BACKGROUND With an increase in the elderly population,the frequency of hospitalizations in recent years has also risen at a rapid pace.This,in turn,has resulted in poor outcomes and costly treatments.Hospitalization r...BACKGROUND With an increase in the elderly population,the frequency of hospitalizations in recent years has also risen at a rapid pace.This,in turn,has resulted in poor outcomes and costly treatments.Hospitalization rates increase in elderly patients due to a decline in glomerular filtration rate(GFR).AIM To investigate the connection between GFR and comorbidity and reasons for hospitalization in elderly patients.METHODS We analyzed patients aged 75 years and over who were admitted to the internal medicine clinic of a tertiary hospital in Eskisehir.At admission,we calculated GFR values using the Modification of Diet in Renal Disease study formula and classified them into six categories:G1,G2,G3a,G3b,G4,and G5.We analyzed associations with hospitalization diagnoses and comorbidity factors.RESULTS The average age of the patients was 80.8 years(±4.5 years).GFR was 57.287±29.5 mL/kg/1.73 m2 in women and 61.3±31.5 mL/kg/1.73 m2 in men(P=0.106).Most patients were admitted to the hospital at G2 stage(32.8%).The main reasons for hospitalization were anemia(34.4%and 28.6%)and malnutrition(20.9%and 20.8%)in women and men,respectively(P=0.078).The most frequent comor-bidity leading to hospitalization was arterial hypertension(n=168,28%),fo-llowed by diabetes(n=166,27.7%)(P=0.001).CONCLUSION When evaluating geriatric patients,low GFR alone does not provide sufficient information.Patients’comorbid factors should also be taken into account.There is no association between low GFR during hospitalization and hospitalization-Hamarat H.Aging and GFR related diagnoses.Knowing the GFR value before hospitalization will be more informative in such studies.展开更多
The discussion on renal biopsies and biomarkers highlights the essential aspects of nephrology.Although novel diagnostic biomarkers are emerging,renal biopsy remains critical for accurate diagnosis and treatment owing...The discussion on renal biopsies and biomarkers highlights the essential aspects of nephrology.Although novel diagnostic biomarkers are emerging,renal biopsy remains critical for accurate diagnosis and treatment owing to the lack of sufficiently validated biomarkers with high sensitivity and specificity.Puspitasari et al highlighted the significant changes in renal biopsy indications and histological outcomes before and after the coronavirus disease 2019(COVID-19)pandemic,reflecting the complex interactions between clinical workflows,public health issues,and patient demographics.Although biomarkers are increasingly utilized in nephrology,their importance remains balanced with traditional practices.Advancements in precision medicine are exemplified by tests like plasma anti-phospholipase A2 receptor levels.However,the COVID-19 pandemic revealed significant vulnerabilities in nephrology services,emphasizing the necessity for adaptable and robust healthcare strategies to manage chronic conditions during global crises.In conclusion,while biomarkers are poised to assume a more prominent role in nephrology,the significance of renal biopsies and thorough histopathological analysis remains paramount in understanding complex disease processes and guiding personalized patient management.The ongoing integration of traditional diagnostic approaches with innovative biomarker strategies promises to improve patient care and long-term health outcomes.展开更多
BACKGROUND Equations for estimation glomerular filtration rate(eGFR)have been associated with poor clinical performance and their clinical accuracy and reliability have been called into question.AIM To assess the long...BACKGROUND Equations for estimation glomerular filtration rate(eGFR)have been associated with poor clinical performance and their clinical accuracy and reliability have been called into question.AIM To assess the longitudinal changes in measured glomerular filtration rate(mGFR)in patients with autosomal dominant polycystic kidney disease(ADPKD).METHODS Analysis of an ambispective data base conducted on consecutive patients diagnosed with ADPKD.The mGFR was assessed by iohexol clearance;while eGFR was calculated by three different formulas:(1)The chronic kidney disease epidemiology collaboration(CKD-EPI);(2)Modification of diet in renal disease(MDRD);and(3)The 24-hour urine creatinine clearance(CrCl).The primary end-points were the mean change in mGFR between the baseline and final visit,as well as the comparison of the mean change in mGFR with the change estimated by the different formulas.RESULTS Thirty-seven patients were included in the study.As compared to baseline,month-6 mGFR was significantly decrease by-4.4 mL/minute±10.3 mL/minute(P=0.0132).However,the CKD-EPI,MDRD,and CrCl formulas underestimated this change by 48.3%,89.0%,and 45.8%respectively,though none of these differences reached statistical significance(P=0.3647;P=0.0505;and P=0.736,respectively).The discrepancies between measured and estimated glomerular filtration rate values,as evaluated by CKD-EPI(r=0.29,P=0.086);MDRD(r=0.19,P=0.272);and CrCl(r=0.09,P=0.683),were not correlated with baseline mGFR values.CONCLUSION This study indicated that eGFR inaccurately reflects the decline in mGFR and cannot reliably track changes over time.This poses significant challenges for clinical decision-making,particularly in treatment strategies.展开更多
Aging is an inevitable process that is usually measured by chronological age,with people aged 65 and over being defined as"older individuals".There is disagreement in the current scientific literature regard...Aging is an inevitable process that is usually measured by chronological age,with people aged 65 and over being defined as"older individuals".There is disagreement in the current scientific literature regarding the best methods to estimate glomerular filtration rate(eGFR)in older adults.Several studies suggest the use of an age-adjusted definition to improve accuracy and avoid overdiagnosis.In contrast,some researchers argue that such changes could complicate the classification of chronic kidney disease(CKD).Several formulas,including the Modification of Diet in Renal Disease,CKD-Epidemiology Collaboration,and Cockcroft-Gault equations,are used to estimate eGFR.However,each of these formulas has significant limitations when applied to older adults,primarily due to sarcopenia and malnutrition,which greatly affect both muscle mass and creatinine levels.Alternative formulas,such as the Berlin Initiative Study and the Full Age Spectrum equations,provide more accurate estimates of values for older adults by accounting for age-related physiological changes.In frail older adults,the use of cystatin C leads to better eGFR calculations to assess renal function.Accurate eGFR measurements improve the health of older patients by enabling better medication dosing.A thorough approach that includes multiple calibrated diagnostic methods and a detailed geriatric assessment is necessary for the effective management of kidney disease and other age-related conditions in older adults.展开更多
Objective To investigate whether glomerular density （GD） could be an independent prognostic factor for patients of IgA nephropathy with estimated glomerular filtration rate （eGFR） of 30 to 60 ml/min per 1.73 m2, ...Objective To investigate whether glomerular density （GD） could be an independent prognostic factor for patients of IgA nephropathy with estimated glomerular filtration rate （eGFR） of 30 to 60 ml/min per 1.73 m2, or for patients with time-average proteinuria 〈 0.5 g/d. Methods A total of 173 patients with biopsy-confirmed IgA nephropathy diagnosed from January 2000 to December 2010 were included. All of these patients were followed up for more than 5 years. The endpoint was a 〉 30% of decline in eGFR from baseline after 5-year follow-up. The optimal cut-off value of GD was calculated by ROC curve. Kaplan-Meier method and Cox regression analysis was used for survival analysis. Results A 30% of decline in eGFR occurred in 14.5% of all patients. The optimal diagnostic cut-off value of GD was 1.99/mm2 （AUC = 0.90, sensitivity = 84.0%, specificity = 81.8%） determined by ROC curve. The low GD group （GD 〈 1.99 per mm2） experienced a significant increase in renal endpoint for patients with eGFR of 30 to 60 ml/min per 1.73 m2 （six patients in lower GD group, while one patient in the other group）. For patients with time-average proteinuria 〈 0.5 g/d, the lower GD group showed a higher eGFR decline from baseline （4.5±16.7 ml/min per 1.73 m2 vs. –8.1±21.4 ml/min per 1.73 m2, P = 0.038）; two patients in this group reached the endpoint, while no patients in the higher GD group did. Conclusion GD could be an independent prognostic factor for patients of IgA nephropathy with eGFR at 30 to 60 ml/min per 1.73 m2 of body surface, particularly for those with time-averaged amount of urine protein less than 0.5 g per day.展开更多
