Exploring the Complexity of Death-Censored Kidney Allograft Failure

2021 ◽  
pp. ASN.2020081215
Author(s):  
Manuel Mayrdorfer ◽  
Lutz Liefeldt ◽  
Kaiyin Wu ◽  
Birgit Rudolph ◽  
Qiang Zhang ◽  
...  

BackgroundFew studies have thoroughly investigated the causes of kidney graft loss (GL), despite its importance.MethodsA novel approach assigns each persistent and relevant decline in renal function over the lifetime of a renal allograft to a standardized category, hypothesizing that singular or multiple events finally lead to GL. An adjudication committee of three physicians retrospectively evaluated indication biopsies, laboratory testing, and medical history of all 303 GLs among all 1642 recipients of transplants between January 1, 1997 and December 31, 2017 at a large university hospital to assign primary and/or secondary causes of GL.ResultsIn 51.2% of the patients, more than one cause contributed to GL. The most frequent primary or secondary causes leading to graft failure were intercurrent medical events in 36.3% of graft failures followed by T cell–mediated rejection (TCMR) in 34% and antibody-mediated rejection (ABMR) in 30.7%. In 77.9%, a primary cause could be attributed to GL, of which ABMR was most frequent (21.5%). Many causes for GL were identified, and predominant causes for GL varied over time.ConclusionsGL is often multifactorial and more complex than previously thought.

2018 ◽  
Vol 2018 ◽  
pp. 1-6 ◽  
Author(s):  
Gunilla Einecke ◽  
Jan Hinrich Bräsen ◽  
Nils Hanke ◽  
Hermann Haller ◽  
Anke Schwarz

Antibody-mediated rejection (ABMR) is a major cause of late renal allograft dysfunction and graft loss. Risks and benefits of treatment of late ABMR have not been evaluated in randomized clinical trials. We report on a 35-year-old patient with deterioration in renal function and progressive proteinuria 15 years after transplantation. Recurrent infections after a splenectomy following traumatic splenic rupture 3 years earlier had led to reduction of immunosuppression. Renal transplant biopsy showed glomerular double contours, 40% fibrosis/tubular atrophy, peritubular capillaritis, and positive C4d staining indicating chronic-active ABMR. ABMR treatment was initiated with steroids, plasmapheresis, and rituximab. Fourteen days later, she presented to the emergency department with fever, diarrhea, vomiting, and hypotension. Despite antibiotic treatment she deteriorated with progressive hypotension, capillary leak with pleural effusion, peripheral edema, and progressive respiratory insufficiency. She died due to septic shock five days after admission. Blood cultures showed Streptococcus pneumoniae, consistent with a diagnosis of overwhelming postsplenectomy infection syndrome, despite protective pneumococcus vaccination titers. We assume that the infection was caused by one of the strains not covered by the Pneumovax 23 vaccination. The increased immunosuppression with B cell depletion may have contributed to the overwhelming course of this infection.


1998 ◽  
Vol 116 (3) ◽  
pp. 1710-1714 ◽  
Author(s):  
Maria Margarida Galvão ◽  
Zulma Fernandes Peixinho ◽  
Nelson Figueiredo Mendes ◽  
Luiz Estevão Ianhez ◽  
Emil Sabbaga

OBJECTIVE: The aim of the present study was to analyze the long-term evolution of patients submitted to endolymphatic irradiation as a pre-transplant preparation. SETTING: Referral center of university hospital. DESIGN: Case-control study. MAIN OUTCOMES MEASURES: The study was designed to evaluate the incidence of rejection, kidney loss, leukopenia, infection, and graft survival in the group treated (group 1) prior to surgery, compared to a control group (group 2) composed of patients under identical clinical conditions (sex, age, type of donor, immunosuppressive therapy and time of transplant) that did not undergo treatment preparation. PATIENTS: Patients were selected from amongst transplantation candidates on a long-term waiting list, some with a high level of antibodies against panel. The control group was chosen from amongst recently transplanted patients. Patients in the treated group received lipoiodine containing 131I with specific activity ranging between 4 and 6 mCu/ml. RESULTS: A significant difference between the two groups was found with regard to the incidence of rejection crises (21.0% in group 1 and 73.6% in group 2; P= 0.003), and the maintenance dose of azathioprine (smaller in group 1; P< 0.01). As to kidney graft loss due to rejection, a tendency to significance could be identified (10.5% in group 1 and 42.1% in group 2; P= 0.063); however, the difference was not significant between the two groups in terms of reversibility of rejection episodes during the first 60 post-transplant days. CONCLUSIONS: The authors concluded that this method, besides being relatively innocuous (there was no compromising of either the thyroid gland or of gonad function and there was no increase in tumor incidence), has an extended immunosuppressive effect, and can be indicated for cadaveric renal allograft recipients, especially those showing high panel reactivity.


