Received Basiliximab Induction Research Articles

A comparative analysis of kidney allograft outcomes in steroid use versus steroid discontinuation after basiliximab and ATG induction: AUNOS database study.

The relative safety and efficacy of early steroid withdrawal in kidney transplant patients after basiliximab compared to anti-thymocyte globulin (ATG) induction therapy is unknown. We aimed to compare kidney allograft outcomes in steroid use versus steroid discontinuation after basiliximab and ATG induction from the United Network for Organ Sharing (UNOS) database. We conducted a retrospective cohort analysis of the UNOS database and included first kidney transplant recipients who received ATG or basiliximab induction therapy. We compared graft and patient outcomes in those who received steroid maintenance and those who were discharged off steroids. Of 106,061 patients, 25,344 (86.7%) received basiliximab induction and were maintained on steroids (B-Sm), and 3,880 (13.3%) were on a steroid-free regimen (B-Sf). Graft failure rate was significantly higher in the B-Sf compared to B-Sm at 1-year (4.1 vs. 1.8%, p<0.001), 3-year (6.0 vs. 4.3%, p<0.001) and 5-year follow-up (7.7 vs. 6.4%, p=0.0004). The mortality rate was significantly higher in B-Sf at 1-year (3.3 vs. 2.4%, p=0.0005), 3-year (7.6 vs. 5.5%, p<0.001) and 5-year follow-up (11.5 vs. 8.8%, p<0.001) when compared to the B-Sm. 76,837 recipients received ATG induction therapy, 51,745 (72.4%) were on steroid maintenance therapy (A-Sm) and 25,092 (32.6%) were on a steroid-free regimen (A-Sf). The graft failure rate was significantly higher in A-Sf compared to A-Sm at 1-year follow-up (2.6 vs. 2.3%, p=0.0006), however, there was no difference at 3-year (5.0 vs. 5.0%, p=0.53) or 5-year follow-up (7.2 vs. 8.1%, p=0.17). There was no difference in mortality rates between A-Sf vs. A-Sm at 1 year (2.5 vs. 2.4%, p=0.98) and at 3 years (5.5 vs. 5.4%, p=0.45), respectively. Patients who were maintained on steroids after basiliximab induction had better 5-year allograft survival and patient survival compared to those who were not maintained on steroids. However, steroid maintenance conferred no additional benefit after ATG induction and was associated with higher mortality.

Efficacy and Safety of Bleselumab in Preventing the Recurrence of Primary Focal Segmental Glomerulosclerosis in Kidney Transplant Recipients: A Phase 2a, Randomized, Multicenter Study.

Focal segmental glomerulosclerosis (FSGS) is a common cause of end-stage kidney disease and frequently recurs after kidney transplantation. Recurrent FSGS (rFSGS) is associated with poor allograft and patient outcomes. Bleselumab, a fully human immunoglobulin G4 anti-CD40 antagonistic monoclonal antibody, disrupts CD40-related processes in FSGS, potentially preventing rFSGS. A phase 2a, randomized, multicenter, open-label study of adult recipients (aged ≥18 y) of a living or deceased donor kidney transplant with a history of biopsy-proven primary FSGS. The study assessed the efficacy of bleselumab combined with tacrolimus and corticosteroids as maintenance immunosuppression in the prevention of rFSGS >12 mo posttransplantation, versus standard of care (SOC) comprising tacrolimus, mycophenolate mofetil, and corticosteroids. All patients received basiliximab induction. The primary endpoint was rFSGS, defined as proteinuria (protein-creatinine ratio ≥3.0 g/g) with death, graft loss, or loss to follow-up imputed as rFSGS, through 3 mo posttransplant. Sixty-three patients were followed for 12 mo posttransplantation. Relative decrease in rFSGS occurrence through 3 mo with bleselumab versus SOC was 40.7% (95% confidence interval, -89.8 to 26.8; P = 0.37; absolute decrease 12.7% [95% confidence interval, -34.5 to 9.0]). Central-blinded biopsy review found relative (absolute) decreases in rFSGS of 10.9% (3.9%), 17.0% (6.2%), and 20.5% (7.5%) at 3, 6, and 12 mo posttransplant, respectively; these differences were not statistically significant. Adverse events were similar for both treatments. No deaths occurred during the study. In at-risk kidney transplant recipients, bleselumab numerically reduced proteinuria occurrence versus SOC, but no notable difference in occurrence of biopsy-proven rFSGS was observed.

