Unfavorable response to cyclophosphamide in steroid-dependent nephrotic syndrome

Kemper, Markus J.; Altrogge, H; Ludwig, Kerstin U.; Timmermann, Kirsten; Müller‐Wiefel, D. E.

doi:10.1007/pl00013435

Cited by 42 publications

(30 citation statements)

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“…In the Prasad et al study [19], renal biopsy was only performed for 54% of patients; 36% of them had focal segmental glomerulosclerosis, while all our patients had biopsy-proven MCNS. Additionally, racial and genetic factors may alter the pattern of response to therapy so that the widely variable response rate to oral cyclophosphamide therapy seen in these patients reported in the literature (19%-75% at 1-3 years [19,20,21,22,23,24,25,26,27]) may be extrapolated to intravenous form. Furthermore, the conclusion of the previous two studies [4,19], that the I.V.…”

Section: Discussionmentioning

confidence: 92%

Long-term results of two unconventional agents in steroid-dependent nephrotic children

et al. 2005

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Children with steroid-dependent minimal change nephrotic syndrome are prone to serious steroid side effects. Alternative therapies, such as oral cyclophosphamide, may also have serious side effects. We conducted this novel prospective study to compare the long-term efficacies of levamisole and I.V. pulse cyclophosphamide as therapies with potentially fewer side effects. This study included 40 children with idiopathic steroid-dependent minimal change nephrotic syndrome (age 3-15 years; 31 boys and 9 girls). The patients were randomized into two equal groups. One group received levamisole 2.5 mg/kg on alternate days (levamisole group) while the other group received I.V. cyclophosphamide 500 mg/m2/month for six months (cyclophosphamide group). Prednisolone was gradually withdrawn. After stopping treatment, the number of patients that maintained remission was five (25%) in each group at six months, four (20%) versus two (10%) at one year and three (15%) versus one (5%) at two years in the levamisole and cyclophosphamide groups respectively, and one (5%) in each group at three and four years. The overall side effects were mild and both drugs were well tolerated. In view of the results, we recommend trial of levamisole before adopting other therapies with more serious side effects in such patients.

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Section: Discussionmentioning

confidence: 92%

Long-term results of two unconventional agents in steroid-dependent nephrotic children

et al. 2005

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“…However, the risk of developing malignancy and gonadal toxicity in adolescent children and the poor responsiveness in patients with steroid dependent NS or steroid resistant NS to these agents have limited their use. [12][13][14][15] In an attempt to improve the management of these patients, CsA was first used in 1985 in children with NS. Since then, numerous reports have shown that CsA is effective in children with steroid dependent NS and steroid resistant NS to relieve steroid toxicity and to achieve remission, respectively.…”

Section: Discussionmentioning

confidence: 99%

Independent risk factors for chronic cyclosporine induced nephropathy in children with nephrotic syndrome

Fujinaga

Kaneko²,

Muto³

et al. 2006

Archives of Disease in Childhood

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Background: Cyclosporine A (CsA) has been widely used in children with steroid dependent and steroid resistant nephrotic syndrome (NS) because of its efficacy in relieving these patients from systemic side effects of steroids. However, its long term use is controversial, since chronic CsA induced nephropathy (CsAN) may develop in a considerable number of patients. Aims and Methods: In order to clarify the risk factors for the development of CsAN, the clinical characteristics of children with steroid dependent or steroid resistant NS taking CsA (target blood trough levels 50-150 ng/ml) for more than six months, managed at a single centre, were retrospectively analysed. Results: Thirteen of 30 children (24 boys and 6 girls) taking CsA (mean duration 43 months, range 6-144) had CsAN defined as the presence of CsA associated arteriopathy with or without striped tubulointerstitial lesions. The multivariate analysis revealed that CsA treatment for more than 36 months and an age younger than 5 years at the start of CsA treatment were independent risk factors for the development of CsAN. The univariate analysis also showed that patients with CsAN had more frequent relapses during CsA treatment than those without CsAN. Conclusion: An alternative treatment should be seriously considered after a 36 month administration of CsA in order to prevent CsAN. Data also suggest that CsA treatment in children younger than 5 years should be avoided if possible.

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“…For these patients various therapeutic strategies have been suggested, including other immunosuppressive agents such as tacrolimus [3] or mycophenolate mofetil [4,5], or the immunostimulatory drug levamisole [6]. However, these strategies often fail to maintain complete remission of nephrotic syndrome [7].…”

Section: Introductionmentioning

confidence: 99%

Change of the course of steroid-dependent nephrotic syndrome after rituximab therapy

Benz

Dötsch²,

Rascher

et al. 2004

Pediatric Nephrology

171

139

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A 16-year-old patient with steroid-dependent nephrotic syndrome with more than 35 relapses developed severe relapsing idiopathic thrombocytopenic purpura (ITP). At the age of 2 years, nephrotic syndrome was diagnosed and successfully treated with a standard prednisone regimen. Frequent relapses occurred. Treatment with oral cyclophosphamide followed by cyclosporine was successful, but several attempts to withdraw steroids failed and the patient suffered from multiple relapses. At the age of 12 years, renal biopsy revealed focal segmental glomerulosclerosis and cyclosporine toxicity. A second course of oral cyclophosphamide was unsuccessful and tacrolimus resulted in the development of diabetes mellitus, which was reversed after discontinuation of the drug. At the age of 15 years the patient, still being steroid dependent, developed ITP. Neither steroids nor intravenous immunoglobulins induced permanent remission. Only weekly immunoglobulin infusions could temporarily restore the platelet count. To treat ITP in this desperate situation we decided to deplete B-cells with the monoclonal anti-CD20 antibody rituximab. Intravenous infusions of rituximab (375 mg/m(2)) were given once weekly for 4 consecutive weeks without adverse events. Four weeks after the first rituximab dosage, the thrombocyte count increased to normal values. There has been no subsequent relapse of either thrombocytopenia or nephrotic syndrome (on cyclosporine, without steroids) to date. We conclude that B-cell depletion with rituximab might have altered the course of steroid-dependent nephrotic syndrome in our patient.

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Unfavorable response to cyclophosphamide in steroid-dependent nephrotic syndrome

Cited by 42 publications

References 0 publications

Long-term results of two unconventional agents in steroid-dependent nephrotic children

Long-term results of two unconventional agents in steroid-dependent nephrotic children

Independent risk factors for chronic cyclosporine induced nephropathy in children with nephrotic syndrome

Change of the course of steroid-dependent nephrotic syndrome after rituximab therapy

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