Long-term follow-up after cyclophosphamide and cyclosporine-A therapy in steroid-dependent and -resistant nephrotic syndrome

Sümegi, Viktória; Haszon, Ibolya; Bereczki, Csaba; Papp, Ferenc; Túri, Sándor

doi:10.1007/s00467-008-0771-8

Cited by 26 publications

(25 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Initial [22] but also recent [23] studies have compared this drug to cytotoxic treatment. In these studies, cyclophosphamide seemed to induce long-term remission without further treatment in a larger proportion of patients than cyclosporine.…”

Section: Cylosporinementioning

confidence: 99%

New therapies in steroid-sensitive and steroid-resistant idiopathic nephrotic syndrome

2011

View full text Add to dashboard Cite

Although many children with idiopathic nephrotic syndrome (INS) respond initially to steroid therapy, repeated courses for patients with relapses often cause significant steroid toxicity. Patients with frequent relapses who develop steroid dependency thus require alternative treatment. The first such options have been considered to be cyclophosphamide or levamisole, although the latter is no longer available in many countries. There is also an increasing body of data indicating that mycophenolic acid (MPA) may be an alternative for these patients. Calcineurin inhibitors (cyclosporine A or tacrolimus) are usually effective and often used after cytotoxic treatment, but long-term treatment with these agents is necessary, raising concerns of a possible accumulation of side effects. Some patients show a tendency to relapse even on such maintenance regimens, and some even have a refractory course that creates a medical dilemma. For this situation, recent data indicate that monoclonal antibodies directed to B-cells (e.g. rituximab) may have some effect and that such drugs may also prove to be a therapeutic option in less complicated cases. Patients that do not respond to steroid treatment need genetic testing and a renal biopsy since focal segmental glomerulosclerosis (FSGS) may be present. Treatment options include pulse methylprednisolone, often in addition to calcineurin inhibitors, mainly in the form of cyclosporine, but tacrolimus has also come into recent favor. Some studies have found cytotoxic treatment, especially intravenous cyclophosphamide, to be effective in steroid resistant nephrotic syndrome, but it seems to be inferior to calcineurin inhibitors. MPA and rituximab have also been used in children with primary FSGS, but the response seems to be inferior to that in patients with steroid sensitive nephrotic syndrome. Taken together, INS in both steroid-sensitive and steroid-resistant patients is a potentially complicated disorder, and despite a wide arsenal of immunological interventions, some patients have a treatment refractory course. Prospective studies or at least standardized treatment for complicated cases is urgently needed.

show abstract

Section: Cylosporinementioning

confidence: 99%

New therapies in steroid-sensitive and steroid-resistant idiopathic nephrotic syndrome

2011

View full text Add to dashboard Cite

show abstract

“…The aim of minimization of the cumulative steroid dosage, however, necessitates the use of alternative immunosuppressive agents. Cyclosporine A (CsA), mycophenolate mofetil (MMF), azathioprine (AZA), tacrolimus, levamisole, cyclophosphamide (CPA) and chlorambucil are options for second- and third-line treatment [5,6,7,8,9], but adverse events and toxicities attributed to these drugs also limit their long-term use.…”

Section: Introductionmentioning

confidence: 99%

Rituximab Treatment for Relapsing Minimal Change Disease and Focal Segmental Glomerulosclerosis: A Systematic Review

