Acute Rejection Rates Research Articles

Low-Dose Antithymocyte Globulin Has No Disadvantages to Standard Higher Dose in Pediatric Kidney Transplant Recipients: Report From the Pediatric Nephrology Research Consortium

IntroductionRabbit antithymocyte globulin (rATG) dosing strategies for induction in pediatric kidney transplantation vary between centers. It is not known whether a lower rATG induction dose provides safe and effective immunosuppression compared with a “standard” higher dose.MethodsWe performed a retrospective multicenter study of all isolated first-time kidney transplant recipients <21 years old who received rATG induction between 1 January 2010 and 31 December 2014 at 9 pediatric centers. An a priori cutoff of a 4.5-mg/kg cumulative rATG dose was used to identify low (≤ 4.5 mg/kg) and standard (> 4.5 mg/kg) exposure groups. Outcomes examined included 12 months posttransplant graft function (estimated glomerular filtration rate [eGFR]); the occurrence of acute rejection, donor-specific antibody (DSA), neutropenia, and viral infection (cytomegalovirus [CMV], Epstein-Barr virus [EBV], and BK virus); and 24-month outcomes of posttransplant lymphoproliferative disorder (PTLD) occurrence and patient and graft survival.ResultsTwo hundred thirty-five patients were included. Baseline features of the low and standard rATG dose groups were similar. By 12 months, the rATG dose group had no significant impact on the occurrence of neutropenia, positive DSA, or viral polymerase chain reaction (PCR). Graft function was similar. Acute rejection rates were similar at 17% (low dose) versus 19% (standard dose) (P = 0.13). By 24 months, graft survival (96.4% vs. 94.6%) and patient survival (100% vs. 99.3%) were similar between the low- and standard-dose groups (P = 0.54 and 0.46), whereas the occurrence of PTLD trended higher in the standard-dose group (0% vs. 2.6%, P = 0.07).ConclusionA low rATG induction dose ≤ 4.5 mg/kg provided safe and effective outcomes in this multicenter low immunologic risk pediatric cohort. Prospective studies are warranted to define the optimal rATG induction dose in pediatric kidney transplantation.

Predictive Value of Immune Cell Functional Assay for Non-Cytomegalovirus Infection in Lung Transplant Recipients: A Multicenter Prospective Observational Study

IntroductionImmune cell functional assay (ImmuKnow®) is a non-invasive method that measures the state of cellular immunity in immunosuppressed patients. We studied the prognostic value of the assay for predicting non-cytomegalovirus (CMV) infections in lung transplant recipients. MethodsA multicenter prospective observational study of 92 patients followed up from 6 to 12 months after transplantation was performed. Immune cell functional assay was carried out at 6, 8, 10, and 12 months. ResultsTwenty-three patients (25%) developed 29 non-CMV infections between 6 and 12 months post-transplant. At 6 months, the immune response was moderate (ATP 225–525ng/mL) in 14 (15.2%) patients and low (ATP<225ng/mL) in 78 (84.8%); no patients had a strong response (ATP≥525ng/mL). Only 1 of 14 (7.1%) patients with a moderate response developed non-CMV infection in the following 6 months compared with 22 of 78 (28.2%) patients with low response, indicating sensitivity of 95.7%, specificity of 18.8%, positive predictive value (PPV) of 28.2%, and negative predictive value (NPV) of 92.9% (AUC 0.64; p=0.043). Similar acute rejection rates were recorded in patients with mean ATP≥225 vs. <225ng/mL during the study period (7.1% vs. 9.1%, p=0.81). ConclusionAlthough ImmuKnow® does not seem useful to predict non-CMV infection, it could identify patients with a very low risk and help us define a target for an optimal immunosuppression.

