Induction With Basiliximab in Renal Transplantation

Introduction

The use of monoclonal antibodies in renal transplantation for induction therapy has been associated with a marked reduction in acute rejection rates with an impact on graft and patient survivals.

Objective

We sought to evaluate the efficacy of renal transplant induction protocols using Basiliximab based on the rates of acute rejection episodes (ARE) and delayed graft function (DGF) of infectious complications in the first 6 months posttransplant, as well as patient and graft survivals.

Methods

We retrospectively evaluated all renal transplants performed between 2000 and 2008 that were primary grafts from cadaveric heart-beating donors, into recipients with a panel reactive antibody titer <5% and who were treated with an immunosuppression scheme based on cyclosporine, mycophenolate mofetil/mycophenolic acid plus corticosteroids, with (group 1) or without basiliximab (group 2).

Results

We enrolled 52 recipients in group 1 (induction with basiliximab) and 189 in group 2 (without basiliximab). The baseline characteristics were similar among the groups, except for time on dialysis which was longer in group 1 and the number of HLA matches, which was lower in group 1. The ARE rate was lower among group 1 (7.8% vs 27.8%; P = .001); rates of DGF and infectious complications were similar. There was no significant difference in graft and patient survivals.

Conclusion

In this study, induction with basiliximab was associated with a reduced rate rate of ARE, despite a lower number of HLA matches and a longer previous time on dialysis. The use of this induction modality was not associated with a greater rate of infectious complications.     

Low-dose Thymoglobulin vs Basiliximab Induction Therapy in Low-Risk Living Related Kidney Transplant Recipients: A Prospective Randomized Trial

ContextThymoglobulin is used effectively as induction agent in kidney transplantation but the optimal dose is not well established.ObjectiveDemonstrate that low-dose thymoglobulin (3 mg/kg) has similar efficacy and safety compared to basiliximab induction in low-risk kidney transplantation under standard maintenance immunosuppressionDesign, Setting, ParticipantsProspective randomized study in kidney transplant patients (12/2016-05/2018). Inclusion criteria: Recipients > 18 years, first living donor transplant. Exclusion criteria: Second and multiorgan transplant, ABO incompatibility, positive cross-match, panel reactive antibodies (PRA) > 30%, positive donor-specific antibody, human immunodeficiency virus, hepatitis B surface antigen, hepatitis C virus positive, white blood cells < 2000 cells/mm³, platelets < 75,000 cells/mm³ and malignancy.InterventionGroup A: basiliximab (20 mg D0 and D4). Group B: thymoglobulin (3 mg/kg total). Maintenance immunosuppression: tacrolimus, mycophenolate mofetil, and steroids.Main Outcome MeasuresBiopsy-proven acute rejection (BPAR), delayed graft function, slow graft function, leukopenia, infections, adverse events, graft loss, estimated glomerular filtration rate, and death within 12 months.Results100 patients (basiliximab, n = 53) (thymoglobulin, n = 47) were included. Donor and recipient characteristics were similar except for longer dialysis (basiliximab), PRA class I (1.2% basiliximab, 4.5% thymoglobulin), HLA match (basiliximab 2.8, thymoglobulin 2.2), and cytomegalovirus status. BPAR rate was basiliximab 3.8% and thymoglobulin 6.4% (P = ns). Delayed graft function (basiliximab 3.8%; thymoglobulin 4.3%), slow graft function, and 12-month leukopenia (basiliximab 11.3%, thymoglobulin 21.3%) were similar between groups (P = ns). There was no difference in infections and adverse events between groups. Patient and graft survival were as follows: basiliximab 98.1% and 92.5%, thymoglobulin 100% and 93.6% (P = ns).ConclusionLow-dose thymoglobulin induction (3 mg/kg) can be used effectively and safely in low-risk kidney transplantation with good results during the first year post-transplant.     

Basiliximab or Antithymocyte Globulin for Induction Therapy in Kidney Transplantation: A Meta-analysis

Objective

To compare efficacy and safety of basiliximab versus antithymocyte globulin (ATG) for induction therapy in kidney transplantation.

