Steroid Dependent and Steroid Resistent Nephrotic Syndrome Clinical Trial
Official title:
A Descriptive Study on the Effectiveness and Safety of Cyclosporin A Therapy in Steroid Dependent and Steroid Resistant Childhood Nephrotic Syndrome
Nephrotic syndrome (NS) is among the most common pediatric kidney diseases and is defined as massive proteinuria (>40 mg/m2/h or urine protein to creatinine ratio >2 g/g) leading to hypoalbuminemia (<2.5 g/dL), edema, and hyperlipidemia. 60-70 % of patients present prior to age of 6 years
. Most children with NS are treated initially with oral corticosteroids, and they can be
clinically classified based on their ability to achieve remission (i.e., complete
normalization of proteinuria). Approximately 85 % of children under the age of 6 years are
steroid-sensitive, whereas the remainder have steroid-resistant disease. Older children are
more likely to have steroid-resistant NS. Children with steroid-resistant disease may have an
underlying genetic cause for NS, and providers should consider genetic testing in this
population, depending on the age of the child . While inherited causes of NS are often
resistant to all therapies, there are reports of complete or partial remission in some
children .
For those children who respond to steroids, the majority will have one or more relapses and
half will have frequently relapsing (≥4 relapses/year) or steroid-dependent (two consecutive
relapses during steroid therapy or within 14 days of stopping steroids). NS Children with
frequently relapsing NS and steroid-dependent NS may have significant side effects from
cumulative corticosteroid therapy so treatment with other agents is often required .
Cyclosporine and tacrolimus are calcineurin inhibitors that are commonly used as
immunosuppressive agents in solid organ transplantation. CNIs are recommended as first-line
therapy for children with steroid-resistant NS and as steroid-sparing agents for children
with frequently relapsing or steroid-dependent NS .Calcineurin inhibitors (CNIs) inhibit
T-cell activation and may be exerting their effect in nephrotic syndrome through this
mechanism.
Alternately, cyclosporine has been shown to directly target the podocyte and stabilize the
actin cytoskeleton responsible for maintaining cell shape(5) .. Although the majority of
studies in nephrotic syndrome have been performed with cyclosporine, tacrolimus appears to be
equally efficacious.
Cyclosporin A therapy is well recognised regarding its steroid sparing effect in steroid
dependant patients and is responsible for maintaining remission in more than 75% of patients
with Steroid dependent nephrotic syndrome even after discontinuation of steroids Furthermore,
it has been shown to be effective in inducing remission in steroid resistant nephrotic
syndrome. However ,Cyclosporin A is associated with a plethora of side effects such as
hypertension, nephrotoxicity hypertrichosis, gum hyperplasia, gastrointestinal disturbances
and tremor.
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