Received Kidney Grafts Research Articles

#1836 Post-transplant evolution of kidney grafts from expanded criteria donors with diabetes

Abstract Background and Aims The increase in the number of potential kidney transplant (KT) recipients has led to efforts to increase the donor pool, including organs from expanded criteria donors (ECD) with diabetes mellitus (DM). However, doubts persist about their viability, especially with DM donors. Our aim is to analyze the post-transplant evolution of KT patients who have received kidney grafts from ECD with or without DM. Method Retrospective observational study of KT who received ECD kidney graft in our center between January 2014 and November 2023. We divided KT patients into two groups based on donor DM; ECD with DM and ECD without DM. We analyzed baseline characteristics and post-KT evolution. Univariate and multivariate statistical analysis was performed using Cox regression (SPSS Statistics 29.0). Results During the study period, 161 patients received grafts from ECD at our center. Pre-implant biopsies were performed on all grafts, with 15 discarded due to high histological score. Of these, 13 (86%) were diabetic donors (p < 0.001). The mean age of donors was 66 years, and that of recipients was 61. Forty-three (26%) KT recipients had a diabetic donor. Clinical characteristics of patients are reflected in Table 1. Conclusion Donors with DM showed adequate survival in our experience, similar to that of other ECD. This may be due to a more stringent pre-transplant clinical selection or pre-KT histological assessment. The development of new techniques is necessary to more precisely asses the viability of these grafts pre-KT, allowing for an increased utilization.

CYP3A5 Expressor Genotype of the Transplanted Kidney Increases the Risk of Preterm Graft Loss and Acute Rejection

Introduction: Tacrolimus is metabolized mainly in the liver by the CYP3A enzyme family, with a particularly well-documented role of CYP3A5. CYP3A5 is also expressed in the renal tissue and is present in the transplanted kidney. To date, the association between donor CYP3A5 polymorphisms and transplant outcome remains poorly understood. The aim of this study was to assess the effect of donor CYP3A5 expression on early and long-term transplant outcomes. Methods: A retrospective cohort study including 207 patients who received kidney grafts from 110 deceased donors was conducted at a single Central European Center. Tissue samples from all donors were studied for CYP3A5 single-nucleotide polymorphism (rs776746). Death-censored graft loss within 5-year follow-up, acute rejection occurrence, and kidney function, measured using serum creatinine and MDRD eGFR, were compared between groups of patients with allografts from rs776746 carriers (CYP3A5 expressors) and noncarriers (CYP3A5 nonexpressors). Results: Recipients who received kidneys from CYP3A5 expressors (n = 24) were at significantly higher risk of death-censored graft loss within 5-year follow-up (adjusted HR, 95% CI: 6.82, 2.01–23.12; p = 0.002) and acute rejection within the 1st posttransplant year (adjusted OR, 95% CI: 4.62, 1.67–12.77; p = 0.003) than those who did not (n = 183). The median time to loss of function was 1.93 [IQR; 0.77–3.19] years. Conclusions: Donor CYP3A5 expressor status is associated with worse renal graft survival and a higher risk of acute rejection. Determination of donor CYP3A5 genotype is a potentially useful tool that may improve kidney transplant outcomes.

Lymphocele in Kidney Transplantation: A Comparison of Ligation and Non-ligation Technique of Iliac Lymphatic Dissection

To compare the incidence of lymphocele in kidney recipients following 2 lymphatic vessel division techniques: ligation and non-ligation. Retrospective reviews of the records of 402 patients with end-stage renal disease who underwent kidney transplantation from April 2015 to December 2019 at Siriraj Hospital. Four hundred two patients were included in the study: 54.9% of the patients were male, and the patient's mean age was 41 years. There were 25.1% and 74.9% that received kidney grafts from living and deceased donors, respectively. The preoperative renal replacement therapies were 83.3% hemodialysis, 12.9% peritoneal dialysis, and 3.7% preemptive transplantation. Two hundred forty-nine patients received lymphatic division with the ligation technique and 153 patients received the non-ligation. Lymphoceles were found in 31 cases (7.7%). Lymphocele occurrence in the ligation group was lower than in the non-ligation group: 5.2% compared to 11.8% (P value=.017). There were 22.6% of lymphoceles that had a spontaneous resolution with no treatment. The ligation of iliac lymphatic vessels during division reduced the incidence of lymphoceles non-ligation.

