Inhibition of Vascular Permeability Factor Production by Ciclosporin in Minimal Change Nephrotic Syndrome

Maruyama, Kei; Tomizawa, Shuichi; Seki, Yusuke; Arai, Hideyuki; Kuroume, Takayoshi

doi:10.1159/000186990

Cited by 24 publications

(10 citation statements)

References 11 publications

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“…It has been shown to decrease proteinuria even in patients who are cyclosporine-resistant even though both these agents are calcineurin inhibitors [24, 44, 45]. Possible explanations include better inhibition of vascular permeability factor in patients with minimal change disease compared to cyclosporine [46, 47] and better cytokine suppression [20]. …”

Section: Discussionmentioning

confidence: 99%

Management of Steroid-Resistant Focal Segmental Glomerulosclerosis in Children Using Tacrolimus

et al. 2006

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Background: The use of tacrolimus in steroid-resistant (SR) focal segmental glomerulosclerosis (FSGS) has been reported in single and small series case reports. Aim: To determine the efficacy of tacrolimus in the management of SR FSGS in children. Study Design: This was a prospective study of 20 children with SR FSGS treated with tacrolimus (0.2–0.4 mg/kg/day in two divided doses over 12 h adjusted to a trough level between 7 and 15 ng/ml) for 12 months in combination with low-dose steroids. Other therapies included angiotensin-converting enzyme inhibitors, folic acid, multivitamins and lipid-lowering agents. Results: The mean age at study entry was 11.1 years (range 5.6–16.8). The mean duration of nephrotic syndrome before initiation of tacrolimus therapy was 4.7 years (range 2.1–7.6). At the end of the treatment period, 8 (40%) children were in complete remission, 9 (45%) were in partial remission, and 3 (15%) failed to respond. The average follow-up period following cessation of tacrolimus treatment was 27.5 months (range 13.7–43.7). At last hospital follow-up, 5 (25%) children were in complete remission, 10 (50%) in partial remission, and 2 (10%) in relapse. Three children died from dialysis-related complications following cessation of tacrolimus treatment. Adverse events included sepsis (2), nausea (2), diarrhea (2), anemia (4) and worsening of hypertension (4). Conclusion: Tacrolimus is a safe and effective treatment for SR FSGS. However, like cyclosporine, some children tend to relapse following cessation of treatment.

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Section: Discussionmentioning

confidence: 99%

Management of Steroid-Resistant Focal Segmental Glomerulosclerosis in Children Using Tacrolimus

et al. 2006

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“…There are some data to suggest that tacrolimus has differing effects on proteinuria in NS compared with cyclosporine [34,35]. Maruyama et al [36,37] also demonstrated better inhibition of the vascular permeability factor cultured from patients with MCD with tacrolimus than with cyclosporine. Tacrolimus also has better cytokine suppression than cyclosporine, which may also influence the differing responses to therapy [24].…”

Section: Discussionmentioning

confidence: 99%

Tacrolimus therapy in pediatric patients with treatment-resistant nephrotic syndrome

Loeffler

Gowrishankar

Yiu

2004

Pediatric Nephrology

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This is a retrospective analysis of 16 children started on tacrolimus with various types of treatment-resistant nephrotic syndrome. There are 13 patients with focal glomerulosclerosis, 1 minimal change disease, and 2 IgA nephropathy with nephrosis. The mean age of the children was 11.4 years (range 3.5-18.1 years) with a mean age at diagnosis of 5.6 years (range 1.6-13.3 years). All patients initially received prednisone 2 mg/kg per day. Other therapies for 15 of 16 included cyclosporine (n=15), chlorambucil (n=5), mycophenolate mofetil (n=5), levamisole (n=3), i.v. methylprednisolone (n=3), and cyclophosphamide (n=2). The major indication for the initiation of tacrolimus included treatment resistance/dependence (n=15) and intolerable side effects from other therapies (n=1). The average time from the diagnosis to initiation of tacrolimus was 5.3 years (range 0.3-13.3 years, median 6 years). The initial dosage of tacrolimus utilized was 0.1 mg/kg per day divided into two doses. The mean follow-up period was 6.5 months (range 2.5-18 months). Thirteen patients (81%) went into a complete remission within an average of 2 months (range 0.5-5.5 months), with 3 patients relapsing while on treatment. Three patients did not respond. Of these, 2 had partial remissions (13%) and 1 failed to respond. Adverse events included anemia (n=1), seizure (n=1), worsening or new-onset hypertension (n=5), and sepsis (n=1). All patients remain on tacrolimus. Tacrolimus is an effective, well-tolerated medication for treatment-resistant forms of nephrotic syndrome in children, with a complete remission rate of 81% and a partial remission rate of 13% (totaling 94%).

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“…This finding suggests that corticosteroids can reduce edemaand prevent angiogenesis in patients with a high serum VEGFlevel. Maruyama et al reported that VEGFprotein production is suppressed by cyclosporin A in vitro (19). Cyclosporin A inhibits the activity of calcineurin in the cell through tyrosine kinase-related signal transduction.…”

Section: Discussionmentioning

confidence: 99%

High Fever, Renal Failure, Disseminated Intravascular Coagulation and Myelodysplasia Accompanied with Enhanced Angiogenesis Possibly due to Overexpression of Vascular Endothelial Growth Factor.

et al. 2000

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A 44-year-old womansuffered from recurrent fever, edema and fatigue. Laboratory data revealed renal dysfunction, low proteinemia, disseminated intravascular coagulation (DIC) and myelodysplasia. A renal and lymph node biopsy showed a marked angiogenesis. Serum levels of vascular endothelial growth factor (VEGF), and interleukin (IL)-6 were markedly increased, suggesting a pathogenesis related to VEGF-inducedangiogenesis. The symptomswere remitted after treatment with cyclosporin A. No evidence of solid tumors, malignant lymphoma, Castleman's disease or POEMS(polyneuropathy, organomegaly, endocrine disorder, M-proteinemia and skin change) syndrome, reported to induce a high serum VEGFlevel, was obtained. This case mayhave involved an unknownmechanismwhich induced an overexpression of VEGFand IL-6.

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Inhibition of Vascular Permeability Factor Production by Ciclosporin in Minimal Change Nephrotic Syndrome

Cited by 24 publications

References 11 publications

Management of Steroid-Resistant Focal Segmental Glomerulosclerosis in Children Using Tacrolimus

Management of Steroid-Resistant Focal Segmental Glomerulosclerosis in Children Using Tacrolimus

Tacrolimus therapy in pediatric patients with treatment-resistant nephrotic syndrome

High Fever, Renal Failure, Disseminated Intravascular Coagulation and Myelodysplasia Accompanied with Enhanced Angiogenesis Possibly due to Overexpression of Vascular Endothelial Growth Factor.

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