Chronic kidney disease (CKD) is a progressive disease and affects approximately 10% of the population. The major late pathologic feature of CKD is interstitial fibrosis in the kidney characterized by extracellular mat...Chronic kidney disease (CKD) is a progressive disease and affects approximately 10% of the population. The major late pathologic feature of CKD is interstitial fibrosis in the kidney characterized by extracellular matrix deposition but in early stage, several profibrotic and proinflammatory cytokines as well as growth factors are expressed. The renin-angiotensin and ET systems both play an important role in the pathogenesis of CKD and the blockade of these systems has been shown to suppress proinflammatory cytokines and to arrest the progression of CKD. We have demonstrated earlier also the renoprotective effect of physical activity on the experimental CKD progression (Pechter et al., 2003). Aim of the study was to investigate the effects of non-drug treatment, physical activity, to the extent of gene expression in experimental CKD and to compare with endothelin receptor blocker (ERB, sitaxentan) and standard nephroprotective drug, angiotensin receptor blocker (ARB, losartan) treatments. Expression of mRNA was assessed by real-time reverse transcription-polymerase chain reaction. CCL2/MCP-1 and nuclear factor-κB (NFκB) gene expression was measured in whole kidneys. Results revealed that CCL2/MCP-1 gene expression (data presented in poster presentation ASN Renal Week 2010, Pechter et al.) was increased in the 5/6 NPX rat kidneys, and the increase was lessened significantly after physical activity and losartan therapy. ERB treatment appeared less effective. Combined ARB and ERB treatment as well as drugs alone or physical therapy prevented the increase in systemic blood pressure, albuminuria and CCL2/MCP-1 as well as NFκB gene expression. We conclude that non-drug and drug treatments both were effective regarding the rate of the progression of experimental CKD measured by physiological and molecular biomarkers of chronic inflammation in kidney tissue.展开更多
Kidney disease remains a condition with an increasing incidence,high morbidity and mortality associated with cardiovascular events.The incidence of end-stage renal disease is expected to increase.Despite of the techni...Kidney disease remains a condition with an increasing incidence,high morbidity and mortality associated with cardiovascular events.The incidence of end-stage renal disease is expected to increase.Despite of the technical improvement,dialysis never achieved a full clearance of the blood dialysis.Therefore,the demand for new renoprotective measures has never been greater.Here,we report new strategies for preventing renal damage.展开更多
Solid organ transplantation offers life-saving treatment for patients with endorgan dysfunction.Patient survival and quality of life have improved over the past few decades as a result of pharmacological development,e...Solid organ transplantation offers life-saving treatment for patients with endorgan dysfunction.Patient survival and quality of life have improved over the past few decades as a result of pharmacological development,expansion of the donor pool,technological advances and standardization of practices related to transplantation.Still,transplantation is associated with cardiovascular complications,of which post-transplant diabetes mellitus(PTDM)is one of the most important.PTDM increases mortality,which is best documented in patients who have received kidney and heart transplants.PTDM results from traditional risk factors seen in patients with type 2 diabetes mellitus,but also from specific posttransplant risk factors such as metabolic side effects of immunosuppressive drugs,post-transplant viral infections and hypomagnesemia.Oral hypoglycaemic agents are the first choice for the treatment of type 2 diabetes mellitus in non-transplanted patients.However,the evidence on the safety and efficacy of oral hypoglycaemic agents in transplant recipients is limited.The favourable risk/benefit ratio,which is suggested by large-scale and long-term studies on new glucoselowering drug classes such as glucagon-like peptide 1 receptor agonists and sodium-glucose cotransporter 2 inhibitors,makes studies warranted to assess the potential role of these agents in the management of PTDM.展开更多