Expression of human CD47 in pig glomeruli prevents proteinuria and prolongs graft survival following pig-to-baboon xenotransplantation.

Nephrotic syndrome is a common complication of pig-to-baboon kidney xenotransplantation (KXTx) that adversely affects outcomes. We have reported that upregulation of CD80 and down-regulation of SMPDL-3b in glomeruli have an important role in the development of proteinuria following pig-to-baboon KXTx. Recently we found induced expression of human CD47 (hCD47) on endothelial cells and podocytes isolated from hCD47 transgenic (Tg) swine markedly reduced phagocytosis by baboon and human macrophages. These observations led us to hypothesize that transplanting hCD47 Tg porcine kidneys could overcome the incompatibility of the porcine CD47-baboon SIRPα interspecies ligand-receptor interaction and prevent the development of proteinuria following KXTx. Ten baboons received pig kidneys with vascularized thymic grafts (n=8) or intra-bone bone marrow transplants (n=2). Baboons were divided into three groups (A, B, and C) based on the transgenic expression of hCD47 in GalT-KO pigs. Baboons in Group A received kidney grafts with expression of hCD47 restricted to glomerular cells (n=2). Baboons in Group B received kidney grafts with high expression of hCD47 on both glomerular and tubular cells of the kidneys (n=4). Baboons in Group C received kidney grafts with low/no glomerular expression of hCD47, and high expression of hCD47 on renal tubular cells (n=4). Consistent with this hypothesis, GalT-KO/hCD47 kidney grafts with high expression of hCD47 on glomerular cells developed minimal proteinuria. However, high hCD47 expression in all renal cells including renal tubular cells induced an apparent destructive inflammatory response associated with upregulated thrombospondin-1. This response could be avoided by a short course of weekly anti-IL6R antibody administration, resulting in prolonged survival without proteinuria (mean 170.5 days from 47.8 days). Data showed that transgenic expression of hCD47 on glomerular cells in the GalT-KO donor kidneys can prevent xenograft nephropathy, a significant barrier for therapeutic applications of xenotransplantation. The ability to prevent nephrotic syndrome following KXTx overcomes a critical barrier for future clinical applications of KXTx.

Impact of HLA polymorphisms among cadaveric donors on kidney graft allocation

This study provides data on HLA-A, -B, and -DRB1 frequencies among 861 end-stage renal disease (ESRD) patients from Croatia and estimates the benefit of the kidney exchange program by comparing HLA distribution and assessing HLA mismatches (MMs) within a group of ESRD patients who received kidney grafts from 707 cadaveric donors (422 from Croatia and 285 from Eurotransplant).Patients positive for HLA-B*07, -B*08, or -B*44 genes more often received a kidney from ET donors, while HLA-DRB1*11 and -DRB1*16 positive patients more frequently received a kidney from CRO donors.ABDR MM 000 was more frequently present in the case of transplantation from ET donors, while MM 222 was significantly more frequent when the donor was from Croatia. Sensitized patients received kidney more frequently from ET donors (P < .0001). A large pool of organ donors with different HLA gene distributions allows for a higher probability of transplantation from HLA highly matched donor.

