P1776HLA TYPING BY NGS ENHANCES MISMATCH DETECTION IN LIVING KIDNEY TRANSPLANTATION

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Sarah Pehnke ◽  
Tom H Lindner ◽  
Bernt Popp ◽  
Ilias Doxiadis ◽  
Ramona Landgraf ◽  
...  
Keyword(s):  
Kidney Transplantation ◽  
Kidney Transplant ◽  
Graft Loss ◽  
Hla Typing ◽  
University Hospital ◽  
Kidney Transplant Recipients ◽  
Antibody Mediated Rejection ◽  
Typing Methods ◽  
Long Range Pcr ◽  
Hla Mismatches

Abstract Background and Aims Antibody mediated rejection (ABMR) due to the development of donor specific HLA antibodies is the most common cause for graft loss in kidney transplant recipients. Therefore, a low count of HLA mismatches is favorable in the course of transplantation. Hitherto, several techniques for HLA typing have been adapted in parallel, e.g. serological or low-resolution PCR. In this single-center study, we aimed to perform “HLA re-typing” by next generation sequencing (NGS) in a living kidney transplant cohort (n=143), in order to identify HLA mismatches in donor/recipient pairs, that were missed by previous HLA typing methods. Method We isolated DNA of 102 donor/recipient pairs, that received a living kidney transplantation at the University Hospital Leipzig (Germany) between 1998 and 2018, and performed long range PCR of all known HLA loci. Using these NGS results, we compiled a genomic HLA mismatch formula. We evaluated, if genomic HLA typing identifies more HLA mismatches compared to the results of previous HLA typing methods, that were recorded in the Eurotransplant database for our donor/recipient pairs. Results By genomic HLA typing, we were able to identify HLA mismatches in 10.2 % of donor/recipient pairs, that have been missed by previous methods. In our cohort, we recognized most mismatches in the DRB1 locus, that were missed with other HLA typing techniques. Conclusion Our results suggest, that genomic HLA typing can be more precise in detecting HLA mismatches in donor recipient/pairs. Especially in the course of living kidney transplantation, a higher accuracy in HLA typing might enhance donor selection. Furthermore, accurate HLA typing can influence graft management in the course of ABMR, as it may improve the detection of donor specific HLA directed antibodies.

Risk Factors for Graft Loss in Kidney Transplant Recipients With Antibody Mediated Rejection and Three Consecutive Biopsies.

2014 ◽  
Vol 98 ◽  
pp. 441
Author(s):  
K. Cunningham ◽  
D. Hager ◽  
W. Zhong ◽  
B. Muth ◽  
T. Ellis ◽  
...  
Keyword(s):  
Risk Factors ◽  
Kidney Transplant ◽  
Graft Loss ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Antibody Mediated Rejection

scholarly journals P1706THE GRAFT SURVIVAL OF KIDNEY TRANSPLANTATION ACCORDING TO ETHNICITY IN KIDNEY TRANSPLANT RECIPIENTS

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Yeonsoon Jung ◽  
Jisu Kim ◽  
Haesu Jeon ◽  
Ye Na Kim ◽  
Ho Sik Shin ◽  
...  
Keyword(s):  
African American ◽  
Kidney Transplantation ◽  
Kidney Transplant ◽  
Graft Survival ◽  
Cox Regression ◽  
Patient Survival ◽  
Graft Loss ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Data Set

Abstract Background African American kidney transplant recipients experience disproportionately high rates of graft loss. The aim of this analysis was to use a UNOS data set that contains detailed baseline and longitudinal clinical data to establish and quantify the impact of the current overall graft loss definition on suppressing the true disparity magnitude in US AA kidney transplant outcomes. Methods Longitudinal cohort study of kidney transplant recipients using a data set created by United Network for Organ Sharing (UNOS), including 266,128 (African American 70,215, Non-African American 195,913) transplant patient between 1987 and December 2016. Multivariable analysis was conducted using 2-stage joint modeling of random and fixed effects of longitudinal data (linear mixed model) with time to event outcomes (Cox regression). Results 195,913 non-African American (AA) (73.6%) were compared with 70,215 AA (26.4%) recipients. 10-year-graft survival of AA in all era is lower than that of non-AA (31% in deceased kidney transplants (DKT) AA recipient and 42% in living kidney transplantation (LKT) non-AA recipient). 10-year-patient survival of AA with functioning graft in all era is similar that of non-AA. Multivariate Cox regression of factors associated with patient survival with functioning graft are acute rejection within 6 months, DM, hypertension and etc. Pre-transplant recipient BMI in AA show the trend as a protective factor in patient survival with functioning graft although not significantly in statistics Conclusions African American kidney transplant recipients experience a substantial disparity in graft loss, but not patient death with functioning graft.

scholarly journals MO995DO THE TIMELINE AND SPECTRUM OF INFECTIONS CHANGE AFTER ANTI-REJECTION THERAPY IN KIDNEY TRANSPLANT RECIPIENTS?