Preliminary Analysis of Contamination in Liver Preservation Solution and Prophylaxis for Post-transplant Infection

Objective To discuss the preservation solution (PS) contamination and initial experience of liver transplantation from organ donation by citizens after death and initial experience. Methods The 78 liver transplant recipients were divided into positive group and negative group based on the finding of the culture of PS. The positive group received the sequential therapy of antibiotics with ertapenem and imipenem for one week, and the negative group stopped using imipenem. The situation of PS contamination and infection after liver transplantation and prognosis during the follow-up 3 months of the recipients were analyzed. Results PS culture positive rate was 41.03%, and 33 strains of pathogens were isolated. The most common pathogenic bacteria were gram-negative bacilli (9 strains, 27.27%) and <i>coagulase –negative staphylococci</i> (9 strains, 27.27%). The infection rate after liver transplantation was 31.25% and 13.04%, respectively, in positive group and negative group (χ²=3.837, <i>P</i>=0.048). The most frequent infection sites were lower respiratory tract (5 cases, 31.25%), abdominal cavity (5 cases, 31.25%) and surgical incision (4 cases, 25.00%). There was no significant difference in postoperative infection rate among patients with different CTP, MELD and surgical methods (<i>P</i>>0.05). One case (1.28%) was infected with the same pathogenic bacteria as PS contamination 3 weeks after liver transplantation, and died of multiple organ failure. There was no significantly difference in the acute rejection rate (1,3.13% and 2, 4.35%) and mortality (2,6.25% and 5,10.87%) between the two groups (<i>P</i>>0.05). Conclusion Contamination of the PS is frequent in liver transplantation, and it is the risk factor for postoperative infection of recipients. Early targeted antimicrobial treatment against pathogens cultured from PS play a positive role in reducing the contamination-associated infection rate after liver transplantation.

Outcomes of Kidney Transplantation in the Elderly Recipients.

Introduction:In a developing country with a predominantly young population, the valid assumption is directed toward medical care toward the young. However, as medical technology has advanced, quality care has ensured better survival for the elderly population also. The aim of this study was to determine the clinical outcomes in elderly patients undergoing kidney transplantation.Materials and Methods:A retrospective analysis of 1150 patients who had undergone live related renal transplantation was done from January 2006 to December 2014. These patients were divided into two groups; Group 1: age >60 years (N = 150), Group 2: age 18–60 years (N = 1000). The clinical outcomes were compared.Results:The mean age in Group 1 was 69 ± 7.5 years (SD ± 7.5), and group 2 was 41 ± 8 years. In groups 1 and 2, males were 80% and 82%; death censored graft survival at 5 years was 82% and 87%; patient survival at 5 years was 86% and 94%, respectively. The incidence of biopsy-proven acute rejection was similar in both groups (11.3 vs. 10.2%, P = 0.12). Urinary tract infection was the most common infectious complication. Sepsis was the primary cause of death in both groups.Conclusion:In the elderly patients who underwent kidney transplantation, satisfactory graft function, and patient survival were maintained over a period of 60 months. Urinary tract infections were common, and sepsis was the most common cause of death with a surviving allograft. The acute rejection and mortality rates were comparable to the literature published from India so far.

Immunosuppression trends in solid organ transplantation: The future of individualization, monitoring, and management.

Immunosuppression regimens used in solid organ transplant have evolved significantly over the past 70years in the United States. Early immunosuppression and targets for allograft success were measured by incidence and severity of allograft rejection and 1-year patient survival. The limited number of agents, infancy of human leukocyte antigen (HLA) matching techniques and lack of understanding of immunoreactivity limited the early development of effective regimens. The 1980s and 1990s saw incredible advancements in these areas, with acute rejection rates halving in a short span of time. However, the constant struggle to achieve the optimal balance between under- and overimmunosuppression is weaved throughout the history of transplant immunosuppression. The aim of this paper is to discuss the different eras of immunosuppression and highlight the important milestones that were achieved while also discussing this in the context of rational agent selection and regimen design. This discussion sets the stage for how we can achieve optimal long-term outcomes during the next era of immunosuppression, which will move from universal protocols to patient-specific optimization.