The renoprotective effects of Chinese chive water and ethanol extracts(CCWE and CCEE)on adenineinduced chronic renal failure(CRF)mice were evaluated in this study.Results showed that the renal pathological damages and...The renoprotective effects of Chinese chive water and ethanol extracts(CCWE and CCEE)on adenineinduced chronic renal failure(CRF)mice were evaluated in this study.Results showed that the renal pathological damages and the enhancement of serum creatinine and blood urea nitrogen of CRF mice could be significantly alleviated by the treatment of CCWE,but not CCEE.When the concentration of CCWE reached 200 mg/kg/day,the area of renal pathological damage was decreased to the 48.1%of model group,and the levels of serum creatinine and blood urea nitrogen were decreased to the 87.7%and 83.9%of model group,respectively.Meanwhile,it could be found that renal oxidative stress and inflammation of CRF mice were remarkably inhibited by CCWE.These results indicated CCWE could improve the kidney function of CRF mice via enhancing antioxidant ability and inhibiting inflammation,and was the main renoprotective fraction of Chinese chive.展开更多
Background：Renin-angiotensin system inhibitor and calcium channel blocker （CCB） are widely used in controlling blood pressure （BP） in patients with chronic kidney disease （CKD）.We carried out a meta-analysis to...Background：Renin-angiotensin system inhibitor and calcium channel blocker （CCB） are widely used in controlling blood pressure （BP） in patients with chronic kidney disease （CKD）.We carried out a meta-analysis to compare the renoprotective effect of the combination of angiotensin-converting enzyme inhibitor （ACEI） or angiotensin receptor blocker （ARB） and CCB （i.e.,ACEI/ARB ＋ CCB） with ACEI/ ARB monotherapy in patients with hypertension and CKD.Methods：Publications were identified from PubMed,Embase,Medline,and Cochrane databases.Only randomized controlled trials （RCTs） of BP lowering treatment for patients with hypertension and CKD were considered.The outcomes of end-stage renal disease （ESRD）,cardiovascular events,BP,urinary protein measures,estimated glomerular filtration rate （GFR）,and adverse events were extracted.Results：Based on seven RCTs with 628 patients,ACEI/ARB ＋ CCB did not show additional benefit for the incidence of ESRD （risk ratio [RR] =0.84;95% confidence interval [CI]：0.52-1.33） and cardiovascular events （RR =0.58;95% CI：0.21-1.63） significantly,compared with ACEI/ARB monotherapy.There were no significant differences in change from baseline to the end points in diastolic BP （weighted mean difference [WMD] =-1.28 mmHg;95% CI：-3.18 to-0.62）,proteinuria （standard mean difference =-0.55;95% CI：-1.41 to-0.30）,GFR （WMD =-0.32 ml/min;95% CI：-1.53 to-0.89）,and occurrence of adverse events （RR =1.05;95% CI：0.72-1.53）.However,ACEI/ARB ＋ CCB showed a greater reduction in systolic BP （WMD =-4.46 mmHg;95% CI：-6.95 to-1.97）,compared with ACEI/ARB monotherapy.Conclusion：ACEI/ARB ＋ CCB had no additional renoprotective benefit beyond than what could be achieved with ACEI/ARB monotherapy.展开更多
Background:Renal ischemia–reperfusion(R-I/R)injury is the most prevalent cause of acute kidney injury,with high mortality and poor prognosis.However,the underlying pathological mechanisms are not yet fully understood...Background:Renal ischemia–reperfusion(R-I/R)injury is the most prevalent cause of acute kidney injury,with high mortality and poor prognosis.However,the underlying pathological mechanisms are not yet fully understood.Therefore,this study aimed to investigate the role of N‐myc downstream‐regulated gene 2(Ndrg2)in R-I/R injury.Methods:We examined the expression of Ndrg2 in the kidney under normal physiological conditions and after R-I/R injury by immunofluorescence staining,real-time polymerase chain reaction,and western blotting.We then detected R-I/R injury in Ndrg2-deficient(Ndrg2^(-/-))mice and wild type(Ndrg2+/+)littermates in vivo,and detected oxygen and glucose deprivation and reperfusion(OGD-R)injury in HK-2 cells.We further conducted transcriptomic sequencing to investigate the role of Ndrg2 in R-I/R injury and detected levels of oxidative stress and mitochondrial damage by dihydroethidium staining,biochemical assays,and western blot.Finally,we measured the levels of mitophagy in Ndrg2+/+and Ndrg2^(-/-)mice after R-I/R injury or HK-2 cells in OGD-R injury.Results:Ndrg2 was primarily expressed in renal proximal tubules and its expression was significantly decreased 24 h after R-I/R injury.Ndrg2^(-/-)mice exhibited significantly attenuated R-I/R injury compared to Ndrg2+/+mice.Transcriptomics profiling showed that Ndrg2 deficiency induced perturbations of multiple signaling pathways,downregulated inflammatory responses and oxidative stress,and increased autophagy following R-I/R injury.Further studies revealed that Ndrg2 deficiency reduced oxidative stress and mitochondrial damage.Notably,Ndrg2 deficiency significantly activated phosphatase and tensin homologue on chromosome ten-induced putative kinase 1(PINK1)/Parkin-mediated mitophagy.The downregulation of NDRG2 expression significantly increased cell viability after OGD-R injury,increased the expression of heme oxygenase-1,decreased the expression of nicotinamide adenine dinucleotide phosphate oxidase 4,and increased the expression of the PINK1/Parkin pathway.Conclusion:Ndrg2 deficiency might become a therapy target for R-I/R injury by decreasing oxidative stress,maintaining mitochondrial homeostasis,and activating PINK1/Parkin-mediated mitophagy.展开更多