P0212IMMUNOSUPPRESSIVE TREATMENT OF PATIENTS WITH ANCA ASSOCIATED VASCULITIS (AAV) IN CHRONIC DIALYSIS PROGRAM

Abstract Background and Aims There are numerous studies on AAV, however, data describing the use of immunosuppressive treatment in AAV patients (pts) on chronic dialysis are limited. Most studies found that the incidence of infection is much higher than that of relapses (0.05-0.1 pt per year), suggesting that immunosuppression should be stopped after 3 months in pts with end-stage renal failure. Material, Method Retrospective analysis of immunosuppressive treatment in pts on chronic dialysis due to AAV. From 1995 to 2019 139 pts were diagnosed with AAV. Among them 38 patients (26 female, 12 male, mean age 58 years) needed chronic dialysis (&amp;gt;90 days) due to severe renal AAV (29), relapsing renal disease (6) or progressive CKD without active vasculitis (3). Results Microscopic polyangiitis was diagnosed in 20, granulomatosis with polyangiitis in 14, eosinophilic granulomatosis with polyangiitis in 4 cases. MPO-ANCA was more frequent than PR3-ANCA (23 vs 12), in one case both ANCAs were positive, and in two cases both were negative. The mean dialysis duration was 55 months (4–180 months). 18 pts (47%) had at least one relapse during the observation period. The mean age, the clinical diagnosis, the type of ANCA did not cause any difference, the dialysis time was longer in the relapsed pts group (72+/-38 vs. 40+/-29 months) compared to pts without relapse. High relapse rate was seen in 6 cases. Three patient had continuously high level of PR3-ANCA without relapse or any sign of disease. Relapses were treated mostly with combined therapy of corticosteroids and oral/intravenous cyclophosphamide followed by azathioprin maintenance therapy. Cortocosteroid alone was used in 7 pts, rituximab in five pts as maintenance therapy. Serious infection (needing hospital care) rate during any immunosuppressive treatment was 0.12 per patient-years. There were 12 deaths on dialysis, the median time to death was 61 months (range 3–132). The deaths rate was higher (9/18 vs. 4/20) in relapsed pts, 4 occurring during immunosuppressive treatment. Causes of deaths were cardiovascular (8), sepsis (3), malignancy (2 pts). Seven pts received kidney grafts, 15 pts remained on dialysis, but in three case dialysis could be discontinued after 16, 35 and 36 months. Conclusion Our study points to higher relapse rate and lower serious infection rate in AAV pts on chronic dialysis compared to previous studies. It seems reasonable to continue immunosuppression above 3 months in pts remaining on chronic dialysis. This approach may decrease the relapse rate preventing damage of other organs, allowing transplantation and in some pts recovery of renal function could be achieved.

Dialysis therapy is associated with peripheral marginal zone B-cell augmentation

Chronic kidney disease stage 5 (CKD5) dialysis patients who stay long term in uremic environment often exhibit several, poorly defined, immune impairments. In this study, we assessed peripheral virus-specific effector/memory cells and subpopulations of T, B and DC cells using ELISPOT and FACS methods in 74 low-risk kidney transplant candidates without anti-HLA antibodies, prior to transplantation in pre-emptive (never experienced dialysis) and dialysis cohorts. There was difference in circulating marginal zone B cells (MZB) (IgDhighCD27high) between dialysis patients and those receiving kidney grafts pre-emptively (P = .002). Patients treated on dialysis >12 months had also 4.2-fold greater risk of increased absolute numbers of MZB (95%CI:1.6–11.2; P = .004). There were no other differences in B-, T- and DC-cell subsets. Numbers of effector/memory T cells reactive to major opportunistic virus-specific antigens (CMV, BKV and EBV) were not affected by dialysis. Non-sensitised dialysis-treated patients displayed significantly more circulating MZB compared to those CKD5 patients that had never undergone dialysis therapy.

Midterm Outcome of Kidney Transplantation From Donors With Thin Basement Membrane Nephropathy.

