Background： The efficacy and safety of telmisartan combined with clopidogrel, leflunomide, or both drugs for immunoglobulin A nephropathy （IgAN） are unclear. This study was designed to evaluate the efficacy and saf...Background： The efficacy and safety of telmisartan combined with clopidogrel, leflunomide, or both drugs for immunoglobulin A nephropathy （IgAN） are unclear. This study was designed to evaluate the efficacy and safety of telmisartan combined with clopidogrel, leflunomide, or both drugs for IgAN. Methods： It is a multicenter, prospective, double-dummy randomized controlled trial. Primary IgAN patients were recruited in 13 renal units across Beijing, China, from July 2010 to June 2012. After a 4-week telmisartan （80 mg/d） wash-in, 400 patients continuing on 80 mg/d telmisartan were randomly assigned to additionally receive placebo （Group A）, 50 mg/d clopidogrel （Group B）, 20 mg/d leflunomide （Group C）, or 50 mg/d clopidogrel and 20 mg/d leflunomide （Group D）. The 24-week intervention was completed by 360 patients. The primary endpoint was change in 24-h proteinuria at 24 weeks. A linear mixed-effect model was used to analyze the changes at 4, 12, and 24 weeks. Generalized estimating equations were used to evaluate changes in hematuria grade. This trial was registered at the Chinese Clinical Trial Registry. Results： The effects oftelmisartan combined with leflunomide on changes in proteinuria （0.36 [95% confidence interval （CI） 0.18 0.55] g/d, P 〈 0.001）, in serum uric acid （76.96 [95% CI 57.44-96.49] μmol/L, P 〈 0.001）, in serum creatinine （9.49 [95% CI 6.54-12.44]μmol/L, P 〈 0.001）, and in estimated glomerular filtration rate （-6.72 [95% CI-9.46 to -3.98] ml.min -1. 1.73 m -2, p 〈 0.001） were statistically significant, whereas they were not statistically significant on changes in systolic and diastolic blood pressure and weight （P 〉 0.05）.Telmisartan combined with clopidogrel had no statistical effect on any outcome, and there was no interaction between the interventions. No obvious adverse reactions were observed. Conclusions： Telmisartan combined with leflunomide, not clopidogrel, is safe and effective for decreasing proteinuria in certain IgAN patients.展开更多
Background：Cyclosporine A （CsA） is a commonly used clinical immunosuppressant.However,CsA exposure in rabbits during the gestation period was shown to cause a postnatal decrease in the number of nephrons,with the e...Background：Cyclosporine A （CsA） is a commonly used clinical immunosuppressant.However,CsA exposure in rabbits during the gestation period was shown to cause a postnatal decrease in the number of nephrons,with the effects remaining unknown.In this study,we aimed to explore the effects of CsA on metanephros development in the pregnant BALB/c mice.Methods：Pregnant mice were randomly divided into two groups,and CsA （10 mg·kg^-1·d^-1） was subcutaneously injected from gestation day 10.5 to day 16.5 in the CsA group,whereas a comparable volume of normal saline was given to the control group.All of the mice were sacrificed on gestation day 17.5 and serum CsA concentration was measured.The fetuses were removed and weighed,and their kidneys were prepared for histological assessment and polymerase chain reaction assay.In an in vitro experiment,embryo kidneys of fetal mice on gestation day 12.5 were used,and CsA （10 tmol/L） was added in the culture of the CsA group.The growth pattern of the ureteric bud and nephrons was assessed by lectin staining.Results：No significant differences in the weight of embryo （4.54 ± 1.22 vs.3.26 ± 1.09 mg） were observed between the CsA and control groups,the thickness of the cortical （510.0 ± 30.3 vs.350.0 ± 29.7 μm,P 〈 0.05） and nephrogenic zone （272.5 ± 17.2 vs.173.3 ± 24.0 μm,P 〈 0.05）,and the number of glomeruli （36.5 ± 0.7 vs.27.5 ± 2.1,P 〈 0.05） were reduced in the CsA group when compared to the control group.The cell proliferation of Ki-67 positive index between control and CsA group （307.0 ± 20.0 vs.219.0 ± 25.0,P 〈 0.05） in the nephrogenic zone was decreased with the increase of apoptotic cells （1 7.0 ± 2.0 vs.159.0 ± 33.0,P 〈 0.05）.The mRNA expression of WT-1,Pax2,and Pax8 was downregulated by CsA treatment.As for the in vitro CsA group,the branch number of the ureteric bud was decreased in the CsA-treated group with the nephrons missing in contrast to control after the incubation for 24 h and 72 h （all P〈 0.0001）.Conclusion：Treatment of CsA suppressed metanephros development in the pregnant mice;however,the potential action of mechanism needs to be further investigated.展开更多
