ABSTRACT
BACKGROUND: It is commonly believed that mTOR inhibitors (mTORi) should not be used in high-immunological risk kidney transplant recipients due to a perceived increased risk of rejection. However, almost all trials that examined the association of optimal-dose mTORi with calcineurin inhibitor (CNI) have excluded hypersensitized recipients from enrollment. METHODS: To shed light on this issue, we examined 71 consecutive patients with a baseline calculated panel reactive antibody (cPRA) ≥50% that underwent kidney transplantation from June 2013 to December 2016 in our unit. Immunosuppression was based on CNI (tacrolimus), steroids and alternatively mycophenolic acid (MPA; n = 38), or mTORi (either everolimus or sirolimus, n = 33, target trough levels 3-8 ng/mL). RESULTS: Demographic and immunological risk profiles were similar, and almost 90% of patients in both groups received induction with lymphocyte-depleting agents. Cox-regression analysis of rejection-free survival revealed better results for mTORi versus MPA in terms of biopsy-proven acute rejection (hazard ratio [confidence interval], 0.32 [0.11-0.90], P = 0.031 at univariable analysis and 0.34 [0.11-0.95], P = 0.040 at multivariable analysis). There were no differences in 1-year renal function, Banff chronicity score at 3- and 12-month protocol biopsy and development of de novo donor-specific antibodies. Tacrolimus trough levels along the first year were not different between groups (12-mo levels were 8.72 ± 2.93 and 7.85 ± 3.07 ng/mL for MPA and mTORi group respectively, P = 0.277). CONCLUSIONS: This single-center retrospective cohort analysis suggests that in hypersensitized kidney transplant recipients receiving tacrolimus-based immunosuppressive therapy similar clinical outcomes may be obtained using mTOR inhibitors compared to mycophenolate.
Subject(s)
Desensitization, Immunologic/methods , Graft Rejection/prevention & control , Immunosuppressive Agents/administration & dosage , Kidney Transplantation/adverse effects , TOR Serine-Threonine Kinases/antagonists & inhibitors , Adult , Aged , Calcineurin Inhibitors/administration & dosage , Calcineurin Inhibitors/adverse effects , Desensitization, Immunologic/adverse effects , Drug Therapy, Combination/adverse effects , Drug Therapy, Combination/methods , Everolimus/administration & dosage , Everolimus/adverse effects , Female , Glucocorticoids/administration & dosage , Glucocorticoids/adverse effects , Graft Rejection/immunology , HLA Antigens/immunology , Humans , Immunosuppressive Agents/adverse effects , Isoantibodies/immunology , Male , Middle Aged , Mycophenolic Acid/administration & dosage , Mycophenolic Acid/adverse effects , Retrospective Studies , Sirolimus/administration & dosage , Sirolimus/adverse effects , TOR Serine-Threonine Kinases/immunology , Tacrolimus/administration & dosage , Tacrolimus/adverse effects , Treatment OutcomeABSTRACT
We describe the first known case of symptomatic infection resulting from human herpesvirus-6 (HHV-6) in simultaneous pancreas-kidney transplant recipients. The role of HHV-6 in solid-organ transplant recipients is not well defined. In hematopoietic stem cell transplantation (SCT) HHV-6 may cause fever, rash, myelosuppression, interstitial pneumonitis, and encephalitis.
