Infectious complications with quadruple immunosuppression in the management of persistent rejection in kidney transplants

BACKGROUND: Persistent rejection despite aggressive management is common among kidney transplant recipients (KTRs). One approach is to treat the rejection and also intensify the maintenance immunosuppression by adding belatacept to the standard triple immunosuppressive regimen. To the best of our knowledge, the safety of this approach has not been previously reported. MATERIALS AND METHODS: In this study, we included all patients who had persistent microvascular inflammation (MVI) on two or more sequential biopsies and were treated according to the standard of care for rejection. Cases were selected based on the maintenance of quadruple immunosuppression after persistent rejection management. Controls were selected by matching some of the baseline characteristics for patients who were maintained on a standard triple immunosuppressive regimen only. RESULTS: 15 KTR cases were compared with 21 KTR controls. The median number of rejection episodes before adding belatacept was 3 (IQR 2 - 4), with a mean interval from transplant to the initiation of quadruple immunosuppression of 43.6 months. By the end of the analysis, 10 (67%) cases and 15 (71%) controls (p = 0.76) had infectious complications. The most common infectious complications in the cases were urinary tract infection and pyelonephritis, while BKV was more common in controls. All but 1 case had a follow-up biopsy after quadruple immunosuppression. Of the cases and controls, all but control had persistent rejection. CONCLUSION: While many infectious complications were observed in this high-risk population with resistant MVI, the safety profile of quadruple immunosuppression seems comparable to that of triple immunosuppression. Although initial efficacy experience was not encouraging in this series, larger controlled studies are needed to better define the benefits and risks of this approach.