et al. 2014

View full text Add to dashboard Cite

Background: Minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS) remain a therapeutic challenge, since steroids and other immunosuppressive agents exhibit an unfavorable adverse event spectrum. The aim of this review was to systematically summarize and analyze data from preexisting studies reporting the outcome of rituximab (RTX) treatment in these patients. Methods: Study data on adult patients with either steroid-dependent or frequently relapsing MCD/FSGS were identified by a PubMed and Embase search. The number of relapses was calculated and the use of immunosuppressive co-medication prior to and after RTX treatment was quantified. Results: We identified14 studiesincluding 86 patients with frequently relapsing and steroid-dependent MCD or FSGS. Treatment with RTX reduced the number of relapses per year from 1.3 (0-9) relapses prior to treatment compared to 0 (0-2) after therapy (p < 0.001). Proteinuria decreased from 2.43 (0-15) g/day to 0 (0-4.89) g/day (p < 0.001), while serum albumin increased from 2.9 (1.2-4.6) at baseline to 4.0 (1.8-5.09) g/l after RTX (p = 0.001). The use of immunosuppression used at the time of RTX administration was also reduced after RTX therapy (p < 0.001). Baseline serum albumin was lower (p = 0.018), whereas the number of immunosuppressants prior to RTX was higher (p = 0.018) in patients with relapse after RTX. Conclusions: The published data suggest that RTX is effective in reducing the number of relapses and sparing immunosuppression in frequently relapsing and steroid-dependent nephrotic syndrome due to MCD and FSGS. These promising findings have to be confirmed in controlled and prospective studies.

show abstract

“…However, the efficacy of alkylating agents used in steroid-resistant FSGS patients is limited [6]. In contrast, randomized controlled studies have shown that cyclosporine (CsA), a calcineurin inhibitor, is a more effective immunosuppressive agent for the treatment in steroid-dependent or steroid-resistant FSGS patients [7]. …”

Section: Introductionmentioning

confidence: 99%

Tacrolimus versus Cyclophosphamide in Steroid-Dependent or Steroid-Resistant Focal Segmental Glomerulosclerosis: A Randomized Controlled Trial

Ren

Shen

et al. 2013

Am J Nephrol

View full text Add to dashboard Cite

Background: The efficacy and safety of tacrolimus (TAC) and cyclophosphamide (CTX) were prospectively examined in steroid-dependent or steroid-resistant primary focal segmental glomerulosclerosis (FSGS). Methods: Patients with biopsy-proven FSGS were enrolled and randomly divided into two groups: CTX and TAC. Patients treated with CTX (0.5–0.75 g/m²·month, i.v.) received prednisone at 0.8 mg/kg·day, while patients treated with TAC (0.1 mg/kg·day) received prednisone at 0.5 mg/kg·day. The plasma concentration of TAC was monitored and maintained at 5–10 ng/ml. After a 6-month treatment the patients were evaluated. Patients with complete remission (CR) and partial remission (PR) continued the treatment for 12 months with the dose tapered, whereas the patients with no response were excluded from the study and underwent an alternative treatment. Results: A total of 33 patients were recruited and 27 completed the 12-month follow-up. The TAC-treated patients (n = 15) showed a quick remission. The initial remission time averaged 1.23 ± 0.21 versus 2.21 ± 0.77 months in the CTX group (n = 18), but no significant difference was achieved (p > 0.05). At 6 months, the two groups showed a similar outcome. Ten patients from each group showed remission (7 CR and 3 PR). At 12 months, the CTX group had 9 CR and 3 PR while the TAC group had 6 CR and 5 PR. Remission rates in TAC tended to be higher than that in CTX, but there was no difference. CTX patients had a high prevalence of infections (50.0 vs. 13.3% in TAC, p < 0.05). In contrast, TAC-treated patients showed a high incidence of hyperglycemia (26.7 vs. 0.0% in CTX, p < 0.05). Conclusion: These results suggest that CTX and TAC had a similar efficacy in steroid-dependent and steroid-resistant FSGS as manifested by reduced proteinuria, improved serum albumin level and renal function.

show abstract

Long-term follow-up after cyclophosphamide and cyclosporine-A therapy in steroid-dependent and -resistant nephrotic syndrome

Cited by 26 publications

References 33 publications

New therapies in steroid-sensitive and steroid-resistant idiopathic nephrotic syndrome

New therapies in steroid-sensitive and steroid-resistant idiopathic nephrotic syndrome

Rituximab Treatment for Relapsing Minimal Change Disease and Focal Segmental Glomerulosclerosis: A Systematic Review

Tacrolimus versus Cyclophosphamide in Steroid-Dependent or Steroid-Resistant Focal Segmental Glomerulosclerosis: A Randomized Controlled Trial

Contact Info

Product

Resources

About