Thin basement membrane nephropathy (TBMN) is the most common cause of persistent glomerular hematuria. Most individuals with TBMN show a benign course, although it can be difficult to distinguish it from early stages of progressive renal diseases. However, only limited studies address the prognosis of donors with TBMN and their recipients. From 2007 to 2016, 11 recipients received kidney grafts from donors with TBMN, and their clinical data were analyzed retrospectively. Follow-up protocol kidney biopsies were given to the recipients at 10 days and 1 year after transplantation. The donors were also received a follow-up evaluation of their renal function and were interviewed via telephone survey. All donors were living, and their kidney grafts showed TBMN on pretransplantation biopsy. The recipients were followed for 57.4 ± 28.6 months posttransplantation. Seven recipients showed acute rejection by a median of 9.7 months, and all recipients recovered their renal function after treatment. Although 1 kidney failed due to graft arterial occlusion, the functions of the others were preserved during the follow-up period. The donors were followed for 41.0 ± 39.1 months and additionally contacted via telephone survey (in total, 56.8 ± 32.0 months). All the donors maintained their renal function upon clinical follow-up without significant complications and denied any discomfort at the time of the telephone interview. Kidney transplant donors with TBMN and their recipients maintained their renal function through midterm follow-up without significant complications. Therefore, kidney transplantation from donors with TBMN could be a safe option.

A model of acute antibody mediated rejection in mouse renal transplantation

Objective To establish a model of acute antibody mediated rejection (AMR) in mouse kidney transplantation. Methods 6-8 weeks old male C3H (H2k) and BALB/c (H2d) mice were used as skin or kidney graft donors and recipients, respectively. All animals were provided by Beijing vital river experimental animal technical limited company. Recipient animals were divided into 2 groups. AMR group, recipient animals were presensitized by transplanting skin grafts before one week of kidney transplantation (n=10). Cell mediated rejection (CMR) group, recipient animals received kidney grafts without being presensitized by skin transplantation (n=10). Normal balb/c mice acted as control (n=3). Animal survival time was recorded and renal allograft function of creatinine (Cr) and blood urea nitrogen (BUN) was monitored. On the fifth day after kidney transplantation, recipient animals were sacrificed, analysis of renal graft histology based on Banff 2013 for rejection diagnosis, immunohistochemistry for mouse IgG, complement fragment C3d deposition detection intragraft, and flow cytometry for circulating donor specific antibody (DSA)-IgG, IgM detection were performed. Results The mean survival time of AMR group was (4.4±1.1) d and longer than 60 days for CMR goup. Graft function of serum Cr [ (415.6±25.6) μmol/L] and BUN [ (2 394.0±94.0) pmol/L] were remarkably increased on postoperative 2 d in AMR group. CMR control group showed normal serum levels of Cr [ (77.8±7.2) μmol/L] and BUN [ (1 343.0±233.9) pmol/L] on 60 days after kidney transplantation. On 5 d after kidney transplantation, the macroscopic morphology of renal grafts in AMR group was significantly swelling while grafts in CMR group were normal. The circulating IgG DSA level in AMR group was remarkably higher than CMR group with mean fluorescence intensity (MFI) values 223.0±29.0 vs. 134.5±39.6. The serum IgM DSA level did not change significantly with MFI values 9.2±0.1 vs. 10.0±0.7. Grafts in AMR group demonstrated dilation of peritubular capillaries (PTC), peritubular capillaritis, glomerulitis, glomerular/tubular necrosis and interstitial inflammation, hemorrhage, and edema. Extensively deposition of IgG and C3d intragraft were also observed in AMR group, while mild changes presented in CMR group which showed no significant difference from the normal control BALB/c mice. Conclusion We successfully established a model of acute AMR in C3H→BALB/c mouse kidney transplantation by presensitizing recipient mice using donor-strain derived skin transplantation at 1 week prior to kidney transplantation, which showed significantly different from non-presensitized recipient mice. Key words: Kidney transplantation; Antibody mediated rejection; Model, animal; Mice

Kidney Transplantation in Slovenia From 1970 to 2015

This report gives an overview of kidney transplantation in Slovenia, a country with a population of 2.1 million and one transplant center. The establishment of a national transplant organization resulted in the acceptance of Slovenia into Eurotransplant (ET) in 2000. Between 1970 and 2015, 1158 kidney transplantations were performed. From 1970 to 2009, 126 patients were transplanted from living related donors, only two in the ET period. From 1986 to 1999, 239 patients received kidney grafts from deceased donors, while 793 patients were transplanted from deceased donors after joining ET. In ET period, 1- and 5-year patient survival rates were 98.1% and 93.8%, and the concomitant graft survival rates were 94.3% and 87.5%, respectively. During the ET period, the number of deceased donor kidney transplants per year was three times higher than in the 14 years before. Patient and graft survival rates have been very good and entirely comparable to those in large reports.