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Arvind Krishnakumar ◽  
Selvin Sundar Raj Mani ◽  
Rizwan Alam ◽  
Manish Lalwani ◽  
Athul Thomas ◽  
...  
Keyword(s):  
Acute Rejection ◽  
Kidney Transplant ◽  
Median Time ◽  
Graft Loss ◽  
Renal Transplant Recipients ◽  
Care Hospital ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Antibody Mediated Rejection

Abstract Background and Aims The infections in kidney transplant recipients has been well defined. The timeline of infections and type of infection among patients who received anti-rejection therapy for acute rejection when compared to the patients who did not develop an acute rejection. Method Renal transplant recipients with post-transplant median follow up of four years from July 2009-June 2018 were included in a retrospective cohort study at a tertiary care hospital. Demographic characteristics, biopsy proven rejections, infections and graft and patient outcome were collected from transplant records and the hospital clinical workstation. Early and late acute rejections were defined as less than and more than 3 months respectively. The rates of various infections, type and time to develop an infection in the acute rejection group were compared with the patients who did not develop any rejection. Results A total of 794 patients underwent kidney transplant during the study with mean age of 35.5±12 years and 78% being male. Two hundred and eight four patients (35.8 %) had one or more biopsy proven rejections during the median follow up of 48 months (IQR 28,77). 213 patients (75%) developed early acute rejection (less than 3 months) while the remainder developed late acute rejection. The median time to develop the first acute rejection was 12 days (IQR 6,93.3). Majority of the patients (176, 62%) developed biopsy proven acute cellular rejection, 77 patients (27.1%) acute antibody mediated rejection and rest (10.9%) either mixed or borderline rejection who were treated. The proportion of BKV infection and infective diarrhea were more in rejection group when compared to no rejection group which was statistically significant (refer Table 1). At follow up, the patients who developed rejection had more graft loss (p value 0.010) but no increase in mortality. The predictors of infection among the patients who received anti-rejection therapy were identified. The median time to develop any infection in both groups were also compared. The spectrum of infections and outcome following early and late rejections were compared. Subgroup analysis was done to look at the eGFR, proteinuria trend, graft outcomes in patients with no rejection, rejection without any infection at follow up and rejection with any infection at follow up. The effect of type of anti-rejection therapy on spectrum of infections was also studied. Conclusion This is one of the few studies which looked at the effect of anti-rejection therapy in kidney transplant recipients. Anti-rejection treatment received post kidney transplant resulted in increased rates of BKV infection and infective diarrhea. Patients with acute rejection had more graft loss during follow up with no significant effect on mortality.

scholarly journals Recurrence of FSGS after Kidney Transplantation in Adults

2020 ◽  
Vol 15 (2) ◽  
pp. 247-256 ◽  
Author(s):  
Audrey Uffing ◽  
Maria José Pérez-Sáez ◽  
Marilda Mazzali ◽  
Roberto C. Manfro ◽  
Andrea Carla Bauer ◽  
...  
Keyword(s):  
Kidney Transplantation ◽  
Kidney Transplant ◽  
Graft Loss ◽  
Small Sample ◽  
Glomerular Disease ◽  
Response To Treatment ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Post Transplant ◽  
Native Kidney