Acute kidney injury(AKI) is a major health threat worldwide. The literature on herbal intervention in AKI was searched from English and Chinese databases and reports were critically analyzed in terms of preventing AKI...Acute kidney injury(AKI) is a major health threat worldwide. The literature on herbal intervention in AKI was searched from English and Chinese databases and reports were critically analyzed in terms of preventing AKI, promoting repair and regeneration, enhancing extrarenal clearance of uremic toxins, and preventing progression to chronic kidney disease(CKD). Altogether, 16 herbal formulae and a few extracts derived from individual herbs were reported to prevent or mitigate AKI in animal models induced by renal ischemia/reperfusion, cisplastin,gentamicin, glycerol, adenine, sepsis or physical exhaustion. Four formulae and six individual herbs were reported to accelerate recovery and/or to prevent CKD in established AKI animal models. Intrarectal herbal medicines, with or without simultaneous oral administration, were reported in six clinical trials and in an animal model to increase extrarenal clearance of uremic toxins. Additional 13 clinical trials reported oral or intravenous herbal interventions in AKI of different etiologies. Despite recurring problems, notably poor compliance with good practice guidelines for clinical trials and for authentication, naming and quality control of herbal materials, accumulating experimental data on the preventive effects of herbal medicines in AKI look encouraging and urge for better, definitive trials to guide clinical practice. Herbal enemas promoting extrarenal clearance of uremic toxins seem cost-effective, but better clinical evidence is certainly needed before any affirmative recommendation be made for AKI patients without access to dialysis. New frontiers, however, lie in those herbal remedies that promote repair/regeneration and prevent chronicity after AKI. Recent experimental data suggest that this may be possible.展开更多
Advanced glycation end-products(AGEs)are complex and heterogeneous compounds generated through various steps and are naturally produced during the glycation reaction.Excessively generated AGEs bind to long-lived prote...Advanced glycation end-products(AGEs)are complex and heterogeneous compounds generated through various steps and are naturally produced during the glycation reaction.Excessively generated AGEs bind to long-lived proteins such as collagen and cause renal dysfunction,leading to AGE-related diabetic nephropathy(DN).In this study,we aimed to confirm the therapeutic potential of marine biological resources by evaluating the role of diphlorethohydroxycarmalol(DPHC),a major phlorotannin compound contained in edible brown algae Ishige okamurae,in the key mechanisms involved in the pathogenesis and progression of AGE-induced DN.The AGE formation inhibitory and AGE-collagen cross-link inhibiting/breaking ability assay were performed to evaluate the anti-glycation effect of DPHC.The AGE-RAGE interaction inhibitory effect was evaluated through molecular docking study.The renoprotective effect of DPHC was confirmed in mouse glomerular mesangial cells.DPHC treatment exhibited anti-glycation ability through suppression of AGE formation and AGE-collagen cross-linking generation,and disruption of cross-links formed between AGE-collagen.In addition,DPHC pre-treatment significantly suppressed reactive oxygen species(ROS)production,intracellular methylglyoxal(MGO)/AGEs accumulation,and activation of apoptosis cascade by MGO.Moreover,DPHC suppressed AGE-receptor for AGE(RAGE)interaction by competing with MG-H1 for the binding site of RAGE.Furthermore,DPHC pre-treatment regulated apoptosis-related protein expression and increased Nrf2,Glo-1,HO-1,CAT,NQO1,and SOD1.These findings prove that the chemical structural characteristics of DPHC have the potential to prevent or manage AGE-induced DN by effectively mediating the key mechanisms responsible for its pathogenesis.展开更多
