Modern Era Of Immunosuppression Research Articles

Post-Transplant Cardiovascular Disease in Kidney Transplant Recipients: Incidence, Risk Factors, and Outcomes in the Era of Modern Immunosuppression.

Introduction: Post-transplant cardiovascular disease (PTCVD) poses a significant challenge in kidney transplantation, potentially impacting graft outcomes and patient survival. This retrospective study aimed to investigate the incidence, risk factors, and consequential impact of PTCVD in kidney transplant recipients (KTRs) devoid of pre-existing cardiovascular disease (CVD). Method: The cohort comprised 1114 KTRs, with 749 individuals included after excluding those with pre-existing CVD and early graft loss. PTCVD encompasses ischemic heart disease, myocardial infarction, arrhythmias, heart failure, stroke, peripheral vascular disease, and valvular heart disease. Competing risk regression analysis was performed to identify predictors of PTCVD, while Cox proportional hazards analysis assessed the impact of PTCVD on graft and recipient survival. Results: The cumulative incidence of PTCVD at 5, 10, and 20 years was 5.4%, 14.3%, and 22.5%, respectively. Competing risk regression identified increased age (sub-hazard ratio [SHR], 1.22; p = 0.036) per decade, duration of dialysis (SHR, 1.07; p = 0.048) per year on dialysis, and the slope of the estimated glomerular filtration rate (SHR, 1.08; p = 0.008) mL/min/year decline as independent predictors of higher-risk PTCVD. A higher baseline estimated glomerular filtration rate (eGFR) was protective (SHR, 0.98; p = 0.032). PTCVD was not significantly associated with death-censored graft loss (adjusted hazard ratio [aHR] 1.31; p = 0.48) but was correlated with higher all-cause graft loss (aHR, 1.71; p = 0.011) and recipient mortality (aHR, 1.97; p = 0.004). Conclusion: This study provides insights into PTCVD predictors. Although not directly associated with graft loss, PTCVD significantly correlates with heightened mortality in kidney transplant recipients, emphasizing the need for enhanced clinical management and surveillance strategies.

Incidence, Risk Factors, and Outcomes of Posttransplant Erythrocytosis Among Simultaneous Pancreas-Kidney Transplant Recipients.

Posttransplant erythrocytosis (PTE) is a well-known complication of kidney transplantation. However, the risk and outcomes of PTE among simultaneous pancreas-kidney transplant (SPKT) recipients are poorly described. We analyzed all SPKT recipients at our center between 1998 and 2021. PTE was defined as at least 2 consecutive hematocrit levels of >51% within the first 2 y of transplant. Controls were selected at a ratio of 3:1 at the time of PTE occurrence using event density sampling. Risk factors for PTE and post-PTE graft survival were identified. Of 887 SPKT recipients, 108 (12%) developed PTE at a median of 273 d (interquartile range, 160-393) after transplantation. The incidence rate of PTE was 7.5 per 100 person-years. Multivariate analysis found pretransplant dialysis (hazard ratio [HR]: 3.15; 95% confidence interval [CI], 1.67-5.92; P < 0.001), non-White donor (HR: 2.14; 95% CI, 1.25-3.66; P = 0.01), female donor (HR: 1.50; 95% CI, 1.0-2.26; P = 0.05), and male recipient (HR: 2.33; 95% CI, 1.43-3.70; P = 0.001) to be associated with increased risk. The 108 cases of PTE were compared with 324 controls. PTE was not associated with subsequent pancreas graft failure (HR: 1.36; 95% CI, 0.51-3.68; P = 0.53) or kidney graft failure (HR: 1.16; 95% CI, 0.40-3.42; P = 0.78). PTE is a common complication among SPKT recipients, even in the modern era of immunosuppression. PTE among SPKT recipients was not associated with adverse graft outcomes, likely due to appropriate management.

European multicenter study on the real-world use and clinical impact of extracorporeal photopheresis after heart transplantation

Aim of this study was to describe the real-world use of extracorporeal photopheresis (ECP) and assess its impact on clinical outcomes in the modern era of heart transplantation. Seven transplant centers from 5 European countries participated in this retrospective, observational, single-arm chart review study. All patients received ECP after heart transplantation in 2015 or later. Data were extracted from medical records between November 2020 and December 2021. Overall, 105 patients were enrolled and followed for an average of 2 years after initiation of ECP. Reasons to start ECP were acute cellular rejection (35.2%), rejection prevention (32.4%), mixed rejection (18.1%), and antibody-mediated rejection (14.3%). Rejection ISHLT grades improved from start to end of ECP treatment in 92% of patients treated with ECP for rejection. Of patients who started ECP to prevent rejection, 88% remained free from any rejection despite a reduction of calcineurin inhibitors. Overall survival was 95%, and no deaths were related to ECP. Safety events occurred in 18 patients, of which 13 experienced complications with venous access. This study, the largest European ECP study in heart transplantation, demonstrates that ECP can effectively be used to treat different rejection types and to prevent rejection in the modern era of immunosuppression. Patients with rejections who have received ECP have shown high response as measured by histological improvements in ISHLT classification. A high percentage of patients in the prevention group remained free from rejection despite reduction in immunosuppression, in particular calcineurin inhibitors.

