Renin angiotensin system (RAS) activation has a significant influence on renal disease progression. The classical angiotensin-converting enzyme (ACE)-angio-tensin Ⅱ (Ang Ⅱ)-Ang Ⅱ type 1 (AT1) axis is consid...Renin angiotensin system (RAS) activation has a significant influence on renal disease progression. The classical angiotensin-converting enzyme (ACE)-angio-tensin Ⅱ (Ang Ⅱ)-Ang Ⅱ type 1 (AT1) axis is considered to control the effects of RAS activation on renal disease. However, since its discovery in 2000 ACE2 has also been demonstrated to have a significant impact on the RAS. The synthesis and catabolism of Ang Ⅱ are regulated via a complex series of interactions, which involve ACE and ACE2. In the kidneys, ACE2 is expressed in the proximal tubules and less strongly in the glomeruli. The synthesis of inactive Ang 1-9 from Ang Ⅰ and the catabolism of Ang Ⅱ to produce Ang 1-7 are the main functions of ACE2. Ang 1-7 reduces vasoconstriction, water retention, salt intake, cell proliferation, and reactive oxygen stress, and also has a renoprotective effect. Thus, in the non-classical RAS the ACE2-Ang 1-7-Mas axis counteracts the ACE-Ang Ⅱ-AT1 axis. This review examines recent human and animal studies about renal ACE and ACE2.展开更多
Obesity is an important worldwide challenge that must be faced in most developed and developing countries because of unhealthy nutritional habits.The consequences of obesity and being overweight are observed in differ...Obesity is an important worldwide challenge that must be faced in most developed and developing countries because of unhealthy nutritional habits.The consequences of obesity and being overweight are observed in different organs,but the kidney is one of the most affected.Excess adipose tissue causes hemodynamic alterations in the kidney that can result in renal disease.However,obesity is also commonly associated with other comorbidities such as chronic inflammation,hypertension and diabetes.This association of several aggravating factors is still a matter of concern in clinical and basic research because the pathophysiologic mechanisms surrounding chronic kidney disease development in obese patients remain unclear.This review will discuss the consequences of obesity in the context of renal injury.展开更多
Human pluripotent stem cell(hPSC)-derived kidney organoids share similarities with the fetal kidney.However,the current hPSC-derived kidney organoids have some limitations,including the inability to perform nephrogene...Human pluripotent stem cell(hPSC)-derived kidney organoids share similarities with the fetal kidney.However,the current hPSC-derived kidney organoids have some limitations,including the inability to perform nephrogenesis and lack of a corticomedullary definition,uniform vascular system,and coordinated exit path-way for urinary filtrate.Therefore,further studies are required to produce hPSC-derived kidney organoids that accurately mimic human kidneys to facilitate research on kidney development,regeneration,disease modeling,and drug screening.In this review,we discussed recent advances in the generation of hPSC-derived kidney organoids,how these organoids contribute to the understanding of human kidney development and research in disease modeling.Additionally,the limitations,future research focus,and applications of hPSC-derived kidney organoids were highlighted.展开更多
To minimize graft rejection,it is crucial to reduce immunosuppression.In the present study,we investigated immunological markers in the blood of transplant patients who did not receive tacrolimus.We also assessed allo...To minimize graft rejection,it is crucial to reduce immunosuppression.In the present study,we investigated immunological markers in the blood of transplant patients who did not receive tacrolimus.We also assessed alloreactive CD4+CD25+FoxP3+Tregs both before transplantation and after tacrolimus reduction.The comparative analysis included 50 individuals experiencing early rejection after tacrolimus discontinuation and 100 non-rejectors.Before reducing tacrolimus,rejectors exhibited elevated levels of memory CD8+T cells compared to Tregs,while non-rejectors displayed a lower ratio of memory CD4+T cells to Tregs.Following tacrolimus removal,rejectors showed an increase in naïve T cells and a decrease in effector T cells.After transplantation,CD4+Treg levels declined,but their anti-donor regulatory function remained consistent in both rejectors and non-rejectors.Immunological correlation revealed an association between acute rejection after tacrolimus discontinuation and the pre-reduction ratio of memory T cells to regulatory T cells.These indicators identified individuals whose immunosuppression could be safely reduced.展开更多