文摘Chronic kidney disease (CKD) is a progressive disease and affects approximately 10% of the population. The major late pathologic feature of CKD is interstitial fibrosis in the kidney characterized by extracellular matrix deposition but in early stage, several profibrotic and proinflammatory cytokines as well as growth factors are expressed. The renin-angiotensin and ET systems both play an important role in the pathogenesis of CKD and the blockade of these systems has been shown to suppress proinflammatory cytokines and to arrest the progression of CKD. We have demonstrated earlier also the renoprotective effect of physical activity on the experimental CKD progression (Pechter et al., 2003). Aim of the study was to investigate the effects of non-drug treatment, physical activity, to the extent of gene expression in experimental CKD and to compare with endothelin receptor blocker (ERB, sitaxentan) and standard nephroprotective drug, angiotensin receptor blocker (ARB, losartan) treatments. Expression of mRNA was assessed by real-time reverse transcription-polymerase chain reaction. CCL2/MCP-1 and nuclear factor-κB (NFκB) gene expression was measured in whole kidneys. Results revealed that CCL2/MCP-1 gene expression (data presented in poster presentation ASN Renal Week 2010, Pechter et al.) was increased in the 5/6 NPX rat kidneys, and the increase was lessened significantly after physical activity and losartan therapy. ERB treatment appeared less effective. Combined ARB and ERB treatment as well as drugs alone or physical therapy prevented the increase in systemic blood pressure, albuminuria and CCL2/MCP-1 as well as NFκB gene expression. We conclude that non-drug and drug treatments both were effective regarding the rate of the progression of experimental CKD measured by physiological and molecular biomarkers of chronic inflammation in kidney tissue.
文摘Kidney disease remains a condition with an increasing incidence,high morbidity and mortality associated with cardiovascular events.The incidence of end-stage renal disease is expected to increase.Despite of the technical improvement,dialysis never achieved a full clearance of the blood dialysis.Therefore,the demand for new renoprotective measures has never been greater.Here,we report new strategies for preventing renal damage.
文摘Solid organ transplantation offers life-saving treatment for patients with endorgan dysfunction.Patient survival and quality of life have improved over the past few decades as a result of pharmacological development,expansion of the donor pool,technological advances and standardization of practices related to transplantation.Still,transplantation is associated with cardiovascular complications,of which post-transplant diabetes mellitus(PTDM)is one of the most important.PTDM increases mortality,which is best documented in patients who have received kidney and heart transplants.PTDM results from traditional risk factors seen in patients with type 2 diabetes mellitus,but also from specific posttransplant risk factors such as metabolic side effects of immunosuppressive drugs,post-transplant viral infections and hypomagnesemia.Oral hypoglycaemic agents are the first choice for the treatment of type 2 diabetes mellitus in non-transplanted patients.However,the evidence on the safety and efficacy of oral hypoglycaemic agents in transplant recipients is limited.The favourable risk/benefit ratio,which is suggested by large-scale and long-term studies on new glucoselowering drug classes such as glucagon-like peptide 1 receptor agonists and sodium-glucose cotransporter 2 inhibitors,makes studies warranted to assess the potential role of these agents in the management of PTDM.
基金the National Natural Science Foundation of China(Grant No.31271814No.21702040)+1 种基金the Fundamental Research Funds for the Central Universities(Grant No.JZ2017HGPB0169No.2014HFCH0011).
文摘The renoprotective effects of Chinese chive water and ethanol extracts(CCWE and CCEE)on adenineinduced chronic renal failure(CRF)mice were evaluated in this study.Results showed that the renal pathological damages and the enhancement of serum creatinine and blood urea nitrogen of CRF mice could be significantly alleviated by the treatment of CCWE,but not CCEE.When the concentration of CCWE reached 200 mg/kg/day,the area of renal pathological damage was decreased to the 48.1%of model group,and the levels of serum creatinine and blood urea nitrogen were decreased to the 87.7%and 83.9%of model group,respectively.Meanwhile,it could be found that renal oxidative stress and inflammation of CRF mice were remarkably inhibited by CCWE.These results indicated CCWE could improve the kidney function of CRF mice via enhancing antioxidant ability and inhibiting inflammation,and was the main renoprotective fraction of Chinese chive.