Background and objectivesFSGS recurrence after kidney transplantation is a major risk factor for graft loss. However, the natural history, clinical predictors, and response to treatment remain unclear because of small sample sizes and poor generalizability of single-center studies, and disease misclassification in registry-based studies. We therefore aimed to determine the incidence, predictors, and treatment response of recurrent FSGS in a large cohort of kidney transplant recipients.Design, setting, participants, & measurementsThe Post-Transplant Glomerular Disease (TANGO) project is an observational, multicenter, international cohort study that aims to investigate glomerular disease recurrence post-transplantation. Transplant recipients were screened for the diagnosis of idiopathic FSGS between 2005 and 2015 and details were recorded about the transplant, clinical outcomes, treatments, and other risk factors.ResultsAmong 11,742 kidney transplant recipients screened for FSGS, 176 had a diagnosis of idiopathic FSGS and were included. FSGS recurred in 57 patients (32%; 95% confidence interval [95% CI], 25% to 39%) and 39% of them lost their graft over a median of 5 (interquartile range, 3.0–8.1) years. Multivariable Cox regression revealed a higher risk for recurrence with older age at native kidney disease onset (hazard ratio [HR], 1.37 per decade; 95% CI, 1.09 to 1.56). Other predictors were white race (HR, 2.14; 95% CI, 1.08 to 4.22), body mass index at transplant (HR, 0.89 per kg/m2; 95% CI, 0.83 to 0.95), and native kidney nephrectomies (HR, 2.76; 95% CI, 1.16 to 6.57). Plasmapheresis and rituximab were the most frequent treatments (81%). Partial or complete remission occurred in 57% of patients and was associated with better graft survival.ConclusionsIdiopathic FSGS recurs post-transplant in one third of cases and is associated with a five-fold higher risk of graft loss. Response to treatment is associated with significantly better outcomes but is achieved in only half of the cases.

scholarly journals P1738COULD ADDING BORTEZOMIB HAVE BENEFIT FOR ANTIBODY MEDIATED REJECTION AFTER KIDNEY TRANSPLANTATION?

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Nooshin Dalili ◽  
Mohsen Nafar
Keyword(s):  
Kidney Transplantation ◽  
Intravenous Immunoglobulin ◽  
Kidney Transplant ◽  
Graft Survival ◽  
Vascular Inflammation ◽  
Standard Of Care ◽  
Kidney Transplant Recipients ◽  
Standard Regimen ◽  
Antibody Mediated Rejection ◽  
Protocol Biopsies

Abstract Background and Aims Antibody Mediated Rejection (ABMR) is a severe complication that frequently occurs after kidney transplantation. The present RCT designed to evaluate the role of adding Bortezomib to standard regimen with plasma exchange, intravenous immunoglobulin and Rituximab in treatment of AMR after kidney transplantation. Method 26 kidney transplant recipients (KTRs) with a biopsy proven diagnosis of AMR and positive DSA in a randomized clinical trial were compared: Thirteen KTRs treated with plasmapheresis, intravenous immunoglobulin and rituximab (PE-IVIG- RTX ) plus bortezomib versus 13 patients treated with standard of care regimen without bortezomib. We evaluated graft survival and DSA titer with MFI during a year after biopsy proven diagnosis. Results Statistical difference in graft survival between the two groups was noted: three out of 13 patients in the PE-IVIG-RTX group (23%) and 1/13 in the bortezomib group (7.5%) experienced loss of allograft function at a median time after diagnosis of 6 month and 12 month, respectively. DSA MFI titers 12 month after AMR diagnosis showed significant reducing slope in Bortezomib group. Regarding pathological changes micro vascular inflammation (glomerulitis + peritubular capillaritis score) reduced after PE-IVIG- RTX plus bortezomib in 7 out of 13 patients whom underwent protocol biopsies after treatment (53%) (Median score 3 in pre- treatment biopsy vs. 1 in post-treatment biopsy; P = 0.036). Conclusion Although DSA titer may not differ at 6 months after treatment of AMR between those who received standard regimen and those treated with adding Bortezomib, but at the end of one year patients treated with standard regimen plus Bortezomib reached lower MFI DSA titer. Adding Bortezomib to PE-IVIG- RTX for the treatment of AMR after kidney transplantation may enable clinicians to fight the DSA better and change the future of next generation of highly sensitized kidney transplant candidates.

scholarly journals Donor-Specific Antibodies in Kidney Transplant Recipients

2017 ◽  
Vol 13 (1) ◽  
pp. 182-192 ◽  
Author(s):  
Rubin Zhang
Keyword(s):  
Kidney Transplant ◽  
De Novo ◽  
Binding Capacity ◽  
Graft Loss ◽  
Igg Subclasses ◽  
Kidney Transplant Recipients ◽  
Specific Antibodies ◽  
Antibody Mediated Rejection ◽  
Donor Specific Antibodies ◽  
Transplant Glomerulopathy