Allokation von Nieren im Zeitalter des Organmangels in Deutschland

Due to the opt-in solution currently in place in Germany, there is a substantial shortage of deceased organ donors. Therefore, it is critical that the allocation of available organs follows an optimized algorithm and that the potential of living donations is maximized; however, in this respect the current German legislation has major shortcomings. The human leukocyte antigen (HLA) matching system has a large impact on the standard kidney allocation (Eurotransplant kidney allocation system, ETKAS), that is no longer necessary to this extent in the era of modern immunosuppression but continues to put patients with rare HLA types at a disadvantage. As most points are effectively awarded for the accrual of waiting time, kidneys are often awarded to recipients with poor perspectives for organ survival. The aim of the Eurotransplant Senior Program (ESP) is primarily to minimize the cold ischemia time (CIT) even though it has been shown that CIT can be increased to up to 18 h without impairing allograft survival, also for high-risk organs from ≥ 70-year-old donors. At the same time, the preferential allocation of ESP organs within one subregion results in greatly different waiting times within Germany. Also, the only inclusion criterion for the ESP is recipient age, whereas other medical conditions and thus other recipient risk groups (e.g., diabetics) are disadvantaged. The ban on altruistic living kidney donations in Germany impairs the implementation of modern strategies, such as crossover donations, that have become standard internationally. In turn, the full potential of living kidney donations cannot currently be exploited in Germany. The allocation system should be modernized by incorporating new advances from transplantation research, e.g., by allocation according to life years gained.

Bacterial Urinary Tract Infection and Early Asymptomatic Bacteriuria in Kidney Transplantation Still Negatively Affect Kidney Transplant Outcomes in the Era of Modern Immunosuppression and Cotrimoxazole Prophylaxis.

Risk factors and consequences of urinary tract infection (UTI) post-kidney transplant have been variously reported by studies that were heterogenous in immunosuppressants and prophylactic protocols. We aimed to clarify the risks and consequences of UTI in kidney transplant recipients with post-transplantation cotrimoxazole prophylaxis in the context of modern immunosuppression. This retrospective cohort included kidney transplant recipients receiving tacrolimus, mycophenolate, prednisolone, and cotrimoxazole for bacterial UTI prophylaxis. Recipients were categorized into non-UTI and UTI groups. Asymptomatic bacteriuria (ASB) was screened in the first 3 months and was evaluated for association with UTI. Of 348 kidney transplant recipients, 129 were in the UTI group and 219 in the non-UTI group. UTI risk factors were female sex, body mass index ≥ 25 kg/m2, human leukocyte antigen mismatch, and panel reactive antibody ≥ 50%. Recipients with recurrent UTI had inferior allograft function compared with non-UTI recipients. Patient survival was significantly lower in recipients with UTI in the first post-transplant month. Higher degree of immunosuppressions was associated with recurrent UTI and drug-resistant organisms. In conclusion, UTI continues to negatively affect graft function and survival of kidney transplant recipients. Treating ASB in the first 3 months did not reduce the UTI incidence in the first transplantation year.

Relapse and Outcome of Lupus Nephritis After Renal Transplantation in the Modern Immunosuppressive Era.

BackgroundRecurrence of lupus nephritis in the graft is a concern in lupus patients with end-stage renal disease undergoing renal transplantation. The recurrence of lupus nephritis has been variable among different studies depending on the patient characteristics, immunosuppressive regimen, and indications of renal biopsy. Therefore, we investigated the recurrence of lupus nephritis among our patients to see if the new post-transplant regimen has impacted the recurrence.MethodsWe collected data on all recipients with end-stage renal disease secondary to lupus nephritis, who received renal transplants between 2006-2017 in our center. Patient demographics, transplant, and dialysis-related information have been recorded including kidney biopsy, graft loss, and survival were recorded. An association between recurrent lupus nephritis with survival and/or graft loss was examined using survival models.ResultsThe overall mean±SD age at baseline was 42±13 years; 89% were female; 89% were African American; the previous time on dialysis was a median of 4 years (IQR: 2-8 years), 81% received hemodialysis and 31% received living donor transplantation in the cohort. Our patients received the standard immunosuppressive regimen consisting of prednisone, tacrolimus, and mycophenolate mofetil. Four (10.5%) of the 38 patients had biopsy-proven lupus nephritis recurrence. A total of 10 patients (26%) had graft loss or died during the median follow-up time of 1,230 days (IQR: 460-2,227 days). Recurrence of lupus nephritis showed a trend for increased risk of graft loss or patient death (Hazard Ratio: 3.14, 95%Confidence Interval: 0.65-15.24) compared to the recipient without recurrence in our unadjusted proportional Cox regression model.ConclusionThe recurrence rate of lupus nephritis in our patient population is much lower compared to past studies from different immunosuppressive eras. Patients with recurrent lupus nephritis showed an increased risk of graft loss or death.