2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Sarah Pehnke ◽  
Tom H Lindner ◽  
Bernt Popp ◽  
Ilias Doxiadis ◽  
Ramona Landgraf ◽  
...  

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.


2017 ◽  
Vol 78 ◽  
pp. 15
Author(s):  
Ahmed Mostafa ◽  
Abubaker M. Sidahmed ◽  
Salim Ghandorah ◽  
Serdar Yilmaz ◽  
Lee Anne Tibbles ◽  
...  

2017 ◽  
Vol 17 (8) ◽  
pp. 2092-2102 ◽  
Author(s):  
C. Wehmeier ◽  
G. Hönger ◽  
H. Cun ◽  
P. Amico ◽  
P. Hirt-Minkowski ◽  
...  

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Diana Rodríguez Espinosa ◽  
Jose Jesus Broseta Monzo ◽  
Evelyn Hermida-Lama ◽  
Elena Cuadrado ◽  
Jimena Del Risco ◽  
...  

Abstract Background and Aims Early graft failure (EGL) is a devastating complication of kidney transplantation. Patients with EGL have an increased risk of mortality of up to twelve times compared to patients who received grafts that survive beyond 30 days. Moreover, they may have become sensitized to antigens from the failed graft and that human leukocyte antigen antibodies (anti-HLA), identified on single antigen bead assays, may not be reliable until several weeks after transplantation. Thus, if rapid re-transplantation occurs, there is no certainty regarding the recipient's immunological status. Hence, there could be an increased immunological risk with the consequent disturbance of the new graft's survival. Method We performed a retrospective single-center observational study in re-transplanted patients with EGL (defined as graft loss before 30 days from transplant) between January 1977 and November 2019 from our center to analyze the outcomes of rapid re-transplantation (occurred within 30 days of EGL) vs late re-transplantation (occurred beyond those 30 days). Results: T here were 82 re-transplants after EGL. The median overall patient survival after re-transplantation was 32 years. Eight patients died within the first year. Among the mortality causes, there were four septic shocks, one cardiogenic shock, one massive pulmonary thromboembolism, one myocardial infarction, and one unknown cause. When analyzed for periods, death censored graft survival was 89% at one and five years after re-transplantation. One graft was lost at eight days due to antibody-mediated rejection (AMR), while there was one death with a functioning graft three months after re-transplantation secondary to a pulmonary embolism. Seventy-three late re-transplants occurred. When analyzed for periods, death censored graft survival was 81% and 69% at one and five years after re-transplantation, respectively. The median patient survival after late re-transplantation was 32 years. There were fewer deaths after rapid re-transplantation than late re-transplantation, but given the small number of cases in the former, this difference did not reach statistical significance (p = 0.3). There was no association between the timing of re-transplantation and an increased risk of graft failure (HR 0.30 [0.04 – 2.2]). While four rapid re-transplants did not share any incompatibilities between donors, four did share at least one HLA type I incompatibility, and one shared an incompatibility of HLA class I and class II. There were no T-cell mediated rejections (TCMR), and there was only one AMR in the rapid rapid re-transplantation group, whereas there were six TCMRs and fifteen AMRs in the late re-transplantation group (p = 0.03 and p = 0.4, respectively). Conclusion Rapid re-transplantation appears to be safe and does not entail increased rejection risk, nor it diminishes long-term graft survival when compared to late re-transplantation.