A multi-center study on safety and efficacy of immune checkpoint inhibitors in cancer patients with kidney transplant

Immune checkpoint inhibitors (ICIs) are widely used for various malignancies. However, their safety and efficacy in patients with a kidney transplant have not been defined. To delineate this, we conducted a multicenter retrospective study of 69 patients with a kidney transplant receiving ICIs between January 2010 and May 2020. For safety, we assessed the incidence, timing, and risk factors of acute graft rejection. For efficacy, objective response rate and overall survival were assessed in cutaneous squamous cell carcinoma and melanoma, the most common cancers in our cohort, and compared with stage-matched 23 patients with squamous cell carcinoma and 14 with melanoma with a kidney transplant not receiving ICIs. Following ICI treatment, 29 out of 69 (42%) patients developed acute rejection, 19 of whom lost their allograft, compared with an acute rejection rate of 5.4% in the non-ICI cohort. Median time from ICI initiation to rejection was 24 days. Factors associated with a lower risk of rejection were mTOR inhibitor use (odds ratio 0.26; 95% confidence interval, 0.09-0.72) and triple-agent immunosuppression (0.67, 0.48-0.92). The objective response ratio was 36.4% and 40% in the squamous cell carcinoma and melanoma subgroups, respectively. In the squamous cell carcinoma subgroup, overall survival was significantly longer in patients treated with ICIs (median overall survival 19.8 months vs. 10.6 months), whereas in the melanoma subgroup, overall survival did not differ between groups. Thus, ICIs were associated with a high risk of rejection in patients with kidney transplants but may lead to improved cancer outcomes. Prospective studies are needed to determine optimal immunosuppression strategies to improve patient outcomes.

Impact of transiting from fluorescent polarisation immunoassay to high-performance liquid chromatography–tandem mass spectrometry for immunosuppressant levels analysis in kidney transplant patients

Background: High-performance liquid chromatography–tandem mass spectrometry (HPLC-TMS) is preferred to fluorescent polarisation immunoassay (FPIA) in therapeutic drug monitoring (TDM), as it only measures active drug. Our hospital replaced FPIA with HPLC-TMS for analysis of calcineurin inhibitor (CNI) levels. Preliminary studies demonstrated significantly lower CNI levels with HPLC-TMS versus FPIA in kidney transplant recipients (KTRs). Most studies evaluating CNI exposure in KTRs used FPIA, posing challenges in interpreting HPLC-TMS levels. This study aimed to compare the effectiveness and safety outcomes in the one-year period before (FPIA period) and after (HPLC-TMS period) the switch. Methods: A retrospective cohort study was conducted on KTRs receiving ciclosporin (CsA) or tacrolimus (FK). Primary effectiveness end points were biopsy-proven acute rejection (BPAR) rate and estimated glomerular filtration rate (eGFR); safety end points were viral infections and hospitalisation for infection. The secondary end point was change in CNI levels during the FPIA versus HPLC-TMS periods. Results: A total of 307 patients were analysed (CsA n=182, FK n=125). BPAR only occurred in two patients in the HPLC-TMS period among the CsA cohort ( p=0.50), but it occurred in six patients in the FPIA period and one patient in the HPLC-TMS period ( p=0.13) among the FK cohort. Median eGFR were similar in both periods (CsA: 52.2 mL/min/1.73 m2 (interquartile range (IQR) 39.8–67.6) vs. 52.5 mL/min/1.73 m2 (IQR 37.1–68.0), p=0.65; FK: 57.7 mL/min/1.73 m2 (IQR 39.1–80.0) vs. 56.4 mL/min/1.73 m2 (IQR 33.5–76.7), p=0.08). There were no significant differences in safety outcomes. The median change in CNI levels from the FPIA period to the HPLC-TMS period was –20.5% (IQR –32.5 to –3.9) and –6.9% (IQR –17.7 to 8.0) among CsA and FK cohorts, respectively ( p&lt;0.01). Conclusion: The switch from FPIA to HPLC-TMS for CNI TDM in KTRs did not yield significant changes in clinical end points.

