Preemptive Conversion to mTOR Inhibition to Prevent Primary Cytomegalovirus Infection in Kidney Transplantation with High-Risk Serostatus

Abstract

Background

Kidney transplantation (KTx) is the treatment of choice for patients with end-stage renal disease. Cytomegalovirus (CMV) infection remains a serious complication of KTx. The most vulnerable patients are naïve recipients (R-) transplanted from a CMV-seropositive donor (D+). Mammalian target of rapamycin inhibitors (mTOR-I) have been shown to have advantages over mycophenolate in terms of CMV infections. In this study, we addressed the effect of preemptive conversion to mTOR-I before ending prophylaxis with valganciclovir in high-risk patients with a D+/R- CMV serostatus.

Methods

The study involved inclusion and analysis of all patients with D+/R- CMV serostatus before and after the protocol change with a conversion to mTOR-I at 6 months after KTx. The main study endpoints were primary CMV infection, maximal viral load, and hospitalization for CMV infection. Because prevention of primary CMV infections was the primary endpoint, we excluded breakthrough infections under prophylaxis.

Results

The primary analysis included 44 patients in the control group and 39 patients in the mTOR group. The 2 groups did not have any significant differences in clinical characteristics, immunosuppressive treatment, transplant function, and rates of rejection. Between 6 and 12 months (when mTOR-I were established), the mTOR group showed a numerically lower incidence of CMV infections, as well as numerically fewer hospitalizations. No serious complications were observed with mTOR-I.

Conclusion

Preemptive conversion from mycophenolate to mTOR-I may be helpful to prevent or attenuate primary infection in CMV high-risk kidney transplant recipients. Differences were not statistically significant. A larger study, ideally a prospective randomized trial, is needed to validate these findings.