The Changing Landscape of Pneumocystis Jiroveci Infection in Kidney Transplant Recipients: Single-Center Experience of Late-Onset Pneumocystis Pneumonia

Pneumocystis jiroveci pneumonia (PCP) is a life-threatening pulmonary infection after kidney transplantation (KTx). Its onset in the current era of modern immunosuppression and of routine use of universal PCP prophylaxis seems to differ from its onset in previous decades in terms of late onset with subtle clinical presentation, indicating a need for increased vigilance. We retrospectively studied all KTx recipients from our center who underwent bronchoscopy and bronchoalveolar lavage (BAL) between 2009 and 2018. Of these, all cases with confirmed PCP any time after the first post-KTx year were included in the analysis. Among 60 patients with KTx who had undergone bronchoscopy and BAL, 12 cases with late-onset PCP were identified. PCP appeared late at a median of 10.8 (interquartile range, 2.4-15.8) years after transplantation. Patients' mean age was 59 years, and all were receiving stable low-dose immunosuppression. Most of the patients (67%) had received PCP prophylaxis after KTx. Five out of 12 patients (42%) had concomitant cytomegalovirus (CMV) reactivation at the time of PCP. In almost all cases, clinical presentation was mild. Treatment consisted of trimethoprim-sulfamethoxazole (TMP-SMX) and intravenous corticosteroid administration, and concomitant immunosuppression was temporarily reduced or withdrawn. Outcome was generally good. None of the patients developed respiratory insufficiency or required mechanical ventilation. One patient died as a result of sepsis, and 3 more with preexisting advanced chronic kidney disease subsequently lost their grafts. Renal transplant recipients are at risk of late-onset PCP, even at a steady state of low-dose maintenance immunosuppression. Because of its subtle clinical presentation, high suspicion of the disease is warranted. Its early recognition and proper management are essential for a successful outcome.

P0408KIDNEY TRANSPLANTATION OUTCOMES IN PATIENTS WITH IGA NEPHROPATHY IN THE MODERN ERA OF IMMUNOSUPPRESSION: A CASE CONTROL STUDY

Abstract Background and Aims Advances in immunosuppressants, used for kidney transplantation (KTx) have significantly improved outcomes in this field. We aimed to compare the long-term results of KTx in recipients with IgAN, as cause of end stage kidney disease (ESKD), with those of patients, with non-glomerular causes of renal failure, during the modern era of immunosuppression for KTx. Method This is a retrospective, case control study, in which were included patients who received a KTx after 2000. Patients were eligible to be included, if they had IgAN in a native kidney biopsy specimen and follow up longer than 1 year after KTx. IgAN patients were compared to a control-group of patients with non-glomerular primary causes of ESKD matched for age, gender, date of KTx and donor source. Graft biopsies were performed by clinical indication. Patients with ABO incompatible KTx, preemptive KTx, re-KTx, PRA&amp;gt;50%, major surgical complications during the 1st post-KTx month or non-compliance were excluded from the analysis of outcome. Primary outcomes of interest included graft function, patient and graft survival at end of follow up. The rate of IgAN recurrence in the graft and its impact in renal function and survival were also recorded. Computed GFR was calculated using the Modification of Diet in Renal Disease formula. Results A total of 102 KTx recipients with biopsy-proven IgAN, were compared to 204 controls with non-glomerular causes of ESKD. The mean age of patients with IgAN was 43.2(±10.15) years and 68(66.7%) were men. The mean time in dialysis was 50.2(±48.7) months and 59(57.8%) of them received a graft from a living donor. The mean cold ischemia time was 17.5(±6.7) hours, while 22(21.6%) of patients experienced delayed graft function. 97.05% of patients received induction therapy with an anti-CD25 inhibitor and 99.3% were maintained with a triple immunosuppressive regimen consisted of a mycophenolate mofetil formulation, a calcineurin inhibitor and glucocorticoids. The mean serum creatinine and eGFR at end of follow up were significantly lower for the IgAN group (p=0.001 and p=0.02 respectfully) with no difference in the frequency of acute rejection. However, graft and patient survival were not different even after controlling for follow up longer than one decade. During a mean follow up time of 120.8(±49.1) months, IgAN recurrence in the graft was documented in 23(22.5%) patients. The mean time to recurrence was 47.8(41.8) months, with a mean serum creatinine 1.83(±0.52) mg/dl and eGFR of 43.45(±18.4) ml/min/1.73m2 at the end of follow up. Within the IgAN group, although graft function was significantly lower in patients with disease recurrence, compared with that of patients without recurrence (p=0.003), graft loss remained not different between these two subgroups (p=0.49). Conclusion In the newer era of immunosuppression, long-term outcomes of KTx in patients with IgAN, as primary disease, appear significantly improved, and although graft function was significantly lower in patients with IgAN at the end of follow up, graft and patient survival was not different, compared to patients with non-glomerular causes of ESKD. Recurrence of IgAN in the graft was documented in 22.5% of patients and was associated with significantly lower eGFR at end of follow up compared to patients without recurrence but it did not impact graft survival in this time period.

