diagnosis and prognosis being strongly correlated.Mycophenolate mofetil(MMF)is a drug with a good immunomodulatory effect and is commonly used clinically.However,its effects in IgAN have not yet been clearly demonstrated.Therefore,herein,we retrospectively compared the effectiveness and safety of prednisone alone or combined with MMF for the treatment of primary IgAN with moderate-to-severe renal impairment.METHODS Between January 2011 and December 2020,200 patients with moderate-to-severe IgAN were included in this study,all of whom were admitted to Wuxi People's Hospital affiliated with Nanjing Medical University.All patients underwent a renal puncture biopsy,which revealed primary IgAN with a glomerular filtration rate(GFR)of 30–60 mL/min.The patients were divided into a glucocorticoid therapy group(GTG)and an immunosuppressive therapy group(ITG)according to the different treatment regimens,with 100 patients in each group.Based on general treatments,such as angiotensin-converting enzyme inhibitors/angiotensin receptor blockers,patients in the GTG were administered prednisone 0.5–0.8 mg/(kg·d^(-1))for 4–8 wk,which was reduced by 5 mg every two weeks until the maintenance(30 mg/d)dose was reached and maintained for 12 mo.In the ITG,MMF was administered at 1.0 g/d for 6–12 mo,followed by a maintenance dosage of 0.5 g/d for 12 mo.Age,sex,blood pressure,24-h urinary egg white measurement,serum creatinine(Scr),blood uric acid,blood albumin,blood potassium(K),hemoglobin,GFR,alanine aminotransferase,total cholesterol(T-CHO),fasting blood glucose,and body mass index were recorded.The 24-h urinary protein,Scr,and GFR levels were recorded 3,6,9,and 12 mo after treatment.Follow-up data were also collected.RESULTS No discernible differences existed between the two groups in terms of age,sex,blood pressure,creatinine,24-h urinary protein level,GFR,or other biochemical indicators at the time of enrollment.Both regimens significantly reduced the 24-h urinary protein quantitation and stabilized renal function.Nine months after treatment,the 24-h urinary protein and Scr of the ITG decreased more significantly than those of the GTG.By the 12th month of treatment,the 24-h urinary protein and Scr in both groups continued to decrease compared to those by the 9th month.In addition,the overall response rate in the ITG was significantly higher than that in the GTG.The occurrence of side effects did not vary significantly between the two regimens;however,endpoint events were significantly more common in the GTG than in the ITG.The follow-up time for the GTG was noticeably lower than that for the ITG.CONCLUSION Prednisone combined with MMF was effective for the treatment of IgAN with moderate-to-severe renal dysfunction.

Values of Donor Serum Lipids and Calcium in Predicting Graft Function after Kidney Transplantation:A Retrospective Study

Objective Delayed graft function(DGF)and early graft loss of renal grafts are determined by the quality of the kidneys from the deceased donor.As“non-traditional”risk factors,serum biomarkers of donors,such as lipids and electrolytes,have drawn increasing attention due to their effects on the postoperative outcomes of renal grafts.This study aimed to examine the value of these serum biomarkers for prediction of renal graft function.Methods The present study consecutively collected 306 patients who underwent their first single kidney transplantation(KT)from adult deceased donors in our center from January 1,2018 to December 31,2019.The correlation between postoperative outcomes[DGF and abnormal serum creatinine(SCr)after 6 and 12 months]and risk factors of donors,including gender,age,body mass index(BMI),past histories,serum lipid biomarkers[cholesterol,triglyceride,high-density lipoprotein(HDL)and low-density lipoprotein(DL)],and serum electrolytes(calcium and sodium)were analyzed and evaluated.Results(1)Donor age and pre-existing hypertension were significantly correlated with the incidence rate of DGF and high SCr level(≥2 mg/dL)at 6 and 12 months after KT(P<0.05);(2)The donor’s BMI was significantly correlated with the incidence rate of DGF after KT(P<0.05);(3)For serum lipids,merely the low level of serum HDL of the donor was correlated with the reduced incidence rate of high SCr level at 12 months after KT[P<0.05,OR(95%CI):0.425(0.202–0.97)];(4)The serum calcium of the donor was associated with the reduced incidence rate of high SCr level at 6 and 12 months after KT[P<0.05,OR(95%CI):0.184(0.045–0.747)and P<0.05,OR(95%CI):0.114(0.014–0.948),respectively].Conclusion The serum HDL and calcium of the donor may serve as predictive factors for the postoperative outcomes of renal grafts after KT,in addition to the donor’s age,BMI and pre-existing hypertension.

