Abstract
Immunosuppression (IS) is delivered in the clinic without a direct measure of the net state of IS. Therapeutic drug monitoring aside, IS dosing is largely empiric and event-driven (as in cases of rejection, infection, neoplasia, intolerance). We studied the clinical phenotype of immunosuppression reduction (ISR) among kidney transplant recipients (KTXR). Methods: We studied adult KTXR 2005-12, grouping patients into: no ISR, ISR for infection, or ISR for intolerance. Outcome measures were rejection, rejection-free survival, and IFTA-free survival. ISR was defined as tacrolimus trough <8 ng/mL or MMF dose <1000 mg/day for at least 1 month during the first year post-transplant. Results: 1,114 KTXR were included: 57% had no ISR, 16% had ISR for infection, 27% had ISR for intolerance. Table 1 shows baseline demographics and clinical outcomes. ISR for infection was mainly on MMF while ISR for intolerance was mainly on FK. ISR was more intense for infection (65% reduction in MMF dose). KTXR who had ISR for intolerance had higher rates of acute rejection, particularly donor-specific antibody (DSA)+ antibody-mediated rejection. Kaplan-Meier curves for interstitial fibrosis/tubular atrophy (IFTA) and rejection-free graft survival show divergence in outcomes that become amplified at 6-years post-transplant. Among patients that had both infection and rejection, 66 % developed infection before rejection. Mean time from infection to rejection was 280 days. Conclusion: ISR is associated with increased incidence of IFTA at a time point remote from the onset of ISR. Solely focusing on acute rejection may underestimate effects of ISR on graft function and survival. The clinical phenotype of ISR is dominated by IFTA. Better methods to measure net IS state are needed to deliver optimal IS in the clinic. DISCLOSURE:Srinivas, T.: Grant/Research Support, Astellas, Bristol Myers Squibb, Novartis.Table: No Caption available.Figure: No Caption available.Figure: No Caption available.
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