文摘Background： The efficacy and safety of telmisartan combined with clopidogrel, leflunomide, or both drugs for immunoglobulin A nephropathy （IgAN） are unclear. This study was designed to evaluate the efficacy and safety of telmisartan combined with clopidogrel, leflunomide, or both drugs for IgAN. Methods： It is a multicenter, prospective, double-dummy randomized controlled trial. Primary IgAN patients were recruited in 13 renal units across Beijing, China, from July 2010 to June 2012. After a 4-week telmisartan （80 mg/d） wash-in, 400 patients continuing on 80 mg/d telmisartan were randomly assigned to additionally receive placebo （Group A）, 50 mg/d clopidogrel （Group B）, 20 mg/d leflunomide （Group C）, or 50 mg/d clopidogrel and 20 mg/d leflunomide （Group D）. The 24-week intervention was completed by 360 patients. The primary endpoint was change in 24-h proteinuria at 24 weeks. A linear mixed-effect model was used to analyze the changes at 4, 12, and 24 weeks. Generalized estimating equations were used to evaluate changes in hematuria grade. This trial was registered at the Chinese Clinical Trial Registry. Results： The effects oftelmisartan combined with leflunomide on changes in proteinuria （0.36 [95% confidence interval （CI） 0.18 0.55] g/d, P 〈 0.001）, in serum uric acid （76.96 [95% CI 57.44-96.49] μmol/L, P 〈 0.001）, in serum creatinine （9.49 [95% CI 6.54-12.44]μmol/L, P 〈 0.001）, and in estimated glomerular filtration rate （-6.72 [95% CI-9.46 to -3.98] ml.min -1. 1.73 m -2, p 〈 0.001） were statistically significant, whereas they were not statistically significant on changes in systolic and diastolic blood pressure and weight （P 〉 0.05）.Telmisartan combined with clopidogrel had no statistical effect on any outcome, and there was no interaction between the interventions. No obvious adverse reactions were observed. Conclusions： Telmisartan combined with leflunomide, not clopidogrel, is safe and effective for decreasing proteinuria in certain IgAN patients.
文摘Background：Cyclosporine A （CsA） is a commonly used clinical immunosuppressant.However,CsA exposure in rabbits during the gestation period was shown to cause a postnatal decrease in the number of nephrons,with the effects remaining unknown.In this study,we aimed to explore the effects of CsA on metanephros development in the pregnant BALB/c mice.Methods：Pregnant mice were randomly divided into two groups,and CsA （10 mg·kg^-1·d^-1） was subcutaneously injected from gestation day 10.5 to day 16.5 in the CsA group,whereas a comparable volume of normal saline was given to the control group.All of the mice were sacrificed on gestation day 17.5 and serum CsA concentration was measured.The fetuses were removed and weighed,and their kidneys were prepared for histological assessment and polymerase chain reaction assay.In an in vitro experiment,embryo kidneys of fetal mice on gestation day 12.5 were used,and CsA （10 tmol/L） was added in the culture of the CsA group.The growth pattern of the ureteric bud and nephrons was assessed by lectin staining.Results：No significant differences in the weight of embryo （4.54 ± 1.22 vs.3.26 ± 1.09 mg） were observed between the CsA and control groups,the thickness of the cortical （510.0 ± 30.3 vs.350.0 ± 29.7 μm,P 〈 0.05） and nephrogenic zone （272.5 ± 17.2 vs.173.3 ± 24.0 μm,P 〈 0.05）,and the number of glomeruli （36.5 ± 0.7 vs.27.5 ± 2.1,P 〈 0.05） were reduced in the CsA group when compared to the control group.The cell proliferation of Ki-67 positive index between control and CsA group （307.0 ± 20.0 vs.219.0 ± 25.0,P 〈 0.05） in the nephrogenic zone was decreased with the increase of apoptotic cells （1 7.0 ± 2.0 vs.159.0 ± 33.0,P 〈 0.05）.The mRNA expression of WT-1,Pax2,and Pax8 was downregulated by CsA treatment.As for the in vitro CsA group,the branch number of the ureteric bud was decreased in the CsA-treated group with the nephrons missing in contrast to control after the incubation for 24 h and 72 h （all P〈 0.0001）.Conclusion：Treatment of CsA suppressed metanephros development in the pregnant mice;however,the potential action of mechanism needs to be further investigated.
