scholarly journals Pretransplant C3d-Fixing Donor-Specific Anti-HLA Antibodies Are Not Associated with Increased Risk for Kidney Graft Failure

2018 ◽  
Vol 29 (9) ◽  
pp. 2279-2285 ◽  
Author(s):  
Elena G. Kamburova ◽  
Bram W. Wisse ◽  
Irma Joosten ◽  
Wil A. Allebes ◽  
Arnold van der Meer ◽  
...  
Keyword(s):  
Kidney Transplant ◽  
Graft Survival ◽  
Graft Failure ◽  
Kidney Graft ◽  
Kidney Transplant Recipients ◽  
Serum Samples ◽  
Hla Antibodies ◽  
Transplant Patients ◽  
Increased Risk ◽  
Positive Serum

Background Complement-fixing antibodies against donor HLA are considered a contraindication for kidney transplant. A modification of the IgG single-antigen bead (SAB) assay allows detection of anti-HLA antibodies that bind C3d. Because early humoral graft rejection is considered to be complement mediated, this SAB-based technique may provide a valuable tool in the pretransplant risk stratification of kidney transplant recipients.Methods Previously, we established that pretransplant donor-specific anti-HLA antibodies (DSAs) are associated with increased risk for long-term graft failure in complement-dependent cytotoxicity crossmatch-negative transplants. In this study, we further characterized the DSA-positive serum samples using the C3d SAB assay.Results Among 567 pretransplant DSA-positive serum samples, 97 (17%) contained at least one C3d-fixing DSA, whereas 470 (83%) had non–C3d-fixing DSA. At 10 years after transplant, patients with C3d-fixing antibodies had a death-censored, covariate-adjusted graft survival of 60%, whereas patients with non–C3d-fixing DSA had a graft survival of 64% (hazard ratio, 1.02; 95% confidence interval, 0.70 to 1.48 for C3d-fixing DSA compared with non–C3d-fixing DSA; P=0.93). Patients without DSA had a 10-year graft survival of 78%.Conclusions The C3d-fixing ability of pretransplant DSA is not associated with increased risk for graft failure.

scholarly journals Impact of diabetes mellitus developing after kidney transplantation on patient mortality and graft survival: a meta-analysis of adjusted data

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Hailing Lin ◽  
Jiqiang Yan ◽  
Lei Yuan ◽  
Beibei Qi ◽  
Zhujing Zhang ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Kidney Transplant ◽  
Graft Survival ◽  
Graft Failure ◽  
Meta Analysis ◽  
Pooled Analysis ◽  
Diabetic Patients ◽  
Kidney Transplant Recipients ◽  
Increased Risk ◽  
All Cause Mortality

Abstract Background Post-transplant diabetes mellitus (PTDM) occurs in 10–30% of kidney transplant recipients. However, its impact on mortality and graft survival is still ambiguous. Therefore, the current study aimed to analyze if PTDM increases mortality and graft failure by pooling multivariable-adjusted data from individual studies. Methods PubMed, Embase, and CENTRAL, and Google Scholar were searched for studies comparing mortality and graft failure between PTDM and non-diabetic patients. Multivariable-adjusted hazard ratios (HR) were pooled in a random-effects model. Results Fourteen retrospective studies comparing 9872 PTDM patients with 65,327 non-diabetics were included. On pooled analysis, we noted a statistically significant increase in the risk of all-cause mortality in patients with PTDM as compared to non-diabetics (HR: 1.67 95% CI 1.43, 1.94 I2 = 57% p < 0.00001). The meta-analysis also indicated a statistically significant increase in the risk of graft failure in patients with PTDM as compared to non-diabetics (HR: 1.35 95% CI 1.15, 1.58 I2 = 78% p = 0.0002). Results were stable on sensitivity analysis. There was no evidence of publication bias on funnel plots. Conclusion Kidney transplant patients developing PTDM have a 67% increased risk of all-cause mortality and a 35% increased risk of graft failure. Further studies are needed to determine the exact cause of increased mortality and the mechanism involved in graft failure.

