title: Poor tolerance of sirolimus in a steroid avoidance regimen for renal transplantation.
abstract: Vascular disease and chronic allograft nephropathy have prompted re-evaluation of steroids and calcineurin inhibitors (CNIs) in renal transplantation. Sirolimus (SRL) can facilitate early CNI withdrawal. We report on the Early CNI and Steroid Elimination in Leeds (ECSEL) study, which was terminated early due to poor tolerability of SRL. Basiliximab/methylprednisolone induction was used, then 2 months of tacrolimus (TAC) and mycophenolate mofetil (MMF) treatment. A total of 51 patients were randomized to continue TAC/MMF or switch to SRL/MMF. In ECSEL1, patients were switched at 2 months (n=10). In ECSEL2, SRL was introduced at months 4-6 and TAC was tapered (n=13). Median overall follow up was 701 days. All 10 ECSEL1 and 10 of 13 (77%) ECSEL2 patients discontinued SRL due to adverse events, including leucopenia, rash, mucosal ulceration, arthralgia, and possible pneumonitis. Mean end-of-study creatinine was comparable in all groups. Sirolimus should be used with caution in complete CNI and steroid withdrawal, due to the resultant intolerable adverse event profile.
authors.affiliation: Department of Nephrology, St. James' University Hospital, Leeds, United Kingdom. mattws1@googlemail.com
authors.forename: Matthew P Welberry
authors.initials: MP
authors.lastname: Smith
authors.forename: Chas G
authors.initials: CG
authors.lastname: Newstead
authors.forename: Niaz
authors.initials: N
authors.lastname: Ahmad
authors.forename: Andrew J P
authors.initials: AJ
authors.lastname: Lewington
authors.forename: Stephen
authors.initials: S
authors.lastname: Tibble
authors.forename: J Peter A
authors.initials: JP
authors.lastname: Lodge
authors.forename: Stephen G
authors.initials: SG
authors.lastname: Pollard
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Baker
mesh_terms: D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D000328:Adult; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D000077552:Basiliximab; D004359:Drug Therapy, Combination; D004361:Drug Tolerance; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use; D007674:Kidney Diseases / Q000145:classification / Q000601:surgery; D016030:Kidney Transplantation / Q000276:immunology*; D008297:Male; D008775:Methylprednisolone / Q000627:therapeutic use*; D008875:Middle Aged; D011993:Recombinant Fusion Proteins / Q000627:therapeutic use; D020123:Sirolimus / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D000305:Adrenal Cortex Hormones; D000911:Antibodies, Monoclonal; D007166:Immunosuppressive Agents; D011993:Recombinant Fusion Proteins; D000077552:Basiliximab; D020123:Sirolimus; D008775:Methylprednisolone