Trasplante renal de donante vivo entre gemelos monocigotos sin inmunosupresión de mantenimiento

Standard immunosuppression is used in about 60% of patients receiving kidney grafts from their monozygotic twins living donor although an alloimmune response can not take place. The aim of the study was to asses the clinical response in patients receiving renal grafts from a monozygotic twin living donor when no immunosuppressive therapy is used. MethodsThis is a retrospective observational study of patients receiving kidney grafts from their monozygotic twins from 1969 to 2013. The following data were recorded: age, renal graft recipient's primary disease, renal function, renal survival and overall survival. Immu- nosuppressive therapy included a single intraoperative dose of methylprednisolone 500 mg and no maintenance immunosuppression. ResultsFive patients with kidney grafts from their monozygotic twins were dentified in our centre. Mean age at transplantation was 33 years (27-39). One-year overall survival and graft survival were 100%. Mean creatinine level was 0.96 ± 0.2 one year after transplantation, and 1.2 ± 0.37 mg/dl at most recent follow-up. Two patients died with a functional graft more than 15 years after kidney transplantation (causes were melanoma and cardiovascular event respectively). Follow-up was lost in a patient one year after transplantation. Two patients are alive with a functioning graft at 18 months and 42.5 years after transplantation respectively. ConclusionKidney transplantation from a monozygotic twin living donor is associated with excellent clinical outcomes. Immunosuppressive therapy to suppress alloimmune response is probably unnecessary if zygosity has been confirmed.

Kidney transplant from a monozygotic twin living donor with no maintenance immunosuppression

Standard immunosuppression is used in about 60% of patients receiving kidney grafts from their monozygotic twins living donor although an alloimmune response can not take place. The aim of the study was to asses the clinical response in patients receiving renal grafts from a monozygotic twin living donor when no immunosuppressive therapy is used. MethodsThis is a retrospective observational study of patients receiving kidney grafts from their monozygotic twins from 1969 to 2013. The following data were recorded: age, renal graft recipient's primary disease, renal function, renal survival and overall survival. Immunosuppressive therapy included a single intraoperative dose of methylprednisolone 500 mg and no maintenance immunosuppression. ResultsFive patients with kidney grafts from their monozygotic twins were dentified in our centre. Mean age at transplantation was 33 years (27–39). One-year overall survival and graft survival were 100%. Mean creatinine level was 0.96±0.2 one year after transplanta tion, and 1.2±0.37 mg/dl at most recent follow-up. Two patients died with a functional graft more than 15 years after kidney transplantation (causes were melanoma and cardiovascu lar event respectively). Follow-up was lost in a patient one year after transplantation. Two patients are alive with a functioning graft at 18 months and 42.5 years after transplantation respectively. ConclusionKidney transplantation from a monozygotic twin living donor is associated with excellent clinical outcomes. Immunosuppressive therapy to suppress alloimmune response is probably unnecessary if zygosity has been confirmed.

Female Sexual Function and Depression After Kidney Transplantation: Comparison Between Deceased- and Living-Donor Recipients

Disturbances in sexual function and depression are a common feature in women with chronic renal failure. Living-donor kidney transplantation seems to warrant better results than its cadaveric counterpart in many aspects but its impact on post-transplantation sexual function remains unknown. This study aimed to compare post-transplantation sexual function and depression in women receiving kidney grafts from living and deceased donors. From a single-center prospective database of 2016 renal transplantations between June 2011 and June 2013, we enrolled 50 sexually active women after kidney transplantation. Female sexual function was evaluated with the Female Sexual Function Index Questionnaire (FSFI) and depression was assessed using the Beck Depression Inventory–II (BDI-II) scale. Thirty-four patients referred the questionnaires. The sexual domains of satisfaction and desire were significantly better in living-donor receptors; in all other domains evaluated by FSFI no statistically significant difference was encountered between groups, although living-donor receptors tended to report better function. Total BDI-II was well correlated with total FSFI score in our study cohort (Spearman's rho = −0.80, P < .001). Only 34.6% of women referred to have discussed sexual issues with their physicians before transplantation, whereas 73.1% stated it would have been important. In conclusion, living-donor transplantation exerted a positive effect on women's sexual function.

