title: Improved outcome after 'bottom-up' immunosuppression in liver transplant recipients with preoperative renal impairment.
abstract: BACKGROUND
  Most patients with high MELD scores have impaired renal function prior to transplantation.
  
  
  METHODS
  A retrospective case control study was conducted with initial low immunosuppression, which was increased when patients rejected or were clinically stable beyond day 30 ('bottom-up').
  
  
  RESULTS
  Thirty patients with impaired renal function were included. Fifteen were treated with de novo cyclosporine A (CsA; group A), and 15 had 'bottom-up' immunosuppression (group B). Baseline renal function was similar: serum creatinine (SCr) median 1.8 mg/dl (range: 1.5-4.0 mg/dl; group A) versus 2.4 mg/dl (range: 1.5-4.0 mg/dl; group B; p = 0.24). The requirement for renal replacement therapy was significantly lower in group B (p = 0.032). Ten received 'bottom-up' immunosuppression [4 CsA/1 sirolimus (Sir) 'on demand' after rejection, 5 Sir (stable)] beyond day 30. By months 6 and 12 (1.6 mg/dl vs. 1.2 mg/dl), SCr values were significantly better in group B (p = 0.006). Renal function in group B did not differ between patients receiving CsA or Sir. Overall complication rates, survival and biopsy-proven acute rejection were similar, although BANFF scores were higher in group B (p = 0.004).
  
  
  CONCLUSIONS
  Successful implementation of 'bottom-up' immunosuppression in liver transplant recipients with high lab-MELD scores and renal dysfunction at the time of transplantation has the potential to substantially improve short- and long-term outcomes.
authors.affiliation: Kliniken und Polikliniken für Chirurgie, Universitätsklinikum Regensburg, Regensburg, Germany. schnitzbauer @ klinik.uni-r.de
authors.forename: Andreas A
authors.initials: AA
authors.lastname: Schnitzbauer
authors.forename: Axel
authors.initials: A
authors.lastname: Doenecke
authors.forename: Johannes L
authors.initials: JL
authors.lastname: Sothmann
authors.forename: Martin
authors.initials: M
authors.lastname: Loss
authors.forename: Stefan A
authors.initials: SA
authors.lastname: Farkas
authors.forename: Janine
authors.initials: J
authors.lastname: Hartl
authors.forename: Tung-Yu
authors.initials: TY
authors.lastname: Tsui
authors.forename: Lucia
authors.initials: L
authors.lastname: Baier
authors.forename: Gabriele
authors.initials: G
authors.lastname: Kirchner
authors.forename: Aiman
authors.initials: A
authors.lastname: Obed
authors.forename: Thomas
authors.initials: T
authors.lastname: Bein
authors.forename: Edward K
authors.initials: EK
authors.lastname: Geissler
authors.forename: Marcus N
authors.initials: MN
authors.lastname: Scherer
authors.forename: Hans J
authors.initials: HJ
authors.lastname: Schlitt
mesh_terms: D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D003404:Creatinine / Q000097:blood; D016572:Cyclosporine / Q000008:administration & dosage; D005260:Female; D006801:Humans; D007165:Immunosuppression Therapy / Q000009:adverse effects / Q000379:methods*; D007166:Immunosuppressive Agents / Q000008:administration & dosage; D008107:Liver Diseases / Q000150:complications* / Q000601:surgery*; D016031:Liver Transplantation / Q000276:immunology* / Q000502:physiology; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D051437:Renal Insufficiency / Q000150:complications* / Q000503:physiopathology / Q000628:therapy; D012189:Retrospective Studies; D020123:Sirolimus / Q000008:administration & dosage; D016896:Treatment Outcome
chemical_list: D007166:Immunosuppressive Agents; D016572:Cyclosporine; D003404:Creatinine; D020123:Sirolimus