PEDIATRICS

P.D. Acott, P.A. O'regan, A.O. Skotnicki, J.F.S. Crocker
Pediatric Nephrology, IWK Health Center, Halifax/NS/CANADA

Body: Introduction: Pediatric renal transplantation has made significant improvements in 1^st year allograft survival but chronic interstitial fibrosis / tubular atrophy (IF/TA) is a major contributor to late allograft decline and loss. Sirolimus (SRL) has been promoted as a calcineurin inhibitor (CNI) sparing or replacement strategy with variable outcomes. This study evaluates the first 24 months pediatric patients with biopsy evidence of IF/TA and loss of glomerular filtration measured by 24 hr urine creatinine clearance (CrCl) that were converted from CNIs to SRL. Data is presented as mean ± SE. Statistical assessment was paried T-test relative to baseline. Methods: Fourteen children (8 female; 6 male; 9 LD; 5 DD) all had biopsy proven IF/TA and reduced CrCl = 36.0 ± 3.0 ml/min/1.73 m² at point of conversion to SRL. The patients (age= 9.3 ± 1.6 yr) were 3.1 ± 0.7 yr post renal transplant and their baseline immunosuppressant therapy prior to conversion to SRL consisted of CNI (Cyclosporin A = 13; FK506 = 1), Cellcept or Myfortic, and alternate day prednisone. SRL dosing was altered to achieve SRL drug levels 5 to 15 mcg/ml. Follow-up included laboratory data (monthly), CrCl (3, 12 & 24 month), and renal biopsies (3 & 12 months) to exclude sub-clinical rejection. Results: No child had biopsy evidence of sub-clinical rejection (3 & 12 month post conversion) and stabilization of CrCl (ml/min/1.73 m²) with trend to improvement (baseline CrCl = 36.0 ± 3.0; 3 month CrCl = 40.8 ± 4.2 [p = 0.404]; 12 month CrCl = 42.6 ± 4.8 [p=0.286]; 24 month CrCl = 43.2 ± 5.4 [p=0.320]). Potential SRL related side effects included vulvar ulceration (n=1); necrotizing pneumonitis (n=2); and progressive anemia requiring blood transfusion and/or erythropoietin (n=4). Baseline hemoglobin levels (g/l) (91.9 ± 4.2) initially reduced at 3 months (79.2 ± 3.7 [p=0.107]) but were above baseline at 12 months (95.9 ± 4.2 [p=0.285]) and 24 months (104.0 ± 2.8 [p=0.018]). No child had to be taken off SRL and there was a single allograft loss during the observation period related to chronic ureteric obstruction. Conclusions: This is the first Sirolimus conversion study documenting no increase of sub-clinical rejection in the first year post cessation of CNI therapy. In pediatric patients with renal biopsy established IF/TA with reduced CrCl, serious SRL side effects were infrequent and amenable to SRL dose reduction and medical management. Conversion from CNIs to SRL in pediatric renal transplant recipients with biopsy proven CAN is well tolerated with improved renal function and no increased risk of rejection.

Disclosure: All authors have declared no conflicts of interest.