Outcomes of older Black renal transplant recipients receiving basiliximab induction and early steroid withdrawal

AbstractThe efficacy and safety of early steroid withdrawal (ESW) in Black renal transplant recipients (RTR) remains uncertain, especially when combined with non‐lymphocyte depleting induction. This study compared patient and graft outcomes of older Black and Non‐Black RTR who received basiliximab induction followed by ESW.Included subjects in this single center, retrospective study were first‐time deceased and living donor RTR aged over 65 years who received basiliximab induction therapy and ESW. Black RTR and Non‐Black deceased donor RTR received an oral prednisone taper starting POD3 which was discontinued by POD21 per protocol.Of 139 patients (55 Black and 84 Non‐Black), the Black patient group included a higher percentage of deceased donors and hepatitis C positive donors, and more frequently underwent renal replacement therapy prior to transplant. One Black and zero Non‐Black RTR experienced graft loss within 3 years (p = 1.0). Patient survival was similar at 1 year (93% vs. 97%, p = .16) and 3 years (91% vs. 96%, p = .17). Rejection‐free survival and biopsy‐proven rejection did not differ at 1 or 3 years. Median eGFR and change in eGFR also did not differ between groups. Black patients were maintained on significantly higher median mycophenolate doses from 6 months post‐transplant to the end of the study period (p = .03 and .048).In older Black RTR, basiliximab induction followed by ESW produced comparable patient, graft, and rejection‐free survival compared to Non‐Black RTR over 3 years post‐transplant.

Kidney transplant outcomes in patients with antibodies to human neutrophil antigen 3a

BackgroundAntibody mediated rejection (ABMR) of kidney transplants has been shown to occur in the absence of a known donor specific antibody to human leucocyte antigen (HLA). Antibodies to the human neutrophil antigen (HNA) system have been detected in kidney transplant recipients and linked to ABMR in the absence of an HLA donor specific antibody (DSA), but there remains limited literature regarding this. MethodsCase series analysis was carried out examining three cases of HNA-3a antibody positive flow cytometry cross match (FC-XM) from two transplant centres in Scotland. ResultsAll patients included were female and had been sensitised as a result of pregnancy. One live donor recipient with HNA-3a antibodies identified prior to transplant received ATG induction and has had a good outcome. The remaining two patients received deceased donor transplants. HNA-3a antibodies were indicated following a retrospective flow cytometry crossmatch. Both patients received Basiliximab induction and both have experienced ABMR requiring supplementary immunosuppression. ConclusionsThe predicted rate of HNA-3a antibodies amongst patients awaiting kidney transplant in the UK is <1%. However, with increasing evidence to support a role for HNA-3a antibodies in the development of ABMR there may be value in screening at risk groups to allow for augmented immunosuppression to be considered at the time of kidney transplant.

#5095 THE CURIOUS CASE OF GAS IN THE GRAFT KIDNEY

Abstract Background and Aims Emphysematous pyelonephritis (EPN) denotes a severe infection of renal parenchyma resulting in necrosis and gas accumulation in the renal and perirenal tissue. Risk factors for urinary tract infections in renal transplant recipients include advanced age, female gender, reflux nephropathy prior to transplantation, diabetes mellitus, deceased donor kidney, kidney–pancreas transplant, retransplantation, antibody induction for immunosuppression, urinary bladder catheterisation, history of allograft rejection with subsequent escalation of immunosuppressive therapy and use of ureteral stents. There are no definite guidelines for management of EPN in renal allografts. If unstable and deteriorating, graft nephrectomy should be undertaken as soon as possible. Any delay in surgical intervention, be it percutaneous drainage or nephrectomy may result in death. Method A 25-year old male, diagnosed with IgA Nephropathy (IgAN) received a living donor renal transplant from his mother in 2013 after a dialysis vintage of 3 years. He received Basiliximab induction followed by maintenance immunosuppression with Tacrolimus, Mycophenolate mofetil and Prednisolone. He had no history of UTI in the immediate post-transplant period. His blood glucose levels were within normal limits and he had not had any urological intervention. In 2019, patient was diagnosed with IgAN recurrence as a cause of chronic renal allograft injury. His Creatinine at last follow up in July 2022 was 4.1 mg/dL. He presented in September 2022 with fever, chills, vomiting, pain in the right iliac fossa and inability to extend his right leg. At presentation, his BP was 86/60mmHg, with pyrexia and tachycardia. Ultrasonography revealed an ill-defined collection superomedial to the graft kidney with doubtful posterior extension and air foci. Non-contrast CT study revealed a large subcapsular collection, extending posteriorly into the right iliac fossa involving the right psoas major and inferiorly into the pelvis, with air foci and no evidence of any urinary tract obstruction suggestive of Acute Emphysematous pyelonephritis with ruptured abscess. He was started on broad-spectrum iv antibiotics- Meropenem and Levofloxacin. Immunosuppression was reduced. Laboratory investigations revealed total leucocyte count of 37,000 cells/mm3, Creatinine of 11 mg/dL, urine routine microscopy revealed field full of pus cells. Blood and urine cultures grew ESBL Escherichia coli. He was taken up for urgent urological intervention in the form of percutaneous drain insertion. Frank pus was aspirated and 200mL drained instantaneously, cultures of which demonstrated the same organism. Within 24 hours of pus drainage, patient became afebrile and had pain relief. He was given 3 weeks of culture-appropriate iv antibiotics, to continue another 3 weeks of oral Carbapenem. However, his graft dysfunction persisted, with no recovery and he became dialysis-dependent. Discussion EPN of the renal allograft is a rare occurrence. A study of EPN in renal transplant recipients by Alexander et al from 2012 revealed 18 out of 22 patients were diabetics, 9 necessitated graft nephrectomy and 7 required percutaneous drainage in addition to antibiotics4. Till date, up to 30 cases of graft EPN have been reported in English literature. The striking feature is that more than 90% of these cases were diabetic. Conclusion The complete pathogenesis of renal allograft EPN, especially in patients with no apparent traditionally described risk factors remains yet to be understood. A high degree of suspicion and early intervention may help to save the allograft.