Donor-specific antibodies have become an established biomarker predicting antibody-mediated rejection. Antibody-mediated rejection is the leading cause of graft loss after kidney transplant. There are several phenotypes of antibody-mediated rejection along post-transplant course that are determined by the timing and extent of humoral response and the various characteristics of donor-specific antibodies, such as antigen classes, specificity, antibody strength, IgG subclasses, and complement binding capacity. Preformed donor-specific antibodies in sensitized patients can trigger hyperacute rejection, accelerated acute rejection, and early acute antibody-mediated rejection. De novo donor-specific antibodies are associated with late acute antibody-mediated rejection, chronic antibody-mediated rejection, and transplant glomerulopathy. The pathogeneses of antibody-mediated rejection include not only complement-dependent cytotoxicity, but also complement-independent pathways of antibody-mediated cellular cytotoxicity and direct endothelial activation and proliferation. The novel assay for complement binding capacity has improved our ability to predict antibody-mediated rejection phenotypes. C1q binding donor-specific antibodies are closely associated with acute antibody-mediated rejection, more severe graft injuries, and early graft failure, whereas C1q nonbinding donor-specific antibodies correlate with subclinical or chronic antibody-mediated rejection and late graft loss. IgG subclasses have various abilities to activate complement and recruit effector cells through the Fc receptor. Complement binding IgG3 donor-specific antibodies are frequently associated with acute antibody-mediated rejection and severe graft injury, whereas noncomplement binding IgG4 donor-specific antibodies are more correlated with subclinical or chronic antibody-mediated rejection and transplant glomerulopathy. Our in-depth knowledge of complex characteristics of donor-specific antibodies can stratify the patient’s immunologic risk, can predict distinct phenotypes of antibody-mediated rejection, and hopefully, will guide our clinical practice to improve the transplant outcomes.

scholarly journals ABO-Incompatible Kidney Transplant Outcomes

2018 ◽  
Vol 13 (8) ◽  
pp. 1234-1243 ◽  
Author(s):  
Annelies E. de Weerd ◽  
Michiel G.H. Betjes
Keyword(s):  
Kidney Transplantation ◽  
Confidence Interval ◽  
Kidney Transplant ◽  
Blood Group ◽  
Observational Studies ◽  
Abo Blood Group ◽  
Safe Procedure ◽  
Kidney Transplant Recipients ◽  
Antibody Mediated Rejection ◽  
Statistical Heterogeneity

Background and objectivesABO blood group–incompatible kidney transplantation is considered a safe procedure, with noninferior outcomes in large cohort studies. Its contribution to living kidney transplantation programs is substantial and growing. Outcomes compared with center-matched ABO blood group–compatible control patients have not been ascertained.Design, setting, participants, & measurementsComprehensive searches were conducted in Embase, Medline, Cochrane, Web-of-Science, and Google Scholar. Meta-analyses Of Observational Studies in Epidemiology study guidelines for observational studies and Newcastle Ottawa bias scale were implemented to assess studies. Meta-analysis was performed using Review Manager 5.3. A subgroup analysis on antibody removal technique was performed.ResultsAfter identifying 2728 studies addressing ABO-incompatible kidney transplantation, 26 studies were included, describing 1346 unique patients who were ABO-incompatible and 4943 ABO-compatible controls. Risk of bias was low (all studies ≥7 of 9 stars). Baseline patient characteristics revealed no significant differences in immunologic risk parameters. Statistical heterogeneity of studies was low (I2 0% for graft and patient survival). One-year uncensored graft survival of patients who were ABO-incompatible was 96% versus 98% in ABO-compatible controls (relative risk, 0.97; 95% confidence interval, 0.96 to 0.98; P<0.001). Forty-nine percent of reported causes of death in patients who were ABO-incompatible were of infectious origin, versus only 13% in patients who were ABO-compatible (P=0.02). Antibody-mediated rejection (3.86; 95% confidence interval, 2.05 to 7.29; P<0.001), severe nonviral infection (1.44; 95% confidence interval, 1.13 to 1.82; P=0.003), and bleeding (1.92; 95% confidence interval, 1.36 to 2.72; P<0.001) were also more common after ABO-incompatible transplantation.ConclusionsABO-incompatible kidney transplant recipients have good outcomes, albeit inferior to center-matched ABO-compatible control patients.

