NDT Advance Access originally published online on November 25, 2005
Nephrology Dialysis Transplantation 2006 21(7):1848-1854; doi:10.1093/ndt/gfi274
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© The Author [2005]. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org
Original Articles: Clinical Nephrology
Treatment of severe steroid-dependent nephrotic syndrome (SDNS) in children with tacrolimus
Department of Paediatric Nephrology, Room 64, Sky Level, Evelina Children's Hospital, Guys & St Thomas NHS Foundation Trust, London SE1 7EH, UK
Correspondence and offprint requests to: Dr Manish D. Sinha, Department of Paediatric Nephrology, Guys & St Thomas NHS Foundation Trust, London SE1 7EH, UK. Email: manish.sinha{at}gstt.nhs.uk
Background. Severe steroid-dependent nephrotic syndrome (SDNS) is a common type of nephrotic syndrome (NS) observed in childhood. Steroid-sparing agents such as calcineurin inhibitors (CNIs) are used to avoid steroid toxicity in SDNS. Tacrolimus (TAC) has been prescribed for maintaining remission of NS in patients who have developed treatment resistance or adverse effects with cyclosporin A (CYA) at our institution since 1995. The aim of this study was to compare the efficacy and complications of TAC with CYA in the management of severe SDNS.
Methods. We report a retrospective longitudinal clinical series of patients with SDNS, all of whom have been treated with TAC.
Results. Ten SDNS children (eight males) were reviewed quarterly from time of initial referral to the present day during 93 completed treatment patient years. Nine patients had minimal change disease and one had focal segmental glomerulosclerosis on their first biopsy. The median age at diagnosis was 2.9 years (range 1.6–12.9). The median age at initial referral was 3.9 years (range 2.2–12.9). All patients initially responded to prednisolone at 60 mg/m2/day, and subsequent frequent relapses were treated sequentially with oral cyclophosphamide 168 mg/kg over 8–12 weeks (n = 10), CYA (n = 10), intravenous mustine or a second course of cyclophosphamide (n = 7) and then TAC (n = 10). The initial daily treatment of CYA and TAC in two divided doses was 5 and 0.1 mg/kg/day, respectively; targeted 12 h blood drug levels were of 50–100 µg/l for CYA and 5–10 µg/l for TAC. Patients underwent renal biopsy and the formal glomerular filtration rate (GFR) was measured using plasma clearance of the Inutest® method every 2–3 years while receiving CNIs. Six patients continued with TAC; in four patients, TAC was discontinued because of poor response (n = 2), hypertension (n = 1) and glucose intolerance (n = 1). For CYA and TAC treatment periods, the median NS relapse rate was two and one relapses per year, respectively, and cumulative steroid dosage was 73.9 and 105.2 mg/kg/day, respectively (P = 0.54). The reduction in GFR was 5.8 and 11.7 ml/min/1.73 m2 during these periods. Three of the 10 patients showed histological evidence of mild CNI nephrotoxicity over the whole of the CNI treatment period despite achieving target therapeutic drug levels; no significant change in measured or calculated GFR over this prolonged CNI therapy was observed. Antihypertensive medication was prescribed for 11 of 31 CYA and 22 of 40 TAC treatment years. Growth was maintained during the entire CNI therapy period with median change in height SD scores (SDS) of +0.37 and –0.03 over CYA and TAC, respectively (P = 0.13).
Conclusion. In conclusion, we observed that the replacement of CYA by TAC does not lead to a better management of severe SDNS.
Keywords: calcineurin inhibitors; children; cyclosporin A; nephrotic syndrome; steroid dependency; tacrolimus
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