Description of the Cystatin C as an Early Nephrotoxic Bio-marker in Pediatric Oncology

Study Overview
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Brief Summary
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Cisplatin and ifosfamide are commonly used drugs in chemotherapy. They are known to involve renal toxic threats in children given their immature kidney. This toxicity is increased especially after nephrectomy and/or concomitant radiotherapy. In pediatric oncology, the available evaluation methods of the renal function could be very restrictive to perform on children. In this study, the investigators intend to test the use of the cystatin C as an effective and reliable biological marker of renal toxicity in children treated with cisplatin and / or ifosfamide.

Detailed Description
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Cisplatin and ifosfamide are commonly used drugs in chemotherapy. They are known to involve renal toxic threats in children given their immature kidney. This toxicity is increased especially after nephrectomy and/or concomitant radiotherapy. In pediatric oncology, the evaluation of the renal function is carried out according to the clinical trial protocols and to the center practices. To date, the standard methods (eg. creatinine clearance), as well as the available predictive formula (eg. Schwartz formula) are not well adapted to monitor children renal function. Indeed, the reliability of these methods depends on several parameters such as the diet and the muscle mass and could be very restrictive to perform on children. To circumvent these practical difficulties, the investigators intend to use the cystatin C as a biological marker of renal toxicity in children treated with cisplatin and / or ifosfamide. This cysteine protease has witnessed an upsurge of interest as an endogenous glomerular filtration rate marker and could be a good candidate to assess tubular toxicity when measured in urine. This study aims to describe the kinetic of the appearance of the urinary cystatin C and explore its proprieties as an early and cost-effective marker for glomerular and tubular renal toxicity in children. In addition, this method could allow enhancing the calculation models routinely used for glomerular filtration rate.

Official Title
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Assessment of Cystatin C as a Tubular and Glomerular Marker of Nephrotoxicity in Pediatric Oncology

Conditions
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Kidney Diseases

Intervention / Treatment
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* Dietary Supplement: Urinary and blood sample for Cystatine dosage


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Children of 0 to18 years treated with cisplatin and / or ifosfamide in the hematology-oncology unit of Toulouse University Hospital of children regardless to the pathology they have been treated for Children with more than 4kg Written informed consent given by both parents or legal representative Patient covered by a social security agreement Exclusion Criteria: Impossibility to monitor and follow up the patient until the foreseeable end of the treatment (geographic reasons, etc.) Contraindication to EDTA clearance performing

Ages Eligible for Study
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Maximum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Urinary and blood sample<br>Urinary and blood samples for cystatin C dosage | Dietary Supplement: Urinary and blood sample for Cystatine dosage<br>* Urinary and blood cystatin C are sampled in patient with nephrotoxic risks before the treatment beginning, after the first course of chemotherapy, in the middle and at the end of the treatment. A follow up assessment is also required at 2 and 5 years. The cystatin C measurements are compared to traditional nephrology markers. Their sampling requires additional blood and urinary collection but involve minimal risks for patient.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Urinary cystatin C rate |  | 1 month | 
| Urinary cystatin C rate | at T2a and T2b (at the middle of treatment). It can depend on pathology | 6 months | 
| Urinary cystatin C rate | at T3 (at the end of treatment)It can depend on pathology | 1 year | 
| Urinary cystatin C rate |  | 2 years | 
| Urinary cystatin C rate |  | 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sensibility, specificity and positive predictive value for urinary CysC | CysC is positive when it is detectable in urine, i.e when one or more reference biomarkers are positive | 5 years | 
| Predictive value for Glomerular Filtration Rate with blood rate of CysC (with Bouvet calculation method) |  | 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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kidney toxicity