Assessing the risk of infection and rejection in Hispanic renal transplant recipients by means of an adenosine triphosphate release assay

Abstract

Introduction: Because of the necessary immunosuppression, transplant recipients have a high risk of infection. Conversely, underimmunosuppression carries with it the risk of rejection. It would be quite useful to have a test that could differentiate between infection and rejection in renal transplant patients and better still, to predict which patients are at risk of complications. A new assay, which measures adenosine triphosphate (ATP) synthesis by CD4+ T cells in response to stimulation by phytohemagglutinine (Immuknow assay, Cylex, Inc) is undergoing clinical evaluations. Preliminary investigations suggest that this test could be useful to assess and predict the immune status of patients with other conditions.

Methods: We examined the records of all patients who received a kidney transplant in our program between August 2004 and January 2005. Of 64 patients, 58 had pretransplant and posttransplant ATP level determinations. We searched for associations between ATP levels and immunosuppression type, doses, and levels; creatinine levels; white blood cell count; tissue typing; preformed antibodies; as well as ATP levels on infection and rejection, and changes in ATP levels with time. Chi-square, Fisher, t test, analysis of variance (ANOVA), and relative risks were used for analysis of data.

Results: There was no relation between ATP levels and immunosuppression type, doses, or levels; creatinine levels; white blood cell counts; HLA; and panel-reactive antibody (P > 0.05). However, patients with moderate or high pretransplant ATP levels had more rejection episodes (8/10) while patients with ATP levels in the low immune response had more infections (6/11) (P < .001; relative risk [RR] for rejection = 1.2; RR for infection = 4.4). The mean ATP levels for rejection was 423.3 ng/mL versus 268.45 ng/mL for infection and 277.15 ng/mL for no events (ANOVA, P = .0145). Although acute rejections occurred mostly above 300, this was not significant (P = .059; RR = 0.9). Infections were more frequent with ATP under 300 (RR = 7.3) and severe infection (endocarditis, meningitis, peritoneal abscesses, pneumonia, etc) were more frequent under 200 (P < .001). Comparing pretransplant with posttransplant values at the second week an increase correlated with rejection (P < .001, RR = 15.3), while a decrease did not correlate with the infection (P = .845, RR = 1.4). Patients who received antirejection treatment had a decrease in their ATP levels at 5 days (P = .002).

Conclusion: This ATP release assays helpful in determining the risk of developing infection or rejection, as well as follow-up in the response to therapy.