Comparison of different induction dosing of CD3+ cell count based anti-thymocyte globulin for deceased donor kidney transplantation: single center experience

Background: The rabbit anti-thymocyte globulin (ATG) is the most widely used lymphocyte depleting agent in renal transplanta tion. This can be expected to have a profound immune inducing effect, but it has been not widely used in Korea due to concerns about side effects such as leukopenia, thrombocytopenia, and infection. This has made it necessary to find the minimum dosing to show adequate immunosuppressive effects. So, we compared the clinical features of CD3+ cell count based ATG use with a cumulative dose of 3 mg/kg and 4 mg/kg as an induction immunosuppressant. Methods: Fifty-one patients have received deceased donor kidney transplantation with ATG induction therapy in Bongseng Me morial Hospital from 2013 to 2020. And they were divided into two groups: patients who treated with cumulative dose 3.0 mg/kg of ATG (group A) and 4.0 mg/kg (group B). We compared patient’s survival and graft’s survival in both groups. The data were col lected regarding recipients’ panel reactive antibody, CD3+ lymphocyte count, immunosuppressant, viral infection, acute rejection, and adverse events. Results: The demographic characteristics of the two groups were comparable. The incidence of delayed graft function was sta tistically significantly lower in the cumulative dose 4 mg/kg group. There was no statistically significant difference in the graft’s survival and serum creatinine between the two groups, but it was slightly better in 4 mg/kg group. The incidence rates of acute rejection and infectious events as cytomegalovirus disease or urinary tract infection were not significantly different between the two groups. CD3+ lymphocyte count was statistically significantly decreased until 6 months after transplantation in both groups compared to before transplantation. Conclusions: We suggest that ATG induction with cumulative dose of 4 mg/kg would be safe and effective for deceased donor kidney transplantation in Korea.

Impact of kidney and recipient weight incompatibility on the allograft outcomes in kidney transplant recipients with pre-transplant diabetes mellitus: a single center retrospective cohort study

Background: The aim of this study was to analyze the impact on the adverse allograft outcome of transplanting relatively small kidneys in patients with pre-transplant diabetes mellitus (DM). Methods: From January 2010 to December 2018, 1,290 kidney transplants (KTs) were performed in Seoul St. Mary’s Hospital. Of these, 793 cases of non-sensitized living donor KT recipients were enrolled. They were divided into four groups (non-DM large kidney, non-DM small kidney, DM large kidney, and DM small kidney) according to the median kidney weight and recipient weight ratio (2.9 g/kg) and presence or absence of pre-transplant DM. The primary outcome of this study was death censored graft loss (DCGL) rate. Results: There was no significant difference in the biopsy-proven acute rejection rate among the four groups. DM small kidney group showed the highest DCGL rate (18/131 [13.7%], P=0.004) and was to be the independent risk factor for DCGL (adjusted haz ard ratio, 2.829; P=0.003). Moreover, renal function after 4 years of transplantation worsened faster in the DM small kidney group compared to other groups, and allograft survival decreased after 1 year of transplantation. Conclusions: Our results suggest that transplanting large kidneys rather than small kidneys is considered to have an advantage in terms of allograft outcome in pre-transplant DM patients, and this should be considered in donor selection.

Optimization of de novo belatacept-based immunosuppression administered to renal transplant recipients.