FC 128NON-HLA ANTIBODIES AND EPLET MISMATCHES IN KIDNEY TRANSPLANT RECIPIENTS WITH A HISTOLOGICAL PICTURE OF ANTIBODY-MEDIATED REJECTION WITH AND WITHOUT HLA DONOR-SPECIFIC ANTIBODIES

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Marta Crespo ◽  
Laura Llinas ◽  
Dolores Redondo Pachon ◽  
Carrie L Butler ◽  
Javier Gimeno ◽  
...  
Keyword(s):  
Kidney Transplant ◽  
Graft Survival ◽  
Kidney Transplant Recipients ◽  
Serum Samples ◽  
Hla Antibodies ◽  
Aortic Endothelial Cells ◽  
Specific Antibodies ◽  
Antibody Mediated Rejection ◽  
Before And After ◽  
Donor Specific Antibodies

Abstract Background and Aims Correlation between antibody-mediated rejection (ABMR) and HLA donor-specific antibodies (DSA) is strong but imperfect in kidney transplant (KT) recipients, raising the possibility of other detrimental antibodies contributing to ABMR. The role of non-HLA antibodies on outcomes is not well known. Method We retrospectively assessed KT biopsies scored according to Banff’15 classification. Pre- and post-KT serum samples were checked for HLA and non-HLA antibodies (MICA-Ab, angiotensin II type 1 receptor (AT1R)-Ab, endothelin-1 type A receptor (ETAR)-Ab and crossmatches with primary aortic endothelial cells (EC-XM)). We also analyzed HLA epitope mismatches between donors and recipients. Results One-hundred eighteen patients with normal (n=19), ABMR histology (n=52) or IFTA (n=47) in their biopsy were studied. Graft survival was worse in ABMR patients (p=0.003). Pre-KT HLA-DSA were more frequent in ABMR cases (p=0.006). At biopsy, 73% ABMR patients had HLA-DSA (p&lt;0.001). Pre-KT AT1R-Ab were more frequent in ABMR compared with IFTA and normal cases (p=0.003), without differences in other non-HLA antibodies. Fourteen patients with histological ABMR (27%) had no detectable HLA-DSA post-KT and only 3 had non-HLA Ab. However, these ABMR-DSA- cases showed similar biopsy changes and graft survival compared with ABMR-DSA+. Pre- or post-KT non-HLA antibodies other than AT1R-Ab were detected similarly in ABMR and in normal or IFTA cases. Both total class II and DRB1 epitope mismatches were associated with postransplant DSA and ABMR-DSA+. Multivariate analysis showed that both pre-KT HLA-DSA and AT1R-Ab (DSA: OR: 3.39 [1.20-9.59], p=0.021; AT1R-Ab: OR: 5.31 [1.75-16.10], p=0.003) were strong independent predictors of postransplant ABMR-DSA+ (Table 1). Conclusion Despite highly prevalent HLA-DSA before and after transplantation in KT with histological ABMR, 27% of cases did not show circulating HLA-DSA. Pre-KT AT1R-Ab associated with ABMR-DSA+, but not MICA-Ab, ETAR-Ab or EC-XM+. Any of them associated significantly with ABMR-DSA-. Epitope mismatch predicted both postransplant DRB-DSA and ABMR-DSA+. Detection of pre-KT HLA-DSA and/or AT1R-Ab, together with HLA epitope mismatch assessment, are valuable tools for better DSA and ABMR prediction in KT patients.

scholarly journals Integrative Analyses of Circulating Small RNAs and Kidney Graft Transcriptome in Transplant Glomerulopathy

2021 ◽  
Vol 22 (12) ◽  
pp. 6218
Author(s):  
Canan Kuscu ◽  
Manjari Kiran ◽  
Akram Mohammed ◽  
Cem Kuscu ◽  
Sarthak Satpathy ◽  
...  
Keyword(s):  
Gene Expression ◽  
Kidney Transplant ◽  
Small Rna ◽  
Kidney Graft ◽  
Kidney Transplant Recipients ◽  
Serum Samples ◽  
Tissue Integration ◽  
Transplant Patients ◽  
Mrna Targets ◽  
Transplant Glomerulopathy

