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Risk Stratification for Rejection and Infection after Kidney Transplantation


Cippà, Pietro E; Schiesser, Marc; Ekberg, Henrik; van Gelder, Teun; Mueller, Nicolas J; Cao, Claude A; Fehr, Thomas; Bernasconi, Corrado (2015). Risk Stratification for Rejection and Infection after Kidney Transplantation. Clinical Journal of the American Society of Nephrology, 10(12):2213-2220.

Abstract

BACKGROUND AND OBJECTIVES Definition of individual risk profile is the first step to implement strategies to keep the delicate balance between under- and overimmunosuppression after kidney transplantation. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS 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.

Abstract

BACKGROUND AND OBJECTIVES Definition of individual risk profile is the first step to implement strategies to keep the delicate balance between under- and overimmunosuppression after kidney transplantation. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS 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.

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3 citations in Web of Science®
3 citations in Scopus®
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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Nephrology
04 Faculty of Medicine > University Hospital Zurich > Clinic for Infectious Diseases
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:7 December 2015
Deposited On:21 Dec 2015 10:26
Last Modified:05 Apr 2016 19:43
Publisher:American Society of Nephrology
ISSN:1555-9041
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.2215/CJN.01790215
PubMed ID:26430088

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