Kidney transplant recipients administered belatacept‐based maintenance immunosuppression present with a more favorable metabolic profile, reduced incidence of de novo donor‐specific antibodies (DSAs), and improved renal function and long‐term patient/graft survival relative to individuals receiving calcineurin inhibitor (CNI)‐based immunosuppression. However, the rates and severity of acute rejection (AR) are greater with the approved belatacept‐based regimen than with CNI‐based immunosuppression. Although these early co‐stimulation blockade‐resistant rejections are typically steroid sensitive, the higher rate of cellular AR has led many transplant centers to adopt immunosuppressive regimens that differ from the approved label. This article summarizes the available data on these alternative de novo belatacept‐based maintenance regimens. Steroid‐sparing, belatacept‐based immunosuppression (following T cell–depleting induction therapy) has been shown to yield AR rates comparable to those seen with CNI‐based regimens. Concomitant treatment with belatacept plus a mammalian target of rapamycin inhibitor (mTORi; sirolimus or everolimus) has yielded AR rates ranging from 0 to 4%. Because the optimal induction agent and number of induction doses; blood levels of mTORi; and dose, duration, and use of corticosteroids have yet to be determined, larger prospective clinical trials are needed to establish the optimal alternative belatacept‐based regimen for minimizing early cellular AR occurrence.

Tailored immunosuppression after kidney transplantation - a single center real-life experience

BackgroundKidney allograft survival continuously improved with introduction of novel immunosuppressants. However, also immunologically challenging transplants (blood group incompatibility and sensitized recipients) increase. Between 2006 and 2008, a new tailored immunosuppression scheme for kidney transplantation was implemented at the University Hospital in Zurich, together with an ABO-incompatible transplant program and systematic pre- and posttransplant anti-human leukocyte antigen (HLA) antibody screening by Luminex technology. This study retrospectively evaluated the results of this tailored immunosuppression approach with a particular focus on immunologically higher risk transplants.MethodsA total of 204 consecutive kidney transplantations were analyzed, of whom 14 were ABO-incompatible and 35 recipients were donor-specific anti-HLA antibodies (DSA) positive, but complement-dependent cytotoxicity crossmatch (CDC-XM) negative. We analyzed patient and graft survival, acute rejection rates and infectious complications in ABO-compatible versus -incompatible and in DSA positive versus negative patients and compared those with a historical control group.ResultsOverall patient, death-censored allograft survival and non-death-censored allograft survival at 4 years were 92, 91 and 87%, respectively. We found that (1) there were no differences between ABO-compatible and -incompatible and between DSA positive and DSA negative patients concerning acute rejection rate and graft survival; (2) compared with the historical control group there was a significant decrease of acute rejection rates in sensitized patients who received an induction with thymoglobulin; (3) there was no increased rate of infection among the patients who received induction with thymoglobulin compared to no induction therapy.ConclusionsWe observed excellent overall mid-term patient and graft survival rates with our tailored immunosuppression approach. Induction with thymoglobulin was efficient and safe in keeping rejection rates low in DSA positive patients with a negative CDC-XM.

Pre-emptive immunosuppression using tacrolimus monotherapy does not reduce the rate of early acute rejection in renal transplantation from live donors: a comparative cohort study.

The planned nature of live donor kidney transplantation allows for immunosuppression to be initiated in the pretransplant period. The aim of this study was to determine the effect of pre-emptive immunosuppression on acute rejection rates after live donor kidney transplantation. In two consecutive cohorts of live donor kidneys transplants, 99 patients received pre-emptive immunosuppression with tacrolimus monotherapy for 2weeks prior to transplantation (PET group - first era) and 100 patients received tacrolimus-based immunosuppression commencing on the day of transplantation (control group - second era). The main outcome measure was the incidence of biopsy-proven acute rejection (BPAR) in the first 3months post-transplantation. Tacrolimus levels were significantly higher in the PET group at day 4 post-transplant (PET 9.08±4.57 vs. control 5.92±3.64ng/ml; P<0.0001), but there were no significant differences in tacrolimus levels at day 7 (PET 8.22±3.58 vs. control 7.63±3.56ng/ml; P=0.2452). BPAR was numerically higher in the PET group, but this difference did not reach statistical significance (PET 13/99 vs. control 6/100; P=0.097). There were no differences in allograft function measured by serum creatinine at 1year (PET 130±36 vs. control 142±69μmol/l; P=0.6829). Graft survival at 1year was equivalent in both groups (PET 96.9 vs. control 97.0%; P=0.9915). This study suggests that there is little role for the use of pre-emptive tacrolimus monotherapy in ABO blood group and HLA-compatible live donor kidney transplantation in patients on triple maintenance immunosuppression.