Analysis of Factors Influencing on Living Kidney Donors and Deceased Kidney Donors Transplantation Results

Introduction Recognizing factors influencing kidney transplantation results may significantly affect therapeutic decisions made before, during and post transplantation. Aim of the study The aim of the study was to analyse factors influencing kidney graft function. Material and methods The group of 993 patients who received kidney graft from deceased and living donors, at Department of General and Transplantation Surgery, Baby Jesus Clinical Hospital in Warsaw, between January 1996 and August 2010 was analysed regarding factors that may have an influence on kidney transplantation results. Factors contingent from donor, recipient and time of kidney preservation were analysed. Results A multivariate analysis exhibited that time of dialyses prior transplantation is statistically significant factor influencing recipient’s survival (p=0.017). We proved that donor age is a variable that affects both recipient and graft survival. The higher number of mismatches HLA, the lower graft survival (p=0,0028). Cold ischaemia time (CIT) (OR=1.182), HBV infection (OR=1.58) as well as number of mismatch HLA (OR=1.1496), are the factors that influenced on frequency of delayed graft function (DGF) episodes. Moreover, we evidenced that the cause of graft failure affects graft survival. Patients, who suffer from IgA nephropathy, as well as hypertensive nephropathy, have the worst survival ratio after kidney transplantation. Patients who had had received a kidney graft from cadaveric donor with intracranial bleeding had higher creatinine serum concentration up to 5 years post transplantation in comparison with recipients whose kidney had come from donor with cranial trauma (p<0.005). Conclusions Factors that significantly influence on kidney graft function are: time of dialyses prior transplantation, number of mismatch HLA, cause of renal failure, HBV infection and CIT.

CTLA4 Gene Polymorphisms Influence the Incidence of Infection after Renal Transplantation in Chinese Recipients

BackgroundImmunosuppressive therapy is usually administered following renal transplantation to protect the graft from rejection. However, this often causes complications such as infections to occur. Single nucleotide polymorphisms (SNPs) within the CTLA4 gene, such as −1772T/C (rs733618), +49A/G (rs231775) and +6230 G/A (rs3087243), can affect graft rejection and the long-term clinical outcome of organ transplantation. The role of CTLA4 SNPs in T cell-mediated immunity in renal transplantation and association with infection after transplantation is unknown.MethodsIn this study, the risk of infection according to CTLA4 SNPs was investigated in 304 patients who received kidney graft transplants between 2008 and 2012.ResultsThe frequency of the rs4553808 GG genotype was significantly higher in recipients with viral infection (14.89%) than in those without infections (3.50%) (Bonferroni-adjusted p = 0.005). A significant difference (p = 0.001) in patients with the rs4553808 GG genotype from those with the AA+AG genotypes was found in the viral cohort using the log-rank test. A significant association was found between the rs4553808 genotype and onset of viral infection in transplant recipients (p = 0.001). The frequencies of the CGTAG and CGCAG haplotypes were significantly higher in the viral infection group (9.6% and 5.3%) than in the non-viral infection group (3.8% and 1.4%) (p = 0.0149 and p = 0.0111). No association between any CTLA4 SNP and bacterial infection was found. Multivariate analyses revealed that one risk factor, the use of antibody induction therapy (p = 0.007), was associated with bacterial infection, and two risk factors, antibody use (p = 0.015) and recipient rs4553808 genotype (p = 0.001), were associated with viral infection.ConclusionsThe rs4553808 GG genotype may be a risk factor for viral infection in kidney transplantation. The CTLA4 haplotypes CGTAG and CGCAG were partially associated with the development of viral infection in Chinese kidney transplant recipients.