(1168) Perioperative Tacrolimus Levels Do Not Impact Early Acute Rejection Rates in Lung Transplant Recipients Receiving Basiliximab Induction

(1168) Perioperative Tacrolimus Levels Do Not Impact Early Acute Rejection Rates in Lung Transplant Recipients Receiving Basiliximab Induction

Outcomes of abo-incompatible kidney transplantation: Novel ways of reducing rejection, complications, and cost

AimOur objective was to report the outcomes of ABO-incompatible (ABOi) transplants and seek solutions to pretransplant desensitization, peri and postoperative bleeding events, acute rejection and infection-related mortality. MethodsWe retrospectively analyzed 247 consecutive ABOi kidney transplantations at our center from June 2012 to March 2020. The primary outcomes were patient, graft, and death-censored graft survival over 5 years. ResultsA total of 31 patients received thymoglobulin and 216 patients received basiliximab induction. Patient survival rates with basiliximab induction at 1, 3, and 5 years were 97.8%, 93.5%, and 93.5%, respectively; corresponding graft survival rates were 95.1%, 86.6%, and 85.2%, respectively. Overall, biopsy-proven acute rejection occurred in 11.7% recipients; primarily due to antibody-mediated rejections. Cumulative incidence of graft loss was 7.5% at 5 years and overall incidence of death was 6.07%. ConclusionReplacement of filtered plasma by donor group fresh frozen plasma rather than albumin reduced bleeding, IVIG administration, number of plasmapheresis sessions and the need for filters. Thymoglobulin avoidance decreased acute rejection rates. Rapid reduction and lower doses of prednisolone and MMF reduced infectious complications. These steps can help reduce rejection rates, complications and cost (up to USD 7000) comparable to ABO compatible transplantation in other centers as well.

Outcomes after anti-thymocyte globulin vs Basiliximab induction before deceased donor kidney transplants

BackgroundDeceased donor kidney transplants represent an important source of renal replacement for the 100 000 patients initiating hemodialysis annually. We compared the association of induction therapy, anti-thymocyte globulin [rabbit] (rATG) or basiliximab, with posttransplant rejection, graft and patient survival. MethodsUsing the United Network for Organ Sharing (UNOS) database, we identified patients that received deceased donor kidney transplants. The outcomes analyzed were 6- month rejection, 1-year rejection, patient survival and graft survival. Multivariate logistic regression models were constructed to understand the association of induction therapy and rejection. Cox-proportional hazards models were constructed to ascertain the association of choice of induction therapy with both patient and graft survival. ResultsOf 45 339 patients, 33 906 patients received rATG induction therapy and 11 433 patients received basiliximab induction therapy. The rATG group were younger (53.44 years vs 55.28 years, P < 0.001), more frequently female (58.74% male vs 66.08%, P < 0.001) and more frequently Black (34.78% vs 25.66%, p < 0.001) compared with patients in the basiliximab group.Rejection was more likely with basiliximab compared with rATG at 6 months(OR = 1.64, P < 0.001; 7.81% Basiliximab vs 5.23% rATG)and at 12 months (OR = 1.56, P < 0.001; 8.81% Basiliximab vs 6.31% rATG). Basiliximab induction therapy was associated with worse patient survival, (HR = 1.05, P = 0.017). Basiliximab induction therapy was associated with worse graft survival, (HR = 1.03, P = 0.037). ConclusionThe analysis of the national experience demonstrated favorable rejection, patient survival, and graft survival with rATG usage. Further prospective data are necessary to provide treatment recommendations.