Extracorporeal membrane oxygenation bridge to heart transplant: Trends following the allocation change.

This study compared outcomes of patients bridged with extracorporeal membrane oxygenation (ECMO) to orthotopic heart transplantation (OHT) following the recent heart allocation policy change. The United Network of Organ Sharing Registry (UNOS) database was queried to examine OHT patients between 2010 and 2020 that were bridged with ECMO. Waitlist outcomes and 1-year posttransplant survival were compared between patients waitlisted and/or transplanted before and after the heart allocation policy change. Secondary outcomes included posttransplant stroke, renal failure, and 1-year rejection. A total of 285 waitlisted patients were included, 173 (60.7%) waitlisted under the old policy and 112 (39.3%) under the new policy. New policy patients were more likely to receive OHT (82.2% vs. 40.6%), and less likely to be removed from the waitlist due to death or clinical deterioration (15.0% vs. 41.3%; both p < .001). A total of 165 patients bridged from ECMO to OHT were analyzed, 72 (43.6%) transplanted during the old policy and 93 (56.3%) under the new. Median waitlist time was reduced under the new policy (4 days [interquartile range {IQR}: 2-6] vs. 47 days [IQR: 10-228]). Postoperative renal failure was higher in the new policy group (23% vs. 6%; p = .002), but rates of stroke and 1-year acute rejection were equivalent. One-year survival was lower the new policy but was not significant (79.8% vs. 90.3%; p = .3917). The UNOS heart allocation policy change has resulted in decreased waitlist times and higher likelihood of transplant in patients supported with ECMO. Posttransplant 1-year survival has remained comparable although absolute rates are lower.

Long-term Outcomes After Facial Allotransplantation: Systematic Review of the Literature

Background Facial vascularized composite allotransplantation (fVCA) represents a reconstructive approach that enables superior improvements in functional and esthetic restoration compared to conventional craniomaxillofacial reconstruction. Outcome reports of fVCA are usually limited to short-term follow-up or single-center experiences. We merge scientific literature on reported long-term outcome data to better define the risks and benefits of fVCA. Methods We conducted a systematic review of PubMed/MEDLINE databases in accordance with PRISMA guidelines. English full-text articles providing data on at least 1 unique fVCA patient, with ≥ 3 years follow-up, were included. Results The search yielded 1812 articles, of which 28 were ultimately included. We retrieved data on 23 fVCA patients with mean follow-up of 5.3 years. More than half of the patients showed improved quality of life, eating, speech, and motor and sensory function following fVCA. On average, the patients had 1 acute cell-mediated rejection and infectious episode per year. The incidence rates of acute rejection and infectious complications were high within first year posttransplant but declined thereafter. Sixty-five percent of the patients developed at least 1 neoplastic and/or metabolic complication after transplantation. Chronic vascular rejection was confirmed in 2 patients, leading to allograft loss after 8 and 9 years. Two patient deaths occurred 3.5 and 10.5 years after transplant due to suicide and lung cancer, respectively. Conclusions Allograft functionality and improvements in quality of life suggest a positive risk-benefit ratio for fVCA. Recurrent acute rejection episodes, chronic rejection, immunosuppression related complications, and heterogeneity in outcome reporting present ongoing challenges in this field.

Ex vivo delivery of Mirococept: A dose-finding study in pig kidney after showing a low dose is insufficient to reduce delayed graft function in human kidney.