BACKGROUND Many guidelines have recommended renin-angiotensin system inhibitors(RASI)as the first-line treatment for patients with chronic kidney disease(CKD).We studied RASI prescription trends from 2010 to 2019,and ...BACKGROUND Many guidelines have recommended renin-angiotensin system inhibitors(RASI)as the first-line treatment for patients with chronic kidney disease(CKD).We studied RASI prescription trends from 2010 to 2019,and analyzed the characteristics associated with RASI prescription in Chinese hospitalized CKD patients.AIM To study the prescription of renin angiotensin system inhibitors in hospitalized patients with CKD in China.METHODS It was retrospectively,cross-sectional reviewed RASI prescriptions in hospitalized CKD patients in China from 2010 to 2019.RASI prescribing trends were analyzed from 2010 to 2019,and bivariate and multivariate logistic regression analyses were conducted to identify characteristics associated with RASI prescription.RESULTS A total of 35090 CKD patients were included,with 10043(28.6%)RASI prescriptions.Among these patients,18919(53.9%)met the criteria for RASI treatments based on the 2012 kidney disease:Improving global outcomes guidelines.Of these,7246(38.3%)patients received RASI prescriptions.RASI prescriptions showed an initial rapid increase from 2011 to 2012,reached its peak around 2015 and 2016,and then exhibited a subsequent slight decreasing trend.Both bivariate and multivariate analyses showed that several characteristics,including the male gender,age less than 60-year-old,nephrology department admission,lower CKD stage,history of hypertension or diabetes,proteinuria,glomerulonephritis as the CKD etiology,and non-acute kidney injury were associated with RASI prescriptions.CONCLUSION The frequency of RASI prescriptions showed an initial increase but a slight decreasing trend in more recent years.CKD patients with certain characteristics such as elderly age,advanced disease stage,surgery department admission,or acute kidney injury were less likely to receive RASI prescriptions.In the application of RASI in hospitalized CKD patients is insufficient.The actual clinical practice needs to be improved.The development of related research is helpful to guide the correct choice of clini展开更多
基金Supported by The Toho University School of Medicine Research Foundation
文摘Renin angiotensin system (RAS) activation has a significant influence on renal disease progression. The classical angiotensin-converting enzyme (ACE)-angio-tensin Ⅱ (Ang Ⅱ)-Ang Ⅱ type 1 (AT1) axis is considered to control the effects of RAS activation on renal disease. However, since its discovery in 2000 ACE2 has also been demonstrated to have a significant impact on the RAS. The synthesis and catabolism of Ang Ⅱ are regulated via a complex series of interactions, which involve ACE and ACE2. In the kidneys, ACE2 is expressed in the proximal tubules and less strongly in the glomeruli. The synthesis of inactive Ang 1-9 from Ang Ⅰ and the catabolism of Ang Ⅱ to produce Ang 1-7 are the main functions of ACE2. Ang 1-7 reduces vasoconstriction, water retention, salt intake, cell proliferation, and reactive oxygen stress, and also has a renoprotective effect. Thus, in the non-classical RAS the ACE2-Ang 1-7-Mas axis counteracts the ACE-Ang Ⅱ-AT1 axis. This review examines recent human and animal studies about renal ACE and ACE2.
基金Supported by Fundação de AmparoàPesquisa do Estado de São Paulo(São Paulo Research´s Foundation,FAPESP)and Conselho Nacional de Desenvolvimento Científico e Tecnológico(CNPq,INCT Complex Fluids and Renal Immunopathology Laboratory INSERM/CNPq),No.12/15205-4,12/02270-2,12/16794-3,12/23347-3
文摘Obesity is an important worldwide challenge that must be faced in most developed and developing countries because of unhealthy nutritional habits.The consequences of obesity and being overweight are observed in different organs,but the kidney is one of the most affected.Excess adipose tissue causes hemodynamic alterations in the kidney that can result in renal disease.However,obesity is also commonly associated with other comorbidities such as chronic inflammation,hypertension and diabetes.This association of several aggravating factors is still a matter of concern in clinical and basic research because the pathophysiologic mechanisms surrounding chronic kidney disease development in obese patients remain unclear.This review will discuss the consequences of obesity in the context of renal injury.