Is Body Mass Index a Significant Independent Risk Factor for Graft Failure and Patient Death in the Modern Immunosuppressive Era?

ObjectivesPrevious studies have shown that kidney transplant recipients with a high body mass index (BMI) have inferior graft and patient outcomes compared to patients with a lower BMI. We hypothesized that there would be secular improvements in outcomes among high BMI recipients. We used data from the United Network for Organ Sharing (UNOS) to determine whether obesity affects patient and graft outcomes following kidney transplantation in the modern immunosuppressive era. MethodsThe study sample consisted of 69,749 recipients from 1987 to 1999 and 197,986 recipients from 2000 to 2016. BMI values were categorized into 11 tiers: below 18 kg/m2, from 18 to 36 kg/m2 at 2 kg/m2-unit increments, and above 36 kg/m2. We created multivariate models to evaluate the independent effect of BMI on graft and patient outcomes, adjusting for factors known to affect graft success and patient survival. ResultsOverall graft and patient survival has improved for all BMI categories. Cox regression modeling hazard ratios showed that the relative risk for graft loss, patient death, and patient death with a functioning graft in the modern immunosuppressive era (2000 to 2016) has significantly decreased compared to the earlier era (1987 to 1999), especially for living kidney transplant recipients. ConclusionsThe relative risk of graft failure and patient death with increasing BMI has appreciably decreased in the modern immunosuppressive era, especially for living donor transplant recipients. Withholding transplantation from patients with higher BMIs may no longer be justifiable on grounds of worse clinical outcomes.

SAT-092 IS BODY MASS INDEX A SIGNIFICANT INDEPENDENT RISK FACTOR FOR GRAFT FAILURE AND PATIENT DEATH IN THE MODERN IMMUNOSUPPRESSION ERA?

Previous studies have shown that kidney transplant recipients with a high body mass index (BMI) have an inferior graft and patient outcomes compared to patients with a lower BMI. We used data from the United Network for Organ Sharing (UNOS) to determine whether obesity affects patient and graft outcomes following kidney transplantation in the modern immunosuppressive era. The study sample consisted of 69,749 recipients from 1987-1999 and 197,986 recipients from 2000-2016. We created multivariate models to evaluate the independent effect of BMI on graft and patient outcomes, adjusting for factors known to affect graft success and patient survival. Cox regression modeling hazard ratios showed that the relative risk for graft loss, patient death and patient death with a functioning graft in the modern immunosuppressive era (2000-2016) has significantly decreased compared to the earlier era (1987-1999) especially for living kidney transplant recipients. Figure 1. The distribution of pretransplantation BMI according to era. Figure 2. Cox proportional hazards model for graft loss and patient death with graft function according to period by categorized BMI in living kidney transplantation.(A: Relative risk for graft loss in year 1987-1999, B: Relative risk for graft loss in year 2000-2016, C: Relative risk for patient death with graft function in year 1987-1999, D: Relative risk for patient death with graft function in year 2000-2016) The relative risk of graft failure and patient death with increasing BMI has appreciably decreased in the modern immunosuppressive era, especially for living donor transplant recipients. Withholding transplantation from patients with higher BMIs may no longer be justifiable on grounds of worse clinical outcomes.

Epidemiology, Risk Factors, and Outcomes of Opportunistic Infections after Kidney Allograft Transplantation in the Era of Modern Immunosuppression: A Monocentric Cohort Study.

Epidemiology of opportunistic infections (OI) after kidney allograft transplantation in the modern era of immunosuppression and the use of OI prevention strategies are poorly described. We retrospectively analyzed a single-center cohort on kidney allograft adult recipients transplanted between January 2008 and December 2013. The control group included all kidney recipients transplanted in the same period, but with no OI. We analyzed 538 kidney transplantations (538 patients). The proportion of OI was 15% (80 and 72 patients). OI occurred 12.8 (6.0–31.2) months after transplantation. Viruses were the leading cause (n = 54, (10%)), followed by fungal (n = 15 (3%)), parasitic (n = 6 (1%)), and bacterial (n = 5 (0.9%)) infections. Independent risk factors for OI were extended criteria donor (2.53 (1.48–4.31), p = 0.0007) and BK viremia (6.38 (3.62–11.23), p < 0.0001). High blood lymphocyte count at the time of transplantation was an independent protective factor (0.60 (0.38–0.94), p = 0.026). OI was an independent risk factor for allograft loss (2.53 (1.29–4.95), p = 0.007) but not for patient survival. Post-kidney transplantation OIs were mostly viral and occurred beyond one year after transplantation. Pre-transplantation lymphopenia and extended criteria donor are independent risk factors for OI, unlike induction therapy, hence the need to adjust immunosuppressive regimens to such transplant candidates.