Transplant glomerulopathy develops through multiple mechanisms, including donor-specific antibodies, T cells and innate immunity. This study investigates circulating small RNA profiles in serum samples of kidney transplant recipients with biopsy-proven transplant glomerulopathy. Among total small RNA population, miRNAs were the most abundant species in the serum of kidney transplant patients. In addition, fragments arising from mature tRNA and rRNA were detected. Most of the tRNA fragments were generated from 5′ ends of mature tRNA and mainly from two parental tRNAs: tRNA-Gly and tRNA-Glu. Moreover, transplant patients with transplant glomerulopathy displayed a novel tRNA fragments signature. Gene expression analysis from allograft tissues demonstrated changes in canonical pathways related to immune activation such as iCos-iCosL signaling pathway in T helper cells, Th1 and Th2 activation pathway, and dendritic cell maturation. mRNA targets of down-regulated miRNAs such as miR-1224-5p, miR-4508, miR-320, miR-378a from serum were globally upregulated in tissue. Integration of serum miRNA profiles with tissue gene expression showed that changes in serum miRNAs support the role of T-cell mediated mechanisms in ongoing allograft injury.

scholarly journals Urinary Carnosinase-1 Excretion is Associated with Urinary Carnosine Depletion and Risk of Graft Failure in Kidney Transplant Recipients: Results of the TransplantLines Cohort Study

Antioxidants ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1102
Author(s):  
Angelica Rodriguez-Niño ◽  
Diego O. Pastene ◽  
Adrian Post ◽  
M. Yusof Said ◽  
Antonio W. Gomes-Neto ◽  
...  
Keyword(s):  
Kidney Transplant ◽  
Graft Failure ◽  
Cox Regression ◽  
Carbonyl Stress ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Increased Risk ◽  
High Concentrations ◽  
Kidney Function Decline

Carnosine affords protection against oxidative and carbonyl stress, yet high concentrations of the carnosinase-1 enzyme may limit this. We recently reported that high urinary carnosinase-1 is associated with kidney function decline and albuminuria in patients with chronic kidney disease. We prospectively investigated whether urinary carnosinase-1 is associated with a high risk for development of late graft failure in kidney transplant recipients (KTRs). Carnosine and carnosinase-1 were measured in 24 h urine in a longitudinal cohort of 703 stable KTRs and 257 healthy controls. Cox regression was used to analyze the prospective data. Urinary carnosine excretions were significantly decreased in KTRs (26.5 [IQR 21.4–33.3] µmol/24 h versus 34.8 [IQR 25.6–46.8] µmol/24 h; p < 0.001). In KTRs, high urinary carnosinase-1 concentrations were associated with increased risk of undetectable urinary carnosine (OR 1.24, 95%CI [1.06–1.45]; p = 0.007). During median follow-up for 5.3 [4.5–6.0] years, 84 (12%) KTRs developed graft failure. In Cox regression analyses, high urinary carnosinase-1 excretions were associated with increased risk of graft failure (HR 1.73, 95%CI [1.44–2.08]; p < 0.001) independent of potential confounders. Since urinary carnosine is depleted and urinary carnosinase-1 imparts a higher risk for graft failure in KTRs, future studies determining the potential of carnosine supplementation in these patients are warranted.

scholarly journals Review of Outcomes after Diagnosis of Malignancy in Kidney Transplant Patients: UNOS Database

2021 ◽  
Vol 2 (3) ◽  
pp. 253-263
Author(s):  
Het Patel ◽  
Nikhil Agrawal ◽  
Voravech Nissaisorakarn ◽  
Ridhi Gupta ◽  
Francesca Cardarelli
Keyword(s):  
Kidney Transplant ◽  
Graft Failure ◽  
Event Analysis ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Time To Event ◽  
Transplant Patients ◽  
Kaplan Meier ◽  
Lung Malignancy ◽  
Kidney Transplant Patients

