0
views
0
recommends
+1 Recommend
1 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Consolidation Treatment and Long-Term Prognosis of Rituximab in Minimal Change Disease and Focal Segmental Glomerular Sclerosis

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Purpose

          There is currently a lack of studies investigating long-term prognosis and the necessity of further rituximab (RTX) consolidation treatment for minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS). The aim of this study was to evaluate the efficacy of RTX for these diseases and to investigate whether a consolidation treatment can lower risks of relapse and reinforce long-term remission.

          Patients and Methods

          A retrospective study was conducted. The relapse and remission of 70 patients treated with 1 course of RTX treatment (4 infusions of 375 mg/m2) over a median follow-up time of 27 months (12–60 months) were analyzed. The rates of patients that were able to achieve non-relapse for a duration of 24 months between RTX consolidation therapy and non-consolidation therapy were compared.

          Results

          There were 67 cases (95.71%) of remission and 3 cases (4.29%) of non-remission. The average number of relapses decreased from 3.7±2.5 times before the treatment to 0.8±1.8 times after treatment (P <0.001). The average avannual number of relapses decreased from 1.3±1.2 times/year to 0.2±0.3 times/year (P <0.001). The results from the Cox proportional-hazards model showed that the risk of relapse in patients who received RTX non-consolidation treatment was significantly higher than those with consolidation treatment (odds ratios (OR) 20.9, 95% confidence intervals (CI) OR 5.7–75.7, p<0.001). The 24-month relapse-free rate was also significantly higher in patients with consolidation therapy compared with non-consolidation therapy (86.36% vs 25%, p<0.001). No adverse events were recorded.

          Conclusion

          RTX is highly effective in treating MCD and FSGS, and RTX consolidation therapy may be recommended to reinforce long-term remissions.

          Related collections

          Most cited references 33

          • Record: found
          • Abstract: found
          • Article: not found

          Rituximab targets podocytes in recurrent focal segmental glomerulosclerosis.

          Focal segmental glomerulosclerosis (FSGS) is a glomerular disease characterized by proteinuria, progression to end-stage renal disease, and recurrence of proteinuria after kidney transplantation in about one-third of patients. It has been suggested that rituximab might treat recurrent FSGS through an unknown mechanism. Rituximab not only recognizes CD20 on B lymphocytes, but might also bind sphingomyelin phosphodiesterase acid-like 3b (SMPDL-3b) protein and regulate acid sphingomyelinase (ASMase) activity. We hypothesized that rituximab prevents recurrent FSGS and preserves podocyte SMPDL-3b expression. We studied 41 patients at high risk for recurrent FSGS, 27 of whom were treated with rituximab at time of kidney transplant. SMPDL-3b protein, ASMase activity, and cytoskeleton remodeling were studied in cultured normal human podocytes that had been exposed to patient sera with or without rituximab. Rituximab treatment was associated with lower incidence of posttransplant proteinuria and stabilization of glomerular filtration rate. The number of SMPDL-3b(+) podocytes in postreperfusion biopsies was reduced in patients who developed recurrent FSGS. Rituximab partially prevented SMPDL-3b and ASMase down-regulation that was observed in podocytes treated with the sera of patients with recurrent FSGS. Overexpression of SMPDL-3b or treatment with rituximab was able to prevent disruption of the actin cytoskeleton and podocyte apoptosis induced by patient sera. This effect was diminished in cultured podocytes where SMPDL-3b was silenced. Our study suggests that treatment of high-risk patients with rituximab at time of kidney transplant might prevent recurrent FSGS by modulating podocyte function in an SMPDL-3b-dependent manner.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Adult minimal-change disease: clinical characteristics, treatment, and outcomes.

