Kidney Diseases
Conditions
Keywords
Pediatric renal transplantation,Bone metabolism (DXA-pQCT), mRNAFOXP3/IL-17,Steroid withdrawal
Brief 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
Interventions
DRUGTacrolimus (TAC)+ Mycophenolate Mofetil (MMF) + Withdrawal Prednisone
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
DRUGTacrolimus (TAC)+ Mycophenolate Mofetil (MMF) + prednisolone
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
Sponsors
Fondo Nacional de Desarrollo Científico y Tecnológico, Chile
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
1 Years to 16 Years
Healthy volunteers
No
Inclusion criteria
* Age \< 16.0 years * Bone age of boys \< 15 years, of girls \< 13 years * Prepuberal Tanner Status I * First or second kidney transplant, living or deceased kidney donation * Immunosuppression with Tacrolimus (TAC),Mycophenolate mofetil (MMF) * Patients and parents, respectively, have given their written consent after enlightenment (informed consent)
Exclusion criteria
* Irreversible rejection of former transplant * Highly reactive (\> 30%) lymphocytotoxic antibodies within 12 months prior to transplantation * Suspected insufficient medication compliance in dialysis * Patients receiving a basic immunosuppression other than that prescribed in this protocol * Simultaneous therapy with growth hormone after renal transplant
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Stimulation of Growth After 12 Months (Delta Z-score) | 12 months |
Secondary
| Measure | Time frame |
|---|---|
| Growth-factors (IGF-I, IGFBP-3) Bone Metabolism (FA, Ca/Cru, CaxP, 25(OH)VitD, FGF23, Klotho, PTH, DXA, pQCT) Insulin-sensitivity by ISI Method. Molecular Markers - Acute Rejection (FOXP3/IL-17). Acute Rejection Incidence/Protocol Renal Biopsy | 12 months |
Countries
Chile
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| A: Withdrawal Steroids Arms A: TAC + 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
Tacrolimus (TAC)+ Mycophenolate Mofetil (MMF) + Withdrawal Prednisone: 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 | 12 |
| B: Control Steroids Arms B: TAC + 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
Tacrolimus (TAC)+ Mycophenolate Mofetil (MMF) + prednisolone: 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 | 12 |
| Total | 24 |
Baseline characteristics
| Characteristic | A: Withdrawal Steroids | B: Control Steroids | Total |
|---|---|---|---|
| Age, Continuous | 6.0 years STANDARD_DEVIATION 3.3 | 6.9 years STANDARD_DEVIATION 3.9 | 6.5 years STANDARD_DEVIATION 3.6 |
| Height Z-score | -2.5 units on a scale STANDARD_DEVIATION 1 | -2.0 units on a scale STANDARD_DEVIATION 1.2 | -2.3 units on a scale STANDARD_DEVIATION 1.1 |
| Region of Enrollment Chile | 12 participants | 12 participants | 24 participants |
| Sex: Female, Male Female | 6 Participants | 4 Participants | 10 Participants |
| Sex: Female, Male Male | 6 Participants | 8 Participants | 14 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 12 | 0 / 12 |
| serious Total, serious adverse events | 0 / 12 | 0 / 12 |
Outcome results
Primary
Stimulation of Growth After 12 Months (Delta Z-score)
Time frame: 12 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| A: Withdrawal Steroids | Stimulation of Growth After 12 Months (Delta Z-score) | 1.2 units on a scale | Standard Deviation 0.2 |
| B: Control Steroids | Stimulation of Growth After 12 Months (Delta Z-score) | 0.6 units on a scale | Standard Deviation 0.1 |
Secondary
Growth-factors (IGF-I, IGFBP-3) Bone Metabolism (FA, Ca/Cru, CaxP, 25(OH)VitD, FGF23, Klotho, PTH, DXA, pQCT) Insulin-sensitivity by ISI Method. Molecular Markers - Acute Rejection (FOXP3/IL-17). Acute Rejection Incidence/Protocol Renal Biopsy
Time frame: 12 months