De novoTherapy with Everolimus, Low‐Dose Ciclosporine A, Basiliximab and Steroid Elimination in Pediatric Kidney Transplantation

Abstract

The number of acute rejections and infections after pediatric kidney transplantation (KTX) could not be reduced in the last years. To reduce these events, we investigated a new immunosuppressive protocol in a prospective trial. After KTX, 20 children (median age 12 years, range 1-17) were initially treated with Basiliximab, ciclosporine A (CsA) (trough-level = C0 200-250 ng/mL) and prednisolone. After 2 weeks, CsA dose was reduced to 50% (C0 75-100 ng/mL, after 6 months: 50-75 ng/mL) and everolimus (1.6 mg/m 2 /day) was started (C0 3-6 ng/mL). Six months after KTX prednisolone was set to alternate dose and stopped 3 months later. All 20 protocol biopsies 6 months after KTX showed no acute rejection or borderline findings. Indication biopsies resulted in no acute rejections and two borderline findings. Mean glomerular filtration rate (GFR) 1 year after KTX was 71 ± 25 mL/min/ 1.73 m 2 . Without cytomegalovirus (CMV)-prophylaxis, only two primary CMV infections were seen despite a donor/recipient-CMV-constellation pos./neg. in 10/ 20 children. In pediatric KTX, de novo immunosuppression with low-dose CsA, everolimus and steroid withdrawal after 9 months led to promising results according to numbers of acute rejections and infections. Further follow up is needed. Future larger trials will have to confirm our findings.

Pediatric Kidney Transplantation Followed by De Novo Therapy With Everolimus, Low-Dose Cyclosporine A, and Steroid Elimination: 3-Year Data

“…However, this is in opposition to results from another randomized trial in which wound healing problems were not observed when everolimus was introduced 5-week post-KTX (22). Other side effects observed in this study were generally limited to aphthae, which seldom required treatment (6). In contrast to previous studies that did not include treatment with mTOR inhibitors, the levels of proteinuria and hyperlipidemia were not increased after everolimus treatment.…”

“…As administered in this study, everolimus did seem to inhibit wound healing after post-KTX surgery (6). However, this is in opposition to results from another randomized trial in which wound healing problems were not observed when everolimus was introduced 5-week post-KTX (22).…”

“…We recently reported the results from the 12-month follow-up of a prospective trial investigating de novo therapy with basiliximab, CsA, and steroids, followed by treatment with everolimus and low-dose CsA combined with discontinuation of steroids 9 months post-KTX in children (basiliximab/ everolimus/low-dose CsA) (6). The inclusion of basiliximab induction allowed us to decrease the CsA dose by 50% at 2-week post-KTX and to introduce everolimus at a dose normally used in pediatric long-term transplant patients.…”

Long-Term Everolimus Treatment in Individuals With Tuberous Sclerosis Complex: A Review of the Current Literature

“…Use of everolimus for up to 11 years in pediatric transplant patients has also not been associated with any growth disturbances or impact on sexual maturation. 73,74 Metabolic disturbances Lipid abnormalities (including hypercholesterolemia, hyperlipidemia, and hypertriglyceridemia) may be common with everolimus treatment. 47,71 In TSC patients treated with sirolimus and everolimus, dyslipidemia occurred in 11%-50% of patients.…”

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“…32 At 2 weeks after transplant, cyclosporine doses were reduced by 50% (to trough levels of 75-100 ng/mL) and to 50 to 75 ng/mL after 6 months, with everolimus started at 1.6 mg/m²/day and targeted trough levels of 3 to 6 ng/mL. At 6 months after kidney transplant, prednisone was given on alternate days and then stopped 3 months later.…”