Malignancy is the third major cause of death among transplant recipients. Patient and kidney transplant outcomes after the diagnosis of malignancy are not well described. We reviewed incidences and outcomes of colorectal, lung, PTLD, and renal malignancy after transplant among patients who received a transplant from January 2000 to December 2018 using the UNOS/OPTN database. Incidence of each malignancy was measured at 5 years and 10 years of transplant. The Kaplan–Meier curve was used for time-to-event analysis (graft and patient outcomes). Additionally, we sought to identify the causes of graft failure among these recipients. We found that 12,764 (5.5%) patients suffered malignancy, excluding squamous and basal cell skin carcinoma after transplant. During the first 5 years of transplant, incidence of colorectal, lung, PTLD, and renal malignancies was 2.99, 9.21, 15.61, and 8.55 per 10,000 person-years, respectively. Rates of graft failure were 10.3%, 7.6%, 19.9%, and 18.8%, respectively, among these patients at 5 years. Mortality rate was highest among patients who suffered lung malignancy (84%), followed by colorectal (61.5%), PTLD (49.1%), and renal (35.5%) at 5 years after diagnosis of malignancy. In conclusion, kidney transplant recipients diagnosed with lung malignancy have the lowest graft survival, compared to PTLD, colorectal, and renal malignancy. PTLD has the highest incidence rate in the first 5 years of transplant.

MO941CLINICAL OUTCOMES IN KIDNEY RE-TRANSPLANTATION

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Clara Pardinhas ◽  
Rita Leal ◽  
Francisco Caramelo ◽  
Teofilo Yan ◽  
Carolina Figueiredo ◽  
...  
Keyword(s):  
Acute Rejection ◽  
Kidney Transplant ◽  
Graft Survival ◽  
Graft Failure ◽  
Graft Function ◽  
Delayed Graft Function ◽  
First Year ◽  
Kidney Transplant Recipients ◽  
Post Transplant

Abstract Background and Aims As kidney transplants are growing in absolute numbers, so are patients with failed allografts and thus potential candidates for re-transplantation. Re-transplantation is challenging due to immunological barriers, surgical difficulties and clinical complexities but it has been proven that successful second transplantation improves life expectancy over dialysis. It is important to evaluate re-transplantation outcomes since 20% of patients on the waiting list are waiting for a second graft. Our aim was to compare major clinical outcomes such as acute rejection, graft and patient survival, between patients receiving a first or a second kidney transplant. Method We performed a retrospective study, that included 1552 patients submitted to a first (N=1443, 93%) or a second kidney transplant (N=109, 7%), between January 2008 and December 2018. Patients with more than 2 grafts or multi-organ transplant were excluded. Demographic, clinical and histocompatibility characteristics of both groups were registered from our unit database and compared. Delayed graft function was defined has the need of dialysis in the first week post-transplant. All acute rejection episodes were biopsy proven, according to Banff 2017 criteria. Follow-up time was defined at 1st June 2020 for functioning grafts or at graft failure (including death with a functioning graft). Results Recipients of a second graft were significantly younger (43 ±12 vs 50 ± 13 years old, p&lt;0.001) and there were significantly fewer expanded-criteria donors in the second transplant group (31.5% vs 57.5%, p&lt;0.001). The waiting time for a second graft was longer (63±50 vs 48±29 months, p=0.011). HLA mismatch was similar for both groups but PRA was significantly higher for second KT patients (21.6±25% versus 3±9%; p&lt;0.001). All patients submitted to a second KT had thymoglobulin as induction therapy compared to 16% of the first KT group (p&lt;0.001). We found no difference in primary dysfunction or delayed graft function between groups. Acute rejection was significantly more frequent in second kidney transplant recipients (19% vs 5%, p&lt;0.001), being 10 acute cellular rejections, 7 were antibody mediated and 3 were borderline changes. For the majority of the patients (85%), acute rejection occurred in the first-year post-transplant. Death censored graft failure occurred in 236 (16.4%) patients with first kidney transplant and 25 (23%) patients with a second graft, p=0.08. Survival analysis showed similar graft survival for both groups (log-rank p=0.392). We found no difference in patients’ mortality at follow up for both groups. Conclusion Although second graft patients presented more episodes of biopsy proven acute rejection, especially at the first-year post-transplant, we found no differences in death censored graft survival or patients’ mortality for patients with a second kidney transplant. Second transplants should be offered to patients whenever feasible.

