title: Low-dose RATG with or without basiliximab in renal transplantation: a matched-cohort observational study.
abstract: OBJECTIVE
  In renal transplantation, peri-operative low-dose rabbit-antithymocyte-globulin (RATG) plus basiliximab induction prevented acute allograft rejection more effectively than post-operative RATG plus basiliximab induction. We investigated the specific antirejection contribution of basiliximab in this context.
  
  
  METHODS
  This single-center, observational, matched-cohort study evaluated allograft rejections (primary outcome), steroid exposure and side effects, GFR (iohexol plasma clearance) and treatment costs in 16 deceased-donor renal transplant recipients induced with RATG (0.5 mg/kg/day) and 32 age-, gender- and treatment-matched reference-patients given RATG plus basiliximab (20 mg on days 0 and 4).
  
  
  RESULTS
  Induction was well tolerated. At 18 months, 8 patients (50%) vs. 3 reference-patients (9.4%) rejected the graft [HR (95% CI): 6.53 (1.73-24.70), p = 0.006]. Difference was significant (p < 0.01) even after adjusting for recipient/donor age and gender, cold ischemia time and HLA mismatches. There were 1 antibody-mediated rejection and 2 moderate cellular rejections in patients vs. none in reference-patients (p = 0.032). The median (interquartile range) prednisone cumulative dose was remarkably higher in patients than reference-patients [4.78 (1.12-6.10) vs. 0.19 (0.18-3.81) grams, p = 0.002]. Three patients vs. 24 reference-patients were off-steroid at study end (p < 0.001). Three patients vs. no reference-patient developed new-onset diabetes (p = 0.003). Both inductions similarly depleted B-cells. Outcomes of AZA- vs. MMF-treated participants were similar. GFR was similar in all groups. Compared to MMF, AZA therapy saved ≈ EUR 2,500/year and by month 14.3 post-transplant compensated basiliximab costs.
  
  
  CONCLUSIONS
  In renal transplantation, basiliximab plus peri-operative low-dose RATG more efficiently prevented allograft rejection than RATG monotherapy, and minimized steroid exposure and toxicity. AZA- vs MMF-based maintenance immunosuppression largely compensated the extra costs of basiliximab.
authors.affiliation: IRCCS - Istituto di Ricerche Farmacologiche Mario Negri, Clinical Research Center for Rare Diseases 'Aldo e Cele Daccò', Bergamo, Italy.
authors.forename: Giorgio
authors.initials: G
authors.lastname: Gentile
authors.forename: Chiara
authors.initials: C
authors.lastname: Somma
authors.forename: Alessia
authors.initials: A
authors.lastname: Gennarini
authors.forename: Daniela
authors.initials: D
authors.lastname: Mastroluca
authors.forename: Giovanni
authors.initials: G
authors.lastname: Rota
authors.forename: Francesco
authors.initials: F
authors.lastname: Lacanna
authors.forename: Bruno
authors.initials: B
authors.lastname: Locatelli
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Remuzzi
authors.forename: Piero
authors.initials: P
authors.lastname: Ruggenenti
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000009:adverse effects; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000191:economics / Q000627:therapeutic use*; D000961:Antilymphocyte Serum / Q000008:administration & dosage* / Q000009:adverse effects; D001379:Azathioprine / Q000191:economics / Q000627:therapeutic use; D000077552:Basiliximab; D018791:CD4 Lymphocyte Count; D015331:Cohort Studies; D003920:Diabetes Mellitus / Q000209:etiology; D004359:Drug Therapy, Combination; D005260:Female; D005919:Glomerular Filtration Rate; D006084:Graft Rejection / Q000276:immunology / Q000517:prevention & control*; D006801:Humans; D007165:Immunosuppression Therapy / Q000379:methods*; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D060828:Induction Chemotherapy / Q000379:methods; D016030:Kidney Transplantation / Q000009:adverse effects; D060046:Maintenance Chemotherapy / Q000191:economics; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000031:analogs & derivatives / Q000191:economics / Q000627:therapeutic use; D019990:Perioperative Care; D011241:Prednisone / Q000008:administration & dosage / Q000009:adverse effects; D011817:Rabbits; D011993:Recombinant Fusion Proteins / Q000009:adverse effects / Q000191:economics / Q000627:therapeutic use*
chemical_list: D000893:Anti-Inflammatory Agents; D000911:Antibodies, Monoclonal; D000961:Antilymphocyte Serum; D007166:Immunosuppressive Agents; D011993:Recombinant Fusion Proteins; D000077552:Basiliximab; D009173:Mycophenolic Acid; D001379:Azathioprine; D011241:Prednisone