The crude polysaccharide was obtained by means of the decolorization of porphyrized Cordyceps minlitaris stroma with organic solvent, extraction with hot water, precipitation in 80% ethanol, and protein removal with t...The crude polysaccharide was obtained by means of the decolorization of porphyrized Cordyceps minlitaris stroma with organic solvent, extraction with hot water, precipitation in 80% ethanol, and protein removal with the Sevag method. After purification with Sephadex G-75, two of its components, CMP-1 and CMP-2, were obtained. Through the assay of gel chromatography and polarimetry, CMP-1 was identified as pure polysaccharide. The results demonstrated that CMP-1 had favorable oxidation resistance activity, which could scavenge not only oxygen-free radicals in the self-oxidation system of pyrogallic acid, but also the hydroxide-free radicals in the Fenton system. The study focused on the effects of low, medium, and high dosages of CMP-1 in rat blood serum on the proliferation of glomerular mesangial cells in vitro. Through MTT Colorimetric analysis, the activities were compared among the blank control group and the Niaoduqing positive control group CMP-1 and CMP-2. The results shows that CMP-1 was able to inhibit the proliferation of rat glomerular mesangial cells effectively. Therefore, CMP-1, one component of polysaccharides of Cordyceps minlitaris, was certainly a potential remedy for hyperplastic glomerular nephritis, whose antioxidant activity could slow down the process of chronic renal failure（CRF） to some extent.展开更多
Diabetic kidney disease (DKD)is a microvascular complication of type 2 diabetes.The study of DKD mechanisms is the most important target for the prevention of DKD.Renal senescence is one of the important pathogeneses ...Diabetic kidney disease (DKD)is a microvascular complication of type 2 diabetes.The study of DKD mechanisms is the most important target for the prevention of DKD.Renal senescence is one of the important pathogeneses for DKD,but the mechanism of renal and cellular senescence is unclear.Decreased expression of circulating miR-126 is associated with the development of DKD and may be a promising blood-based biomarker for DKD.This study is to probe the effect and mechanism of miR-126 on the aging of human glomerular mesangial cells (HGMCs)induced by high glucose.HGMCs were cultured with Roswell Park Memorial Institute (RPMI-1640)in vitro.The effect of high glucose on morphology of HGMCs was observed 72h after intervention.The cell cycle was examined by flow cytometry.The telomere length was measured by Southern blotting.The expression levels of p53,p21 and Rb proteins in p53-p21-Rb signaling pathway and p-statl,p-stat3 in JAK/STAT signaling pathway were detected by Western blotting respectively.The expression of miR-126 was examined by qRT-PCR.MiR-126 mimics was transfected into HGMCs.The effects of miR-126 mimics transfection on cell morphology,cell cycle,telomere length,p53,p21,Rb,p-stat1 and p-stat3 were observed. The results showed that high glucose not only arrested the cell cycle in G1phase but also shortened the telomere length.High glucose led to high expression of p53,p21,Rb,p-statl and p-stat3 and premature senescence of HGMCs by activating the telomere-p53-p21-Rb and JAK/STAT signaling pathways.Moreover,the miR-126 was decreased in HGMCs induced by high glucose.It was suggested that the transfection of miR-126 mimics could inhibit the telomere-p53-p21-Rb and JAK/STAT signaling pathway activity in vitro and delay the senescence of HGMCs.The results may serve as a new strategy for the treatment of DKD.展开更多
Objectives To study the relationship between plasma hemoglobin concentration and estimated glomerular filtration rate （eGFR） in elderly patients with ischemic cardiomyopathy （ICM）.Methods Clinical data of patients...Objectives To study the relationship between plasma hemoglobin concentration and estimated glomerular filtration rate （eGFR） in elderly patients with ischemic cardiomyopathy （ICM）.Methods Clinical data of patients with coronary heart disease who were discharged from The First Affiliated Hospital,Chongqing Medical University between 2005 and 2007 were analyzed retrospectively. Echocardiography results,plasma hemoglobin and creatinine concentration were abstracted from the medical records.The study included 235 Chinese Hart patients with age 60 years and older with angiography confirmed coronary heart disease,silent myocardial ischemia or angina pectoris,of whom 154 had ICM defined as left ventricular end-diastolic diameter （LVDd）,male≥56 mm,female≥51 mm （63. 51±7.70 mm） measured by M-mode echocardiography.The differences in plasma hemoglobin concentration were analyzed retrospec- tively between patients with and without ICM,and between patients with an eGFR【60 ml·min<sup>-1</sup>·1.73m<sup>-2</sup> and those with an eGFR≥60 ml·min<sup>-1</sup>·1.73m<sup>-2</sup>.Results There were no significant differences in plasma hemoglobin concentration and eGFR between ICM and non-ICM group (118.49±20.52 g·L<sup>-1</sup> vs.115.80±23.32 g·L<sup>-1</sup> and 75.13±24.21 ml·min<sup>-1</sup>·1.73m<sup>-2</sup> vs.79.09±28.41 ml·min<sup>- 1</sup>·1.73m<sup>-2</sup>,respectively,both P】0.05).However,in both ICM and non-ICM groups,plasma hemoglobin concentration was lower in those with an eGFR【60 ml·min<sup>-1</sup>·1.73m<sup>-2</sup> compared with compared with those with an eGFR≥60 ml·min<sup>-1</sup>·1.73m<sup>-2</sup> group (112. 29±18.61 g·L<sup>-1</sup> vs.119.92±20.74L<sup>-1</sup>,P【0.05);plasma hemoglobin concentration was related positively to eGFR.Conclusions There were no significant changes in plasma hemoglobin concentration and eGFR;however,plasma hemoglobin concentration was related to eGFR significantly positively in elderly patients with ICM due to coronary heart展开更多
OBJECTIVE Diabetic nephropathy(DN)has been one of the most common complications of diabetes and the leading cause of end-stage renal disease.Glomerular hyperfiltrationis central in earlystage of DN and leads to the pr...OBJECTIVE Diabetic nephropathy(DN)has been one of the most common complications of diabetes and the leading cause of end-stage renal disease.Glomerular hyperfiltrationis central in earlystage of DN and leads to the progression of renal architectonic and functional abnormalities.Salvianolic acid A(SalA)has been proved to protect diabetic complications such as hepatic fibrosis and neuropathy.The present study was designed to investigate the effects of SalA on glomerular endothelial dysfunctionand diabetic nephropathy.METHODS Primary glomerular endothelial cells were subjected to assess permeability under injury of advanced glycation end-products(AGEs).AGEs-induced changes of Rho A/ROCK pathway and cytoskeleton rearrangement were assessed bywestern blotandimmunofluorescence.The beneficial effects of SalA on diabetic nephropathy were investigated in a rat model induced by high-fat and high-glucose diet combined with low dose of streptozocin(35 mg·kg^(-1),ip).Renal function and architectonic changes were evaluated by biochemical assay and PAS staining.RESULTS SalA 3μMameliorated AGEs-induced glomerular endothelial permeability(P<0.05)and suppressed rearrangement of cytoskeleton through inhibiting AGE-RAGE-Rho A/ROCK pathway.SalA1 mg·kg^(-1)markedly reduced endothelium loss(P<0.01)and glomerular hyperfiltration(P<0.05)in diabetic kidney.Subsequently,SalA 1 mg·kg^(-1) suppressed glomerular hypertrophy and mesangial matrix expansion,eventually reduced 24 h-urinary albumin and ameliorated renal function by decreasing blood urine nitrogen(BUN),serum creatinine(Scr)and serum n-acetyl-β-d-glucosaminidase(NAG).AGEs-RAGE-Nox4-induced oxidative stress was suppressed by the treatment of SalA 1 mg·kg^(-1).CONCLUSION SalA ameliorated AGEs-induced glomerular endothelial hyperpermeability,and effectively protected against early-stage diabetic nephropathy by reducing hyperfiltration and alleviating renal structural deterioration through inhibiting AGEs and its downstream pathway.Thus,SalA might be a promising therapeutic agent for the treatment of diabetic nephropathy.展开更多
