Low Hydrophobic Mismatch Scores Calculated for HLA-A/B/DR/DQ Loci Improve Kidney Allograft Survival.

We evaluated the impact of human leukocyte antigen (HLA) disparity (immunogenicity; IM) on long-term kidney allograft survival. The IM was quantified based on physicochemical properties of the polymorphic linear donor/recipient HLA amino acids (the Cambridge algorithm) as a hydrophobic, electrostatic, amino acid mismatch scores (HMS\AMS\EMS) or eplet mismatch (EpMM) load. High-resolution HLA-A/B/DRB1/DQB1 types were imputed to calculate HMS for primary/re-transplant recipients of deceased donor transplants. The multiple Cox regression showed the association of HMS with graft survival and other confounders. The HMS integer 0-10 scale showed the most survival benefit between HMS 0 and 3. The Kaplan-Meier analysis showed that: the HMS=0 group had 18.1-year median graft survival, a 5-year benefit over HMS>0 group; HMS ≤ 3.0 had 16.7-year graft survival, a 3.8-year better than HMS>3.0 group; and, HMS ≤ 7.8 had 14.3-year grafts survival, a 1.8-year improvement over HMS>7.8 group. Stratification based on EMS, AMS or EpMM produced similar results. Additionally, the importance of HLA-DR with/without -DQ IM for graft survival was shown. In our simulation of 1,000 random donor/recipient pairs, 75% with HMS>3.0 were re-matched into HMS ≤ 3.0 and the remaining 25% into HMS≥7.8: after re-matching, the 13.5 years graft survival would increase to 16.3 years. This approach matches donors to recipients with low/medium IM donors thus preventing transplants with high IM donors.

BK Virus in Renal Transplant Patients Using Alemtuzumab for Induction Immunosuppression.

OBJECTIVES: Alemtuzumab, a monoclonal antibody utilized as induction immunosuppression in renal transplant, targets CD52-positive lymphocytes, causing profound B- and T-cell depletion. The administration of such novel, potent immunosuppressive agents, with the goal of reducing rejection, poses an increased threat of BK virus infection in renal transplant recipients. MATERIALS AND METHODS: This internal review boardapproved retrospective analysis included 676 renal transplant patients during a 9-year period. All patients were induced with alemtuzumab, and most received a steroid-minimizing regimen. BK viremia was defined as a clinically significant BK virus infection confirmed by polymerase chain reaction. RESULTS: Of total study recipients, 58 (8.6%) were positive for BK viremia. African American race/ethnicity, age > 65 years, and rejection showed significant associations with BK viremia. Kaplan-Meier analyses demonstrated significant differences in 3-year (P = .032), 5-year (P = .025), and overall rejection (P = .031) between patients with and without BK viremia. Differences were found in overall (P = .002) and 5-year (P = .001) death-censored graft survival for patients positive for BK viremia plus another non-BK infection versus patients without BK viremia or other infection. BK viremia-positive patients with other infections had significantly lower overall (P = .010) and 5-year (P = .010) death-censored graft survival than patients with BK viremia but without other infections. When we excluded other infections, we observed no differences between BK viremia-positive and BK viremia-negative patients. CONCLUSIONS: BK viremia incidence following alemtuzumab induction therapy appears to be comparable to that shown in other reports and slightly lower than the incidence in patients receiving non-alemtuzumab immunosuppression. BK virus may increase risk of rejection, and BK virus plus another infection may lead to decreased graft survival. African American patients, patients > 65 years old, and patients with rejection history may be at increased risk of BK virus. Closer screening should be considered in these populations.