Clinical study of different immune induction and BK virus infection after renal transplantation

Objective:To monitor the incidence of BK virus infection in hematuria of renal transplant recipients induced by different immunizations.Methods:A total of 109 patients who underwent renal transplantation in Baogang Hospital of Inner Mongolia from January 2019 to December 2022 were analyzed retrospectively.The results of BK virus DNA detection in urine and blood were observed after operation.They were divided into three groups according to different immunosuppressive induction regimens;35 patients in group A,42 patients in group B,and 32 patients in group C(basiliximab).To explore the effect of different immune induction regimens on BK virus infection in renal transplant recipients.Results:The positive rate of urine BK virus in all patients in 1 month after operation was 10.09%(11/109),which was significantly higher than that of blood BK virus 0%(0/109),and the difference had a statistical significance(p<.05).The positive rate of urine BK virus in all patients in 6 months after operation was 31.19%(34/109),which was significantly higher than that of blood BK virus 3.67%(4/109),and the difference had a statistical significance(p<.05).The positive rate of urine BK virus in all patients in 12 months after operation was 35.79%(39/109),which was significantly higher than that of blood BK virus 5.50%(6/109),and the difference had a statistical significance(p<.05).The urinary BK virus infection rate was increased significantly from 1 month to 6 months after operation,but was not increased significantly from 6 months to 12 months after operation.There was a statistically significant difference between the two groups(p<.05).The BK virus infection rate in renal transplant recipients induced by basiliximab within the first month was significantly lower than that in patients using polyclonal antibodies,but the urinary BK virus infection rate after one year was not significantly different from that in patients using polyclonal antibodies.Conclusions:There are slight differences in BK virus infection after early renal transplantation with different immune induction therapies,but there is no significant difference in the long-term.It is recommended to strengthen the early monitoring of BK virus after renal transplantation,timely adjust immunosuppressive regimens to achieve the early detection and early treatment.

Low-dose immune tolerance induction for severe hemophilia A inhibitor patients:Immunosuppressants are generally not necessary for inhibitor-titer below 200 BU/mL

Importance:It remained unclear that the efficacy comparison between low-dose immune tolerance induction(LD-ITI)incorporating immunosuppressants(IS)when severe hemophilia A(SHA)patients had inhibitor-titer≥200 Bethesda Units(BU)/mL(LD-ITI-IS^(200) regimen)and LD-ITI combining with IS when SHA patients had inhibitor-titer≥40 BU/mL(LD-ITI-IS^(40) regimen).Objective:To compare the efficacy of the LD-ITI-IS^(200) regimen with that of the LD-ITI-IS^(40) regimen for SHA patients with high-titer inhibitors.Methods:A prospective cohort study on patients receiving LD-ITI-IS^(200) compared to those receiving LD-ITI-IS^(40) from January 2021 to December 2023.Both received LD-ITI[FVIII 50 IU/kg every other day].IS(rituximab+prednisone)was added when peak inhibitor tier≥200 BU/mL in the LD-ITI-IS^(200) regimen and≥40 BU/mL in the LD-ITI-IS^(40) regimen.Success is defined as a negative inhibitor plus FVIII recovery≥66%of the expected.Results:We enrolled 30 patients on LD-ITI-IS^(200) and 64 patients on LD-ITI-IS^(40),with similar baseline clinical characteristics.A lower IS-use rate was discovered in the LD-ITI-IS^(200) regimen compared to the LD-ITI-IS^(40) regimen(30.0%vs.62.5%).The two regimens(LD-ITI-IS^(200) vs.LD-ITI-IS^(40))had similar success rate(70.0%vs.79.7%),median time to success(9.4 vs.10.6 months),and annualized bleeding rate during ITI(3.7 vs.2.8).The cost to success was lower for LD-ITI-IS^(200) than for LD-ITI-IS^(40)(2107 vs.3256 US Dollar/kg).Among patients with peak inhibitor-titer 40-199 BU/mL,10 non-IS-using(on LD-ITI-IS^(200) regimen)and 28 IS-using(on LD-ITI-IS^(40) regimen)had similar success rates(70.0%vs.78.6%)and time to success(9.0 vs.8.8 months).Interpretation:In LD-ITI,IS are not necessary for inhibitor titer<200 BU/mL.

Alemtuzumab induction therapy in highly sensitized kidney transplant recipients

Background Immunosuppression for immunologically high-risk kidney transplant patients usually involves antithymocyte globulin induction with triple drug maintenance therapy. Alemtuzumab, a humanized anti-CD52 antibody, was expected to be a promising induction therapy agent for kidney transplantation. However, currently no consensus is available about its efficacy and safety. This study aimed to evaluate the efficacy and safety of alemtuzumab as immune induction therapy in highly sensitized kidney transplant recipients.Methods In this prospective, open-label, randomized, controlled trial, we enrolled 23 highly immunological risk patients （panel reactive antibody 〉20%）. They were divided into two groups： alemtuzumab group （trial group） and anti-thymocyte globulin （ATG） group （control group）. Patients in the alemtuzumab group received intravenous alemtuzumab （15 mg） as a single dose before reperfusion. At the 24th hour post-operation, another dosage of alemtuzumab （15 mg） was given. The control group received a bolus of rabbit ATG （9 mg/kg）, which was given 2 hours before kidney transplantation and lasted until the removal of vascular clamps when the anastomoses were completed. Maintenance immunosuppression in both groups comprised standard triple therapy consisting of tacrolimus, prednisone, and mycophenolate mofetil （MMF）. Acute rejection （AR） and infection episodes were recorded, and kidney function was monitored during a 2-year follow-up. X2 test, ttest and Kaplan-Meier analysis were performed with SPSS17.0 software.Results Median follow-up was 338 days. In both the alemtuzumab group and ATG group, creatinine and blood urea nitrogen values in surviving recipients were similar （P 〉0.05）. White blood cell counts were significantly reduced in the alemtuzumab group for the most time points up to 6 months （P 〈0.05）. One patient receiving alemtuzumab died for acute myocardial infarction at the 65th day post-operation. Two ATG patients died for severe pulmonary infection or cardiac and pulmonary failure. Cumulative 2-year graft survival rate was 90.9% in the alemtuzumab group and 81.8% in ATG group （P 〉0.05） respectively. There was one graft failure in the alemtuzumab group and two graft failures in ATG group, with all graft failures at tributed to rejection episodes. The alemtuzumab group had a 2-year cumulative freedom from rejection rate of 81.8%, compared with 72.7% for the ATG group （P 〉0.05）.Conclusion Alemtuzumab induction therapy for highly sensitized kidney transplant recipients is an effective and safe protocol yielding an acceptable acute rejection rate.