文摘Background：Renin-angiotensin system inhibitor and calcium channel blocker （CCB） are widely used in controlling blood pressure （BP） in patients with chronic kidney disease （CKD）.We carried out a meta-analysis to compare the renoprotective effect of the combination of angiotensin-converting enzyme inhibitor （ACEI） or angiotensin receptor blocker （ARB） and CCB （i.e.,ACEI/ARB ＋ CCB） with ACEI/ ARB monotherapy in patients with hypertension and CKD.Methods：Publications were identified from PubMed,Embase,Medline,and Cochrane databases.Only randomized controlled trials （RCTs） of BP lowering treatment for patients with hypertension and CKD were considered.The outcomes of end-stage renal disease （ESRD）,cardiovascular events,BP,urinary protein measures,estimated glomerular filtration rate （GFR）,and adverse events were extracted.Results：Based on seven RCTs with 628 patients,ACEI/ARB ＋ CCB did not show additional benefit for the incidence of ESRD （risk ratio [RR] =0.84;95% confidence interval [CI]：0.52-1.33） and cardiovascular events （RR =0.58;95% CI：0.21-1.63） significantly,compared with ACEI/ARB monotherapy.There were no significant differences in change from baseline to the end points in diastolic BP （weighted mean difference [WMD] =-1.28 mmHg;95% CI：-3.18 to-0.62）,proteinuria （standard mean difference =-0.55;95% CI：-1.41 to-0.30）,GFR （WMD =-0.32 ml/min;95% CI：-1.53 to-0.89）,and occurrence of adverse events （RR =1.05;95% CI：0.72-1.53）.However,ACEI/ARB ＋ CCB showed a greater reduction in systolic BP （WMD =-4.46 mmHg;95% CI：-6.95 to-1.97）,compared with ACEI/ARB monotherapy.Conclusion：ACEI/ARB ＋ CCB had no additional renoprotective benefit beyond than what could be achieved with ACEI/ARB monotherapy.
基金supported by grants from the National Natural Science Foundation of China(Nos.81970344,82270411,82171464,82003321,and 82100713)the Beijing Hospitals Authority Clinical Medicine Development of Special Funding Support(No.ZYLX202103)+1 种基金the Beijing Hospitals Authority’s Ascent Plan(No.DFL20220203)the China Postdoctoral Science Foundation(No.2021T140791).
文摘Background:Renal ischemia–reperfusion(R-I/R)injury is the most prevalent cause of acute kidney injury,with high mortality and poor prognosis.However,the underlying pathological mechanisms are not yet fully understood.Therefore,this study aimed to investigate the role of N‐myc downstream‐regulated gene 2(Ndrg2)in R-I/R injury.Methods:We examined the expression of Ndrg2 in the kidney under normal physiological conditions and after R-I/R injury by immunofluorescence staining,real-time polymerase chain reaction,and western blotting.We then detected R-I/R injury in Ndrg2-deficient(Ndrg2^(-/-))mice and wild type(Ndrg2+/+)littermates in vivo,and detected oxygen and glucose deprivation and reperfusion(OGD-R)injury in HK-2 cells.We further conducted transcriptomic sequencing to investigate the role of Ndrg2 in R-I/R injury and detected levels of oxidative stress and mitochondrial damage by dihydroethidium staining,biochemical assays,and western blot.Finally,we measured the levels of mitophagy in Ndrg2+/+and Ndrg2^(-/-)mice after R-I/R injury or HK-2 cells in OGD-R injury.Results:Ndrg2 was primarily expressed in renal proximal tubules and its expression was significantly decreased 24 h after R-I/R injury.Ndrg2^(-/-)mice exhibited significantly attenuated R-I/R injury compared to Ndrg2+/+mice.Transcriptomics profiling showed that Ndrg2 deficiency induced perturbations of multiple signaling pathways,downregulated inflammatory responses and oxidative stress,and increased autophagy following R-I/R injury.Further studies revealed that Ndrg2 deficiency reduced oxidative stress and mitochondrial damage.Notably,Ndrg2 deficiency significantly activated phosphatase and tensin homologue on chromosome ten-induced putative kinase 1(PINK1)/Parkin-mediated mitophagy.The downregulation of NDRG2 expression significantly increased cell viability after OGD-R injury,increased the expression of heme oxygenase-1,decreased the expression of nicotinamide adenine dinucleotide phosphate oxidase 4,and increased the expression of the PINK1/Parkin pathway.Conclusion:Ndrg2 deficiency might become a therapy target for R-I/R injury by decreasing oxidative stress,maintaining mitochondrial homeostasis,and activating PINK1/Parkin-mediated mitophagy.