1560. Clinical Presentation of BK Virus-Associated Hemorrhagic Cystitis (HC) After Hematopoietic Cell Transplantation (HCT)

BackgroundBK polyoma virus (BKPyV) has been associated with hemorrhagic cystitis after HCT. Prior studies have examined risk factors for BKPyV-associated HC, but the characteristics of disease, including duration, common presentations, and the spectrum of clinical outcomes, have not been well described. Precise estimates of major clinical endpoints are critical to design clinical trials of novel prevention and treatment agents.MethodsWe retrospectively analyzed HCT patients between 2007 and 2017. Subjects were included if they had macroscopic hematuria (Bedi grade ≥2), a positive urine BKPyV PCR, and at least one plasma BKPyV viral load available after platelet engraftment or Day 28 post-HCT. HC was defined by hematuria and positive urine BKPyV PCR; duration was determined by time to resolution of hematuria. Demographic data, baseline symptoms, and clinical outcomes (e.g., need for bladder irrigation, use of cidofovir) were reviewed.ResultsBKPyV-HC developed in 149 HCT recipients (97.3% allogeneic, 73% myeloablative conditioning) at a median of 54 days post-transplant (IQR 40–73). Seven percent were co-infected with adenovirus at the time of diagnosis. Symptoms and outcomes are shown in Table 1. Of those with plasma viral load testing at the onset of HC, 91% (112/126) had BKPyV viremia with a median viral load of 2,200 copies/mL (IQR 385–9,300). Twenty-nine percent of the cohort received cidofovir.ConclusionWe describe the characteristics of BKPyV-associated HC in HCT recipients in the modern era of immunosuppression. BKPyV-associated HC is a morbid disease in need of improved management strategies; patient-centered estimates of outcomes are crucial for evaluating new agents.Table 1.Symptoms and outcomes of BKPyV-associated HCBKPyV- HC n = 149 (%)Clots in urine*92 (60)Dysuria*124 (81)Frequency*91 (59)Urgency*68 (44)Flank pain*22 (14)Abdominal pain*30 (20)Median duration of symptoms in days (IQR)25 (14–49)Median duration of hematuria or urine clots in days (IQR)18 (12–39)Median duration of phenazopyridine or oxybutynin use in days (IQR)19 (8–34.5)Need for pain medication†109 (71)Need for Foley placement†49 (32)Need for continuous bladder irrigation†26 (17)Need for surgical intervention†9 (6)*At presentation. †Any time during course.Disclosures S. Pergam, Merck: Consultant, Consulting fee; Chimerix: Consultant, Consulting fee. A. Limaye, Novartis: Consultant, Consulting fee. M. Boeckh, Vir Biotechnology: Consultant and Grant Investigator, Consulting fee and Research grant; Chimerix Inc: Consultant, Grant Investigator and Investigator, Consulting fee, Research grant and Research support.

Prospective Analysis of EBV+ PTLD in a Multi-Center Study of Pediatric Transplant Recipients

Post-transplant lymphoproliferative disorder (PTLD) remains a serious problem in the pediatric transplant population. The Clinical Trials of Organ Transplantation in Children (CTOT-C)-06 is an NIH-sponsored multi-institutional study intended to identify viral and immune biomarkers of Epstein-Barr virus (EBV)-associated PTLD. The laboratory studies are ongoing and herein we describe the enrolled and transplanted population to date. Enrollment began in August, 2014 and will continue until August, 2018. At the conclusion of the study all subjects will have a minimum of one year and a maximum of four years of follow-up post-transplant. As of November, 2017 there were 784 pediatric subjects enrolled and 687 children (53% male; 47% female) have received a transplant (50% liver, 22% heart, 22% kidney, 6% small intestine or multi-visceral). The mean age at transplant was 6.4 years (range 0-21 years) and 57% were EBV+, while 35% were EBV- and 8% had unknown EBV status. Of the EBV- subjects, 23% seroconverted during the study period. To date, 17 subjects (6 male, 11 female) have been diagnosed with EBV+ PTLD for an overall incidence of 2.5% (heart, n=5; kidney, n=5; liver, n=5; multivisceral, n=2). The incidence of EBV+ PTLD by organ transplanted was 3.3% in heart, 3.3% in kidney, 1.5% in liver, and 10% in multivisceral. The overall mean time post-transplant of EBV+ PTLD diagnosis was 18.9 months (range 1.7-43.9 months). The mean time post-transplant of EBV+ PTLD diagnosis by organ was 25.9 months in heart recipients, 17.8 months in kidney recipients, 19.6 months in liver recipients and 2.8 months in multivisceral recipients. Eight of the 17 patients diagnosed with EBV+ PTLD received induction medication and 10 were EBV-seronegative at transplantation. The anatomic location of disease was nodal (n=8), tonsillar (n=1) and extranodal (n=8). In summary, we report on the first large prospective US-based multi-center study on EBV+ PTLD in the era of modern immunosuppression and heightened surveillance for EB, and observe a continued incidence of EBV+ PTLD in pediatric transplant recipients. NIH 1UO1AI104342.