Timing of Kidney Clamping and Deceased Donor Kidney Transplant Outcomes

2021 ◽  
pp. CJN.03290321
Author(s):  
Simon Ville ◽  
Marine Lorent ◽  
Clarisse Kerleau ◽  
Anders Asberg ◽  
Christophe Legendre ◽  
...  
Keyword(s):  
Kidney Transplant ◽  
Graft Survival ◽  
Ischemia Reperfusion ◽  
Multivariable Analysis ◽  
Graft Function ◽  
Deceased Donor ◽  
Kidney Graft ◽  
Kidney Transplant Recipients ◽  
Heart Beating ◽  
Deceased Donor Kidney Transplant

BackgroundThe recognition that metabolism and immune function are regulated by an endogenous molecular clock generating circadian rhythms suggests that the magnitude of ischemia-reperfusion and subsequent inflammation on kidney transplantation, could be affected by the time of the day. MethodsAccordingly, we evaluated 5026 first kidney transplant recipients from deceased heart-beating donors. In a cause-specific multivariable analysis, we compare delayed graft function (DGF) and graft survival according to the time of kidney clamping and declamping. Participants were divided into clamping between midnight and noon (AM clamping group, 65%) or clamping between noon and midnight (PM clamping group, 35%), and similarly, AM declamping or PM declamping (25% / 75%). ResultsDGF occurred among 550 participants (27%) with AM clamping and 339 (34%) with PM clamping (adjusted OR = 0.81, 95%CI: 0.67 to 0.98, p= 0.03). No significant association of clamping time with overall death censored graft survival was observed (HR = 0.92, 95%CI: 0.77 to 1.10, p= 0.37). No significant association of declamping time with DGF or graft survival was observed. ConclusionsClamping between midnight and noon was associated with a lower incidence of DGF whilst the declamping time was not associated with kidney graft outcomes.

scholarly journals Is delayed graft function associated with ureteral stenosis in the kidney transplant recipient? A case-control study

2019 ◽  
Vol 13 (11) ◽  
Author(s):  
Axel Cayetano-Alcaraz ◽  
Juan Sebastian Rodriguez-Alvarez ◽  
Mario Vilatobá-Chapa ◽  
Josefina Alberú-Gómez ◽  
Bernardo Gabilondo-Pliego ◽  
...  
Keyword(s):  
Risk Factor ◽  
Kidney Transplant ◽  
Kidney Transplant Recipient ◽  
Graft Function ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Transplant Patients ◽  
Increased Risk ◽  
Kidney Transplant Patients ◽  
Control Study

Introduction: Ureteral stricture (US) in the kidney transplant recipient is a rare complication that can lead to morbidity and graft loss. Risk factor recognition is crucial in the prevention and management of this entity. Delayed graft function (DGF), as defined by the need for dialysis in the first week after transplantation, has been proposed as a risk factor in previous studies. Our objective is to determine the impact of DGF in US development in kidney transplant patients. Methods: We designed a matched case-control study. US cases in kidney transplant recipients were identified in the 2008–2017 period. We defined US as the rise in serum creatinine associated with findings suggesting obstruction in ultrasound, scintigraphy, or retrograde pyelogram; any other cause of graft dysfunction was excluded. Controls were defined as kidney transplant recipients from the same population and period without US, matched in a 1:2 fashion by age, sex, and donor type. Results: From 532 kidney transplant patients, 31 cases and 62 controls were included. Cumulative US incidence was 58 per 1000 cases. When calculating for odds ratio (OR), post-operative urinoma (OR 3.2; 95% confidence interval [CI] 2.36–4.37) and ureteral duplication (OR 3.29; 95% CI 2.40–4.51) were associated with an increased risk for US, while DGF was not found to be statistically significant as a risk factor (OR 3.3; 95% CI 0.96–11.52). No statistically significant differences were found between groups in other pre- and post-transplant-related factors. Conclusions: DGF was not associated with US in our cohort; however, ureteral duplication and postoperative urinoma were associated with an increased risk of graft ureteral stenosis development.