Objective:The main characteristics of diabetic nephropathy(DN)at the early stage are abnormal angiogenesis of glomerular endothelial cells(GECs)and macrophage infiltration.Galectin-3 plays a pivotal role in the pathog...Objective:The main characteristics of diabetic nephropathy(DN)at the early stage are abnormal angiogenesis of glomerular endothelial cells(GECs)and macrophage infiltration.Galectin-3 plays a pivotal role in the pathogenesis of DN via binding with its ligand,advanced glycation end products(AGEs).Catalpol,an iridoid glucoside extracted from Rehmannia glutinosa,has been found to ameliorate vascular inflammation,reduce endothelial permeability,and protect against endothelial damage in diabetic milieu.However,little is known about whether catalpol could exert an anti-angiogenesis and anti-inflammation effect induced by AGEs.Methods:Mouse GECs(mGECs)and RAW 264.7 macrophages were treated with different concentrations of AGEs(0,50,100,200 and 400μg/mL)for different time(0,6,12,24 and 48 h)to determine the optimal concentration of AGEs and treatment time.Cells were treated with catalpol(10μmol/L),GB1107(1μmol/L,galectin-3 inhibitor),PX-478(50μmol/L,HIF-1αinhibitor),adenovirus-green fluorescent protein(Ad-GFP)[3×10^(7)plaque-forming unit(PFU)/mL]or Ad-galectin-3-GFP(2×10^(8)PFU/mL),which was followed by incubation with 50μg/mL AGEs.The levels of galectin-3,vascular endothelial growth factor A(VEGFA)and pro-angiogenic factors angiopoietin-1(Ang-1),angiopoietin-2(Ang-2),tunica interna endothelial cell kinase-2(Tie-2)were detected by enzyme-linked immunosorbent assay(ELISA).Cell counting kit-8(CCK-8)assay was used to evaluate the proliferation of these cells.The expression levels of galectin-3,vascular endothelial growth factor receptor 1(VEGFR1),VEGFR2,and hypoxia-inducible factor-1α(HIF-1α)in mGECs and those of galectin-3 and HIF-1αin RAW 264.7 macrophages were detected by Western blotting and immunofluorescence(IF)staining.The rat DN model was established.Catalpol(100 mg/kg)or GB1107(10 mg/kg)was administered intragastrically once a day for 12 weeks.Ad-galectin-3-GFP(6×10^(7)PFU/mL,0.5 mL)or Ad-GFP(6×10^(6)PFU/mL,0.5 mL)was injected into the tail vein of rats 48 h before the sacrifice of the animals.The expression of galectin-3,VEGFR1,.VEGFR2,and HIF-1αin renal cortices was analyzed by Western blotting.The expression of galectin-3,F4/80(a macrophage biomarker),and CD34(an endothelium biomarker)in renal cortices was detected by IF staining,and collagen accumulation by Masson staining.Results:The expression levels of galectin-3 and VEGFA were significantly higher in mGECs and RAW 264.7 macrophages treated with 50μg/mL AGEs for 48 h than those in untreated cells.Catalpol and GB1107 could block the AGEs-induced proliferation of mGECs and RAW 264.7 macrophages.Over-expression of galectin-3 was found to reduce the inhibitory effect of catalpol on the proliferation of cells.Catalpol could significantly decrease the levels of Ang-1,Ang-2 and Tie-2 released by AGEs-treated mGECs,which could be reversed by over-expression of galectin-3.Catalpol could significantly inhibit AGEs-induced expression of galectin-3,HIF-1α,VEGFR1,and VEGFR2 in mGECs.The inhibitory effect of catalpol on galectin-3 in AGEs-treated mGECs was impaired by PX-478.Moreover,catalpol attenuated the AGEs-activated HIF-1α/galectin-3 pathway in RAW 264.7 macrophages,which was weakened by PX-478.Additionally,catalpol significantly inhibited the expression of galectin-3,macrophage infiltration,collagen accumulation,and angiogenesis in the kidney of diabetic rats.Over-expression of galectin-3 could antagonize these inhibitory effects of catalpol.Conclusion:Catalpol prevented the angiogenesis of mGECs and macrophage proliferation via inhibiting galectin-3.It could prevent the progression of diabetes-induced renal damage.展开更多
Objective Both decreased glomemlar filtration rate （GFR） and arterial stiffness were considered as risk factors for atherosclerosis. Previous studies have suggested the association between central arterial stiffness...Objective Both decreased glomemlar filtration rate （GFR） and arterial stiffness were considered as risk factors for atherosclerosis. Previous studies have suggested the association between central arterial stiffness and the degree of GFR loss. Whether decreased GFR contributes to peripheral artery stiffness remains controversial. Moreover, data analyzed from a cohort of Chinese women are rare. Our aim was to explore the relationship between GFR and regional arterial stiffness in Chinese women. Methods In this cross-sectional study, we randomly recruited 1131 adult women residents with GFR 〉 60 mL/min per 1.73 m2 estimated by the Chinese Modification of Diet in Renal Disease equation from three large communities. Central and peripheral arterial stiffness were estimated simultaneously by measuring carotid-femoral pulse wave velocity （PWVcf） and carotid-radial PWV （PWVcr） using a validated automatic device. Augmentation Index at heart rate 75 beats/minutes （AIx-75） was measured by pulse wave analysis as a composite parameter reflecting both large and distal arterial properties. Results The mean estimated GFR （eGFR） of the study group was 100.05 ＋ 23.26 mL/minute per 1.73 m2. Subjects were grouped by tertiles of eGFR level. PWVef and AIx-75 increased ongoing from the top to the bottom eGFR tertile, while the values of PWVcr were comparable. Both univariate Pearson correlations and multiple stepwise regression analyses showed that eGFR significantly correlated to PWVcf, but not to PWVcr and AJx-75. Conclusions In Chinese women with normal to mildly impaired renal function, decreased eGFR affected carotid-to-femoral rather than carotid-to-radial stiffening. This provides rational to conduct future prospective studies to investigate predictors of atherosclerosis in this population.展开更多
Objective To evaluate the clinical features,renal histopathology and therapeutic response to glucocorticoid and immunosuppressive agents in patients with glomerular disease associated with Takayasu arteritis(TA).Metho...Objective To evaluate the clinical features,renal histopathology and therapeutic response to glucocorticoid and immunosuppressive agents in patients with glomerular disease associated with Takayasu arteritis(TA).Methods Patients with TA and renal biopsy-confirmed glomerular disease were investigated retrospectively.None of them had renal artery stenosis or occlusive changes.Results Six patients with glomerulopathy,accounting for 3.75% of the 160 TA patients admitted to our hospital at the same period,were analyzed.All of them were females with a mean age of 35.5 ± 10.0 years.Four cases presented with lower extremity edema.Laboratory tests showed that one was nephrotic syndrome,three were nephrotic range proteinuria,and two of them had mild renal dysfunction.The other two patients were asymptomatic microscopic hematuria and proteinuria.Renal pathology revealed mild immunoglobulin A nephropathy in two cases,mild mesangial proliferative glomerulonephritis(GN),membranoproliferative GN,minimal change disease,and fibrillary GN in one case respectively.Five cases received glucocorticoids and cyclophosphamide therapy.Proteinuria and microscopic hematuria disappeared in 2 to 4 weeks after the initiation of therapy in three cases.The patient with membranoproliferative GN also reached complete remission of proteinuria and recovered renal function 6 months after the treatment.Conclusions TA may induce glomerular disease as a part of its histological spectrum.Apart from ischemic glomerular disease,glomerular disease should be suspected when TA patients have microscopic hematuria or proteinuria,that may be therapeutically responsive to glucocorticoids and immunosuppressive agent in relative early phase.展开更多
Objective：To investigate the effects of emodin（EMD） on cell proliferation and correlative cytokines secretion of glomerular mesangial in rats. Methods：The effects of EMD on cell proliferation and IL-6, TGF-β1 sec...Objective：To investigate the effects of emodin（EMD） on cell proliferation and correlative cytokines secretion of glomerular mesangial in rats. Methods：The effects of EMD on cell proliferation and IL-6, TGF-β1 secretion of glomerular mesangial in rats were observed. Cell proliferation was measured by MTT method. IL-6 and TGF-β1 secretion was detected with ELISA. Results：EMD was able to inhibit the cell proliferation and down-regulate the IL-6 and TGF-β 1 secretion of glomerular mesangial, as compared to the model group in rats （P 〈 0.05）. Conclusion：EMD could significantly inhibit the cell proliferation, and reduce the creation of extracellular matrix（ECM）, this indicated that it could play an important role in alleviation and prevention of glomerular sclerosis. The mechanism may be that EMD can reduce the IL-6 and TGF-β1 secretion ofglomerular mesangial cell in rats.展开更多
Objective:Diabetic nephropathy is one of the most important microvascular complications of diabetes,which mainly refers to glomerular capillary sclerosis.Podocytes are an important part of glomerular capillaries.Previ...Objective:Diabetic nephropathy is one of the most important microvascular complications of diabetes,which mainly refers to glomerular capillary sclerosis.Podocytes are an important part of glomerular capillaries.Previous clinical and basic studies have shown that fibrosis is the main factor of diabetic nephropathy.This study aimed to assess the protective mechanism of glycyrrhizic acid(GA)on glomerular podocytes induced by high glucose as we hypothesized that GA may have antifibrotic and anti-inflammatory effects on podocytes through regulation of the adenosine 5'-monophosphate-activated protein kinase(AMPK)/sucrose nonfermenting AMPK-related kinase(SNARK)signaling pathway.Methods:SNARK siRNA was used to transfect podocytes.Real-time quantitative polymerase chain reaction and immunofluorescence staining assays were used for molecular and pathological analysis.The expression levels of key pathway proteins(including TGF-β1,α-SMA,SITR1,AMPKα,LKB1,PGC-1α,NF-κB,IL-6,and TNF-α)were verified by Western blotting.The expression of inflammatory factors in podocytes was detected by ELISA.Results:We demonstrated that GA decreased the expression of podocyte fibrosis signaling pathway-related factors by upregulating the AMPK pathway and its related factors.However,after transfection of podocytes with SNARK siRNA,there was an increased expression of fibrosis-related factors and inflammation-related factors.Conclusion:GA can protect podocytes and alleviate fibrosis and inflammation induced by high glucose,which is related to the AMPK signaling pathway.Meanwhile,knockdown of SNARK protein can inhibit the AMPK signaling pathway,aggravate fibrosis,and increase inflammation.展开更多