311.3: A 5-Year Prospective, Randomized, Open-Label Study of Standard Versus Low-Dose Prolonged-Release Tacrolimus With Or Without ACEi/ARB in Kidney Transplantation

Introduction: Optimizing tacrolimus (TAC) exposure and/or using angiotensin-converting enzyme inhibitors (ACEi) or angiotensin II receptor blockers (ARB) may modulate inflammation (i) as well as interstitial fibrosis and tubular atrophy (IFTA) after kidney transplant (KTx). Two-year data from a study in KTx patients receiving prolonged-release TAC coupled with either ACEi/ARB or other antihypertensives (OAHT) showed that low-dose TAC coupled with ACEi/ARB was associated with less IFTA severity and progression, less IFTA + i, and delayed onset of clinical rejection compared with low-dose TAC without ACEi/ARB (Cockfield et al. Am J Transplant 2019;19:1730–44). We now report 5-year results from this study. Methods: This was a Canadian multicenter, prospective, open-label, controlled study in adult de novo KTx recipients randomized in a 2x2 design to standard dose (0.15–0.20 mg/kg) or low dose (LOW; 0.05–0.15 mg/kg) prolonged-release TAC combined with either ACEi/ARB or OAHT. All patients received basiliximab induction, mycophenolate mofetil and prednisone. Protocol biopsies were taken at implantation, 6 and 24 months. Five-year data include patient and graft survival, renal function, proteinuria, blood pressure and the incidence of Class II de novo donor-specific antibody (dnDSA). Results: Overall, 281 patients were randomized. Between 3 and 5 years, mean TAC trough levels were ~6 ng/mL. Patient survival at 5 years was 95.7% and comparable between groups (94.2–97.2% across groups). Overall graft survival was 94.3% (89.7% in the LOW+OAHT group vs 94.4–97.1% in the other groups). Graft function, blood pressure, and proteinuria were similar in all groups. At 5 years, class II dnDSA incidence was 13.2% in the LOW+OAHT group vs 5.6–7.2% in other groups. There were no unexpected safety findings observed at 5 years. Conclusion: KTx patients receiving low-dose prolonged-release TAC combined with ACEi/ARB have comparable outcomes to those receiving standard doses of prolonged-release TAC with or without ACEi/ARB, while treatment with low-dose prolonged release TAC without ACEi/ARB may be associated with worse outcomes. This study was sponsored by Astellas Pharma Inc. Editorial support was provided by Cello Health MedErgy, funded by Astellas Pharma Inc.

Simultaneous Hyperammonemia Syndrome in Multiple Organ Recipients from a Single Donor

<h3>Introduction</h3> Hyperammonemia is a rare complication post solid organ transplant, with a high mortality. We report a case of hyperammonemic encephalopathy in separate cardiac and lung transplant recipients, likely related to donor derived infection acquired from the same donor. <h3>Case Report</h3> A 63-year-old male with sarcoid cardiomyopathy on LVAD support and no known hepatic disease received cardiac transplantation. He was extubated on day (D) 4 with normal allograft function and mentation. He received basiliximab induction, steroids, mycophenolate (MMF) and tacrolimus (TAC) on D6. He developed hallucinations on D8 followed by paranoia and reduced GCS on D9, with no focal neurological deficit. Cranial CT/MRI and CSF were unremarkable. Initial blood results showed raised CRP, WCC with mildly elevated urea, creatinine, bilirubin & transaminase. Serum ammonia (NH₃) was 549µmol/L. He was intubated and diagnosed with hyperammonemic encephalopathy. Hyperammonemic encephalopathy had also been diagnosed in the lung transplant recipient, a 65-year-old male with COPD, from the same donor. He received basiliximab induction, steroids, MMF and Cyclosporine A (CSA) on D1. He developed right sided hypertonia and reduced consciousness on D6, with elevated NH₃ (177µmol/L). Both received <i>Mycoplasma</i> / <i>Ureaplasma</i> combination antibiotics - moxifloxacin and azithromycin (lung), moxifloxacin and minocycline (cardiac); metronidazole, rifaximin, lactulose, ammonia scavengers and dialysis. NH₃ normalised by D12 (lung) and D15 (cardiac) with improvement in mental state. At D30, both remain dependent on dialysis with ongoing antibiotics, steroids, and moderate immunosuppression. Both patients required tracheostomy for critical illness myopathy. The aetiology of hyperammonemia is putative, however both recipients had <i>Mycoplasma hominis</i> identified on blood cultures. <i>M. hominis</i> and <i>Ureaplasma spp.</i> were present in bronchial washings in the lung recipient, and sputum, pleural and pericardial fluid from cardiac recipient. The donor had culture negative urethritis at donation with <i>Mycoplasma</i> and <i>Ureaplasma spp</i>. confirmed on retrospective bronchial washing PCR. <h3>Summary</h3> Hyperammonemia should be suspected in transplant recipients with altered mental state. Transplant units need increased awareness of the potential impact of infection by urease-producing organisms.