Plasmapheresis and Immunoadsorption for Treatment and Prophylaxis of Recurrent Focal Segmental Glomerulosclerosis in Adult Recipients of Deceased Donor Renal Grafts

Recurrent focal segmental glomerulosclerosis has a great impact on kidney graft survival. This retrospective study presents immunoadsorption-plasmapheresis treatment and outcome in our renal graft recipients with significant post-transplant proteinuria (>1 g/day) and focal segmental glomerulosclerosis in native kidneys. Recurrence was defined as occurrence of nephrotic range proteinuria or biopsy-confirmed diagnosis. Successful treatment was defined as sustained reduction of proteinuria to <1 g/day. From 2000 through 2011, 548 adult patients received kidney grafts from deceased donors. In 20 of these patients (3.6%) end-stage renal disease was a consequence of focal segmental glomerulosclerosis. Recurrence was confirmed in five of seven treated patients. Immunoadsorption-plasmapheresis treatment was successful in five patients (70%). Their age at disease diagnosis in native kidneys was 12 to 44 years. Time to end-stage renal disease was 3 to 14 years. Recipient age at transplantation was 21 to 61 years. Onset of significant proteinuria was 2 to 87 days after transplantation. Immunoadsorption or plasmapheresis started 1 to 7 days after recurrence of significant proteinuria. Treatment period was 1 to 103 months and 12 to 206 procedures were performed per patient. Follow-up period after cessation of plasmapheresis was 11 to 58 months. Final urine protein/creatinine ratio was 8.8 to 98.0 mg/mmol and final serum creatinine was 63 to 148 μmol/L. Follow-up after transplantation was 18 to 135 months. One patient was still on treatment. One graft was lost to recurrence. No serious adverse effects occurred during immunoadsorption and plasmapheresis. Immunoadsorption and plasmapheresis appears to be successful in the majority of patients, probably due to their early start.

Long-Term Tolerance to Kidney Allografts After Induced Rejection of Donor Hematopoietic Chimerism in a Preclinical Canine Model.

Abstract 2991Allogeneic hematopoietic cell transplantation provides a reliable method for inducing tolerance towards solid organ grafts. However, this procedure can result in graft-versus-host disease (GVHD) thereby limiting its application. Here we test the hypothesis that mixed chimerism can be intentionally reverted to host hematopoiesis without rejection of a kidney graft. Recipient dogs were given 2 Gy total body irradiation (TBI) before and a short course of immunosuppression after marrow infusion from dog leukocyte antigen-identical littermates. All dogs achieved stable mixed chimerism. After a mean of 20 weeks, one cohort of dogs received kidney transplants from their respective marrow donors. Subsequently, recipients were reconditioned with 2 Gy TBI and given autologous granulocyte-colony stimulating factor-mobilized leukocytes (recipient leukocyte infusion) that had been collected before marrow transplant. Dogs receiving a second TBI and recipient leukocyte infusion without a kidney transplant rejected their donor hematopoietic graft within 3 weeks. Dogs that received kidney grafts, followed by a second TBI and recipient leukocyte infusion, rejected their marrow graft without rejecting their transplanted kidneys for periods greater than one year. Mixed chimerism may be clinically reverted to 100% recipient without rejection of a kidney allograft. This model has potential applications in understanding the mechanism of split tolerance. This finding may have application towards minimizing the risk of GVHD in solid organ transplant patients given hematopoietic cell transplantation from HLA-identical donors. Disclosures:No relevant conflicts of interest to declare.

