Cyclosporin A Therapy in Childhood Nephrotic Syndrome

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

Study Overview

• Status: Unknown
• Conditions: Steroid Dependent and Steroid Resistent Nephrotic Syndrome
• Intervention / Treatment: Diagnostic test: serum protein ,kidney function ,liver function.,serum cholesterol

Detailed Description

. 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.

• Study Type: Observational
• Enrollment (Anticipated): 50

Contacts and Locations

• Study Contact: Name: Muhammed Mahrous, MD; Phone Number: 01003486595; Email: eltellawy270@hotmail.com
• Study Contact Backup: Name: Ahlam Badawy; Phone Number: 01006807866; Email: dr.ahlam_ali@yahoo.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 18 years (Child, Adult)
• Accepts Healthy Volunteers: N/A
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

children from the age of one year to the age of 18 year who are diagnosed as steroid resistent and steroid dependent nephrotic syndrome and on cyclosporin therapy

Description

Inclusion Criteria:

• The study will include all children (on cyclosporine therapy for treatment of Steroid dependent or Steroid resistant nephrotic syndrome ) who present to Nephrology Unit , and clinic at Assiut University Children Hospital during one year duration.

Exclusion Criteria:

• children with adequate response to steroid therapy and without relapses or resistance to steroid therapy

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Cross-Sectional

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
evaluation of nephrotic state of each patient for evaluation of efficacy of cyclosporin A therapy	measurment of serum albumin ,serum cholesterol and urinary protien excretion	one year
evaluation of side effects of cyclosporin A	serial observation of common side effects of cyclosporin A as hypertension, nephrotoxicity hypertrichosis, gum hyperplasia, gastrointestinal disturbances and tremor.	one year

Collaborators and Investigators

• Sponsor: Assiut University

Study record dates

Study Major Dates

• Study Start (Anticipated): April 1, 2018
• Primary Completion (Anticipated): April 1, 2019
• Study Completion (Anticipated): August 1, 2019

Study Registration Dates

• First Submitted: July 11, 2017
• First Submitted That Met QC Criteria: July 13, 2017
• First Posted (Actual): July 17, 2017

Study Record Updates

• Last Update Posted (Actual): July 17, 2017
• Last Update Submitted That Met QC Criteria: July 13, 2017
• Last Verified: July 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Kidney Diseases; Urologic Diseases; Disease; Syndrome; Nephrotic Syndrome; Nephrosis
• Other Study ID Numbers: DSESCSDSRNS

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No