The development of formulas estimating glomerular filtration rate(eG FR) from serum creatinine and cystatin C and accounting for certain variables affecting the production rate of these biomarkers, including ethnicity...The development of formulas estimating glomerular filtration rate(eG FR) from serum creatinine and cystatin C and accounting for certain variables affecting the production rate of these biomarkers, including ethnicity, gender and age, has led to the current scheme of diagnosing and staging chronic kidney disease(CKD),which is based on e GFR values and albuminuria.This scheme has been applied extensively in various populations and has led to the current estimates of prevalence of CKD. In addition, this scheme is applied in clinical studies evaluating the risks of CKD and the efficacy of various interventions directed towards improving its course. Disagreements between creatinine-based and cystatin-based e GFR values and between e GFR values and measured GFR have been reported in various cohorts. These disagreements are the consequence of variations in the rate of production and in factors, other than GFR, affecting the rate of removal of creatinine and cystatin C. The disagreements create limitations for all e GFR formulas developed so far. The main limitations are low sensitivity in detecting early CKD in several subjects, e.g., those with hyperfiltration, and poor prediction of the course of CKD. Research efforts in CKD are currently directed towards identification of biomarkers that are better indices of GFR than the current biomarkers and,particularly, biomarkers of early renal tissue injury.展开更多
The proliferation of glomerular mesangial cells （GMC） and secretion of the extracellular matrix （ECM） in rat with Thy-1 nephritis （Thy-lN） resembling human mesangioproliferative glomerulonephritis have been expl...The proliferation of glomerular mesangial cells （GMC） and secretion of the extracellular matrix （ECM） in rat with Thy-1 nephritis （Thy-lN） resembling human mesangioproliferative glomerulonephritis have been explored for many years; however, the molecular mechanisms of GMC proliferation and ECM production remain unclear. Our previous studies have demonstrated that the thrombospondin-1 （TSP-1） gene was involved in mediating rat GMC proliferation and ECM synthesis induced by sublytic C5b-9 in vitro. 111 the present study, the roles of the TSP-1 gene in GMC proliferation, ECM production, and urinary protein secretion in Thy-lN rats were determined by using TSP-1 small hairpin RNA, and the results revealed that silencing of the TSP-1 gene in rat renal tissues could diminish GMC proliferation （P 〈 0.01） and ECM secretion （P 〈 0.01） as well as urinary protein secretion （P 〈 0.05） in Thy-lN rats. Together, the current findings suggested that TSP-1 gene expression was required for GMC proliferation and ECM production in Thy-lN rats.展开更多
Primary glomerular diseases in the elderly population are a frustrating topic due to difficulties in both the diagnosis and decision making about treatment. The most frequent type of primary glomerular disease in elde...Primary glomerular diseases in the elderly population are a frustrating topic due to difficulties in both the diagnosis and decision making about treatment. The most frequent type of primary glomerular disease in elderly is membranous nephropathy; while its counterpart in younger population is Ig A nephropathy. The most frequent cause of nephrotic syndrome in the elderly is also membranous nephropathy. Pauci-immune crescentic glomerulonephritis(GN) rate increases both in elderly and very elderly population. Pauci-immune crescentic GNs should be regarded as urgencies in elderly patients as in their younger counterparts due to potential for causing end-stage renal disease in case of delayed diagnosis and treatment, and also causing mortality due to alveolar hemorrhage in patients with pulmonary involvement. Renal biopsy is the inevitable diagnostic method in the elderly as in all other age groups. Renal biopsy prevents unnecessary treatments and provides prognostic data. So advanced age should not be the sole contraindication for renal biopsy. The course of primary glomerular diseases may differ in the elderly population. Acute kidney injury is more frequent in the course and renal functions may be worse at presentation. These patients are more prone to be hypertensive. The decision about adding immune suppressive therapies to conservative methods should be made considering many factors like co-morbidities, drug side effects and potential drug interactions, risk of infection, patient preference, life expectancy and renal functions at the time of diagnosis.展开更多
The mechanism of injury on the human glomerular endothelial cells （ciGENC） induced by preeclampsia serum was investigated. Concentration of maternal serum sFlt-1 protein was detected by ELISA. Fluorescently-labeled ...The mechanism of injury on the human glomerular endothelial cells （ciGENC） induced by preeclampsia serum was investigated. Concentration of maternal serum sFlt-1 protein was detected by ELISA. Fluorescently-labeled bovine serum albumin infiltrating through lower chamber of Transwell was measured by multifunction microplate reader. Morphologic change of ciGENC was observed under inverted phase contrast microscope. The concentration of sflt-1 in preeclampsia groups was significantly increased as compared with control group （P〈0.01）. Permeability in preeclampsia groups was significantly increased as compared with control group （P〈0.01）. By contrast with severe preeclampsia group, the permeability of ciGENC monolayer in mild preeclampsia group was decreased significantly （P〈0.05）. Intervention of exogenous VEGF significantly decreased permeability of ciGENC in preeclampsia groups. It was concluded that sFlt-1 increased ciGENC permeability by damaging integrity of endothelial barrier function.展开更多
This study examined the effect of over-expression of sFlt-1 by trophoblasts on the barrier function of glomerular endothelial cells and the role of VEGF in this process in order to explore the pathogenesis of glomerul...This study examined the effect of over-expression of sFlt-1 by trophoblasts on the barrier function of glomerular endothelial cells and the role of VEGF in this process in order to explore the pathogenesis of glomerular disease in preeclampsia. SFlt-1 expression in the human trophoblasts （TEV-1 cells） was enhanced by transfecting sFlt-1 plasmid DNA into TEV-1 cells. The monolayer barrier fimction of glomerular endothelial cells （ciGEnCs） was determined by measuring the fluorescence intensity of bovine serum albumin （BSA） that crossed the monolayer of glomerular endothelial cells. The results showed that the over-expression of sFlt-1 by TEV-1 cells led to the barrier dysfunction of ciGEnCs, and the exogenous VEGF could alleviate the ciGEnCs dysfunction resulting from the over-expression of sFlt- 1 to a certain extent. It was concluded that the dysregulation of sFlt- 1 and VEGF in preeclamptic pregnancy may contribute to the barrier dysfunction of glomerular endothelial cells, and VEGF may play an important role in maintaining the barrier function of glomerular endothelial cells, but it may not be the sole factor.展开更多
Objective: To analyze the correlation between urine retinol binding protein-4 (RBP-4) and serum HbA1c?with glomerular filtration rate (GFR) in type 1 diabetic children. Methods:?This?was a crosssectional observational...Objective: To analyze the correlation between urine retinol binding protein-4 (RBP-4) and serum HbA1c?with glomerular filtration rate (GFR) in type 1 diabetic children. Methods:?This?was a crosssectional observational analytic?study. The subjects?were?type 1 diabetic children aged 2 - 14 years. Sample collection was conducted from October to November 2014. Exclusion criteria were patients with obesity, renal insufficiency?that?was not caused by diabetes, history of hepatic diseases, and history of blood cell disorders. We?performed anamnesis, physical examination, and blood sampling for serum HbA1c?and serum cystatin-C, and urine sampling for RBP-4?on all subjects. Glomerular filtration rate was calculated from the concentration level of cystatin-C using Filler formula. Data analysis was performed?by?Spearman test to determine the correlation between urine RBP-4 and serum HbA1c?with GFR. The Fisher’s exact test was used to determine the correlation between duration of diabetes and RBP-4, HbA1c, and also GFR. Results:?Twelve females (60%) and 8 males (40%) participated in the study. The mean age of the subjects with 95% CI?was: 10.5 (2 - 14) years while the mean age of duration diabetes with 95% CI: 3.8 (0.5 - 10) years. Twelve (60%) subjects had?<5 years duration of diabetes, while eight (40%) subjects had?≥5 years duration of diabetes. Twelve (60%) subjects had normal RBP-4 level, while eight (40%) subjects had?elevated RBP-4 level. The mean level of HbA1c?with 95% CI: 8.9 (5.1 - 15.2)%. Thirteen (65%) subjects had poor metabolic. The mean GFR of the subjects with 95% CI: 99.3 (35.2 - 147.4) mL/1.73/m2. Nineteen (95%) subjects had normal GFR, while 1 (5%) had renal insufficiency. The results of data analysis using Spearman test on the correlation between urine RBP-4 and serum HbA1cwith GFR were not significant. The result of correlation between duration of diabetes and urine RBP-4 was significant?using?Fischer’s test. Conclusion:?The results?showed?no correlation between urine RBP-4 and serum HbA1c?with GFR. Urine RBP-4 could?be considered to assess renal function in type 1 diabetic patients with a duration of diabetes of more than 5 years.展开更多
