Conversion to sirolimus in pediatric renal transplant patients: A single‐center experience

Abstract

We studied efficacy and safety of conversion from CNI- to SRL-based immunosuppression in 92 kidney TX recipients, mainly due to CAN (69%). Median time of conversion was 31 months (r: 0.3-165); median time of follow-up: 36 months (r: 2-102). In the whole group mean eGFR increased from 53 ± 22 to 67 ± 26mL/min/1.73 m(2) at three months (p = 0.02) and did not change subsequently. Patients with grade I CAN had higher eGFR than those with grade II CAN. Patient and graft survival was 96% and 70% 10 yr after conversion. Patients with grade I CAN had better graft survival than those with grade II CAN: 89% vs. 65% at six yr (p = 0.02) post conversion. There were two episodes of BPAR. Baseline proteinuria >20 mg/kg/day (HR: 10) and baseline eGFR <50 mL/min/1.73 m(2) (HR: 8) were independent predictors of graft loss. Sixty-seven of 92 subjects had ≥1 AEs: diarrhea (n = 52), urinary tract infections (n = 35), and lower respiratory tract infections (n = 12) were the most frequent. Patients with >2 AEs had SRL blood levels >9 ng/mL at month 3 (p = 0.01). In conclusion, patients converted from CNI to SRL had good graft survival and tolerable but frequent AEs. Independent predictors of graft loss were baseline proteinuria and eGFR.

Growing experience with mTOR inhibitors in pediatric solid organ transplantation

“…Retrospective single‐center studies in which maintenance pediatric kidney transplant patients have been switched from a standard CNI regimen to an mTOR inhibitor with low‐dose CNI therapy or, more frequently, CNI‐free immunosuppression after introduction of everolimus or sirolimus have indicated that rejection is prevented effectively after conversion, but have generally included no more than 30 patients. Two prospective trials have evaluated conversion of patients from standard‐exposure CNI to sirolimus with low‐dose CNI or with MMF in a CNI‐free regimen , but although efficacy appeared acceptable, the number of patients and rejection episodes was low, limiting interpretation (Table ).…”

“…in 20 unselected de novo patients who received everolimus with reduced cyclosporine and steroid elimination after six months (mean estimated GFR 71 mL/min/1.73 m 2 at one yr, 61 mL/min/1.73 m 2 at three yr) . In the maintenance setting, switch from CNI therapy to sirolimus in one prospective and two large retrospective single‐center studies has been shown to improve graft function based on estimated GFR even in patients converted at up to three yr post‐transplant , although no benefit vs. MMF therapy was seen in a randomized trial of 20 patients followed for two yr .…”

Can withdrawal of CNIs limit the progression of CAN?

“…The study in this issue of Pediatric Transplantation (8) is important in several aspects: (i) in this large cohort of pediatric kidney transplant patients, with biopsy‐proven grade 1 CAN, glomerular filtration rate (GFR) increased and proteinuria did not change following conversion from CNIs to SRL, (ii) lower GFR and higher levels of proteinuria were predictors of graft loss after conversion, (iii) the rate of acute rejection episodes was low, and (iv) side effects were frequent but mostly mild.…”