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  • Title: Treatment of idiopathic nephrotic syndrome with cyclosporine A.
    Author: Meyrier A.
    Journal: J Nephrol; 1997; 10(1):14-24. PubMed ID: 9241620.
    Abstract:
    Cyclosporine A has been empirically used for more than 12 years in the treatment of idiopathic nephrotic syndrome, in both children and adults. There is consistent evidence, from both experimental and human studies, that the highly lipophilic cyclosporine molecule diminishes or abolishes proteinuria by two differing mechanisms. The first is its immunosuppressive action, which is presumably directed toward secretion of a glomerular permeability factor. The second appears to be a non-immunologic effect on glomerular permselectivity, explaining reduced proteinuria in various etiologies of nephrotic syndrome with no immunologic background. The success rate for inducing remission of idiopathic nephrotic syndrome is highest in steroid-dependent forms, essentially observed in minimal change disease where complete remission is achieved in 75% of cases. It is lowest in steroid-resistant idiopathic nephrotic syndrome, especially when accompanied with lesions of focal segmental glomerulosclerosis, with a success rate in the order of 20% complete remission and 25% partial remission. The initial dosage in adults should not exceed 5.5 mg/kg/day which was shown to be the cut-off level of toxicity in renal biopsy-based studies. It is slightly higher in children, and some studies suggest that high serum cholesterol levels should allow higher dosages for increased remission rates without additional toxicity. Long-term treatment of INS requires serial monitoring of renal function with drug dosage reduction when serum creatinine rises by 30% over baseline, and it is recommended to carry out renal biopsy after 1 to 2 years of treatment to verify the absence of interstitial fibrosis even though renal function tests are apparently stable. Renal insufficiency and/or severe hypertension complicate treatment in approximately 10% of cases, essentially in FSG, in which the development of the primary renal disease, which is not controlled by CsA, is additive to the nephrotoxic potential of the drug. Cyclosporine dependency is the rule during the first year of treatment. However, in a meaningful number of cases, tapering CsA dosage to a stop or to a low maintenance dosage is compatible with stable remission without risk of nephrotoxicity. Therefore, cyclosporine, the main advantage of which is its corticosteroid-sparing effect, appears to be a significant advance in the treatment of idiopathic nephrotic syndrome.
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