scholarly journals An adjustable predictive score of graft survival in kidney transplant patients and the levels of risk linked to de novo donor-specific anti-HLA antibodies

PLoS ONE ◽  
2017 ◽  
Vol 12 (7) ◽  
pp. e0180236 ◽  
Author(s):  
Aurélie Prémaud ◽  
Matthieu Filloux ◽  
Philippe Gatault ◽  
Antoine Thierry ◽  
Matthias Büchler ◽  
...  
Keyword(s):  
Kidney Transplant ◽  
Graft Survival ◽  
De Novo ◽  
Predictive Score ◽  
Hla Antibodies ◽  
Transplant Patients ◽  
Kidney Transplant Patients

scholarly journals Non-HLA Antibodies and Epitope Mismatches in Kidney Transplant Recipients With Histological Antibody-Mediated Rejection

2021 ◽  
Vol 12 ◽  
Author(s):  
Marta Crespo ◽  
Laura Llinàs-Mallol ◽  
Dolores Redondo-Pachón ◽  
Carrie Butler ◽  
Javier Gimeno ◽  
...  
Keyword(s):  
Kidney Transplant ◽  
De Novo ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Serum Samples ◽  
Hla Antibodies ◽  
Aortic Endothelial Cells ◽  
Antibody Mediated Rejection ◽  
Donor Specific Antibodies

BackgroundCorrelation between antibody-mediated rejection (ABMR) and circulating HLA donor-specific antibodies (HLA-DSA) is strong but imperfect in kidney transplant (KT) recipients, raising the possibility of undetected HLA-DSA or non-HLA antibodies contributing to ABMR. Detailed evaluation of the degree of HLA matching together with the identification of non-HLA antibodies in KT may help to decipher the antibody involved.MethodsWe retrospectively assessed patients with transplant biopsies scored following Banff’15 classification. Pre- and post-transplant serum samples were checked for HLA and non-HLA antibodies [MICA-Ab, angiotensin-II type-1-receptor (AT1R)-Ab, endothelin-1 type-A-receptor (ETAR)-Ab and crossmatches with primary aortic endothelial cells (EC-XM)]. We also analyzed HLA epitope mismatches (HLA-EM) between donors and recipients to explore their role in ABMR histology (ABMRh) with and without HLA-DSA.ResultsOne-hundred eighteen patients with normal histology (n = 19), ABMRh (n = 52) or IFTA (n = 47) were studied. ABMRh patients were HLA-DSApos (n = 38, 73%) or HLA-DSAneg (n = 14, 27%). Pre-transplant HLA-DSA and AT1R-Ab were more frequent in ABMRh compared with IFTA and normal histology cases (p = 0.006 and 0.003), without differences in other non-HLA antibodies. Only three ABMRhDSAneg cases showed non-HLA antibodies. ABMRhDSAneg and ABMRhDSApos cases showed similar biopsy changes and graft-survival. Both total class II and DRB1 HLA-EM were associated with ABMRhDSApos but not with ABMRhDSAneg. Multivariate analysis showed that pre-transplant HLA-DSA (OR: 3.69 [1.31–10.37], p = 0.013) and AT1R-Ab (OR: 5.47 [1.78–16.76], p = 0.003) were independent predictors of ABMRhDSApos.ConclusionsIn conclusion, pre-transplant AT1R-Ab is frequently found in ABMRhDSApos patients. However, AT1R-Ab, MICA-Ab, ETAR-Ab or EC-XM+ are rarely found among ABMRhDSAneg patients. Pre-transplant AT1R-Ab may act synergistically with preformed or de novo HLA-DSA to produce ABMRhDSApos but not ABMRhDSAneg. HLA epitope mismatch associates with ABMRhDSApos compared with ABMRhDSAneg, suggesting factors other than HLA are responsible for the damage.

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