A split strategy to prevent cytomegalovirus after kidney transplantation using prophylaxis in serological high-risk patients and a pre-emptive strategy in intermediate-risk patients: Combining the best of two options?

Abstract

Cytomegalovirus (CMV) remains an important challenge after kidney transplantation. Current Transplantation Society International Consensus Guidelines recommend antiviral prophylaxis or pre-emptive therapy for high-risk CMV-seronegative recipients with a CMV-seropositive donor (D+/R-) and moderate-risk CMV-seropositive recipients (R+). However, a split strategy according to CMV serostatus is not specifically mentioned. We evaluated a split strategy to prevent CMV infection after kidney transplantation in which D+/R- patients received valganciclovir (VGC) prophylaxis for 200days, and R+patients were treated pre-emptively according to CMV DNAemia. Patients were followed until 1-year post-transplant. Between April 2014 and March 2018, 40 D+/R- and 92 R+patients underwent kidney transplantation. Forty-six percent received antithymocyte globulin (ATG) induction, and 98% was treated with calcineurin inhibitors, mycophenolic acid (MPA), and steroids. No D+/R- patient developed CMV disease during prophylaxis (median 200days), but 15% developed post-prophylaxis or late-onset disease. Fifty-three percent developed neutropenia during prophylaxis, including 16/40 (40%) grade 3 or 4 neutropenia requiring reduction/discontinuation of MPA (30%) and/or VGC (35%), and an occasional need for granulocyte colony-stimulating factor (5%). In the R+group, 40% received antiviral therapy for a median duration of 21days; 5% developed early-onset CMV disease. Only 5% developed neutropenia. D+/R+status (hazard ratio (HR) 2.09,P=.004) and ATG use (HR 2.81, P<.0001) were risk factors for CMV reactivation. Prophylaxis leads to acceptable CMV control in high-risk patients but comes with a high risk of neutropenia. Pre-emptive therapy is effective and limits drug exposure in those at lower risk of CMV.