Long-Term Tolerance to Kidney Allografts After Induced Rejection of Donor Hematopoietic Chimerism in a Preclinical Canine Model

Allogeneic hematopoietic cell transplantation provides a reliable method for inducing tolerance toward solid organ grafts. However, this procedure can result in graft-versus-host disease, thereby limiting its application. Here, we test the hypothesis that mixed chimerism can be intentionally reverted to host hematopoiesis without rejection of a kidney graft. Recipient dogs were given 2-Gy total-body irradiation (TBI) before and a short course of immunosuppression after marrow infusion from dog leukocyte antigen-identical littermates. All dogs achieved stable mixed chimerism. After a mean of 20 weeks, one cohort of dogs received kidney transplants from their respective marrow donors. Subsequently, recipients were reconditioned with 2-Gy TBI and given autologous granulocyte colony-stimulating factor-mobilized leukocytes (recipient leukocyte infusion [RLI]) that had been collected before marrow transplantation. Dogs receiving a second TBI and RLI without a kidney transplant rejected their donor hematopoietic graft within 3 weeks. Dogs that received kidney grafts, followed by a second TBI and RLI, rejected their marrow graft without rejecting their transplanted kidneys for periods greater than 1 year. Mixed chimerism may be clinically reverted to 100% recipient without rejection of a kidney allograft. This finding may have application toward minimizing the risk of graft-versus-host disease in solid organ transplantation patients given hematopoietic cell transplantation from human leukocyte antigen-identical donors.

Intraoperative Resistance Index Measured With Transsonic Flowmeter on Kidney Graft Artery Can Predict Early and Long-term Graft Function

Introduction Resistive index (RI) measured by Doppler sonography in the early period after kidney transplantation is a well-known predictor of kidney transplant outcome. The purpose of this study was to analyze the impact of RI values calculated intraoperatively in renal allograft artery using transit time flowmetry (TTF) on both early and long-term kidney graft function. Material and Methods TTF was performed on 72 patients who received kidney grafts fed by a single artery. TTF was performed before wound closure. We excluded patients with an early acute rejection (n = 8), an early graft loss (n = 2), or primary graft nonfunction (n = 1). Recipients were divided into RI tertile groups. The initial kidney graft function was defined as immediate (IGF), slow or delayed. Kidney graft estimated glomerular filtration rate (eGFR) was analyzed upon long-term follow-up. Results Patients with a low RI (< 0.57) showed the highest incidence of immediate graft function (65% versus 5.3%), whereas the high RI group (> 0.70). Show the most frequent rate of delayed graft function (52.6% versus 15%). Recipients with low RI values displayed significantly better eGFR (by at least 12 mL/min/1.73 m 2) than those with medium or high RI values at all analyzed times; subjects with medium or high RI showed similar eGFR at 48-months. Conclusion An high RI value measured intraoperatively was a valuable predictor of inferior early and long-term kidney graft function.

Terapia de indução com alentuzumabe em receptores de transplante renal

Induction therapy has been used in sensitized patients, re-transplants, and in patients who have high risk to delayed graft function (DGF) after renal transplantation. Retrospective study with aim to compare transplant endpoints between recipients of deceased donors which have received induction with alemtuzumab (n = 9) versus thymoglobulin (n = 18). Patients were matched for age, duration of dialysis treatment and cold ischemia time. There were no differences at demographic characteristics. All patients received kidney grafts from deceased donors and 67% of these donors met the expanded criteria. The incidence of DFG was similar in alemtuzumab and thymoglobulin groups, 55% and 56%. At 12 months, rates of rejection free survival (67% versus 89%, p = 0,13), graft survival (62,5% versus 76,6%; p = 0,73), graft with death censored (62,5% versus 76,6%; p = 0,82) and patient survival (83,3% versus 81,2%; p = 0,63) were similar between the two groups. Viral infections and renal function were similar between groups. At the end of the first month, alemtuzumab patients displayed a fewer lymphocyte number (135 ± 78 versus 263 ± 112 N/mm³, p < 0,05) followed by a more rapid recovery after 3 months (day 90: 683 ± 367 versus 282 ± 72 N/mm³; p < 0,05). Cost associated with alemtuzumab and thymoglobulin inductions therapies were R$ 1,388.00 and R$ 7,398.00. In this cohort of patients, alemtuzumab induction showed efficacy and safety comparable to thymoglobulin but with significant cost reduction.