Utility of Cardiovascular Magnetic Resonance Imaging in Non-HLA Mediated Cardiac Allograft Dysfunction

<h3>Introduction</h3> Cardiac MRI (cMRI) with late gadolinium enhancement may be beneficial in guiding medical therapy in non-HLA mediated allograft dysfunction in heart transplant recipients (HTR). Cardiac MRI utilizing pre/post-contrast T1/T2 mapping and myocardial delayed enhancement imaging were performed in two HTRs with non-HLA mediated allograft dysfunction. <h3>Case Report</h3> Patient A and B were adult males transplanted for non-ischemic cardiomyopathy with compatible crossmatches at the time of transplant. Patient A received basiliximab induction while patient B received no induction. Both were maintained on tacrolimus, mycophenolate, and prednisone. On surveillance echocardiogram (ECHO) at 90-days post-transplant, a decreased ejection fraction (45%) was noted in both patients. Subsequent biopsies, donor specific antibodies, and MICA antibodies were negative. Biopsy immunofluorescence C4d staining was 90% in patient A and negative in patient B (Table 1). Patient A's cMRI demonstrated mildly increased T1 and T2 values that when combined with the clinical history, was suggestive of acute rejection. He subsequently received treatment with plasmapheresis, immunoglobulin, and rituximab. A repeat cMRI at 1-month post-treatment demonstrated normalization of T1 and T2 values. In contrast, patient B had generally normal T1 and T2 values on initial cMRI, indicating likely absence of acute rejection. Given cMRI findings, combined with a possible alternative etiology of mitochondrial disease contributing to decreased cardiac function, rejection treatment was not pursued and instead, sirolimus was initiated to slow disease progression. Follow-up biopsies and ECHOs in both patients indicate stable allograft function with slight improvements in ejection fraction. <h3>Summary</h3> In the absence of typical rejection findings, aspects of cMRI measurement may have favorable clinical utility and help guide medical management of early post-transplant non-HLA mediated allograft dysfunction.

Effect of Redosing Basiliximab in the Setting of Blood Loss in Heart Transplant Recipients on Infection and Rejection

<h3>Purpose</h3> A prior study examining the pharmacodynamics of basiliximab in liver transplant recipients revealed significant medication clearance with blood loss. Dose escalation studies have shown total doses of 40-60 mg are effective and well-tolerated. We sought to examine infection risk when giving a total basiliximab dose of 40 mg vs 60 mg in our heart transplant (OHT) population in the setting of blood loss and requirement of massive transfusion protocol (MTP). <h3>Methods</h3> A single-center retrospective cohort study was performed examining adult OHT patients who received basiliximab induction therapy between June 1, 2010 and October 31, 2019. Cases and controls were matched 1:1. Patients were excluded if they were determined to be immunocompromised prior to transplant. The primary endpoint was incidence of infection. Secondary endpoints included the incidence of cell-mediated or antibody-mediated rejection, as well as the incidence of graft loss within 12 months. <h3>Results</h3> Forty-eight patients who underwent OHT were included, 24 patients in each group (40 mg and 60 mg total dose). Baseline characteristics were similar except for a higher number of LVAD patients in the 60 mg group (16.7% vs 45.8%, p=0.03). A total of 12 patients in the 40 mg group and 18 patients in the 60 mg group experienced at least one infection within 12 months after OHT, although this difference did not meet statistical significance (50% vs 75%, p=0.07). The types of infections were similar between the groups. A stepwise logistic regression showed blood loss and presence of LVAD at the time of transplant were predictors of infection occurrence. Delayed chest closure occurred more frequently in the basiliximab 60 mg group (p=0.002). Acute cellular rejection rates did not differ between groups (p=0.62). Antibody-mediated rejection occurred less frequently in the 40 mg vs 60 mg group (16.7% vs 50%, p=0.03). Two patients experienced graft loss in each group. <h3>Conclusion</h3> In our single-center retrospective study, the administration of an additional dose of basiliximab in the setting of MTP during OHT did not demonstrate a statistically significant increase in the risk of infection nor reduce the risk of rejection. The presence of LVAD at time of transplant was associated with an increased risk of infection and careful consideration should be given to these patients when selecting their induction regimen.

Early Blood Transfusion After Kidney Transplantation Does Not Lead to dnDSA Development: The BloodIm Study.