Different Patterns of Risk Factors for Mortality according Recipient Age after Renal Transplantation. A Multicenter and Prospective Study at Ten Years in the Clinical Practice

The aim of the present study was to define the most important risk factors for mortality after renal transplantation in a population representing the real medicine in the modern immunosuppressive era. In a multicentric study we included 2592 patients (from 14 hospitals) (Renal Forum Group) who received a renal transplant from deceased donors between 2000-2002 and prospectively followed for 10 years always for the same team. According recipient age, 672 were under forty, 1320 among 40-60 yr and 600 were older than 60 yr. They received steroids, TAC preferently than CyA, and MMF with or without induction (KI 2008). Induction therapy Tymo with steroids, TAC/CyA) and MMF was used in hyperimmunized patients (12.5%). Patient survival at 10 years was 80.5%, statistical significant different depending recipient age: 95% youngs, 84% middle age and 55% older people. At ten years 80% of patients were maintained with TAC/CyA and 30% were steroids free. The most frequent causes of mortality were cardiovascular (CDV), infection and cancer in the three categories. Notably in the group under forty, 30% of deaths were of CDV origin, 19% due to infection and 15% due to cancer. Risk factors for mortality in the total group were: recipient and donor age, reciepint hepatitis C positive, pretransplant CDV, pretransplant diabetes and delayed graft function. In the multivariate analysis, recipient age is a strong risk factor in all groups, however in young patients pretransplant diabetes, in the middle age pretransplant CDV and in older people serum creatinine at 6mo were the most significant risk factors for mortality. Censored death graft survival was 72.6% globally, 76%, 71% and 65% in the three categories according recipient age, respectively. In conclusion, In our current clinical practice 20% of patients died at 10 years posttransplant. Recipient age is a dominant risk factor and notably pretransplant diabetes in young people, pretransplant CDV in middle age and renal function in older people are the most significant factors for mortality. Astellas, Spain.

Re-transplants compared to primary kidney transplants recipients: a mate kidney paired analysis of the OPTN/UNOS database.

Outcomes of kidney re-transplant recipients (RTR) were compared to primary recipients (FTR) from paired donor kidneys. Organ Procurement and Transplantation Network (OPTN) database was used to identify deceased donors (n = 6266) who donated one kidney to an RTR and the mate kidney to an FTR between January 2000 to December 2010. As compared to FTR, RTR were younger (45 vs. 52 yr, p < 0.001) and had higher proportion of plasma reactive antibody >80 (25% vs 7%, p < 0.001). There were higher 0 mismatches in RTR (19% vs. 16%, p < 0.001). There were more pre-emptive transplants in RTR (24% vs. 21%, p = 0.002). Delayed graft function (28% vs. 25%, p = 0.007) was higher in RTR. Patient survival was similar in FTR and RTR groups at one, three, and five yr (95.7%, 90.2%, and 82.5% vs. 95.2%, 89.8% and 82.7%). Allograft survival rates were higher in FTR group compared to RTR group at one, three, and five yr (91.1%, 82.4%, and 70.9% vs. 87.8%, 77.4%, and 66.1% p < 0.001). Death-censored allograft survival rates were higher in FTR group at one, three, and five yr (91.3%, 82.7% and 71.4% vs. 88%, 77.7% and 66.5% p < 0.001). In today's era of modern immunosuppression, graft survival in RTR has improved but remains inferior to FTR when controlling for donor factors.

Maternal compared with paternal donor kidneys are associated with poorer graft outcomes after kidney transplantation

Noninherited maternal human leukocyte antigens may be less detrimental on allograft outcomes after kidney transplantation compared with noninherited paternal antigens, but this association in the era of modern immunosuppression remains unknown. Here we determine the association between parental donor kidneys, acute rejection, and graft failure in primary live-donor parental kidney transplant recipients using data from the Australia and New Zealand Dialysis and Transplant Registry between 1997 and 2012. Of the 1139 recipients followed for a median of 7.2 years (8588 person-years), 652 received kidneys from maternal donors. Compared with paternal donor kidneys, maternal donor kidneys were associated with a significantly increased risk of acute rejection (adjusted odds ratio 1.54; 95% confidence interval [CI], 1.14-2.07) and significant overall graft loss. The latter was confined to recipients who have experienced acute rejection (adjusted hazard ratio 1.60; 95%CI, 1.05-2.43) but not in those who did not experience acute rejection. Thus, our study suggests that recipients of maternal donor kidneys have a greater risk of rejection and graft loss. Hence, clinicians and patients should be cognizant of this association when determining which of the 2 parental donors is most suitable for transplantation.

Outcomes following Kidney transplantation in IgA nephropathy: a UNOS/OPTN analysis.

This study updates assessment of post-transplant outcomes in IgAN patients in the modern era of immunosuppression. Using UNOS/OPTN data, patients ≥18yr of age with first kidney transplant (1/1/1999 to 12/31/2008) were analyzed. Multivariable Cox regression models and propensity score-based matching techniques were used to estimate hazard ratios (HRs) for death-censored allograft survival (DCGS) and patient survival in IgAN compared to non-IgAN. Results of multivariable regression were stratified by donor type (living vs. deceased). A total of 107, 747 recipients were included (4589 with IgAN and 103158 with non-IgAN). Adjusted HR for DCGS showed no significant difference between IgAN and non-IgAN. IgAN had higher patient survival compared to non-IgAN (HR 0.54, 95% CI 0.47-0.62, p<0.0001 for deceased donors; HR 0.42, 95% CI 0.33-0.54, p<0.0001 for living donors). Propensity score-matched analysis was similar, with no significant difference in DCGS between matched groups and higher patient survival in IgAN patients compared to non-IgAN group (HR 0.54, 95% CI 0.47, 0.63; p-value <0.0001). IgAN patients with first kidney transplant have superior patient survival and similar graft survival compared to non-IgAN recipients. Results can be used in prognostication and informed decision-making about kidney transplantation in patients with IgAN.

