title: Risk Stratification for Rejection and Infection after Kidney Transplantation.
abstract: OBJECTIVE
  Definition of individual risk profile is the first step to implement strategies to keep the delicate balance between under- and overimmunosuppression after kidney transplantation.
  
  
  METHODS
  We used data from the Efficacy Limiting Toxicity Elimination Symphony Study (1190 patients between 2002 and 2004) to model risk of rejection and infection in the first year after kidney transplantation. External validation was performed in a study population from the Fixed-Dose Concentration-Controlled Trial (630 patients between 2003 and 2006).
  
  
  RESULTS
  Despite different temporal dynamics, rejections and severe infections had similar overall incidences in the first year after transplantation (23.4% and 25.5%, respectively), and infections were the principal cause of death (43.2% of all deaths). Recipient older age, deceased donor, higher number of HLA mismatches, and high risk for cytomegalovirus disease were associated with infection; deceased donor, higher number of HLA mismatches, and immunosuppressive therapy including cyclosporin A (compared with tacrolimus), with rejection. These factors were integrated into a two-dimensional risk stratification model, which defined four risk groups: low risk for infection and rejection (30.8%), isolated risk for rejection (36.1%), isolated risk for infection (7.0%), and high risk for infection and rejection (26.1%). In internal validation, this model significantly discriminated the subgroups in terms of composite end point (low risk for infection/rejection, 24.4%; isolated risk for rejection and isolated risk for infection, 31.3%; high risk for infection/rejection, 54.4%; P<0.001), rejection episodes (isolated risk for infection and low risk for infection/rejection, 13.0%; isolated risk for rejection and high risk for infection/rejection, 24.2%; P=0.001), and infection episodes (low risk for infection/rejection and isolated risk for rejection, 12.0%; isolated risk for infection and high risk for infection/rejection, 37.6%; P<0.001). External validation confirmed the applicability of the model to an independent cohort.
  
  
  CONCLUSIONS
  We propose a two-dimensional risk stratification model able to disentangle the individual risk for rejection and infection in the first year after kidney transplantation. This concept can be applied to implement a personalized immunosuppressive and antimicrobial treatment approach.
authors.affiliation: Divisions of Nephrology.
authors.forename: Pietro E
authors.initials: PE
authors.lastname: Cippà
authors.affiliation: Visceral and Transplantation Surgery, and.
authors.forename: Marc
authors.initials: M
authors.lastname: Schiesser
authors.affiliation: Department of Nephrology and Transplantation, Skåne University Hospital, Malmö, Sweden;
authors.forename: Henrik
authors.initials: H
authors.lastname: Ekberg
authors.affiliation: Departments of Hospital Pharmacy and Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands;
authors.forename: Teun
authors.initials: T
authors.lastname: van Gelder
authors.affiliation: Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, Zurich, Switzerland;
authors.forename: Nicolas J
authors.initials: NJ
authors.lastname: Mueller
authors.affiliation: Praxis Riesbach, Zurich, Switzerland;
authors.forename: Claude A
authors.initials: CA
authors.lastname: Cao
authors.affiliation: Divisions of Nephrology, Department of Internal Medicine, Cantonal Hospital Graubünden, Graubünden, Switzerland; and thomas.fehr@uzh.ch.
authors.forename: Thomas
authors.initials: T
authors.lastname: Fehr
authors.affiliation: Limites Medical Research, Vacallo, Switzerland.
authors.forename: Corrado
authors.initials: C
authors.lastname: Bernasconi
mesh_terms: D000328:Adult; D000890:Anti-Infective Agents / Q000627:therapeutic use; D003141:Communicable Diseases / Q000175:diagnosis / Q000276:immunology* / Q000401:mortality; D003661:Decision Support Techniques; D005260:Female; D006084:Graft Rejection / Q000175:diagnosis / Q000276:immunology / Q000401:mortality / Q000517:prevention & control*; D006801:Humans; D016867:Immunocompromised Host; D007166:Immunosuppressive Agents / Q000009:adverse effects*; D015994:Incidence; D053208:Kaplan-Meier Estimate; D016030:Kidney Transplantation / Q000009:adverse effects* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D015337:Multicenter Studies as Topic; D009894:Opportunistic Infections / Q000175:diagnosis / Q000276:immunology* / Q000401:mortality / Q000517:prevention & control; D011237:Predictive Value of Tests; D015995:Prevalence; D016032:Randomized Controlled Trials as Topic; D015203:Reproducibility of Results; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000890:Anti-Infective Agents; D007166:Immunosuppressive Agents
keywords: cause of death; cyclosporin; death; humans; immunosuppression; kidney transplantation; tacrolimus; transplant infectious disease; transplant outcomes; transplant recipients