Outcomes after kidney transplantation are largely driven by the development of de novo donor-specific antibodies (dnDSA), which may be triggered by blood transfusion. In this single-center study, we investigated the link between early blood transfusion and dnDSA development in a mainly anti-thymocyte globulin (ATG)-induced kidney-transplant cohort. We retrospectively included all recipients of a kidney transplant performed between 2004 and 2015, provided they had >3 months graft survival. DSA screening was evaluated with a Luminex assay (Immucor). Early blood transfusion (EBT) was defined as the transfusion of at least one red blood-cell unit over the first 3 months post-transplantation, with an exhaustive report of transfusion. Patients received either anti-thymocyte globulins (ATG) or basiliximab induction, plus tacrolimus and mycophenolic acid maintenance immunosuppression. A total of 1088 patients received a transplant between 2004 and 2015 in our center, of which 981 satisfied our inclusion criteria. EBT was required for 292 patients (29.7%). Most patients received ATG induction (86.1%); the others received basiliximab induction (13.4%). dnDSA-free graft survival (dnDSA-GS) at 1-year post-transplantation was similar between EBT+ (2.4%) and EBT- (3.0%) patients (chi-squared p=0.73). There was no significant association between EBT and dnDSA-GS (univariate Cox’s regression, HR=0.88, p=0.556). In multivariate Cox’s regression, adjusting for potential confounders (showing a univariate association with dnDSA development), early transfusion remained not associated with dnDSA-GS (HR 0.76, p=0.449). However, dnDSA-GS was associated with pretransplantation HLA sensitization (HR=2.25, p=0.004), hemoglobin >10 g/dL (HR=0.39, p=0.029) and the number of HLA mismatches (HR=1.26, p=0.05). Recipient’s age, tacrolimus and mycophenolic-acid exposures, and graft rank were not associated with dnDSA-GS. Early blood transfusion did not induce dnDSAs in our cohort of ATG-induced patients, but low hemoglobin level was associated with dnDSAs-GS. This suggests a protective effect of ATG induction therapy on preventing dnDSA development at an initial stage post-transplantation.

Deceased donor renal transplant outcome in a south Indian tertiary care hospital with zonal allocation model - An observational study

Background: With the rising incidence of diabetes and hypertension, the prevalence of end-stage renal disease has increased greatly so as the need for renal replacement therapy. Availability of suitable living-related donors is a major problem which increases the demand for deceased donor renal transplantation (DDRT), making it a lifeline for the patients on dialysis without any living donors. Methodology: This is a retrospective analysis of 118 DDRT done between 2012 and 2020, in a private quaternary care hospital in a south Indian state. All patients received basiliximab induction, with maintenance immunosuppression using steroids, mycophenolate mofetil (MMF) or mycophenolate sodium, and tacrolimus. Results: In our study, we report unadjusted graft survival of 93.2% and 81.3%, patient survival of 94.9% and 83.1% at the end of 1 and 5 years, respectively. The recipients with age < 60 years had 5 years graft survival of 87%. The study group consisted of 15.25% of the patients with panel reactive antibody (PRA) positive and 10.16% of them with donor-specific antibody (DSA) during renal transplantation, and there was only one allograft loss in this subset of the patients. Conclusion: This study confirms that human leukocyte antigen matching is not very important with the current immunosuppressive protocol using tacrolimus and MMF. Early initiations of tacrolimus do not increase the incidence of delayed graft function. We report 91.6% graft survival in the DSA-positive group, with basiliximab induction and desensitization protocol.

A comparative study of recipients' outcomes receiving a kidney from the same deceased donor: An observational study

Introduction: Kidney transplantation is the renal replacement therapy (RRT) of choice for patients with end-stage renal disease. Although outcomes of deceased-donor kidney transplantation are inferior when compared to live donor kidney transplantation, they are still significantly better than being on chronic dialysis. There are very few studies comparing transplant outcomes between two kidneys obtained from the same donor. Aims: The aim of this study is to compare the graft and patient outcome of the kidneys of the same deceased donor transplanted into two different recipients. Materials and Methods: This is a prospective observational study done at the tertiary care center in South India over 2 years. A total of 29 pairs of deceased-donor transplants were followed up with one-half performed at donor institute (Group 1) and the same number performed at another network hospital (Group 2). Outcomes between the recipients of the two kidneys were compared. Data were statistically analyzed. Results: The majority of donors were relatively young (with a mean age of 37 years) and did not have multiple comorbidities. 1st kidney went to the donor hospital, whereas 2nd kidney was sent to other hospitals in the network. Cold ischemia times were higher (10.3 h vs. 6.5 h) for the 2nd kidneys. The majority of Group 1 patients did not receive induction, whereas 100% of Group 2 patients received basiliximab induction. The incidence of acute rejection (antibody plus cellular rejection) was numerically less in Group 2 compared to Group 1 but was not found to be statistically significant (P = 0.227). The incidence of acute cellular rejection in Group 1 was more compared to Group 2, and was found to be statistically significant (P = −0.038). Graft survival was similar in both groups (95.7 in Group 1 vs. 95.8 in Group 2). Patient survival was similar in both groups (P = −0.555) with a mean follow-up 25.9 months in Group 1 versus 24.6 months in Group 2. The choice of induction agent did not affect the graft or patient survival. In addition, there was no significant difference in the incidence of infections or mortality rate. Conclusion: Overall, the outcomes in the paired kidneys from the same donor transplanted to different recipients at different institutes had similar outcomes. The choice of induction agent did not have any influence on the overall graft and patient survival.