MP85-04 PREDICTIVE RISK FACTORS OF POST-TRANSPLANT HIGH-GRADE CMV REACTIVATION IN CMV-SEROPOSITIVE PATIENTS IN THE MODERN IMMUNOSUPPRESSIVE ERA

You have accessJournal of UrologyTransplantation & Vascular Surgery: Renal Transplantation & Vascular Surgery II1 Apr 2015MP85-04 PREDICTIVE RISK FACTORS OF POST-TRANSPLANT HIGH-GRADE CMV REACTIVATION IN CMV-SEROPOSITIVE PATIENTS IN THE MODERN IMMUNOSUPPRESSIVE ERA Mitsuru Saito, Shigeru Satoh, Hiroshi Tsuruta, Susumu Akihama, Takamitsu Inoue, Shintaro Narita, Norihiko Tsuchiya, and Tomonori Habuchi Mitsuru SaitoMitsuru Saito More articles by this author , Shigeru SatohShigeru Satoh More articles by this author , Hiroshi TsurutaHiroshi Tsuruta More articles by this author , Susumu AkihamaSusumu Akihama More articles by this author , Takamitsu InoueTakamitsu Inoue More articles by this author , Shintaro NaritaShintaro Narita More articles by this author , Norihiko TsuchiyaNorihiko Tsuchiya More articles by this author , and Tomonori HabuchiTomonori Habuchi More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2015.02.1858AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Cytomegalovirus (CMV) prophylaxis is recommended for CMV-seronegative kidney transplant recipients (R-) receiving the grafts from CMV seropositive donors (D+). Meanwhile, whether R+ patients need universal CMV prophylaxis remains unclear. Most of R+ patients with low-grade CMV reactivation show spontaneous remission without deteriorating the graft function and survival. In addition, valganciclovir (VGCV) possibly causes some adverse effects and GCVresistant CMV. Although targeting CMV prophylaxis to R+ patients is ideal, there are few reports addressing the risk factors of highgrade CMV reactivation in R+ patients in the modern immunosuppressive era. METHODS Since July 2004, consecutive 151 R+ patients who received the kidney from D+ in our hospital were enrolled in this study. No recipients received CMV prophylaxis. The induction immunosuppressive therapy was consisted of tacrolimus, MMF, steroid, and basiliximab. Patients with immunological high risks (ABO-incompatible or donor specific anti-HLA antibody positive) received a single-low dose of rituximab and 3 to 4 sessions of apheresis prior to transplantation. High-grade CMV reactivation was defined as CMV-antigenemia (Ag) positive cells becoming higher than 10/200,000 blood leukocytes during the clinical course. The CMV-Ag level was monitored at 2 to 3-weekly intervals until 6 months, and at monthly intervals from 6 to 12 months post-transplantation. We investigated the predictive risk factors of high-grade CMV reactivation in R+ patients. RESULTS The proportion of high-grade CMV reactivation was 29.8% (45/151) in this series. All patients who developed CMV reactivation were cured by VGCV or GCV successfully without inducing GCV-resistant CMV. Although no significant difference was found in the graft function, the graft survival was significantly shorter in the R+ patients with CMV reactivation than those without (p = 0.019). In multivariate analysis, the pre-transplant low-IgG titer against CMV (p = 0.014), potent immunosuppressive protocol (p = 0.019), and high level of MPA AUC 0-12 at 1 month after transplantation (p = 0.045) were independently associated with the development of high-grade CMV reactivation in R+ patients. CONCLUSIONS The development of high-grade CMV reactivation deteriorated the graft survival in R+ patients in the modern immunosuppressive era. Pre-transplant low-IgG titer against CMV, potent immunosuppressive protocol, and high MPA level were predictive risk factors for the development of high-grade CMV reactivation. © 2015 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 193Issue 4SApril 2015Page: e1068 Advertisement Copyright & Permissions© 2015 by American Urological Association Education and Research, Inc.MetricsAuthor Information Mitsuru Saito More articles by this author Shigeru Satoh More articles by this author Hiroshi Tsuruta More articles by this author Susumu Akihama More articles by this author Takamitsu Inoue More articles by this author Shintaro Narita More articles by this author Norihiko Tsuchiya More articles by this author Tomonori Habuchi More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

MP85-05 RADICAL PROSTATECTOMY IN RENAL TRANSPLANT RECIPIENTS: COMPARISON OF FEASIBILITY AND PERIOPERATIVE OUTCOMES BASED ON SURGICAL APPROACH.

