Cyclophosphamide versus cyclosporine A therapy in steroid-resistant nephrotic syndrome: a retrospective study with a mean 5-year follow-up

Liu, Yanwei; Yang, Ruikun; Yang, Chen; Dong, Song; Zhu, Ying; Zhao, Mengnan; Yuan, Feng-Lai; Gui, Keke

doi:10.1177/0300060518782017

Cited by 8 publications

(6 citation statements)

References 26 publications

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“…Podocyte damage causes a reorganization of the complex actin cytoskeleton, leading to an effacement and detachment of foot processes from the GBM (loss of adhesion) and, in the case of chronic damage, to apoptosis 6 . Patients who do not respond to steroids or show severe side effects when exposed to excessive glucocorticoid therapy may be treated with steroid sparing, immunosuppressive substances such as cyclosporin A or cyclophosphamide 7 , 8 , 10 , 34 . However, these drugs do not always prevent relapses or show unacceptable side effects.…”

Section: Discussionmentioning

confidence: 99%

Protective effects of rituximab on puromycin-induced apoptosis, loss of adhesion and cytoskeletal alterations in human podocytes

Jeruschke

Alex

Hoyer

et al. 2022

Sci Rep

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Podocytes are highly specialized cells playing a key role in the filtration function of the kidney. A damaged podocyte ultrastructure is associated with a reorganization of the actin cytoskeleton and accompanied with a loss of adhesion to the glomerular basement membrane leading to proteinuria in many forms of glomerular diseases, e.g. nephrotic syndrome. If the first-line therapy with glucocorticoids fails, alternative immunosuppressive agents are used, which are known to have the potential to stabilize the actin cytoskeleton. A new option for preventing relapses in steroid dependent nephrotic syndrome is the monoclonal antibody rituximab, which, in addition to its B-cell depleting effect, is assumed to have direct effects on podocytes. We here provide data on the non-immunological off-target effects of the immunosuppressant rituximab on podocyte structure and dynamics in an in vitro puromycin aminonucleoside model of podocyte injury. A conditionally immortalized human podocyte cell line was used. Differentiated podocytes were treated with puromycin aminonucleoside and rituximab. Our studies focussed on analyzing the structure of the actin cytoskeleton, cellular adhesion and apoptosis using immunofluorescence staining and protein biochemistry methods. Treatment with rituximab resulted in a stabilization of podocyte actin stress fibers in the puromycin aminonucleoside model, leading to an improvement in cell adhesion. A lower apoptosis rate was observed after parallel treatment with puromycin aminonucleoside and rituximab visualized by reduced nuclear fragmentation. Consistent with this data, Western-blot analyses demonstrated that rituximab directly affects the caspase pathways by inhibiting the activation of Caspases-8, -9 and -3, suggesting that rituximab may inhibit apoptosis. In conclusion, our results indicate an important role of the immunosuppressant rituximab in terms of stability and morphogenesis of podocytes, involving apoptosis pathways. This could help to improve therapeutical concepts for patients with proteinuria mediated by diseased podocytes.

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Section: Discussionmentioning

confidence: 99%

Protective effects of rituximab on puromycin-induced apoptosis, loss of adhesion and cytoskeletal alterations in human podocytes

Jeruschke

Alex

Hoyer

et al. 2022

Sci Rep

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“…Several studies have reported the administration of cyclophosphamide versus cyclosporine and levamisole in idiopathic NS (13,14). It was shown that cyclosporine induces more recurrence in patients with SRNS than cyclophosphamide (15).…”

Section: Discussionmentioning

confidence: 99%

Rituximab versus cyclophosphamide for the treatment of children with steroid resistance nephrotic syndrome; a clinical trial study

et al. 2019

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Introduction: The most common complications of the nephrotic syndrome (NS) are the frequent relapses, steroid resistance, and long-term steroid administration. Objectives: This study aimed to compare the therapeutic effect of rituximab versus cyclophosphamide in the prevention of relapses and the complications of treatment in children with steroid-resistant NS. Patients and Methods: This clinical trial study was performed on 50 patients with resistant steroidal NS referred to Masoumeh hospital in Qom, Iran. Patients were randomly divided into the two groups including intervention (n=20) and control groups (n=30). In addition to the prednisolone, the intervention group received 375 mg/m2/weekly rituximab intravenously for 4 weeks. The control group received oral doses of cyclophosphamide 2 mg/kg/d for 3 months. During treatment, the frequency of relapses, the mean dose of steroid and the complications of treatment were compared with a paired t-test, independent t-test, and chi-square test. Results: A significant decrease in the mean dose of steroids and the mean number of relapses were seen in patients after administration of rituximab and cyclophosphamide (P<0.001). However, rituximab reduced the dose of steroid administration by 12.25 mg/d, while cyclophosphamide reduced only 2.83 mg/d (P<0.001). Rituximab reduced the relapse rate two times on average, while cyclophosphamide reduced only 0.5 times (P<0.001). The incidence of complications in the cyclophosphamide group was found to be more severe than the rituximab group. Conclusion: To compare rituximab versus cyclophosphamide regarding lower the frequency of recurrence after treatment, we found rituximab is a more suitable drug for the treatment of steroid-resistant NS than cyclophosphamide.

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“…A comparative study on the treatment effects of CPM and CSA was performed in 127 children with SRNS. At 5 years of follow-up, a higher response rate has been observed in 65 children receiving CSA for 2 years compared to 62 patients assigned to CPM treatment for 3 to 6 months (70.8% vs. 51.6%, P = 0.027), and a relapse-free survival also favoured CSA over CPM (38.3 vs. 32.5 months, p < 0.001) [ 51 ]. Similarly, superior effects were seen with TAC, showing significantly shorter mean time to remission compared with CPM [ 29 ].…”

Section: Intensified Immunosuppression and Adjuvant Agents For Srnsmentioning

confidence: 99%

Current understandings in treating children with steroid-resistant nephrotic syndrome

et al. 2020

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Steroid-resistant nephrotic syndrome (SRNS) remains a challenge for paediatric nephrologists. SRNS is viewed as a heterogeneous disease entity including immune-based and monogenic aetiologies. Because SRNS is rare, treatment strategies are individualized and vary among centres of expertise. Calcineurin inhibitors (CNI) have been effectively used to induce remission in patients with immune-based SRNS; however, there is still no consensus on treating children who become either CNI-dependent or CNI-resistant. Rituximab is a steroid-sparing agent for patients with steroid-sensitive nephrotic syndrome, but its efficacy in SRNS is controversial. Recently, several novel monoclonal antibodies are emerging as treatment option, but their efficacy remains to be seen. Non-immune therapies, such as angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers, have been proven efficacious in children with SRNS and are recommended as adjuvant agents. This review summarizes and discusses our current understandings in treating children with idiopathic SRNS.

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Cyclophosphamide versus cyclosporine A therapy in steroid-resistant nephrotic syndrome: a retrospective study with a mean 5-year follow-up

Cited by 8 publications

References 26 publications

Protective effects of rituximab on puromycin-induced apoptosis, loss of adhesion and cytoskeletal alterations in human podocytes

Protective effects of rituximab on puromycin-induced apoptosis, loss of adhesion and cytoskeletal alterations in human podocytes

Rituximab versus cyclophosphamide for the treatment of children with steroid resistance nephrotic syndrome; a clinical trial study

Current understandings in treating children with steroid-resistant nephrotic syndrome

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