The complement system plays a pivotal role in the pathogenesis of ischemia-reperfusion injury in solid organ transplantation. Mirococept is a potent membrane-localizing complement inhibitor that can be administered ex vivo to the donor kidney prior to transplantation. To evaluate the efficacy of Mirococept in reducing delayed graft function (DGF) in deceased donor renal transplantation, we undertook the efficacy of mirococept (APT070) for preventing ischaemia-reperfusion injury in the kidney allograft (EMPIRIKAL) trial (ISRCTN49958194). A dose range of 5-25mg would be tested, starting with 10mg in cohort 1. No significant difference between Mirococept at 10mg and control was detected; hence the study was stopped to enable a further dose saturation study in a porcine kidney model. The optimal dose of Mirococept in pig kidney was 80mg. This dose did not induce any additional histological damage compared to controls or after a subsequent 3hours of normothermic machine perfusion. The amount of unbound Mirococept postperfusion was found to be within the systemic dose range considered safe in the Phase I trial. The ex vivo administration of Mirococept is a safe and feasible approach to treat DGF in deceased donor kidney transplantation. The porcine kidney study identified an optimal dose of 80mg (equivalent to 120mg in human kidney) that provides a basis for further clinical development.

Two Decades of Deceased Donor Kidney Transplantation at Ahmedabad, India.

Gujarat, Tamil Nadu, Telangana, Maharashtra, Kerala, Chandigarh, and Karnataka are states in India with active programs for deceased donor kidney transplant. We report our experience of 2 decades of deceased donor kidney transplant at the Institute of Kidney Diseases and Research Center, Dr. H. L. Trivedi Institute of Transplantation Sciences, Ahmedabad, Gujarat, India. This single-center retrospective study comprised data from 831 deceased donor kidney transplant recipients between January 1, 1997 and December 31, 2018. Mean recipient age was 38 ± 14 years; 564 were male, and 267 were female. Mean donor age was 45.3 ± 17.13 years; 565 were men, and 266 were women. Between January 1, 1997 and March 15, 2020, 5838 kidney transplants were completed, including 4895 living donor kidney transplants, 943 deceased donor kidney transplants, and 440 kidney paired donation transplants. Over the mean follow-up time of 8 ± 5.4 years, patient survival rate was 70% (n = 581) and death-censored graft survival rate was 84% (n = 698). Delayed graft function was shown in 210 patients (25%) and biopsy-proven acute rejection rate in 180 patients (21%). Our experience of favorable outcomes with deceased donor kidney transplants has expanded the donor pool in many ways, including transplant from expanded criteria donors to younger recipients; transplant from older donors to older recipients; donation after cardiac death; successful intercity organ procurement; dual-kidney transplant; en bloc transplant from a pediatric deceased donor; and transplant from brain death deceased donors who died from neurotoxic snakebite, recurrent primary brain tumor, bacterial meningitis, or head injury, or with disseminated intravascular coagulation and deranged renal functions. The pathway to increase organ donation was investigated. Deceased donor kidney transplant can achieve acceptable graft function with patient/graft survival, which may encourage the use of this approach to increase the number of available organs.