2021 ◽  
Vol 8 ◽  
Author(s):  
Gaston J. Piñeiro ◽  
Enrique Montagud-Marrahi ◽  
José Ríos ◽  
Pedro Ventura-Aguiar ◽  
David Cucchiari ◽  
...  

Background: Despite recent advances in immunosuppression treatment, antibody-mediated rejection (ABMR) remains the leading cause of kidney graft loss. Information about prognostic markers and the efficacy of treatment is scarce.Methods: Retrospective study with kidney recipients diagnosed an active ABMR from January 1, 2004 to December 31, 2019 to explore the influence of persistent inflammation in follow-up biopsies on graft survival after ABMR treatment.Results: About 116 patients were included. Active ABMR were treated with a combination of plasma exchange (PE), intravenous immunoglobulin (IVIg), rituximab, and steroids. At 6 months of treatment, 63 (54.3%) patients presented a stabilization or improvement in kidney-graft function. The effectiveness varied depending on the timepoint of the presentation between transplantation and rejection, which is lower for those with late ABMR (63 vs. 21% for early vs. late ABMR, respectively). Ninety patients (77%) underwent a control biopsy after ABMR treatment, from which 46 (51%) responded to the treatment. Microvascular inflammation (MVI) persisted in 64 (71%) biopsies, whereas tubulitis persisted in 17 (19%) biopsies. Death-censored graft survival at 1 year was significantly lower in patients with persistent MVI (86% vs. 95% without persistent MVI, P = 0.002), or with persistent tubulitis (44% vs. 66% without tubulitis, P = 0.02). In the Cox Regression analysis, the persistence of MVI [hazard ratio (HR), 4.50 (95%CI, 1.35–14.96), P = 0.01] and tubulitis [HR 2.88 95%CI (1.24–6.69), P = 0.01) in follow-up biopsies significantly increased the risk of graft failure.Conclusion: Persistent inflammation in follow-up biopsies after ABMR treatment was associated with an increased risk of graft loss, even without meeting Banff rejection criteria.Study Registration: Agencia Española de Medicamentos y Productos Sanitarios (AEMPS): 14566/RG 24161. Study code: UTRINM-2017-01.


2019 ◽  
Author(s):  
Hsien-Fu Chiu ◽  
Mei-Chin Wen ◽  
Ming-Ju Wu ◽  
Cheng-Hsu Chen ◽  
Tung-Min Yu ◽  
...  

Abstract Background: A plethora of evidences suggest that the most important cause of late graft loss in renal transplant recipients is chronic active antibody-mediated rejection. However, there are no consensus on treatment strategies. Methods: We retrospectively analyzed clinical and pathological data of renal transplant recipients who received kidney graft biopsy with confirmed diagnosis of chronic active antibody-mediated rejection in the past 7 years. The patients were divided into two groups according to treatment strategy: Group 1: aggressive treatment (double filtration plasmapheresis and one of the followings: rituximab, intravenous immunoglobulin, antithymogycte globulin, bortezomib, or methylprednisolone pulse therapy); and group 2: supportive treatment. Results: From February 2009 to December 2017, a total of 82 graft biopsies with diagnosis of chronic active antibody mediated rejection were identified. Kaplan-Meier analysis of death-censored graft survival showed a worse survival in group 2 (P = 0.015 by log-rank test). Adverse event-free survival was lower in group 1, whereas patient survival was no significant different. Proteinuria and supportive treatment were independent risk factors for graft loss in multivariate analysis. Conclusions: Aggressive treatment was associated with better graft outcome. However, higher incidence of adverse events merit personalized treatment, especially for those with higher risk of infection. Appropriate prophylactic antibiotics are recommended for aggressive treatment patients.


2012 ◽  
Vol 94 (10S) ◽  
pp. 18
Author(s):  
M. Magtinon ◽  
T. Muthukumar ◽  
S. V. Seshan ◽  
M. Suthanthiran ◽  
C. Hartono

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