Roles of biochemistry data, lifestyle, and inflammation in identifying abnormal renal function in old Chinese

BACKGROUND The incidence of chronic kidney disease(CKD)has dramatically increased in recent years,with significant impacts on patient mortality rates.Previous studies have identified multiple risk factors for CKD,but they mostly relied on the use of traditional statistical methods such as logistic regression and only focused on a few risk factors.AIM To determine factors that can be used to identify subjects with a low estimated glomerular filtration rate(L-eGFR<60 mL/min per 1.73 m^(2))in a cohort of 1236 Chinese people aged over 65.METHODS Twenty risk factors were divided into three models.Model 1 consisted of demographic and biochemistry data.Model 2 added lifestyle data to Model 1,and Model 3 added inflammatory markers to Model 2.Five machine learning methods were used:Multivariate adaptive regression splines,eXtreme Gradient Boosting,stochastic gradient boosting,Light Gradient Boosting Machine,and Categorical Features+Gradient Boosting.Evaluation criteria included accuracy,sensitivity,specificity,area under the receiver operating characteristic curve(AUC),F-1 score,and balanced accuracy.RESULTS A trend of increasing AUC of each was observed from Model 1 to Model 3 and reached statistical significance.Model 3 selected uric acid as the most important risk factor,followed by age,hemoglobin(Hb),body mass index(BMI),sport hours,and systolic blood pressure(SBP).CONCLUSION Among all the risk factors including demographic,biochemistry,and lifestyle risk factors,along with inflammation markers,UA is the most important risk factor to identify L-eGFR,followed by age,Hb,BMI,sport hours,and SBP in a cohort of elderly Chinese people.

Renal function and physical fitness after 12-mo supervised training in kidney transplant recipients

AIM To evaluate the effect of a 12-mo supervised aerobic and resistance training, on renal function and exercise capacity compared to usual care recommendations.METHODS Ninety-nine kidney transplant recipients(KTRs) were assigned to interventional exercise(Group A; n = 52) and a usual care cohort(Group B; n = 47). Blood and urine chemistry, exercise capacity, muscular strength, anthropometric measures and health-related quality of life(HRQo L) were assessed at baseline, and after 6 and 12 mo. Group A underwent a supervised training three times per week for 12 mo. Group B received only general recommendations about home-based physical activities.RESULTS Eighty-five KTRs completed the study(Group A, n = 44; Group B, n = 41). After 12 mo, renal function remained stable in both groups. Group A significantly increased maximum workload(+13 W, P = 0.0003), V'O2 peak(+3.1 mL/kg per minute, P = 0.0099), muscular strength in plantar flexor(+12 kg, P = 0.0368), height in the countermovement jump(+1.9 cm, P = 0.0293) and decreased in Body Mass Index(-0.5 kg/m^2, P = 0.0013). HRQo L significantly improved in physical function(P = 0.0019), physical-role limitations(P = 0.0321) and social functioning scales(P = 0.0346). Noimprovements were found in Group B.CONCLUSION Twelve-month of supervised aerobic and resistance training improves the physiological variables related to physical fitness and cardiovascular risks without consequences on renal function. Recommendations alone are not sufficient to induce changes in exercise capacity of KTRs. Our study is an example of collaborative working between transplant centres, sports medicine and exercise facilities.

Long term outcomes of Cohen’s cross trigonal reimplantation for primary vesicoureteral reflux in poorly functioning kidney