文摘BACKGROUND With an increase in the elderly population,the frequency of hospitalizations in recent years has also risen at a rapid pace.This,in turn,has resulted in poor outcomes and costly treatments.Hospitalization rates increase in elderly patients due to a decline in glomerular filtration rate(GFR).AIM To investigate the connection between GFR and comorbidity and reasons for hospitalization in elderly patients.METHODS We analyzed patients aged 75 years and over who were admitted to the internal medicine clinic of a tertiary hospital in Eskisehir.At admission,we calculated GFR values using the Modification of Diet in Renal Disease study formula and classified them into six categories:G1,G2,G3a,G3b,G4,and G5.We analyzed associations with hospitalization diagnoses and comorbidity factors.RESULTS The average age of the patients was 80.8 years(±4.5 years).GFR was 57.287±29.5 mL/kg/1.73 m2 in women and 61.3±31.5 mL/kg/1.73 m2 in men(P=0.106).Most patients were admitted to the hospital at G2 stage(32.8%).The main reasons for hospitalization were anemia(34.4%and 28.6%)and malnutrition(20.9%and 20.8%)in women and men,respectively(P=0.078).The most frequent comor-bidity leading to hospitalization was arterial hypertension(n=168,28%),fo-llowed by diabetes(n=166,27.7%)(P=0.001).CONCLUSION When evaluating geriatric patients,low GFR alone does not provide sufficient information.Patients’comorbid factors should also be taken into account.There is no association between low GFR during hospitalization and hospitalization-Hamarat H.Aging and GFR related diagnoses.Knowing the GFR value before hospitalization will be more informative in such studies.
文摘The discussion on renal biopsies and biomarkers highlights the essential aspects of nephrology.Although novel diagnostic biomarkers are emerging,renal biopsy remains critical for accurate diagnosis and treatment owing to the lack of sufficiently validated biomarkers with high sensitivity and specificity.Puspitasari et al highlighted the significant changes in renal biopsy indications and histological outcomes before and after the coronavirus disease 2019(COVID-19)pandemic,reflecting the complex interactions between clinical workflows,public health issues,and patient demographics.Although biomarkers are increasingly utilized in nephrology,their importance remains balanced with traditional practices.Advancements in precision medicine are exemplified by tests like plasma anti-phospholipase A2 receptor levels.However,the COVID-19 pandemic revealed significant vulnerabilities in nephrology services,emphasizing the necessity for adaptable and robust healthcare strategies to manage chronic conditions during global crises.In conclusion,while biomarkers are poised to assume a more prominent role in nephrology,the significance of renal biopsies and thorough histopathological analysis remains paramount in understanding complex disease processes and guiding personalized patient management.The ongoing integration of traditional diagnostic approaches with innovative biomarker strategies promises to improve patient care and long-term health outcomes.
文摘BACKGROUND Equations for estimation glomerular filtration rate(eGFR)have been associated with poor clinical performance and their clinical accuracy and reliability have been called into question.AIM To assess the longitudinal changes in measured glomerular filtration rate(mGFR)in patients with autosomal dominant polycystic kidney disease(ADPKD).METHODS Analysis of an ambispective data base conducted on consecutive patients diagnosed with ADPKD.The mGFR was assessed by iohexol clearance;while eGFR was calculated by three different formulas:(1)The chronic kidney disease epidemiology collaboration(CKD-EPI);(2)Modification of diet in renal disease(MDRD);and(3)The 24-hour urine creatinine clearance(CrCl).The primary end-points were the mean change in mGFR between the baseline and final visit,as well as the comparison of the mean change in mGFR with the change estimated by the different formulas.RESULTS Thirty-seven patients were included in the study.As compared to baseline,month-6 mGFR was significantly decrease by-4.4 mL/minute±10.3 mL/minute(P=0.0132).However,the CKD-EPI,MDRD,and CrCl formulas underestimated this change by 48.3%,89.0%,and 45.8%respectively,though none of these differences reached statistical significance(P=0.3647;P=0.0505;and P=0.736,respectively).The discrepancies between measured and estimated glomerular filtration rate values,as evaluated by CKD-EPI(r=0.29,P=0.086);MDRD(r=0.19,P=0.272);and CrCl(r=0.09,P=0.683),were not correlated with baseline mGFR values.CONCLUSION This study indicated that eGFR inaccurately reflects the decline in mGFR and cannot reliably track changes over time.This poses significant challenges for clinical decision-making,particularly in treatment strategies.
文摘Aging is an inevitable process that is usually measured by chronological age,with people aged 65 and over being defined as"older individuals".There is disagreement in the current scientific literature regarding the best methods to estimate glomerular filtration rate(eGFR)in older adults.Several studies suggest the use of an age-adjusted definition to improve accuracy and avoid overdiagnosis.In contrast,some researchers argue that such changes could complicate the classification of chronic kidney disease(CKD).Several formulas,including the Modification of Diet in Renal Disease,CKD-Epidemiology Collaboration,and Cockcroft-Gault equations,are used to estimate eGFR.However,each of these formulas has significant limitations when applied to older adults,primarily due to sarcopenia and malnutrition,which greatly affect both muscle mass and creatinine levels.Alternative formulas,such as the Berlin Initiative Study and the Full Age Spectrum equations,provide more accurate estimates of values for older adults by accounting for age-related physiological changes.In frail older adults,the use of cystatin C leads to better eGFR calculations to assess renal function.Accurate eGFR measurements improve the health of older patients by enabling better medication dosing.A thorough approach that includes multiple calibrated diagnostic methods and a detailed geriatric assessment is necessary for the effective management of kidney disease and other age-related conditions in older adults.
基金Supported by the Key Projects in the National Science and Technology Pillar Program During the Twelfth Five-year Plan Period(2011BAI10B03)
文摘Objective To investigate whether glomerular density （GD） could be an independent prognostic factor for patients of IgA nephropathy with estimated glomerular filtration rate （eGFR） of 30 to 60 ml/min per 1.73 m2, or for patients with time-average proteinuria 〈 0.5 g/d. Methods A total of 173 patients with biopsy-confirmed IgA nephropathy diagnosed from January 2000 to December 2010 were included. All of these patients were followed up for more than 5 years. The endpoint was a 〉 30% of decline in eGFR from baseline after 5-year follow-up. The optimal cut-off value of GD was calculated by ROC curve. Kaplan-Meier method and Cox regression analysis was used for survival analysis. Results A 30% of decline in eGFR occurred in 14.5% of all patients. The optimal diagnostic cut-off value of GD was 1.99/mm2 （AUC = 0.90, sensitivity = 84.0%, specificity = 81.8%） determined by ROC curve. The low GD group （GD 〈 1.99 per mm2） experienced a significant increase in renal endpoint for patients with eGFR of 30 to 60 ml/min per 1.73 m2 （six patients in lower GD group, while one patient in the other group）. For patients with time-average proteinuria 〈 0.5 g/d, the lower GD group showed a higher eGFR decline from baseline （4.5±16.7 ml/min per 1.73 m2 vs. –8.1±21.4 ml/min per 1.73 m2, P = 0.038）; two patients in this group reached the endpoint, while no patients in the higher GD group did. Conclusion GD could be an independent prognostic factor for patients of IgA nephropathy with eGFR at 30 to 60 ml/min per 1.73 m2 of body surface, particularly for those with time-averaged amount of urine protein less than 0.5 g per day.
基金the Science Technology Development Project of Jilin Province, China(No.20020503-2).