Heart Transplantation Survival Outcomes of HIV Positive and Negative Recipients

In the era of antiretroviral therapy, HIV-positive patients have reduced mortality from HIV infection and increased morbidity from end-stage heart failure. The number of HIV-positive heart transplantation recipients remains scant. Long-term survival has not been rigorously studied. We compared survival outcomes of heart transplantation in HIV-positive recipients with those of HIV-negative recipients. Clinical data from all adult heart transplantations were extracted from the United Network for Organ Sharing dataset. The impact of recipient HIV status was analyzed with Cox proportional hazards modeling, 1:3 propensity score matching, and Kaplan-Meier survival analysis. Seventy-five HIV-positive recipients and 29,848 HIV-negative recipients were identified. Race distributions differed between the recipient groups, with black patients comprising a larger proportion of the HIV-positive recipient group (46.7% vs 20.9%, P < .001). The mean year of transplant was significantly later in the HIV-positive recipient group. The rate of acute rejection in the HIV-positive group was higher than in the HIV-negative group (38.7% vs 17.7%, P < .001), as was rate of antirejection treatment administration such as intravenous immunoglobulin or plasmapheresis (26.7% vs 10.4%, P < .001). There was no difference in 30-day, 1-year, and 5-year survival of HIV-positive recipients vs HIV-negative recipients. Recipient HIV infection was not a significant covariate in predicting survival in a Cox proportional hazards model. Short-term and moderate-term survival after heart transplantation is similar for HIV-positive recipients and HIV-negative recipients, although data are very limited. This finding suggests that HIV-positive recipients should not be excluded from transplant candidacy solely based on HIV serostatus.

Experience of heart transplantation with an extended cold ischemic time of donor heart

Aim. A retrospective analysis of the outcomes of heart transplantation (HT) with extended cold ischemic time of donor heart (more than 4 hours) versus heart transplantation with short cold ischemia time (less than 4 hours).Material and methods. The retrospective analysis included 52 recipients who underwent HT in the period from July 20, 2012 to October 23, 2019 in Meshalkin National Medical Research Center. The patients were divided into two groups: group 1 (n=26) — orthotopic HT with extended cold ischemic time (more than 240 minutes), group 2 (n=26) — short cold ischemia time (less than 240 minutes). The effect of cold ischemia duration on hospital survival, the function of donor heart, and the postoperative course was assessed.Results. A retrospective analysis revealed a higher rate of hospital survival in the group of recipients with extended cold ischemic time (more than 240 minutes) 88,5% compared to 80,7% in the second group. There was no difference between the groups in the acute rejection rate, the need for inotropic agents, mechanical circulatory support, and cardiac pacing, as well as the incidence of postoperative renal failure and infectious complications.Conclusion. Due to the small number of patients, our experience in HT with extended cold ischemic time does not allow us to draw global conclusions, but a preliminary comparison of HT with extended and short cold ischemic time did not reveal significant advantages in one group or another. This provides a basis for further accumulation of experience and research.

Relationship between antithymocyte globulin, T cell phenotypes, and clinical outcomes in pediatric kidney transplantation.

Depletional induction using antithymocyte globulin (ATG) reduces rates of acute rejection in adult kidney transplant recipients, yet little is known about its effects in children. Using a longitudinal cohort of 103 patients in the Immune Development in Pediatric Transplant (IMPACT) study, we compared T cell phenotypes after ATG or non-ATG induction. We examined the effects of ATG on the early clinical outcomes of alloimmune events (development of de novo donor specific antibody and/or biopsy proven rejection) and infection events (viremia/viral infections). Long-term patient and graft outcomes were examined using the Scientific Registry of Transplant Recipients. After ATG induction, although absolute counts of CD4 and CD8 T cells were lower, patients had higher percentages of CD4 and CD8 memory T cells with a concomitant decrease in frequency of naïve T cells compared to non-ATG induction. In adjusted and unadjusted models, ATG induction was associated with increased early event-free survival, with no difference in long-term patient or allograft survival. Decreased CD4+ naïve and increased CD4+ effector memory T cell frequencies were associated with improved clinical outcomes. Though immunologic parameters are drastically altered with ATG induction, long-term clinical benefits remain unclear in pediatric patients.

HIV-positive deceased donor-to-HIV-positive recipient kidney transplantation: The HOPE must go on.

Nowadays, HIV infection is a chronic disease, this is due to the efficacy of antiretroviral therapy (ART) in the control of viral replication. The prevalence of chronic kidney disease (CKD) among those well-controlled HIV positive (HIV+) patients is higher than in the general population and kidney transplantation has been established as the best therapeutic option for HIV+ patients with end-stage renal disease. However, this population has lower access to transplantation.