BACKGROUND AND AIMS: This multicenter trial compared immediate-release tacrolimus (IR-T) vs prolonged-release tacrolimus (PR-T) in de novo kidney, liver, and heart transplant recipients aged <16 years. Each formulation had similar pharmacokinetic (PK) profiles. Follow-up efficacy and safety results are reported herein. MATERIALS AND METHODS: Patients, randomized 1:1, received once-daily, PR-T or twice-daily, IR-T within 4 days of surgery. After a 4-week PK assessment, patients continued randomized treatment for 48 additional weeks. At Year 1, efficacy assessments included the number of clinical acute rejections, biopsy-confirmed acute rejection (BCAR) episodes (including severity), patient and graft survival, and efficacy failure (composite of death, graft loss, BCAR, or unknown outcome). Adverse events were assessed throughout. RESULTS: The study included 44 children. At Year 1, mean ± standard deviation tacrolimus trough levels were 6.6 ± 2.2 and 5.4 ± 1.6 ng/mL, and there were 2 and 7 acute rejection episodes in the PR-T and IR-T groups, respectively. No cases of graft loss or death were reported during the study. The overall efficacy failure rate was 18.2% (PR-T n = 1; IR-T n = 7). CONCLUSIONS: In pediatric de novo solid organ recipients, the low incidence of BCAR and low efficacy failure rate suggest that PR-T-based immunosuppression is effective and well tolerated to 1-year post-transplantation.

• Keywords
• calcineurin inhibitor: tacrolimus, heart (allograft) function/dysfunction, immunosuppressant, kidney transplantation: living donor, liver transplantation: living donor,
• MeSH
• Child MeSH
• Immunosuppressive Agents therapeutic use   MeSH
• Humans MeSH
• Survival Rate MeSH
• Adolescent MeSH
• Follow-Up Studies MeSH
• Postoperative Complications drug therapy   etiology   MeSH
• Child, Preschool MeSH
• Graft Survival drug effects   MeSH
• Transplant Recipients statistics & numerical data   MeSH
• Prognosis MeSH
• Graft Rejection drug therapy   etiology   MeSH
• Retrospective Studies MeSH
• Risk Factors MeSH
• Tacrolimus therapeutic use   MeSH
• Organ Transplantation adverse effects   MeSH
• Check Tag
• Child MeSH
• Humans MeSH
• Adolescent MeSH
• Male MeSH
• Child, Preschool MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Clinical Trial, Phase II MeSH
• Multicenter Study MeSH
• Research Support, Non-U.S. Gov't MeSH
• Randomized Controlled Trial MeSH
• Comparative Study MeSH
• Names of Substances
• Immunosuppressive Agents MeSH
• Tacrolimus MeSH

BACKGROUND: Variable effects of steroid minimization strategies on blood pressure in pediatric renal transplant recipients have been reported, but data on the effect of steroid withdrawal on ambulatory blood pressure and circadian blood pressure rhythm have not been published so far. METHODS: In a prospective, randomized, multicenter study on steroid withdrawal in pediatric renal transplant recipients (n = 42) on cyclosporine, mycophenolate mofetil, and methylprednisolone, we performed a substudy in 28 patients, aged 11.2 ± 3.8 years, for whom ambulatory blood pressure monitoring (ABPM) data were available. RESULTS: In the steroid-withdrawal group, the percentage of patients with arterial hypertension, defined as systolic and/or diastolic blood pressure values recorded by ABPM > 1.64 SDS and/or antihypertensive medication, at month 15 was significantly lower (35.7%, p = 0.002) than in controls (92.9%). The need of antihypertensive medication dropped significantly by 61.2% (p < 0.000 vs. control), while in controls, it even rose by 69.3%. One year after steroid withdrawal, no patient exhibited hypertensive blood pressure values above the 95th percentile, compared to 35.7% at baseline (p = 0.014) and to 14.3% of control (p = 0.142). The beneficial impact of steroid withdrawal was especially pronounced for nocturnal blood pressure, leading to a recovered circadian rhythm in 71.4% of patients vs. 14.3% at baseline (p = 0.002), while the percentage of controls with an abnormal circadian rhythm (35.7%) did not change. CONCLUSIONS: Steroid withdrawal in pediatric renal transplant recipients with well-preserved allograft function is associated with less arterial hypertension recorded by ABPM and recovery of circadian blood pressure rhythm by restoration of nocturnal blood pressure dipping.

• Keywords
• Ambulatory blood pressure, Nocturnal blood pressure dipping, Pediatric renal transplantation, Randomized controlled trial, Steroid withdrawal,
• MeSH
• Allografts immunology   physiopathology   MeSH
• Blood Pressure Monitoring, Ambulatory MeSH
• Circadian Rhythm physiology   MeSH
• Cyclosporine administration & dosage   adverse effects   MeSH
• Child MeSH
• Glucocorticoids administration & dosage   adverse effects   MeSH
• Glomerular Filtration Rate physiology   MeSH
• Transplantation, Homologous adverse effects   MeSH
• Hypertension chemically induced   diagnosis   prevention & control   MeSH
• Immunosuppressive Agents administration & dosage   adverse effects   MeSH
• Blood Pressure drug effects   MeSH
• Mycophenolic Acid administration & dosage   adverse effects   MeSH
• Kidney immunology   physiopathology   MeSH
• Humans MeSH
• Methylprednisolone MeSH
• Adolescent MeSH
• Withholding Treatment * MeSH
• Prospective Studies MeSH
• Graft Rejection immunology   physiopathology   prevention & control   MeSH
• Kidney Transplantation adverse effects   MeSH
• Check Tag
• Child MeSH
• Humans MeSH
• Adolescent MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Randomized Controlled Trial MeSH
• Names of Substances
• Cyclosporine MeSH
• Glucocorticoids MeSH
• Immunosuppressive Agents MeSH
• Mycophenolic Acid MeSH
• Methylprednisolone MeSH