Methods

A literature search of the MEDLINE, EMBASE, CBMdisc, and Cochrane databases was used to identify randomized controlled trials that compared basiliximab and ATG for induction therapy in kidney transplantation. Inclusion criteria comprised: prospective randomized controlled clinical trials, follow-up time ≥12 months, randomized comparisons of ATG versus basiliximab as induction therapy in kidney transplantation. Meta-analytical techniques were applied to identify differences in outcomes between the two agents.

Results

A total of six studies involving 853 patients were identified. No differences between ATG and basiliximab were seen in terms of biopsy-proven rejection (relative risk [RR] 1.15, 95% confidence interval [CI] 0.88-1.52, P = .31), delayed graft function (RR 1.02, 95% CI 0.69-1.51, P = .93), graft loss (RR 1.15, 95% CI 0.73-1.80, P = .55), and patient death (RR 1.22, 95% CI 0.65-2.30, P = .54). But basiliximab had a lower incidence of infection (RR 0.87, 95% CI 0.78-0.97, P = .02) and neoplasm (RR 0.29, 95% CI 0.09-0.97, P = .04).

Conclusions

Basiliximab is as effective as ATG for induction therapy in kidney transplantation, whereas basiliximab has a lower incidence of infection. Basiliximab may be a safer and preferable option for induction therapy in kidney transplantation.     

Complement Mutation-Associated De Novo Thrombotic Microangiopathy Following Kidney Transplantation

Mutations in one or more genes encoding complement-regulatory proteins predispose to atypical hemolytic uremic syndrome (aHUS) and its recurrence following kidney transplantation. We evaluated plasma complement level and performed a screening for mutations in genes encoding complement Factors H and I (CFH, CFI) and membrane cofactor protein (MCP) in 24 kidney transplant recipients experiencing de novo thrombotic microangiopathy (TMA). Six patients presented with low C3 and/or low Factor B levels suggestive complement alternative pathway. A mutation in the CFH or CFI gene was found in 7/24 patients (29%), two of whom had a mutation in both genes. On the contrary, no mutation was identified in a control kidney transplant patients group (n = 25) without TMA. Patients with or without mutations were similar with regard to clinical features. Eight out of 24 patients lost their graft within 1 year of posttransplantation including six patients with a CFH mutation or a decrease of C3 or CFB in plasma. To conclude, kidney transplant patients with de novo TMA exhibit an unexpectedly high frequency of CFH and CFI mutations. These results suggest that genetic abnormalities may represent risk factors for de novo TMA after kidney transplantation and raise the question of the best therapeutic strategy.     

Opportunistic Infections After Induction With Alemtuzumab or Basiliximab: A 3-Year Kidney Transplantation Experience

BackgroundAntibody induction immunosuppression is commonly used in kidney transplantation to decrease the risk of early acute rejection. However, infectious complications may arise in patients treated with higher intensity induction immunosuppression. In this study, we compared the rate of opportunistic infections during the 3 years after kidney transplantation in recipients who received either alemtuzumab or basiliximab for induction therapy.MethodsAll renal transplant recipients from our center who received induction with alemtuzumab between 2011 and 2016 were included and matched 1:2 (by age and date of transplant) to renal transplant recipients who received basiliximab. The primary outcome was the rate of opportunistic infections.ResultsTwenty-seven patients received alemtuzumab (mean age = 50.8 years; SD ±12), and 54 received basiliximab (mean age = 50.8 years; SD ±11.8). Infections within 3 years posttransplant were not different between groups: BK viremia (P = .99), BK nephritis (P = .48), cytomegalovirus infection (P = .13), varicella zoster virus (P = .22), and all infections (P = .87). Time to infection (P = .67), patient survival (P = .21), and time to rejection (P = .098) were similar in both groups. There were also no group differences in delayed graft function (P = .76), graft loss (P = .97), or rejection (P = .2).ConclusionThe rate of infection was not significantly increased in recipients receiving lymphocyte-depleting alemtuzumab compared to recipients receiving basiliximab induction therapy, despite receiving similar maintenance immunosuppression. Although the immunologic risks differed between the 2 groups, there was no observable difference in clinical outcomes.     

