Drug Levels After Proliferation Signal Inhibitors Initiation and Short-Term Outcomes in Ambulatory Heart Transplant Recipients

Abstract

<h3>Purpose</h3> This study evaluated the impact of proliferation signal inhibitors (PSI) initiation on rejection and renal function based on drug levels in ambulatory heart transplant recipients. <h3>Methods</h3> This is a retrospective cohort study of heart transplant recipients (1994-2019) at Toronto General Hospital who were on tacrolimus (TAC) and initiated on PSI with TAC at any time after 6 months post-transplant. We collected baseline characteristics, renal function prior and post initiation, and episodes of treated cellular rejection 6 months prior to conversion and post conversion. Post-PSI initiation combined PSI and TAC levels were expressed as percentage increase or decrease at a month after PSI initiation in reference to TAC levels prior to PSI. Patients were in 3 groups according to relative drug levels post-PSI: decrease(>15% decrease), increase(>15% increase), and stable (-15% to +15%). Renal function was evaluated in relative terms comparing pre- and post-PSI glomerular filtration rate (GFR). We compared risk of rejection and mortality for one year follow-up post-PSI initiation using chi-square and renal function using one-way ANOVA. <h3>Results</h3> There were 99 recipients, median age of 53 (25th-75th percentile, 41-59), median time from transplant of 1.5 years (1.1-3.2). 28 of these patients experienced rejection 6 months prior to initiation. The median eGFR prior to initiation was 54 ml/min (42-71). Reasons for PSI were CAV (65%), impaired kidney function (16%), cancer (14%), and spurious (5%). 9 patients had decreased drug levels, 75 increased and 15 stable. Post-PSI combined levels were significantly higher in patients with increased levels (17±7 vs 11±4 in stable vs 19±3ng/ml in decreased, p<0.01) There were no differences in drug levels based on reasons for the change. Relatively eGRF 1-month post-PSI initiation increased significantly in patients with decreased levels (47%±89% increase in eGFR) compared to patients with stable (10%±21%) and decreased levels (4%±27%, p=0.01). There was no difference in risk of rejection across groups with different drug levels or reasons for PSI initiation. <h3>Conclusion</h3> We found that the main reason for PSI initiation in combination with TAC reduction was related to CAV followed by impaired kidney function. After PSI initiation, a relative decrease in drug levels was associated with improved renal function.