BACKGROUND Open ureteric reimplantation by cross trigonal technique described by Cohen is considered a common surgical option for correction of vesicoureteral reflux(VUR). There is a lack of evidence in literature though for what happens to such kidneys, in the long run, particularly those which are poorly functioning.AIM To assess the long-term outcomes of ureteric reimplantation in poorly functioning kidneys in children with unilateral primary VUR.METHODS Children with unilateral primary VUR and a relative renal function of less than 35% who underwent open or laparoscopic ureteric reimplantation between January 2005 and January 2017 were included in the study. Patients who had a follow up of less than five years were excluded. Preoperative evaluation consisted of a voiding cystourethrogram and Dimercaptosuccinic acid(DMSA) scan. In the follow-up period, patients underwent a diuretic scan at 6 weeks and 6 months.Follow up ultrasound was done for change in grade of hydronephrosis and retrovesical ureteric diameter. Subsequent follow up was done at 6 monthly intervals with evaluation for proteinuria and hypertension and any recurrent urinary tract infection(UTI). For assessment of cortical function, DMSA was repeated annually for 5 years after surgery. A paired-samples t-test was used to test the mean difference of DMSA between pre-post observations.RESULTS During this period, 36 children underwent ureteric reimplantation for unilateral primary VUR. After excluding those with insufficient follow-up, 31 were included in the analysis. Most of the patients were males(n = 26/31, 83.8%). Patient’s age(mean ± SD, range) was 5.21 ± 3.71, 1-18 years. The grades of VUR were grade Ⅱ(1patient), grade Ⅲ(8 patients), grade Ⅳ(10 patients), and grade Ⅴ(12 patients). The pre and postoperative DMSA was 24.064 ± 12.02 and 24.06 ± 10.93, which was almost the same(statistically equal, paired-samples t-test: P = 0.873). The median(range) follow-up duration was 82(60-120)mo. One patient had persistent reflux after surgery(preoperative: grade Ⅳ, postoperative: grade Ⅲ), and the very same patient developed recurrent UTI. The difference in the preoperative and postoperative DRF was less than 10% in 29 patients. In one patient, the DRF decreased by 17%(22% to 05%) while in another patient, the DRF increased by 12%(25% to 37%) after surgery. None of the patients had an increase in scarring after surgery. 15% of patients were hypertensive before surgery and all of them continued to be hypertensive after surgery while none developed hypertension after surgery. None of the patients had significant proteinuria(> 150 mg/d) during the follow-up period.CONCLUSION Children with unilateral primary VUR and poorly functioning kidney maintain the renal function over the long term in most cases. Hypertension and proteinuria do not progress over time in these patients.

ELABELA protects against diabetic kidney disease by activating high glucose-inhibited renal tubular autophagy

ELABELA(ELA),an endogenous ligand of the apelin receptor(also known as apelin peptide jejunum[APJ]),has been shown to decrease in the plasma of patients with diabetic kidney disease(DKD).In the current study,we explored the potential function as well as the underlying mechanisms of ELA in DKD.We first found that the ELA levels were decreased in the kidneys of DKD mice.Then,we found that ELA administration mitigated renal damage and downregulated the expression of fibronectin,collagenⅣ,and transforming growth factor-β1 in the db/db mice and the high glucose cultured HK-2 cells.Furthermore,the autophagy markers,Beclin-1 and LC3-Ⅱ/LC3-Ⅰratio,were significantly impaired in DKD,but the ELA treatment reversed these alterations.Mechanistically,the inhibitory effects of ELA on the secretion of fibrosis-associated proteins in high glucose conditions were blocked by pretreatment with 3-methyladenine(an autophagy inhibitor).In summary,these in vivo and in vitro results demonstrate that ELA effectively protects against DKD by activating high glucose-inhibited renal tubular autophagy,potentially serving as a novel therapeutic candidate for DKD.

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.

Association of cumulative resting heart rate exposure with rapid renal function decline:a prospective cohort study with 27,564 older adults

OBJECTIVE To evaluate the prospective association between cumulative resting heart rate(cumRHR)and rapid renal function decline(RRFD)in a cohort of individuals aged 60 and older.METHODS In the Tianjin Chronic Kidney Disease Cohort Study,the individuals who underwent three consecutive physical examinations between 2014 and 2017,with estimated glomerular filtration rate(eGFR)greater than 60 mL/min per 1.73 m2 and aged 60 years or older were enrolled.A total of 27,564 patients were prospectively followed up from January 1,2017 to December 31,2020.The 3-year cumRHR was calculated.The primary outcome was RRFD,defined as an annualized decline in eGFR of 5 mL/min per 1.73 m2 or greater.Logistic and restricted spline regression models and subgroup analysis were used to investigate the association of cumRHR with RRFD after adjusting for all confounders.RESULTS During a median follow-up of 3.2 years,a total of 4,347(15.77%)subjects developed RRFD.In fully-adjusted models,compared with the lowest quartile of cumRHR,the odds ratio(OR)for the highest was 1.44(1.28–1.61),P<0.001.Furthermore,each 1-standard deviation(27.97 beats/min per year)increment in cumRHR was associated with a 17%(P<0.001)increased risk of RRFD,with a linear positive correlation(P for non-linear=0.803).Participants with a 3-year cumRHR≥207(beats/min)*year(equivalent to≥69 beats/min per year in 3 years)were found to be at a higher risk of RRFD.CONCLUSIONS The cumRHR is significantly associated with a higher risk of RRFD among older adults.These results might provide an effective goal for managing and delaying the decline of renal function in the older adults.