文摘The crude polysaccharide was obtained by means of the decolorization of porphyrized Cordyceps minlitaris stroma with organic solvent, extraction with hot water, precipitation in 80% ethanol, and protein removal with the Sevag method. After purification with Sephadex G-75, two of its components, CMP-1 and CMP-2, were obtained. Through the assay of gel chromatography and polarimetry, CMP-1 was identified as pure polysaccharide. The results demonstrated that CMP-1 had favorable oxidation resistance activity, which could scavenge not only oxygen-free radicals in the self-oxidation system of pyrogallic acid, but also the hydroxide-free radicals in the Fenton system. The study focused on the effects of low, medium, and high dosages of CMP-1 in rat blood serum on the proliferation of glomerular mesangial cells in vitro. Through MTT Colorimetric analysis, the activities were compared among the blank control group and the Niaoduqing positive control group CMP-1 and CMP-2. The results shows that CMP-1 was able to inhibit the proliferation of rat glomerular mesangial cells effectively. Therefore, CMP-1, one component of polysaccharides of Cordyceps minlitaris, was certainly a potential remedy for hyperplastic glomerular nephritis, whose antioxidant activity could slow down the process of chronic renal failure（CRF） to some extent.
基金This project was supported by grants from the Key Science and Technology Development Program of Nanjing City of the People's Republic of China (No. YKK15057 and No.YKK16097)and the National Natural Science Foundation of China (No.81473684).
文摘Diabetic kidney disease (DKD)is a microvascular complication of type 2 diabetes.The study of DKD mechanisms is the most important target for the prevention of DKD.Renal senescence is one of the important pathogeneses for DKD,but the mechanism of renal and cellular senescence is unclear.Decreased expression of circulating miR-126 is associated with the development of DKD and may be a promising blood-based biomarker for DKD.This study is to probe the effect and mechanism of miR-126 on the aging of human glomerular mesangial cells (HGMCs)induced by high glucose.HGMCs were cultured with Roswell Park Memorial Institute (RPMI-1640)in vitro.The effect of high glucose on morphology of HGMCs was observed 72h after intervention.The cell cycle was examined by flow cytometry.The telomere length was measured by Southern blotting.The expression levels of p53,p21 and Rb proteins in p53-p21-Rb signaling pathway and p-statl,p-stat3 in JAK/STAT signaling pathway were detected by Western blotting respectively.The expression of miR-126 was examined by qRT-PCR.MiR-126 mimics was transfected into HGMCs.The effects of miR-126 mimics transfection on cell morphology,cell cycle,telomere length,p53,p21,Rb,p-stat1 and p-stat3 were observed. The results showed that high glucose not only arrested the cell cycle in G1phase but also shortened the telomere length.High glucose led to high expression of p53,p21,Rb,p-statl and p-stat3 and premature senescence of HGMCs by activating the telomere-p53-p21-Rb and JAK/STAT signaling pathways.Moreover,the miR-126 was decreased in HGMCs induced by high glucose.It was suggested that the transfection of miR-126 mimics could inhibit the telomere-p53-p21-Rb and JAK/STAT signaling pathway activity in vitro and delay the senescence of HGMCs.The results may serve as a new strategy for the treatment of DKD.
基金the Medical Science & Technology Research fund of Health Bureau of Chongqing City,China [No.2004(53)04-2-154]the Nature Science Research fund of Chongqing Science & Technology Com-mission of Chongqing City,China (No.CSTC,2007BB5276).
文摘Objectives To study the relationship between plasma hemoglobin concentration and estimated glomerular filtration rate （eGFR） in elderly patients with ischemic cardiomyopathy （ICM）.Methods Clinical data of patients with coronary heart disease who were discharged from The First Affiliated Hospital,Chongqing Medical University between 2005 and 2007 were analyzed retrospectively. Echocardiography results,plasma hemoglobin and creatinine concentration were abstracted from the medical records.The study included 235 Chinese Hart patients with age 60 years and older with angiography confirmed coronary heart disease,silent myocardial ischemia or angina pectoris,of whom 154 had ICM defined as left ventricular end-diastolic diameter （LVDd）,male≥56 mm,female≥51 mm （63. 51±7.70 mm） measured by M-mode echocardiography.The differences in plasma hemoglobin concentration were analyzed retrospec- tively between patients with and without ICM,and between patients with an eGFR【60 ml·min<sup>-1</sup>·1.73m<sup>-2</sup> and those with an eGFR≥60 ml·min<sup>-1</sup>·1.73m<sup>-2</sup>.Results There were no significant differences in plasma hemoglobin concentration and eGFR between ICM and non-ICM group (118.49±20.52 g·L<sup>-1</sup> vs.115.80±23.32 g·L<sup>-1</sup> and 75.13±24.21 ml·min<sup>-1</sup>·1.73m<sup>-2</sup> vs.79.09±28.41 ml·min<sup>- 1</sup>·1.73m<sup>-2</sup>,respectively,both P】0.05).However,in both ICM and non-ICM groups,plasma hemoglobin concentration was lower in those with an eGFR【60 ml·min<sup>-1</sup>·1.73m<sup>-2</sup> compared with compared with those with an eGFR≥60 ml·min<sup>-1</sup>·1.73m<sup>-2</sup> group (112. 29±18.61 g·L<sup>-1</sup> vs.119.92±20.74L<sup>-1</sup>,P【0.05);plasma hemoglobin concentration was related positively to eGFR.Conclusions There were no significant changes in plasma hemoglobin concentration and eGFR;however,plasma hemoglobin concentration was related to eGFR significantly positively in elderly patients with ICM due to coronary heart
基金supported by National Nature Science Foundation of China(81770847)CAMS Innovation Fund for Medical Sciences(CIFMS)(2016-I2M-3-007,2016-I2M-1-010)National Key Research and Development Plan(2016YFC1000905)
文摘OBJECTIVE Diabetic nephropathy(DN)has been one of the most common complications of diabetes and the leading cause of end-stage renal disease.Glomerular hyperfiltrationis central in earlystage of DN and leads to the progression of renal architectonic and functional abnormalities.Salvianolic acid A(SalA)has been proved to protect diabetic complications such as hepatic fibrosis and neuropathy.The present study was designed to investigate the effects of SalA on glomerular endothelial dysfunctionand diabetic nephropathy.METHODS Primary glomerular endothelial cells were subjected to assess permeability under injury of advanced glycation end-products(AGEs).AGEs-induced changes of Rho A/ROCK pathway and cytoskeleton rearrangement were assessed bywestern blotandimmunofluorescence.The beneficial effects of SalA on diabetic nephropathy were investigated in a rat model induced by high-fat and high-glucose diet combined with low dose of streptozocin(35 mg·kg^(-1),ip).Renal function and architectonic changes were evaluated by biochemical assay and PAS staining.RESULTS SalA 3μMameliorated AGEs-induced glomerular endothelial permeability(P<0.05)and suppressed rearrangement of cytoskeleton through inhibiting AGE-RAGE-Rho A/ROCK pathway.SalA1 mg·kg^(-1)markedly reduced endothelium loss(P<0.01)and glomerular hyperfiltration(P<0.05)in diabetic kidney.Subsequently,SalA 1 mg·kg^(-1) suppressed glomerular hypertrophy and mesangial matrix expansion,eventually reduced 24 h-urinary albumin and ameliorated renal function by decreasing blood urine nitrogen(BUN),serum creatinine(Scr)and serum n-acetyl-β-d-glucosaminidase(NAG).AGEs-RAGE-Nox4-induced oxidative stress was suppressed by the treatment of SalA 1 mg·kg^(-1).CONCLUSION SalA ameliorated AGEs-induced glomerular endothelial hyperpermeability,and effectively protected against early-stage diabetic nephropathy by reducing hyperfiltration and alleviating renal structural deterioration through inhibiting AGEs and its downstream pathway.Thus,SalA might be a promising therapeutic agent for the treatment of diabetic nephropathy.
基金supported by grants from the National Natural Science Foundation of China(No.81374029,No.81073111,No.81874359)Natural Science Foundation of the Higher Education Institutions of Jiangsu Province(No.18KJD360002)+1 种基金a Project Funded by Jiangsu Agri-animal Husbandry Vocational College(No.NSF2021CB04)a Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD)(No.JKLPSE201604).
