G9(W)
USE OF SIROLIMUS IN PAEDIATRIC RENAL TRANSPLANT
RECIPIENTS
McCulloch, M, Taylor, J, Walsh, G, Koffman, G
Evelina Children’s Hospital, Guy’s & St. Thomas’ NHS Foundation Trust, London
INTRODUCTION: Sirolimus (SRL) has been described as an alternative immunosuppressant agent to calcineurin inhibitors with particular benefit due to reduced nephrotoxicity. Paediatric experience in renal transplant patients is limited to only a few cases per centre.
METHODS : Retrospective folder review of paediatric renal transplant patients on SRL based immunosuppression at a single centre from 2002 -2009 auditing demographics, reason for switch to SRL, dosing and levels, length of time on SRL and complications, reasons for subsequent discontinuation of SRL and renal outcome.
RESULTS: Twenty-one paediatric renal transplant recipients. Gender: M: F 14:7.
Age at time of SRL commencement 3.5-16.2 years (mean 8.9 years, median 7.8 years)
Deceased donor: Live related donor: 13:8. De novo use of SRL: 5 %( 1/21) only.
Reasons for switch: rejection (both cellular and vascular), calcineurin toxicity including seizures, chronic allograft nephropathy, glucose intolerance and gingival hypertrophy.
Patients were loaded with Sirolimus for 3 days at 3mg/m
2 bd and then 3mg/ m
2 daily with dose adjustment according to levels. In patients under 7 years, a twice-daily dosing regime was continued.
Side effects included less bone marrow suppression (only Hb lowered but no effect on white cells or platelets) than described in adults. Lipid studies showed raised cholesterol requiring statins in 48 %( 10/21) patients. Infections were a frequent complication especially when SRL levels > 8ug/l – bacterial specifically skin 29 %( 6/21), recurrent
UTI’s 19 %( 4/21), mouth ulcers 10 %( 2/21) and chest infections 19 %( 4/21). Viral infections also a problem – EBV, CMV, Shingles, Herpes all seen. Surgical complications - only 1 lymphocoele.
Renal complications were significant, including haematuria 43%(9/21), proteinuria
38%(8/21) and thrombotic microangiopathy 5%(1/21). Period of time on SRL 0.2-6.5 years (mean 2.8 years) with levels of 3.6-14.2 ug/l (mean 8.9) before this drug was stopped as a result of renal problems in 10/21. The remaining group 52 %( 11/21) remain on SRL for a mean of 3.5 years with levels between 2.5-10ug/l (mean 4.8), stable renal function and non-active urine findings.
CONCLUSION: In the biggest series in paediatric renal transplants using SRL in UK, we found SRL useful in rejection (both vascular and steroid resistant), provided the GFR was still well maintained and haematuria or proteinuria did not develop. Infections are a significant problem and aiming for lower drug levels in range of 4-7ug/l is recommended.
Sirolimus is useful provided there is careful monitoring of urine, adequate GFR and low dosing.