Steroid Withdrawal in Pediatric Renal Transplant: Impact on Growth, Bone Metabolism and Acute Rejection
Condition: Kidney Diseases
MeSH terms: Kidney Diseases
Study type: Interventional
Phase: Phase 3

Summary: 
      The present study investigates the safety and efficacy of steroid withdrawal at six days
      post-transplant in pediatric renal recipients under concomitant immunosuppression based on
      antibodies anti IL2 (interleukin 2), Tacrolimus (TAC) and Mycophenolate Mofetil (MMF). To
      investigate the impact of this protocol in growth, bone metabolism, insulin- sensitivity and
      evaluate the expression of IL17 (interleukin 17) and mRNA FOXP3 (messenger ribonucleic acid
      forkhead box protein 3) as early markers of acute rejection (blood, urine and renal biopsy).

      Hypothesis:Steroid withdrawal in renal pediatric transplant patients improves growth and bone
      metabolism without increasing the risk of acute rejection. The expression of FoxP3/IL17 in
      urine cells could be an early molecular markers of acute rejection.
    

Detailed description: 
      The intention of this investigation is to evaluate a prospective immunosuppressive protocol
      based on antibodies anti IL-2 (Ac-IL-2), Tacrolimus (TAC) and Mycophenolate Mofetil (MMF)and
      withdrawal steroids in renal transplant and to compare with a steroid-based protocol.

      Objectives:

        1. To evaluate growth and the impairment in the GH/IGF (growth hormone/insulin like growth
           factor) axis

        2. To determine the impact of steroids on bone metabolism (biochemical parameters, DXA and
           pQCT)

        3. To determine the steroid effect on metabolic factors (dyslipidemia, insulin- sensitivity
           and arterial hypertension)

        4. To determine acute rejection incidence (protocol renal biopsy)

        5. To evaluate the expression of IL-17 and mRNA FoxP3 as early markers of acute rejection
           (blood, urine and renal biopsy).

      Two treatment regimes (Arms)will be compared in randomized form in the course of 12 months
      after transplantation.

      Arm A: TAC + MMF + withdrawal of steroids over a six-days following randomization.

      Arm B: TAC + MMF + prednisolone (see schedule)/day
    

Intervention name(s): Tacrolimus (TAC)+ Mycophenolate Mofetil (MMF) + Withdrawal Prednisone; Tacrolimus (TAC)+ Mycophenolate Mofetil (MMF) + prednisolone
Intervention type(s): Drug; Drug
Intervention description(s): Arms A: Tacrolimus (TAC)+ Mycophenolate Mofetil (MMF) + withdrawal steroids over a six-days following randomization.
1°day: Methylprednisolone iv, 2-3 mg/kg/d 3 doses
2ºday: Methylprednisolone iv, 2-3 mg/kg/d 3 doses
3°day: Prednisone 2 mg/kg/d in 2 doses
4ºday: Prednisone 1 mg/kg/d in 2 doses
5ºday: Prednisone 0.5 mg/kg/d in 2 doses
6ºday: Prednisone 0.25 mg/kg/d in 2 doses
7ºday: Stop Prednisone; Arms B: Tacrolimus (TAC)+ Mycophenolate Mofetil (MMF) + prednisolone (see schedule)/day
10°days after Tx: 2 mg/kg/d
Day 11 - 20: 1 mg/kg/d
Day 21 - 30: 0.5 mg/kg/d
Day 31 - 60: 0.3 mg/k/d
Week 8 - 12: 0.25 mg/k/d
Week 12 - 16: 0.20 mg/k/d
Week 16 - 20: 0.15 mg/k/d
Month 6 - 12: 0.10 - 0.12 mg/k/d
Intervention MeSH terms: Mycophenolic Acid; Prednisone; Prednisolone; Tacrolimus
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Pediatric renal transplantation,Bone metabolism (DXA-pQCT); mRNAFOXP3/IL-17,Steroid withdrawal