Successful treatment of patients with refractory idiopathic membranous nephropathy with low-dose Rituximab:A single-center experience

BACKGROUND The recognition of idiopathic membranous nephropathy(IMN)as an autoimmune disease has paved the way for the use of B-cell-depleting agents,such as Rituximab(RTX),which is now a first-line drug for treating IMN with proven safety and efficacy.Nevertheless,the usage of RTX for the treatment of refractory IMN remains controversial and challenging.AIM To evaluate the efficacy and safety of a new low-dose RTX regimen for the treatment of patients with refractory IMN.METHODS A retrospective study was performed on refractory IMN patients that accepted a low-dose RTX regimen(RTX,200 mg,once a month for five months)in the Xiyuan Hospital of Chinese Academy of Chinese Medical Sciences’Department of Nephrology from October 2019 to December 2021.To assess the clinical and immune remission data,we performed a 24 h urinary protein quantification(UTP)test and measured the serum albumin(ALB)and serum creatinine(SCr)levels,phospholipase A2 receptor(PLA2R)antibody titer,and CD19+B-cell count every three months.RESULTS A total of nine refractory IMN patients were analyzed.During follow-up conducted twelve months later,the results from the 24 h UTP decreased from baseline[8.14±6.05 g/d to 1.24±1.34 g/d(P<0.05)]and the ALB levels increased from baseline[28.06±8.42 g/L to 40.93±5.85 g/L(P<0.01)].Notably,after administering RTX for six months,the SCr decreased from 78.13±16.49μmol/L to 109.67±40.87μmol/L(P<0.05).All of the nine patients were positive for serum anti-PLA2R at the beginning,and four patients had normal anti-PLA2R titer levels at six months.The level of CD19+B-cells decreased to 0 at three months,and CD19+B-cell count remained at 0 up until six months of follow-up.CONCLUSION Our low-dose RTX regimen appears to be a promising treatment strategy for refractory IMN.

Efficacy and Safety of Niaoduqing Particles for Delaying Moderate-to-severe Renal Dysfunction： A Randomized, Double-blind, Placebo-controlled, Multicenter Clinical Study

Background： Chronic kidney disease （CKD） with moderate-to-severe renal dysfunction usually exhibits an irreversible course, and available treatments for delaying the progression to end-stage renal disease are limited. This study aimed to assess the efficacy and safety of the traditional Chinese medicine, Niaoduqing particles, for delaying renal dysfunction in patients with stage 3b-4 CKD.Methods： The present study was a prospective, randomized, double-blind, placebo-controlled, naulticentcr clinical trial. Frorn May 2013 to December 2013,300 CKD patients with an estimated glomerular filtration rate （eGFR） between 20 and 45 ml ＂rain ~＂ 1.73 m 2, aged 18-70 years were recruited from 22 hospitals in 11 Chinese provinces. Patients were randomized in a 1：1 ratio to either a test group, which was administered Niaoduqing particles 5 g thrice daily and 10 g before bedtime for 24 weeks, or a control group, which was administered a placebo using the same methods. The primary endpoints were changes in baseline serum creatinine （Scr） and eGFR after completion of treatment. The primary endpoints were analyzed using Student＇s t-test or Wilcoxon＇s rank-sum test. The present study reported results based on an intention-to-treat （ITT） analysis. Results： A total of 292 participants underwent the ITT analysis. At 24 weeks, the median （interquartile range） change in Scr was 1.1 （-13.0-24.1） and 11.7 （-2.6-42.9） p, mol/L for the test and control groups, respectively （Z = 2.642, P = 0.008）, and the median change in eGFR was -0.2 （-4.3-2.7） and -2.2 （-5.7-0.8） ml.min-1·1.73 m-2, respectively （Z = -2.408, P = 0.016）. There were no significant differences in adverse events between the groups. Conclusions： Niaoduqing particles safely and effectively delayed CKD progression in patients with stage 3b-4 CKD. This traditional Chinese medicine may be a promising alternative medication for patients with moderate-to-severe renal dysfunction.

Effects of Jian Pi Qu Shi Formula on intestinal bacterial flora in patients with idiopathic membranous nephropathy:A prospective randomized controlled trial

Background:The incidence of idiopathic nlembranous nephropathy(IMN)has recently increased remarkably.Immune dysfunction caused by disordered intestinal flora might be an important factor affecting IMN.The Jian Pi Qu Shi Formula(JPQSF)shows promise in treating IMN.Here,we sequenced 16S rRNA genes to compare intestinal flora between patients with IMN and healthy persons.We also conducted a randomized controlled clinical trial to further compare the intestinal flora of patients with IMN treated with traditional Chinese medicine(TCM)and western medicine(WM).Methods:Among 40 patie nls with IMN treated at Department of Nephrology in Xiyuan Hospital,Chinese Academy of Traditional Chinese Medicine between July 2016 and December 2018,we compared 30 of them with 10 healthy persons(controls).The IMN group was randomly assigned to receive JPQSF(TCM)or immunosuppressant WM therapy in(n=15 per group)for 6 months.Intestinal microbiota diversity was analyzed using alpha diversity and beta diversity.Intestinal flora that significantly differed between the groups was analyzed using MetaStat.The effects and safety of the therapies were determined based on the values for plasma albumin,24-h urine protein excretion,serum creatinine,urea nitrogen,estimate glomerular filtration rate(eGFR),complete blood count,and liver enzymes.All data were statistically analyzed using Statistical Package for the Social Sciences(SPSS)20.0 statistical software.Results:Baseline characteristics did not significanlly differ between the IMN and healthy groups,or the TCM and WM groups.After six months of treatment,24-h urinary protein significantly declined in the TCM and WM groups(before and after treatment:3.24±1.74 vs.1.73±1.85 g,P<0.05 and 3.94±1.05 vs.1.91±1.18 g,P<0.05,respectively).Plasma albumin was significantly increased in the TCM group(before vs.after treatment:32.44±9.04 vs.39.99±7.03 g/L,P<0.05),but did not significantly change in the WM group(31.55±4.23 vs.34.83±9」4 g/L,P>0.05).Values for urea nitrogen,serum creatinine,and eGFR did not significanlly change in either group.The alpha diversity index for intestinal flora differed between the IMN and healthy groups,and the TCM and WM groups.Comparisons of multiple samples(beta diversity)revealed differences in intestinal flora between the IMN and healthy groups,and the TCM and WM groups.The Metastat analysis findings showed that the main genera that differed between the IMN group before treatment and the healthy group were Christensenellaceae_R-7_group,Bifidobacterium(77),Dorea,Escherichia-Shigella,Parabacteroides,Bifidobacterium,and Coprococcus_3.AfterTCM therapy,the main differential genera were Butyricimonas,Bacteroides,Alistipes,and Lachnospira,and after WM therapy,these were Ruminococcus_2,Lachnospiraceae_ND3007_group,Lachnospira,Bifidobacterium,Alistipes,and[Eubacterium]_ventriosum_group.Conclusion:Patients with IMN might have disordered intestinal flora,and JPQSF can regulate intestinal flora in patienls with IMN.