基金the National Natural Science Foundation of China,No.82360148Guizhou Science&Technology Department,No.QKHPTRC2018-5636-2 and No.QKHPTRC2020-2201.
文摘Human pluripotent stem cell(hPSC)-derived kidney organoids share similarities with the fetal kidney.However,the current hPSC-derived kidney organoids have some limitations,including the inability to perform nephrogenesis and lack of a corticomedullary definition,uniform vascular system,and coordinated exit path-way for urinary filtrate.Therefore,further studies are required to produce hPSC-derived kidney organoids that accurately mimic human kidneys to facilitate research on kidney development,regeneration,disease modeling,and drug screening.In this review,we discussed recent advances in the generation of hPSC-derived kidney organoids,how these organoids contribute to the understanding of human kidney development and research in disease modeling.Additionally,the limitations,future research focus,and applications of hPSC-derived kidney organoids were highlighted.
文摘To minimize graft rejection,it is crucial to reduce immunosuppression.In the present study,we investigated immunological markers in the blood of transplant patients who did not receive tacrolimus.We also assessed alloreactive CD4+CD25+FoxP3+Tregs both before transplantation and after tacrolimus reduction.The comparative analysis included 50 individuals experiencing early rejection after tacrolimus discontinuation and 100 non-rejectors.Before reducing tacrolimus,rejectors exhibited elevated levels of memory CD8+T cells compared to Tregs,while non-rejectors displayed a lower ratio of memory CD4+T cells to Tregs.Following tacrolimus removal,rejectors showed an increase in naïve T cells and a decrease in effector T cells.After transplantation,CD4+Treg levels declined,but their anti-donor regulatory function remained consistent in both rejectors and non-rejectors.Immunological correlation revealed an association between acute rejection after tacrolimus discontinuation and the pre-reduction ratio of memory T cells to regulatory T cells.These indicators identified individuals whose immunosuppression could be safely reduced.
文摘BACKGROUND Many guidelines have recommended renin-angiotensin system inhibitors(RASI)as the first-line treatment for patients with chronic kidney disease(CKD).We studied RASI prescription trends from 2010 to 2019,and analyzed the characteristics associated with RASI prescription in Chinese hospitalized CKD patients.AIM To study the prescription of renin angiotensin system inhibitors in hospitalized patients with CKD in China.METHODS It was retrospectively,cross-sectional reviewed RASI prescriptions in hospitalized CKD patients in China from 2010 to 2019.RASI prescribing trends were analyzed from 2010 to 2019,and bivariate and multivariate logistic regression analyses were conducted to identify characteristics associated with RASI prescription.RESULTS A total of 35090 CKD patients were included,with 10043(28.6%)RASI prescriptions.Among these patients,18919(53.9%)met the criteria for RASI treatments based on the 2012 kidney disease:Improving global outcomes guidelines.Of these,7246(38.3%)patients received RASI prescriptions.RASI prescriptions showed an initial rapid increase from 2011 to 2012,reached its peak around 2015 and 2016,and then exhibited a subsequent slight decreasing trend.Both bivariate and multivariate analyses showed that several characteristics,including the male gender,age less than 60-year-old,nephrology department admission,lower CKD stage,history of hypertension or diabetes,proteinuria,glomerulonephritis as the CKD etiology,and non-acute kidney injury were associated with RASI prescriptions.CONCLUSION The frequency of RASI prescriptions showed an initial increase but a slight decreasing trend in more recent years.CKD patients with certain characteristics such as elderly age,advanced disease stage,surgery department admission,or acute kidney injury were less likely to receive RASI prescriptions.In the application of RASI in hospitalized CKD patients is insufficient.The actual clinical practice needs to be improved.The development of related research is helpful to guide the correct choice of clini