Spot Urine Protein Excretion in the First Year Following Kidney Transplantation Associates With Allograft Rejection Phenotype at 1-Year Surveillance Biopsies: An Observational National-Cohort Study.

Introduction: Urine protein excretion is routinely measured to assess kidney allograft injury, but the diagnostic value of this measurement for kidney transplant pathology remains unclear. Here we investigated whether spot urine protein excretion in the first year following transplantation associates with allograft rejection phenotype at 1-year surveillance biopsies and de-novo occurrence of donor-specific antibodies (DSA).Patients and Methods: This prospective, observational national-cohort study included 139 non-sensitized patients who received a deceased donor kidney transplant between December 2014 and 2018. All patients received basiliximab induction and tacrolimus-based immunosuppression. Estimated protein excretion rate (ePER) was calculated monthly from spot urine protein-to-creatinine ratios. At 1-year, all recipients underwent surveillance graft biopsy and were screened for de-novo DSA. Screening-positive sera were subjected to single antigen bead (SAB) testing. The occurrence of de-novo DSA was determined based on SAB reactivity patterns using a mean fluorescence intensity threshold >1,000.Results: Among the 139 study patients, 27 patients (19%) had histologic evidence of T cell-mediated rejection (TCMR), and 9 patients (7%) had histologic evidence of antibody-mediated rejection (AMR) at 1-year surveillance biopsy. One year after transplant, 19 patients (14%) developed de-novo DSA. Compared with patients without rejection and no de-novo DSA, mixed-effects linear regression analysis showed a significant difference in slope of ePER during the first year in patients with AMR and de-novo DSA at 1-year (46, 95% CI 25–68 mg/day/1.73 m2 per month and 34, 95% CI 20–49 mg/day/1.73 m2 per month, respectively). Patients with vascular TCMR also showed a significant difference in ePER slope over time compared with patients with non-rejection findings (31, 95% CI 9–52 mg/day/1.73 m2 per month). The discriminatory power of ePER for intragraft rejection processes was better in patients with AMR (AUC 0.95, 95% CI 0.90–0.99; P < 0.001) than in those with TCMR (AUC 0.68, 95% CI 0.59–0.79; P = 0.002), with 89% sensitivity and 93% specificity for proteinuria >550 mg/day/1.73m2.Conclusions: An increase in ePER in the first year following kidney transplantation associates with AMR, vascular TCMR and de-novo DSA at 1-year and may be used as a non-invasive clinical marker of intragraft endothelial cell injury.

Anti-thymoglobulin induction improves neonatal porcine xenoislet engraftment and survival.

Porcine islet xenotransplantation is a viable strategy to treat diabetes. Its translation has been limited by the pre-clinical development of a clinically available immunosuppressive regimen. We tested two clinically relevant induction agents in a non-human primate (NHP) islet xenotransplantation model to compare depletional versus nondepletional induction immunosuppression. Neonatal porcine islets were isolated from GKO or hCD46/GKO transgenic piglets and transplanted via portal vein infusion in diabetic rhesus macaques. Induction therapy consisted of either basiliximab (n=6) or rhesus-specific anti-thymocyte globulin (rhATG, n=6), combined with a maintenance regimen using B7 costimulation blockade, tacrolimus with a delayed transition to sirolimus, and mycophenolate mofetil. Xenografts were monitored by blood glucose levels and porcine C-peptide measurements. Of the six receiving basiliximab induction, engraftment was achieved in 4 with median graft survival of 14 days. All six receiving rhATG induction engrafted with significantly longer xenograft survival at 40.5 days (P=0.03). These data suggest that depletional induction provides superior xenograft survival to nondepletional induction, in the setting of a costimulation blockade-based maintenance regimen.

Safety of Antithymocyte Globulin Use in Kidney Graft Recipients During the COVID-19 Pandemic.

BackgroundThere are many safety concerns regarding the use of antithymocyte globulin (ATG) in kidney transplant recipients (KTRs) during the ongoing COVID-19 pandemic. Hereby, we present our recent experience with ATG administration both as induction therapy and as an anti-rejection treatment.Material/MethodsWe retrospectively analyzed all patients transplanted during the first 12 months of the COVID-19 pandemic who were treated with thymoglobulin. The ATG dosing, lymphocyte number and percentage in blood smear, adverse effects (thrombocytopenia and infectious complications), and kidney graft function up to 12 months and patients’ outcomes were analyzed and compared to KTRs who received basiliximab induction.ResultsDuring pandemic, a total of 31 patients were treated with ATG and 59 received basiliximab. The median cumulative ATG doses were 275 (175–325) mg in the induction subgroup and 263 (200–275) mg in the anti-rejection treatment subgroup. Mild thrombocytopenia was noted in 7 (22.6%) and 13 (29.5%) patients, respectively. There were more infectious complications among patients treated with ATG as compared with the basiliximab subgroup (32.3 vs 10.2%, P<0.01), but there were similar incidence rates of thrombocytopenia. Kidney graft function up to 12 months after transplant was comparable (1.1 [1.0–1.9] vs 1.1 [1.0–1.4] mg/dl, respectively).Conclusions1. ATG use in the induction protocol or as the anti-rejection treatment during the COVID-19 pandemic appears to be safe and the risk of adverse events is acceptable. 2. During the COVID-19 pandemic the necessary use of ATG should not be postponed, especially in KTRs with increased immunologic risk.

