Efficacy of Leflunomide, Telmisartan, and Clopidogrel for Immunoglobulin A Nephropathy： A Randomized Controlled Trial

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.

Efficacy and safety of Shenyankangfu Tablet,a Chinese patent medicine,for primary glomerulonephritis:A multicenter randomized controlled trial

Background:Shenyankangfu Tablet(SYKFT)is a Chinese patent medicine that has been used widely to decrease proteinuria and the progression of chronic kidney disease.Objective:This trial compared the efficacy and safety of SYKFT,for the control of proteinuria in primary glomerulonephritis patients,against the standard drug,losartan potassium.Design,setting,participants and intervention:This was a multicenter,double-blind,randomized,controlled clinical trial.Primary glomerulonephritis patients,aged 18-70 years,with blood pressure≤140/90 mmHg,estimated glomerular filtration rate(eGFR)>45 mL/min per 1.73 ㎡,and 24-hour proteinuria level of 0.5-3.0 g,were recruited in 41 hospitals across 19 provinces in China and were randomly divided into five groups:SYKFT,losartan potassium 50 mg or 100 mg,SYKFT plus losartan potassium 50 mg or 100 mg.Main outcome measu res:The primary outcome was change in the 24-hour proteinuria level,after 48 weeks of treatment.Results:A total of 735 participants were enrolled.The percent decline of urine protein quantification in the SYKFT group after 48 weeks was 8.78%±2.56%(P=0.006)more than that in the losartan 50 mg group,which was 0.51%±2.54%(P=1.000)less than that in the losartan 100 mg group.Compared with the losartan potassium 50 mg group,the SYKFT plus losartan potassium 50 mg group had a 13.39%±2.49%(P<0.001)greater reduction in urine protein level.Compared with the losartan potassium 100 mg group,the SYKFT plus losartan potassium 100 mg group had a 9.77%±2.52%(P=0.001)greater reduction in urine protein.With a superiority threshold of 15%,neither was statistically significant.eGFR,serum creatinine and serum albumin from the baseline did not change statistically significant.The average change in TCM syndrome score between the patients who took SYKFT(-3.00[-6.00,-2.00])and who did not take SYKFT(-2.00[-5.00,0])was statistically significant(P=0.003).No obvious adverse reactions were observed in any group.Conclusion:SYKFT decreased the proteinuria and improved the TCM syndrome scores of primary glomerulonephritis patients,with no change in the rate of decrease in the eGFR.SYKFT plus losartan potassium therapy decreased proteinuria more than losartan potassium therapy alone.Trial registration number:NCT02063100 on ClinicalTrials.gov.

Microstructures and mechanical properties of a cast Al-Cu-Li alloy during heat treatment procedure

Al-Cu-Li alloy is a huge potential alloy for aerospace industry due to its low density and excellent comprehensive performances.In this study,the microstructures and mechanical properties of a novel cast Al-Cu-Li alloy during the heat treatment were investigated.Results showed that most of the secondary phases along grain boundaries in as-cast state were dissolved into the Al matrix after homogenization and solution treatment,while the Cu-rich phases were slightly segregated once again on grain boundaries after aging.A relatively good combination of strength and ductility(average ultimate tensile strength of 430 MPa and elongation of 8.9%)was obtained after natural aging.Transmission electron microscopy(TEM)results revealed that there was a complicated precipitate distribution in this cast alloy after natural aging.Compared with the similar alloys which introduced dislocations before aging,the density of T1(Al_(2)CuLi)phases was decreased but the size was increased.The low volume fraction of d0 phase,medium density of needle-shaped precipitates and relativity narrow precipitates-free zone with varying widths near grain boundary are the reasons accounting for the improvement of performances.

Relationship between serum C3/C4 ratio and prognosis of immunoglobulin A nephropathy based on propensity score matching

Background:Aberrant activation of the complement system plays an important role in the pathogenesis and development of immunoglobulin A nephropathy(IgAN).The relationship between serum complement and the clinical-histopathological features and outcomes of IgAN is controversial.This retrospective study aimed to examine the relationship between the complement 3/4(C3/C4)ratio and the clinicopathologic changes and prognosis of patients with IgAN.Methods:A total of 397 patients with primary IgAN from January 2007 to December 2012 at the Chinese People's Liberation Army General Hospital were included in this study.The correlation test and Chi-square test or one-way analysis of variance test were performed to evaluate the relationship between the C3/C4 ratio and other clinical-pathological factors.Propensity score matching and a multivariate Cox regression model were used to calculate the risk factors of renal outcome.Results:The median follow-up period was 75 months.During the follow-up period,62 patients(15.6%)developed into the endstage renal disease(ESRD).The C3/C4 ratio at baseline was associated with the level of serum creatinine(SCr),24 h urinary protein excretion(24 h Upre),global glomerular sclerosis,and tubulointerstitial lesion.The level of SCr and 24 h Upre and the degree of chronic kidney injury were statistically different among groups defined by different C3/C4 ratio levels.The survival rates of patients among groups with different C3/C4 ratio levels were different.After propensity score matching,eighty-eight pairs of patients were successfully matched,and the C3/C4 ratio was an influencing factor for the patients5 outcome(hazard ratio 0.587,95%confidence interval 0.329-0.880).Patients with a C3/C4 ratio<3.6 had a poorer outcome compared with the others(P=0.002).Conclusions:IgAN patients with decreased C3/C4 ratio displayed significantly more severe clinical symptoms and chronic renal injury than patients with higher ratios.A low C3/C4 ratio could be a risk factor for patients developing to ESRD.