            Minimal-change disease (MCD) counts for 10 to 15% of cases of primary nephrotic syndrome in adults. Few series have examined this disease in adults. A retrospective review was performed of 95 adults who had MCD and were seen at a single referral center. Examined were presenting features, response to daily versus alternate-day steroids, response to second-line agents, relapse patterns, complications of the disease and therapy, presence of acute renal failure (ARF), and outcome data. Sixty-five patients received daily and 23 received alternate-day steroids initially. There were no differences in remissions, time to remission, relapse rate, or time to relapse between daily- and alternate-day-treated patients. More than one quarter of patients were steroid resistant. At least one relapse occurred in 73% of patients; 28% were frequently relapsing. A significant proportion of frequently relapsing patients became steroid dependent. Second-line agents were used for steroid dependence, steroid resistance, or frequent relapses. No single agent proved superior. There were more remissions with second-line agents in steroid-dependent patients compared with steroid-resistant patients, and remissions were more likely to be complete in steroid-dependent patients. ARF occurred in 24 patients; they tended to be older and hypertensive with lower serum albumin and more proteinuria than those without ARF. At follow up, patients with an episode of ARF had higher serum creatinine than those without ARF. Four patients progressed to ESRD. These patients were less likely to have responded to steroids and more likely to have FSGS on repeat renal biopsy. In this referral MCD population, response to daily and alternate-day steroids is similar. Second-line agents give greater response in patients who are steroid dependent. ARF occurs in a significant number of adult MCD patients and may leave residual renal dysfunction. Few patients progress to ESRD.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Rituximab versus cyclophosphamide for ANCA-associated vasculitis.

              Cyclophosphamide and glucocorticoids have been the cornerstone of remission-induction therapy for severe antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis for 40 years. Uncontrolled studies suggest that rituximab is effective and may be safer than a cyclophosphamide-based regimen. We conducted a multicenter, randomized, double-blind, double-dummy, noninferiority trial of rituximab (375 mg per square meter of body-surface area per week for 4 weeks) as compared with cyclophosphamide (2 mg per kilogram of body weight per day) for remission induction. Glucocorticoids were tapered off; the primary end point was remission of disease without the use of prednisone at 6 months. Nine centers enrolled 197 ANCA-positive patients with either Wegener's granulomatosis or microscopic polyangiitis. Baseline disease activity, organ involvement, and the proportion of patients with relapsing disease were similar in the two treatment groups. Sixty-three patients in the rituximab group (64%) reached the primary end point, as compared with 52 patients in the control group (53%), a result that met the criterion for noninferiority (P<0.001). The rituximab-based regimen was more efficacious than the cyclophosphamide-based regimen for inducing remission of relapsing disease; 34 of 51 patients in the rituximab group (67%) as compared with 21 of 50 patients in the control group (42%) reached the primary end point (P=0.01). Rituximab was also as effective as cyclophosphamide in the treatment of patients with major renal disease or alveolar hemorrhage. There were no significant differences between the treatment groups with respect to rates of adverse events. Rituximab therapy was not inferior to daily cyclophosphamide treatment for induction of remission in severe ANCA-associated vasculitis and may be superior in relapsing disease. (Funded by the National Institutes of Allergy and Infectious Diseases, Genentech, and Biogen; ClinicalTrials.gov number, NCT00104299.) 2010 Massachusetts Medical Society
                Bookmark

                Author and article information

                Journal
                Drug Des Devel Ther
                Drug Des Devel Ther
                dddt
                dddt
                Drug Design, Development and Therapy
                Dove
                1177-8881
                10 May 2021
                2021
                : 15
                : 1945-1953
                Affiliations
                [1 ]Department of Nephrology, Ruijin Hospital, School of Medicine, Shanghai Jiaotong University , Shanghai, People’s Republic of China
                [2 ]Biomedical and Health Informatics, University of Washington , Seattle, WA, USA
                Author notes
                Correspondence: Hong Ren; Nan Chen Department of Nephrology, Ruijin Hospital, School of Medicine, Shanghai Jiaotong University , No. 197, Ruijin Er Road, Shanghai, People’s Republic of ChinaTel +86 21 64370045, extension 665233Fax +86 21 64456419 Email renhong66@126.com; cnrj100@126.com
                Article
                302257
                10.2147/DDDT.S302257
                8121273
                34007154
                © 2021 Lin et al.

                This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms ( https://www.dovepress.com/terms.php).

                Page count
                Figures: 3, Tables: 8, References: 34, Pages: 9
                Funding
                Funded by: No funding;
                No funding was received for the conduct of this study or the preparation of this manuscript.
                Categories
                Original Research

                Pharmacology & Pharmaceutical medicine

                therapeutic effect, consolidation, fsgs, mcd, rtx

                Comments

                Comment on this article