Ofatumumab and Tocilizumab Desensitization in a Highly Sensitized Recipient: A Case Report

<h3>Introduction</h3> Sensitization is a challenge in heart transplant recipients, often increasing wait time and decreasing access to acceptable organs. We present a case of a highly sensitized 47-year-old female listed for re-do heart and kidney transplant who was desensitized utilizing ofatumumab and tocilizumab. <h3>Case Report</h3> The patient received her first heart transplant in 1992 (induction muromonab-CD3) for viral cardiomyopathy at an outside hospital; in 2015 she was treated for antibody mediated rejection with plasma exchange (PLEX), intravenous immunoglobulin (IVIG), and bortezomib. She later developed cardiac allograft vasculopathy. In 2018 she was brought to our center with cardiogenic shock and worsening renal function, required dual inotropic support, and evaluated and listed for a re-do heart and kidney transplant. Her peak PRA was 90% with several class I and II antibodies. She underwent desensitization therapy with PLEX, IVIG (2 g/kg), ofatumumab (1 dose), and monthly tocilizumab (3 doses). No adverse drug events were reported during therapy. Her PRA remained persistently ∼90%; MFI trends of her antibodies are presented in Figure 1. After her 3^rd tocilizumab dose she received an offer which was crossmatch negative and no pre-existing antibodies. She received basiliximab induction and maintenance immunosuppression of tacrolimus, mycophenolate, and prednisone. During the 1 year follow-up post-transplant, she had excellent graft function with ejection fraction >60%, serum creatinine <1.2 mg/dL and no episodes of rejection. Tacrolimus levels remained between 5-13 mcg/ml. Post-transplant infections included BK viremia with persistent PCR levels between 600-1500 copies/mL. <h3>Summary</h3> Desensitization with ofatumumab and tocilizumab resulted in successful heart and kidney transplantation. Although PRA and MFI of pre-existing antibodies were not significantly altered, this regimen may have been helpful in reducing de novo donor specific antibodies and preventing acute rejection post-transplant.

Universal CMV Prophylaxis Mitigates the Risks of Basiliximab Induction in Heart Transplant Recipients at Intermediate Risk (R+) for Post-Transplant CMV Complications

Purpose Induction therapy with either thymoglobulin or basiliximab is used in approximately 50% of patients at the time of heart transplant. While the use of thymoglobulin has been reported to increase the risk of CMV reactivation, it remains unclear if this risk is also seen with basiliximab. In the present analysis, we compared post-transplant CMV outcomes in patients receiving basiliximab vs. no induction in a multicenter, retrospective analysis. We also assess the effects of universal prophylaxis on any attendant risk. Methods Retrospective analysis of 439 intermediate risk (CMV R+) HTx recipients from 6 U.S. centers between 2010-2018 treated with either basiliximab induction (63%, n = 276) or no induction (37%, n = 163). The primary endpoint was the development of CMV viremia or end-organ disease resulting in the escalation of anti-CMV therapy. The secondary endpoint was hospitalization for CMV-related infection. Results Of 439 patients in the analysis, 18.9% (n = 83) developed CMV viremia or end-organ infection requiring escalation of anti-CMV therapy, and 5.7% (n = 25) were hospitalized for CMV infection. Patients who received induction with basiliximab were more likely to meet the primary endpoint (22.8% vs. 12.3%, p = 0.006) and had a trend towards higher risk for CMV hospitalization (7.2% vs. 3.1%, p = 0.068) in the overall group. However, in patients receiving universal CMV prophylaxis, there was no difference in the primary (14.7% vs. 13.1%, p = 0.672) or secondary endpoint (4.1% vs. 3.3%, p = 0.687) when basiliximab was used compared to no induction. Alternatively, 36% of patients receiving basiliximab induction reached the primary endpoint when a preemptive therapy approach to prophylaxis was used (vs. 0% in no induction, p = 0.021). Conclusion Although basiliximab induction increases the risk of CMV viremia/end organ damage and CMV-related hospitalizations, this risk is eliminated when a universal CMV prophylaxis strategy is used.