文摘Objective:The main characteristics of diabetic nephropathy(DN)at the early stage are abnormal angiogenesis of glomerular endothelial cells(GECs)and macrophage infiltration.Galectin-3 plays a pivotal role in the pathogenesis of DN via binding with its ligand,advanced glycation end products(AGEs).Catalpol,an iridoid glucoside extracted from Rehmannia glutinosa,has been found to ameliorate vascular inflammation,reduce endothelial permeability,and protect against endothelial damage in diabetic milieu.However,little is known about whether catalpol could exert an anti-angiogenesis and anti-inflammation effect induced by AGEs.Methods:Mouse GECs(mGECs)and RAW 264.7 macrophages were treated with different concentrations of AGEs(0,50,100,200 and 400μg/mL)for different time(0,6,12,24 and 48 h)to determine the optimal concentration of AGEs and treatment time.Cells were treated with catalpol(10μmol/L),GB1107(1μmol/L,galectin-3 inhibitor),PX-478(50μmol/L,HIF-1αinhibitor),adenovirus-green fluorescent protein(Ad-GFP)[3×10^(7)plaque-forming unit(PFU)/mL]or Ad-galectin-3-GFP(2×10^(8)PFU/mL),which was followed by incubation with 50μg/mL AGEs.The levels of galectin-3,vascular endothelial growth factor A(VEGFA)and pro-angiogenic factors angiopoietin-1(Ang-1),angiopoietin-2(Ang-2),tunica interna endothelial cell kinase-2(Tie-2)were detected by enzyme-linked immunosorbent assay(ELISA).Cell counting kit-8(CCK-8)assay was used to evaluate the proliferation of these cells.The expression levels of galectin-3,vascular endothelial growth factor receptor 1(VEGFR1),VEGFR2,and hypoxia-inducible factor-1α(HIF-1α)in mGECs and those of galectin-3 and HIF-1αin RAW 264.7 macrophages were detected by Western blotting and immunofluorescence(IF)staining.The rat DN model was established.Catalpol(100 mg/kg)or GB1107(10 mg/kg)was administered intragastrically once a day for 12 weeks.Ad-galectin-3-GFP(6×10^(7)PFU/mL,0.5 mL)or Ad-GFP(6×10^(6)PFU/mL,0.5 mL)was injected into the tail vein of rats 48 h before the sacrifice of the animals.The expression of galectin-3,VEGFR1,.VEGFR2,and HIF-1αin renal cortices was analyzed by Western blotting.The expression of galectin-3,F4/80(a macrophage biomarker),and CD34(an endothelium biomarker)in renal cortices was detected by IF staining,and collagen accumulation by Masson staining.Results:The expression levels of galectin-3 and VEGFA were significantly higher in mGECs and RAW 264.7 macrophages treated with 50μg/mL AGEs for 48 h than those in untreated cells.Catalpol and GB1107 could block the AGEs-induced proliferation of mGECs and RAW 264.7 macrophages.Over-expression of galectin-3 was found to reduce the inhibitory effect of catalpol on the proliferation of cells.Catalpol could significantly decrease the levels of Ang-1,Ang-2 and Tie-2 released by AGEs-treated mGECs,which could be reversed by over-expression of galectin-3.Catalpol could significantly inhibit AGEs-induced expression of galectin-3,HIF-1α,VEGFR1,and VEGFR2 in mGECs.The inhibitory effect of catalpol on galectin-3 in AGEs-treated mGECs was impaired by PX-478.Moreover,catalpol attenuated the AGEs-activated HIF-1α/galectin-3 pathway in RAW 264.7 macrophages,which was weakened by PX-478.Additionally,catalpol significantly inhibited the expression of galectin-3,macrophage infiltration,collagen accumulation,and angiogenesis in the kidney of diabetic rats.Over-expression of galectin-3 could antagonize these inhibitory effects of catalpol.Conclusion:Catalpol prevented the angiogenesis of mGECs and macrophage proliferation via inhibiting galectin-3.It could prevent the progression of diabetes-induced renal damage.
文摘Objective Both decreased glomemlar filtration rate （GFR） and arterial stiffness were considered as risk factors for atherosclerosis. Previous studies have suggested the association between central arterial stiffness and the degree of GFR loss. Whether decreased GFR contributes to peripheral artery stiffness remains controversial. Moreover, data analyzed from a cohort of Chinese women are rare. Our aim was to explore the relationship between GFR and regional arterial stiffness in Chinese women. Methods In this cross-sectional study, we randomly recruited 1131 adult women residents with GFR 〉 60 mL/min per 1.73 m2 estimated by the Chinese Modification of Diet in Renal Disease equation from three large communities. Central and peripheral arterial stiffness were estimated simultaneously by measuring carotid-femoral pulse wave velocity （PWVcf） and carotid-radial PWV （PWVcr） using a validated automatic device. Augmentation Index at heart rate 75 beats/minutes （AIx-75） was measured by pulse wave analysis as a composite parameter reflecting both large and distal arterial properties. Results The mean estimated GFR （eGFR） of the study group was 100.05 ＋ 23.26 mL/minute per 1.73 m2. Subjects were grouped by tertiles of eGFR level. PWVef and AIx-75 increased ongoing from the top to the bottom eGFR tertile, while the values of PWVcr were comparable. Both univariate Pearson correlations and multiple stepwise regression analyses showed that eGFR significantly correlated to PWVcf, but not to PWVcr and AJx-75. Conclusions In Chinese women with normal to mildly impaired renal function, decreased eGFR affected carotid-to-femoral rather than carotid-to-radial stiffening. This provides rational to conduct future prospective studies to investigate predictors of atherosclerosis in this population.
文摘Objective To evaluate the clinical features,renal histopathology and therapeutic response to glucocorticoid and immunosuppressive agents in patients with glomerular disease associated with Takayasu arteritis(TA).Methods Patients with TA and renal biopsy-confirmed glomerular disease were investigated retrospectively.None of them had renal artery stenosis or occlusive changes.Results Six patients with glomerulopathy,accounting for 3.75% of the 160 TA patients admitted to our hospital at the same period,were analyzed.All of them were females with a mean age of 35.5 ± 10.0 years.Four cases presented with lower extremity edema.Laboratory tests showed that one was nephrotic syndrome,three were nephrotic range proteinuria,and two of them had mild renal dysfunction.The other two patients were asymptomatic microscopic hematuria and proteinuria.Renal pathology revealed mild immunoglobulin A nephropathy in two cases,mild mesangial proliferative glomerulonephritis(GN),membranoproliferative GN,minimal change disease,and fibrillary GN in one case respectively.Five cases received glucocorticoids and cyclophosphamide therapy.Proteinuria and microscopic hematuria disappeared in 2 to 4 weeks after the initiation of therapy in three cases.The patient with membranoproliferative GN also reached complete remission of proteinuria and recovered renal function 6 months after the treatment.Conclusions TA may induce glomerular disease as a part of its histological spectrum.Apart from ischemic glomerular disease,glomerular disease should be suspected when TA patients have microscopic hematuria or proteinuria,that may be therapeutically responsive to glucocorticoids and immunosuppressive agent in relative early phase.
文摘Objective：To investigate the effects of emodin（EMD） on cell proliferation and correlative cytokines secretion of glomerular mesangial in rats. Methods：The effects of EMD on cell proliferation and IL-6, TGF-β1 secretion of glomerular mesangial in rats were observed. Cell proliferation was measured by MTT method. IL-6 and TGF-β1 secretion was detected with ELISA. Results：EMD was able to inhibit the cell proliferation and down-regulate the IL-6 and TGF-β 1 secretion of glomerular mesangial, as compared to the model group in rats （P 〈 0.05）. Conclusion：EMD could significantly inhibit the cell proliferation, and reduce the creation of extracellular matrix（ECM）, this indicated that it could play an important role in alleviation and prevention of glomerular sclerosis. The mechanism may be that EMD can reduce the IL-6 and TGF-β1 secretion ofglomerular mesangial cell in rats.
基金supported by the Natural Science Foundation of Ningxia Province(No.2021AAC03296).
文摘Objective:Diabetic nephropathy is one of the most important microvascular complications of diabetes,which mainly refers to glomerular capillary sclerosis.Podocytes are an important part of glomerular capillaries.Previous clinical and basic studies have shown that fibrosis is the main factor of diabetic nephropathy.This study aimed to assess the protective mechanism of glycyrrhizic acid(GA)on glomerular podocytes induced by high glucose as we hypothesized that GA may have antifibrotic and anti-inflammatory effects on podocytes through regulation of the adenosine 5'-monophosphate-activated protein kinase(AMPK)/sucrose nonfermenting AMPK-related kinase(SNARK)signaling pathway.Methods:SNARK siRNA was used to transfect podocytes.Real-time quantitative polymerase chain reaction and immunofluorescence staining assays were used for molecular and pathological analysis.The expression levels of key pathway proteins(including TGF-β1,α-SMA,SITR1,AMPKα,LKB1,PGC-1α,NF-κB,IL-6,and TNF-α)were verified by Western blotting.The expression of inflammatory factors in podocytes was detected by ELISA.Results:We demonstrated that GA decreased the expression of podocyte fibrosis signaling pathway-related factors by upregulating the AMPK pathway and its related factors.However,after transfection of podocytes with SNARK siRNA,there was an increased expression of fibrosis-related factors and inflammation-related factors.Conclusion:GA can protect podocytes and alleviate fibrosis and inflammation induced by high glucose,which is related to the AMPK signaling pathway.Meanwhile,knockdown of SNARK protein can inhibit the AMPK signaling pathway,aggravate fibrosis,and increase inflammation.