基金Kidney Research UK and the European Union for fundingChina Scholarship Council for funding
文摘Acute kidney injury(AKI) is a major health threat worldwide. The literature on herbal intervention in AKI was searched from English and Chinese databases and reports were critically analyzed in terms of preventing AKI, promoting repair and regeneration, enhancing extrarenal clearance of uremic toxins, and preventing progression to chronic kidney disease(CKD). Altogether, 16 herbal formulae and a few extracts derived from individual herbs were reported to prevent or mitigate AKI in animal models induced by renal ischemia/reperfusion, cisplastin,gentamicin, glycerol, adenine, sepsis or physical exhaustion. Four formulae and six individual herbs were reported to accelerate recovery and/or to prevent CKD in established AKI animal models. Intrarectal herbal medicines, with or without simultaneous oral administration, were reported in six clinical trials and in an animal model to increase extrarenal clearance of uremic toxins. Additional 13 clinical trials reported oral or intravenous herbal interventions in AKI of different etiologies. Despite recurring problems, notably poor compliance with good practice guidelines for clinical trials and for authentication, naming and quality control of herbal materials, accumulating experimental data on the preventive effects of herbal medicines in AKI look encouraging and urge for better, definitive trials to guide clinical practice. Herbal enemas promoting extrarenal clearance of uremic toxins seem cost-effective, but better clinical evidence is certainly needed before any affirmative recommendation be made for AKI patients without access to dialysis. New frontiers, however, lie in those herbal remedies that promote repair/regeneration and prevent chronicity after AKI. Recent experimental data suggest that this may be possible.
基金supported by a National Research Foundation of Korea(NRF)grant funded by the Korean government(Ministry of Sci-ence and ICT,MSIT)(No.NRF-2020R1A2C2012608)supported by Korea Institute of Marine Science&Technology Promotion(KIMST)funded by the Ministry of Oceans and Fisheries(20220128).
文摘Advanced glycation end-products(AGEs)are complex and heterogeneous compounds generated through various steps and are naturally produced during the glycation reaction.Excessively generated AGEs bind to long-lived proteins such as collagen and cause renal dysfunction,leading to AGE-related diabetic nephropathy(DN).In this study,we aimed to confirm the therapeutic potential of marine biological resources by evaluating the role of diphlorethohydroxycarmalol(DPHC),a major phlorotannin compound contained in edible brown algae Ishige okamurae,in the key mechanisms involved in the pathogenesis and progression of AGE-induced DN.The AGE formation inhibitory and AGE-collagen cross-link inhibiting/breaking ability assay were performed to evaluate the anti-glycation effect of DPHC.The AGE-RAGE interaction inhibitory effect was evaluated through molecular docking study.The renoprotective effect of DPHC was confirmed in mouse glomerular mesangial cells.DPHC treatment exhibited anti-glycation ability through suppression of AGE formation and AGE-collagen cross-linking generation,and disruption of cross-links formed between AGE-collagen.In addition,DPHC pre-treatment significantly suppressed reactive oxygen species(ROS)production,intracellular methylglyoxal(MGO)/AGEs accumulation,and activation of apoptosis cascade by MGO.Moreover,DPHC suppressed AGE-receptor for AGE(RAGE)interaction by competing with MG-H1 for the binding site of RAGE.Furthermore,DPHC pre-treatment regulated apoptosis-related protein expression and increased Nrf2,Glo-1,HO-1,CAT,NQO1,and SOD1.These findings prove that the chemical structural characteristics of DPHC have the potential to prevent or manage AGE-induced DN by effectively mediating the key mechanisms responsible for its pathogenesis.
