Clinical trial NCT05588869: Cyclosporine Adverse Outcomes in Steroid Dependent and Frequent Relapsing Nephrotic Syndrome in Children;Single Center Study
Official title: Cyclosporine Adverse Outcomes in Steroid Dependent and Frequent Relapsing Nephrotic Syndrome in Children;Single Center Study
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Steroid Dependent and Frequent Relapsing Nephrotic Syndrome
Lead sponsor: Sohag University
Sponsor class: OTHER
First posted: 2022-10-20
Enrollment: 30
Sex: ALL
Minimum age (years): 1
Maximum age (years): 15
Standard ages: CHILD
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: CROSS_SECTIONAL
Sampling method: PROBABILITY_SAMPLE
Study population: children and adolescents diagnosed as steroid dependent and frequent relapsing nephrotic syndrome with disease onset from one to fifteen years and treated with cyclosporine A in the Paediatric nephrology clinic, Sohag University Hospital

Brief summary: Nephrotic syndrome (NS) is the most common glomerular disorder in children with significant morbidity and mortality and affects about 1-3 per 100,000 children aged below 16 years. Nephrotic syndrome is characterized by the presence of edema, proteinuria: uPCR (urine protein creatinine ratio) ≥200 mg/mmol (≥2 g/g) or 3+ protein on urine dipstick and hypoalbuminemia less than 3 g/dl).Nephrotic syndrome is classified according to response to steroids into steroid sensitive and steroid resistant. Approximately 90% of all cases are steroid-sensitive with an initial episode successfully treated with a standardized treatment protocol of steroids. However, about 80% of these patients experience further relapses. Of these, 50% are steroid dependent and frequent relapsers. While any relapse can be treated with steroids, children may be vulnerable to the side effects of a high cumulative dose of steroids such as obesity, growth impairment, behavioral alterations and attention problems, as well as reduced quality of life and family stress. To minimize steroid toxicity in patients with steroid-dependent and frequently relapsing nephrotic syndrome, a number of immunosuppressive agents are recommended as maintenance therapeutic agents. Among those are cyclosporine A, tacrolimus, mycophenolate mofetil (MMF), cyclophosphamide, levamisole and rituximab. Cyclosporin-A (CsA) is a calcineurin inhibitor that is well recognized as having a steroid sparing effect in steroid-dependent and frequently relapsing NS and has a role in the maintenance of complete remission in more than 75% of patients with SDNS during discontinuation of steroids. However, early withdrawl of cysclosporine may lead to relapses so the patient may be dependent on cyclosporine for years. The long-term use of CsA has been identified to be a risk factor of unsatisfactory effects such as nephrotoxicity, hypertension and cosmetic symptoms such as (gum hypertrophy and hirsutism). Therefore, close observation of the side effects of cyclosporine is very important as well as regular follow up of blood pressure and kidney function tests. Also, estimation of trough blood levels of CsA is required in patients with suspected non compliance, unsatisfactory response or nephrotoxicity (increase in serum creatinine by 30% or more from the baseline) aiming for the lowest levels that maintain remission and avoid toxicity (target 12-hr trough level of 60-150 ng/ml). Kidney biopsy could be included as a component of the long-term CsA protocol to test for CsA-associated nephropathy if given more than 2-3 years. CsA nephrotoxicity is primarily caused by chronic ischemic insult to the kidney, resulting in arteriolar hyalination and tubulointerstitial changes, including striped interstitial fibrosis, tubular vacuolization, and atrophy.The aim of this study is to determine the adverse outcomes of Cyclosporine in children with steroid dependent and frequent relapsing nephrotic syndrome in Sohag University Hospital.


Eligibility criteria: Inclusion Criteria:

* The study will include children and adolescents diagnosed as steroid dependent and frequent relapsing nephrotic syndrome with disease onset from one to fifteen years and treated with cyclosporine A in the Paediatric nephrology clinic, Sohag University Hospital

Primary outcomes:
measure: observation of the side effects of cyclosporine in steroid dependent and frequent relapsing nephrotic syndrome in children
timeFrame: 6 months
Secondary outcomes:
Other outcomes:
Locations:
city: Sohag
country: Egypt
facility: Sohag University Hospital
Study officials:
References:
citation: Kidney Disease: Improving Global Outcomes (KDIGO) Glomerular Diseases Work Group. KDIGO 2021 Clinical Practice Guideline for the Management of Glomerular Diseases. Kidney Int. 2021 Oct;100(4S):S1-S276. doi: 10.1016/j.kint.2021.05.021. No abstract available.
citation: Ehren R, Benz MR, Brinkkotter PT, Dotsch J, Eberl WR, Gellermann J, Hoyer PF, Jordans I, Kamrath C, Kemper MJ, Latta K, Muller D, Oh J, Tonshoff B, Weber S, Weber LT; German Society for Pediatric Nephrology. Pediatric idiopathic steroid-sensitive nephrotic syndrome: diagnosis and therapy -short version of the updated German best practice guideline (S2e) - AWMF register no. 166-001, 6/2020. Pediatr Nephrol. 2021 Oct;36(10):2971-2985. doi: 10.1007/s00467-021-05135-3. Epub 2021 Jun 6.
citation: Kuroyanagi Y, Gotoh Y, Kasahara K, Nagano C, Fujita N, Yamakawa S, Yamamoto M, Takeda A, Uemura O. Effectiveness and nephrotoxicity of a 2-year medium dose of cyclosporine in pediatric patients with steroid-dependent nephrotic syndrome: determination of the need for follow-up kidney biopsy. Clin Exp Nephrol. 2018 Apr;22(2):413-419. doi: 10.1007/s10157-017-1444-3. Epub 2017 Jul 11.
citation: Hampson KJ, Gay ML, Band ME. Pediatric Nephrotic Syndrome: Pharmacologic and Nutrition Management. Nutr Clin Pract. 2021 Apr;36(2):331-343. doi: 10.1002/ncp.10622. Epub 2021 Jan 19.