Ten-Year Follow-up of Pharmacokinetics-Guided Very Early Cyclosporine Minimization Synchronized With Everolimus Initiation in De Novo Kidney Transplantation

Background

Minimization of calcineurin inhibitor (CNI) from the 1st week after kidney transplantation (KT) may reduce the risk of CNI nephrotoxicity.

A Comparison of Alemtuzumab with Basiliximab Induction in Simultaneous Pancreas–Kidney Transplantation

Alemtuzumab is a humanized, rat monoclonal antibody directed against the CD52 antigen. After binding, alemtuzumab causes profound and durable depletion and has been successfully used as immune induction therapy for organ transplantation.
This was a single center, retrospective review of patients who underwent simultaneous pancreas–kidney transplantation at the University of Wisconsin using alemtuzumab induction therapy compared with historical controls that received induction with basiliximab.
There were no differences in donor or recipient demographics, rates of patient survival, renal or pancreas allograft survival, renal allograft delayed graft function, EBV infection, BKV infection, PTLD or sepsis. There was a statistically significant increase in the incidence of cytomegalovirus (CMV) infection in the alemtuzumab-treated group.
Given the significantly higher incidence of CMV infections, we have since altered our induction protocol to consist of a single 30 mg dose of alemtuzumab instead of two doses. The long-term effects of this change remain to be seen. Due to the results seen in this study, the low initial cost of the drug and the absence of any severe, short-term side effects, alemtuzumab has been selected as the induction drug of choice at our center for patients undergoing SPK.     

Follow-up Survey of Donor Candidates for Living Related Kidney Transplantation With Prostate Cancer

Introduction

With the increasing number of elderly kidney donor candidates due to the lack of available donors, prostate cancer has sometimes been detected in these candidates during pretransplant screening examinations. There are currently no guidelines or consensus on prostate cancer screening and treatment in donors. We retrospectively evaluated the clinical course of donor candidates with prostate cancer.

De Novo Cancer Incidence and Prognosis After Kidney Transplantation: A Single Center Analysis

BackgroundMalignancy is an important cause of mortality in renal transplants recipients. The aim of this study was to evaluate the incidence, prognosis, and survival of patients developing a de novo post-transplant cancer.MethodsUsing a retrospective cohort design, we evaluated the incidence of de novo cancers among kidney transplants patients in our hospital from January 2000 to December 2012. We also evaluated the patient survival after tumor diagnosis.ResultsWe included 535 kidney transplants recipients with a mean follow-up of 7.8 years; among them, 39 (7.2%) developed malignancies. Median time from transplant to cancer diagnosis was 3 years, with a median age at diagnosis of 60 years. Male patients were significantly older at time of cancer diagnosis (68.5 years) compared with women (38 years, P < .05), and cancer diagnosis occurred significantly earlier in men (3.5 years since transplantation) than in women (8.5 years, P < .05). Among 39 patients affected by a de novo post-transplant cancer, 18 patients (46.2%) died, with an average age at death of 58.5 years. The average time from cancer diagnosis to death was 1.5 years. Among the group of patients who did not develop a post-transplant cancer, 83 patients (16.7%) died, with a median age at time of death of 54.5 years (P < .05).ConclusionsKidney transplant recipients are at higher risk of developing a post-transplant cancer. Prognosis after cancer diagnosis is poor, probably as a consequence of a more aggressive behavior of cancer in transplant recipients. Intensive screening protocols could allow for an earlier diagnosis thereby improving the long-term outcome of these patients.     

Safety and Efficacy of Induction Therapy With Thymoglobulin in AB0-Incompatible Kidney Transplantation

Introduction

Data suggest an additional role of T cells in antibody-mediated rejections. In 2001 a protocol for AB0-incompatible kidney transplantation based on B-cell–depleting anti–CD20 antibody rituximab, antigen-specific blood group IgG immunoadsorption, intravenous immunoglobulins, and triple immunosuppression was introduced in Europe, which used induction therapy with the use of interleukin-2 receptor antibody (IL2-RA) basiliximab. We used thymoglobulin in AB0-incompatible patients as induction in the face of high immunologic risk.