基金the Research Service of the Raymond G. Murphy VA Medical Center for its support of this work
文摘The development of formulas estimating glomerular filtration rate(eG FR) from serum creatinine and cystatin C and accounting for certain variables affecting the production rate of these biomarkers, including ethnicity, gender and age, has led to the current scheme of diagnosing and staging chronic kidney disease(CKD),which is based on e GFR values and albuminuria.This scheme has been applied extensively in various populations and has led to the current estimates of prevalence of CKD. In addition, this scheme is applied in clinical studies evaluating the risks of CKD and the efficacy of various interventions directed towards improving its course. Disagreements between creatinine-based and cystatin-based e GFR values and between e GFR values and measured GFR have been reported in various cohorts. These disagreements are the consequence of variations in the rate of production and in factors, other than GFR, affecting the rate of removal of creatinine and cystatin C. The disagreements create limitations for all e GFR formulas developed so far. The main limitations are low sensitivity in detecting early CKD in several subjects, e.g., those with hyperfiltration, and poor prediction of the course of CKD. Research efforts in CKD are currently directed towards identification of biomarkers that are better indices of GFR than the current biomarkers and,particularly, biomarkers of early renal tissue injury.
基金supported by grants from National Natural Science Foundations of China (No. 31000396, and No.81072402)grants from Natural Science Foundations of Jiangsu Province in China (No. BK2009417, No. 10KJB310006, and No. 09hx43)
文摘The proliferation of glomerular mesangial cells （GMC） and secretion of the extracellular matrix （ECM） in rat with Thy-1 nephritis （Thy-lN） resembling human mesangioproliferative glomerulonephritis have been explored for many years; however, the molecular mechanisms of GMC proliferation and ECM production remain unclear. Our previous studies have demonstrated that the thrombospondin-1 （TSP-1） gene was involved in mediating rat GMC proliferation and ECM synthesis induced by sublytic C5b-9 in vitro. 111 the present study, the roles of the TSP-1 gene in GMC proliferation, ECM production, and urinary protein secretion in Thy-lN rats were determined by using TSP-1 small hairpin RNA, and the results revealed that silencing of the TSP-1 gene in rat renal tissues could diminish GMC proliferation （P 〈 0.01） and ECM secretion （P 〈 0.01） as well as urinary protein secretion （P 〈 0.05） in Thy-lN rats. Together, the current findings suggested that TSP-1 gene expression was required for GMC proliferation and ECM production in Thy-lN rats.
文摘Primary glomerular diseases in the elderly population are a frustrating topic due to difficulties in both the diagnosis and decision making about treatment. The most frequent type of primary glomerular disease in elderly is membranous nephropathy; while its counterpart in younger population is Ig A nephropathy. The most frequent cause of nephrotic syndrome in the elderly is also membranous nephropathy. Pauci-immune crescentic glomerulonephritis(GN) rate increases both in elderly and very elderly population. Pauci-immune crescentic GNs should be regarded as urgencies in elderly patients as in their younger counterparts due to potential for causing end-stage renal disease in case of delayed diagnosis and treatment, and also causing mortality due to alveolar hemorrhage in patients with pulmonary involvement. Renal biopsy is the inevitable diagnostic method in the elderly as in all other age groups. Renal biopsy prevents unnecessary treatments and provides prognostic data. So advanced age should not be the sole contraindication for renal biopsy. The course of primary glomerular diseases may differ in the elderly population. Acute kidney injury is more frequent in the course and renal functions may be worse at presentation. These patients are more prone to be hypertensive. The decision about adding immune suppressive therapies to conservative methods should be made considering many factors like co-morbidities, drug side effects and potential drug interactions, risk of infection, patient preference, life expectancy and renal functions at the time of diagnosis.
基金supported by a grant from Doctoral Program of Higher Education Research Fund Project (No.2010014 2110074)
文摘The mechanism of injury on the human glomerular endothelial cells （ciGENC） induced by preeclampsia serum was investigated. Concentration of maternal serum sFlt-1 protein was detected by ELISA. Fluorescently-labeled bovine serum albumin infiltrating through lower chamber of Transwell was measured by multifunction microplate reader. Morphologic change of ciGENC was observed under inverted phase contrast microscope. The concentration of sflt-1 in preeclampsia groups was significantly increased as compared with control group （P〈0.01）. Permeability in preeclampsia groups was significantly increased as compared with control group （P〈0.01）. By contrast with severe preeclampsia group, the permeability of ciGENC monolayer in mild preeclampsia group was decreased significantly （P〈0.05）. Intervention of exogenous VEGF significantly decreased permeability of ciGENC in preeclampsia groups. It was concluded that sFlt-1 increased ciGENC permeability by damaging integrity of endothelial barrier function.
文摘This study examined the effect of over-expression of sFlt-1 by trophoblasts on the barrier function of glomerular endothelial cells and the role of VEGF in this process in order to explore the pathogenesis of glomerular disease in preeclampsia. SFlt-1 expression in the human trophoblasts （TEV-1 cells） was enhanced by transfecting sFlt-1 plasmid DNA into TEV-1 cells. The monolayer barrier fimction of glomerular endothelial cells （ciGEnCs） was determined by measuring the fluorescence intensity of bovine serum albumin （BSA） that crossed the monolayer of glomerular endothelial cells. The results showed that the over-expression of sFlt-1 by TEV-1 cells led to the barrier dysfunction of ciGEnCs, and the exogenous VEGF could alleviate the ciGEnCs dysfunction resulting from the over-expression of sFlt- 1 to a certain extent. It was concluded that the dysregulation of sFlt- 1 and VEGF in preeclamptic pregnancy may contribute to the barrier dysfunction of glomerular endothelial cells, and VEGF may play an important role in maintaining the barrier function of glomerular endothelial cells, but it may not be the sole factor.
文摘Objective: To analyze the correlation between urine retinol binding protein-4 (RBP-4) and serum HbA1c?with glomerular filtration rate (GFR) in type 1 diabetic children. Methods:?This?was a crosssectional observational analytic?study. The subjects?were?type 1 diabetic children aged 2 - 14 years. Sample collection was conducted from October to November 2014. Exclusion criteria were patients with obesity, renal insufficiency?that?was not caused by diabetes, history of hepatic diseases, and history of blood cell disorders. We?performed anamnesis, physical examination, and blood sampling for serum HbA1c?and serum cystatin-C, and urine sampling for RBP-4?on all subjects. Glomerular filtration rate was calculated from the concentration level of cystatin-C using Filler formula. Data analysis was performed?by?Spearman test to determine the correlation between urine RBP-4 and serum HbA1c?with GFR. The Fisher’s exact test was used to determine the correlation between duration of diabetes and RBP-4, HbA1c, and also GFR. Results:?Twelve females (60%) and 8 males (40%) participated in the study. The mean age of the subjects with 95% CI?was: 10.5 (2 - 14) years while the mean age of duration diabetes with 95% CI: 3.8 (0.5 - 10) years. Twelve (60%) subjects had?<5 years duration of diabetes, while eight (40%) subjects had?≥5 years duration of diabetes. Twelve (60%) subjects had normal RBP-4 level, while eight (40%) subjects had?elevated RBP-4 level. The mean level of HbA1c?with 95% CI: 8.9 (5.1 - 15.2)%. Thirteen (65%) subjects had poor metabolic. The mean GFR of the subjects with 95% CI: 99.3 (35.2 - 147.4) mL/1.73/m2. Nineteen (95%) subjects had normal GFR, while 1 (5%) had renal insufficiency. The results of data analysis using Spearman test on the correlation between urine RBP-4 and serum HbA1cwith GFR were not significant. The result of correlation between duration of diabetes and urine RBP-4 was significant?using?Fischer’s test. Conclusion:?The results?showed?no correlation between urine RBP-4 and serum HbA1c?with GFR. Urine RBP-4 could?be considered to assess renal function in type 1 diabetic patients with a duration of diabetes of more than 5 years.