scholarly journals Prediction of kidney transplant outcome based on different DGF definitions in Chinese deceased donation

2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Xiao-jun Hu ◽  
Jin Zheng ◽  
Yang Li ◽  
Xiao-hui Tian ◽  
Pu-xun Tian ◽  
...  
Keyword(s):  
Kidney Transplantation ◽  
Kidney Transplant ◽  
Predictive Value ◽  
Predictive Accuracy ◽  
Graft Loss ◽  
Graft Function ◽  
Reduction Rate ◽  
Kidney Transplant Recipients ◽  
Long Term Outcome ◽  
Transplant Outcome

Abstract Background Delayed graft function (DGF) is an important complication of kidney transplantation and can be diagnosed according to different definitions. DGF has been suggested to be associated with the long-term outcome of kidney transplantation surgery. However, the best DGF definition for predicting renal transplant outcomes in Chinese donations after cardiac death (DCDs) remains to be determined. Method A total of 372 DCD kidney transplant recipients from June 2013 to July 2017 in the First Affiliated Hospital of Xi’an Jiaotong University were included in this retrospective study to compare 6 different DGF definitions. The relationships of the DGF definitions with transplant outcome were analyzed, including graft loss (GL) and death-censored graft loss (death-censored GL). Renal function indicators, including one-year estimated glomerular filtration rate (eGFR) and three-year eGFR, and were compared between different DGF groups. Results The incidence of DGF varied from 4.19 to 35.22% according to the different DGF diagnoses. All DGF definitions were significantly associated with three-year GL as well as death-censored GL. DGF based on requirement of hemodialysis within the first week had the best predictive value for GL (AUC 0.77), and DGF based on sCr variation during the first 3 days post-transplant had the best predictive value for three-year death-censored GL (AUC 0.79). Combination of the 48-h sCr reduction ratio and classical DGF can improve the AUC for GL (AUC 0.85) as well as the predictive accuracy for death-censored GL (83.3%). Conclusion DGF was an independent risk factor for poor transplant outcome. The combination of need for hemodialysis within the first week and the 48-h serum creatinine reduction rate has a better predictive value for patient and poor graft outcome.

scholarly journals Prediction of Kidney Transplant Outcome Based On Different DGF Definitions In Chinese Deceased Donation

2019 ◽  
Author(s):  
Xiao-jun Hu ◽  
Jin Zheng ◽  
Yang Li ◽  
Xiao-hui Tian ◽  
Pu-xun Tian ◽  
...  
Keyword(s):  
Kidney Transplantation ◽  
Kidney Transplant ◽  
Predictive Value ◽  
Predictive Accuracy ◽  
Graft Loss ◽  
Graft Function ◽  
Reduction Rate ◽  
Kidney Transplant Recipients ◽  
Long Term Outcome ◽  
Transplant Outcome

Abstract Background. Delayed graft function (DGF) is an important complication of kidney transplantation and can be diagnosed according to different definitions. DGF has been suggested to be associated with the long-term outcome of kidney transplantation surgery. However, the best DGF definition for predicting renal transplant outcomes in Chinese donations after cardiac death (DCDs) remains to be determined. Method. A total of 372 DCD kidney transplant recipients from June 2013 to July 2017 in the First Affiliated Hospital of Xi’an Jiaotong University were included in this retrospective study to compare 6 different DGF definitions. The relationships of the DGF definitions with transplant outcome were analyzed, including graft loss (GL) and death-censored graft loss (death-censored GL).Renal function indicators, including one-year estimated glomerular filtration rate (eGFR) and three-year eGFR, and were compared between different DGF groups. Results. The incidence of DGF varied from 4.19% to 35.22% according to the different DGF diagnoses. All DGF definitions were significantly associated with three-year GL as well as death-censored GL. DGF based on requirement of hemodialysis within the first week had the best predictive value for GL (AUC 0.77), and DGF based on sCr variation during the first three days post-transplant had the best predictive value for three-year death-censored GL (AUC 0.79). Combination of the 48-h sCr reduction ratio and classical DGF can improve the AUC for GL (AUC 0.85) as well as the predictive accuracy for death-censored GL (83.3%). Conclusion. DGF was an independent risk factor for poor transplant outcome. The combination of need for hemodialysis within the first week and the 48-h serum creatinine reduction rate has a better predictive value for patient and poor graft outcome.

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