De novo Therapy with Everolimus,Low‐Dose Ciclosporine A,Basiliximab and Steroid Elimination in Pediatric Kidney Transplantation

The number of acute rejections and infections after pediatric kidney transplantation (KTX) could not be reduced in the last years. To reduce these events, we investigated a new immunosuppressive protocol in a prospective trial. After KTX, 20 children (median age 12 years, range 1–17) were initially treated with Basiliximab, ciclosporine A (CsA) (trough‐level = C0 200–250 ng/mL) and prednisolone. After 2 weeks, CsA dose was reduced to 50% (C0 75–100 ng/mL, after 6 months: 50–75 ng/mL) and everolimus (1.6 mg/m²/day) was started (C0 3–6 ng/mL). Six months after KTX prednisolone was set to alternate dose and stopped 3 months later. All 20 protocol biopsies 6 months after KTX showed no acute rejection or borderline findings. Indication biopsies resulted in no acute rejections and two borderline findings. Mean glomerular filtration rate (GFR) 1 year after KTX was 71 ± 25 mL/min/1.73 m². Without cytomegalovirus (CMV)‐prophylaxis, only two primary CMV infections were seen despite a donor/recipient‐CMV‐constellation pos./neg. in 10/20 children. In pediatric KTX, de novo immunosuppression with low‐dose CsA, everolimus and steroid withdrawal after 9 months led to promising results according to numbers of acute rejections and infections. Further follow up is needed. Future larger trials will have to confirm our findings.     

De Novo Membranous Nephropathy Associated With Antibody-Mediated Rejection in Kidney Transplant Recipients

BackgroundMembranous nephropathy (MN) is a rare autoimmune disease that can develop a persistent nephrotic syndrome and end-stage kidney disease, with a recurrence rate of 30% to 40% after kidney transplant.MethodsRetrospective case series of membranous nephropathy observed in a cohort of kidney transplant recipients with donor-specific anti–human leukocyte antigen antibodies and biopsy-proven antibody-mediated rejection (AMR).ResultsWe report 4 cases of membranous nephropathy associated with AMR. MN was diagnosed 10 to 92 months posttransplant, associated with de novo donor-specific antibodies, specific to class I in 2 cases, and class II in another 2. All cases presented typical morphology of membranous nephropathy, with subepithelial deposits with spikes at electron microscopy. Immunostaining for immunoglobulin G4 was negative in all cases, and podocyte-expressed M-type phospholipase A2 receptor was detected in glomerular basement membrane of 3 cases. Biopsy specimens from patients with longer follow-up showed more intense microvascular inflammation and chronic injury markers, possibly because of subclinical immunologic injury. AMR therapy included immunoglobulin 2g/kg in 3 patients, isolated or associated with plasmapheresis. One patient was not treated because of an active disseminated infection. Two patients remain with functioning grafts and under antiproteinuric therapy. Two grafts were lost, 1 because of chronic failure and the other because of death secondary to infection. Despite treatment, donor-specific antibodies remain detectable in a 6-month follow-up.ConclusionsDe novo MN is a rare manifestation associated with AMR in kidney transplant recipients. The occurrence of podocyte-expressed M-type phospholipase A2 receptor in de novo MN suggests antibody-mediated activation, despite the use of maintenance immunosuppression.     