INTRODUCTION AND OBJECTIVES: Cytomegalovirus (CMV) prophylaxis is recommended for CMV-seronegative kidney transplant recipients (R-) receiving the grafts from CMV seropositive donors (Dþ). Meanwhile, whether Rþ patients need universal CMVprophylaxis remains unclear. Most of Rþ patients with low-grade CMV reactivation show spontaneous remissionwithout deteriorating thegraft function and survival. In addition, valganciclovir (VGCV) possibly causes some adverse effects and GCVresistant CMV. Although targeting CMV prophylaxis to Rþ patients is ideal, there are few reports addressing the risk factors of highgrade CMV reactivation in Rþ patients in the modern immunosuppressive era. METHODS: Since July 2004, consecutive 151 Rþ patients who received the kidney from Dþ in our hospital were enrolled in this study. No recipients received CMV prophylaxis. The induction immunosuppressive therapy was consisted of tacrolimus, MMF, steroid, and basiliximab. Patients with immunological high risks (ABO-incompatible or donor specific anti-HLAantibody positive) received a single-low dose of rituximab and 3 to 4 sessions of apheresis prior to transplantation. High-grade CMV reactivation was defined as CMV-antigenemia (Ag) positive cells becoming higher than 10/200,000 blood leukocytes during the clinical course. The CMV-Ag levelwasmonitoredat2 to3-weekly intervalsuntil 6months,andat monthly intervals from6 to 12months post-transplantation.We investigated the predictive risk factors of high-grade CMV reactivation in Rþ patients. RESULTS: The proportion of high-grade CMV reactivation was 29.8% (45/151) in this series. All patients who developedCMV reactivation were cured by VGCV or GCV successfully without inducing GCV-resistant CMV. Although no significant difference was found in the graft function, the graft survival was significantly shorter in the Rþ patients with CMV reactivation than those without (p 1⁄4 0.019). In multivariate analysis, the pre-transplant low-IgG titer against CMV (p 1⁄4 0.014), potent immunosuppressive protocol (p 1⁄4 0.019), and high level of MPA AUC 0-12 at 1 month after transplantation (p 1⁄4 0.045) were independently associated with the development of high-grade CMV reactivation in Rþ patients. CONCLUSIONS: The development of high-grade CMV reactivation deteriorated the graft survival in Rþ patients in the modern immunosuppressive era. Pre-transplant low-IgG titer against CMV, potent immunosuppressive protocol, and high MPA level were predictive risk factors for the development of high-grade CMV reactivation.

84 Predictive risk factors of post-transplant high-grade CMV reactivation in CMV-seropositive patients in the modern immunosuppressive era

INTRODUCTION AND OBJECTIVES: Cytomegalovirus (CMV) prophylaxis is recommended for CMV-seronegative kidney transplant recipients (R-) receiving the grafts from CMV seropositive donors (Dþ). Meanwhile, whether Rþ patients need universal CMVprophylaxis remains unclear. Most of Rþ patients with low-grade CMV reactivation show spontaneous remissionwithout deteriorating thegraft function and survival. In addition, valganciclovir (VGCV) possibly causes some adverse effects and GCVresistant CMV. Although targeting CMV prophylaxis to Rþ patients is ideal, there are few reports addressing the risk factors of highgrade CMV reactivation in Rþ patients in the modern immunosuppressive era. METHODS: Since July 2004, consecutive 151 Rþ patients who received the kidney from Dþ in our hospital were enrolled in this study. No recipients received CMV prophylaxis. The induction immunosuppressive therapy was consisted of tacrolimus, MMF, steroid, and basiliximab. Patients with immunological high risks (ABO-incompatible or donor specific anti-HLAantibody positive) received a single-low dose of rituximab and 3 to 4 sessions of apheresis prior to transplantation. High-grade CMV reactivation was defined as CMV-antigenemia (Ag) positive cells becoming higher than 10/200,000 blood leukocytes during the clinical course. The CMV-Ag levelwasmonitoredat2 to3-weekly intervalsuntil 6months,andat monthly intervals from6 to 12months post-transplantation.We investigated the predictive risk factors of high-grade CMV reactivation in Rþ patients. RESULTS: The proportion of high-grade CMV reactivation was 29.8% (45/151) in this series. All patients who developedCMV reactivation were cured by VGCV or GCV successfully without inducing GCV-resistant CMV. Although no significant difference was found in the graft function, the graft survival was significantly shorter in the Rþ patients with CMV reactivation than those without (p 1⁄4 0.019). In multivariate analysis, the pre-transplant low-IgG titer against CMV (p 1⁄4 0.014), potent immunosuppressive protocol (p 1⁄4 0.019), and high level of MPA AUC 0-12 at 1 month after transplantation (p 1⁄4 0.045) were independently associated with the development of high-grade CMV reactivation in Rþ patients. CONCLUSIONS: The development of high-grade CMV reactivation deteriorated the graft survival in Rþ patients in the modern immunosuppressive era. Pre-transplant low-IgG titer against CMV, potent immunosuppressive protocol, and high MPA level were predictive risk factors for the development of high-grade CMV reactivation.