Alefacept Combined With Tacrolimus,Mycophenolate Mofetil and Steroids in De Novo Kidney Transplantation: A Randomized Controlled Trial

Memory T cells play a central role in mediating allograft rejection and are a rational target for immunosuppressive therapy. Alefacept is a recombinant LFA3/IgG1 fusion protein that reduces the number of memory T cells in both psoriatic lesions and the peripheral circulation of psoriasis patients. This study evaluated the efficacy and safety of alefacept compared with placebo when combined with tacrolimus, mycophenolate mofetil and corticosteroids in de novo renal transplant recipients. Between December 2007 and March 2009 patients were randomized in a double‐blind fashion to receive alefacept (n = 105) or placebo (n = 107) for 3 months and were then followed for a further 3 months. The primary efficacy endpoint was the incidence of biopsy‐confirmed acute T cell mediated rejection (Banff grade ≥1) through Month 6. Memory T cell counts were significantly reduced in the alefacept group from Week 3 to study end compared with placebo. However, there was no significant difference between the alefacept and placebo groups for the primary efficacy endpoint (alefacept, 11.0% vs. placebo, 7.0%, p = 0.3). Patient and graft survival as well as renal function was similar between treatment groups. Safety and tolerability were generally similar between the treatment arms. Malignancy was higher in the alefacept treatment arm.     

An Analysis of Lymphocyte Phenotype After Steroid Avoidance With Either Alemtuzumab or Basiliximab Induction in Renal Transplantation

Several studies have analyzed the phenotype of repopulated T‐lymphocytes following alemtuzumab induction; however there has been less scrutiny of the reconstituted B‐cell compartment. In the context of a randomized controlled trial (RCT) comparing alemtuzumab induction with tacrolimus monotherapy against basiliximab induction with tacrolimus and mycophenolate mofetil (MMF) therapy in renal transplantation, we analyzed the peripheral B‐ and T‐lymphocyte phenotypes of patients at a mean of 25 +/? 2 months after transplantation. We examined the relationship between peripheral lymphocyte phenotype and graft function. Patients who received alemtuzumab had significantly higher numbers of B cells including naïve, transitional and regulatory subsets. In contrast, the CD4⁺ T‐cell compartment was dominated by a memory cell phenotype. Following either basiliximab or alemtuzumab induction patients with lower numbers of B cells or B subsets had significantly worse graft function. For alemtuzumab there was also a correlation between these subsets the stability of graft function and the presence of HLA‐specific antibodies. These results demonstrate that a significant expansion of regulatory type B cells is associated with superior graft function and that this pattern is more common after alemtuzumab induction. This phenomenon requires further prospective study to see whether this phenotype could be used to customize immunotherapy.     

Early Outcomes of Living-Donor Kidney Transplantation With Immunosuppression Therapy Induction With Tacrolimus Extended-Release: A Comparison With Cyclosporine

Background

Extended-release tacrolimus (TacER), administered once daily, offers improved adherence with reduced side effects while still maintaining an immunosuppressive potency equivalent to that of conventional tacrolimus preparations.

Trough Level of Mycophenolic Acid Did Not Affect De Novo DSA Development in Kidney Transplantation

IntroductionMycophenolate mofetil has improved long-term outcomes of kidney transplantation. However, the impact of mycophenolic acid (MPA) trough level on the development of de novo donor-specific anti-HLA antibody (DSA) is unclear. We examined the relation between MPA trough level and de novo DSA development.MethodWe retrospectively studied 617 kidney recipients whose MPA trough level and de novo DSA data were available. All patients underwent primary kidney transplant from living donors from 2008 to 2014, and were chronically treated with a calcineurin inhibitor, mycophenolate mofetil, and +/- steroids. They were equally divided into 4 groups according to the mean trough level of MPA (mMPA) at 1 year post-transplantation: Group 1, mMPA < 2.14 ng/mL (n = 152); Group 2, mMPA 2.14-2.83 ng/mL (n = 157); Group 3, mMPA 2.83-3.57 ng/mL (n = 153); and Group 4, mMPA ≥ 3.57 ng/mL (n = 155). The groups were compared by incidence rate of de novo DSA, graft survival rate, and renal function.ResultsThe incidence rates of de novo DSA were 33.3% in Group 1, 23.7% in Group 2, 22.9% in Group 3, and 30.3% in Group 4 (P = .158). Although there was no significant difference in graft survival rates, a significant difference of renal functions was noted: the higher the renal function, the lower the MPA trough level.ConclusionThe mMPA trough level at 1 year post-transplantation was not statistically associated with the incidence rate of de novo DSA after kidney transplantation.