Outcome of 313 Czech Patients With IgA Nephropathy After Renal Transplantation

The recurrence of IgA nephropathy (IgAN) after kidney transplantation occurs in 20–35% of patients. The main aim of this study is to evaluate risk factors affecting the course of IgAN after renal biopsy of native kidney and kidney transplant. We evaluated clinical parameters and histological findings at the time of biopsy of native kidney and after kidney transplantation in 313 patients with IgAN with a follow-up of up to 36 years. Using hierarchical clustering method, patients with graft failure (n=50) were divided into two groups based on the mean time from kidney transplant to graft failure (11.2 versus 6.1 years). The time-to-graft failure corresponded well to the time from the renal biopsy of native kidney to end-stage renal disease (5.9 versus 0.4 years). Body mass index, proteinuria, microscopic hematuria, histological evaluation of fibrosis, and crescents at the time of renal biopsy of native kidney were the main variables for the differentiation of the two groups. Higher age of kidney-transplant donor, histological recurrence of IgAN, antibody-mediated rejection, and the onset of microscopic hematuria and proteinuria within 1 year after kidney transplant were also associated with worse graft survival in multivariate Cox regression analysis.

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Outcomes of Kidney Transplantation in Fabry Disease: A Meta-Analysis

Diseases ◽

10.3390/diseases9010002 ◽

2020 ◽

Vol 9 (1) ◽

pp. 2

Author(s):

Maria L. Gonzalez Suarez ◽

Charat Thongprayoon ◽

Panupong Hansrivijit ◽

Juan Medaura ◽

Pradeep Vaitla ◽

...

Keyword(s):

Kidney Transplantation ◽

Fabry Disease ◽

Kidney Transplant ◽

Allograft Rejection ◽

Graft Failure ◽

Current Therapy ◽

Transplant Recipients ◽

Lysosomal Storage ◽

Kidney Transplant Recipients ◽

Enzyme Replacement

Background: Fabry disease (FD) is a rare X-linked lysosomal storage disorder with progressive systemic deposition of globotriaosylceramide, leading to life-threatening cardiac, central nervous system, and kidney disease. Current therapy involves symptomatic medical management, enzyme replacement therapy (ERT), dialysis, kidney transplantation, and, more recently, gene therapy. The aim of this systematic review was to assess outcomes of kidney transplantation among patients with FD. Methods: A comprehensive literature review was conducted utilizing MEDLINE, EMBASE, and Cochrane Database, from inception through to 28 February 2020, to identify studies that evaluate outcomes of kidney transplantation including patient and allograft survival among kidney transplant patients with FD. Effect estimates from each study were extracted and combined using the random-effects generic inverse variance method of DerSimonian and Laird. Results: In total, 11 studies, including 424 kidney transplant recipients with FD, were enrolled. The post-transplant median follow-up time ranged from 3 to 11.5 years. Overall, the pooled estimated rates of all-cause graft failure, graft failure before death, and allograft rejection were 32.5% (95%CI: 23.9%–42.5%), 14.5% (95%CI: 8.4%–23.7%), and 20.2% (95%CI: 15.4%–25.9%), respectively. In the sensitivity analysis, limited only to the recent studies (year 2001 or newer when ERT became available), the pooled estimated rates of all-cause graft failure, graft failure before death, and allograft rejection were 28.1% (95%CI: 20.5%–37.3%), 11.7% (95%CI: 8.4%–16.0%), and 20.2% (95%CI: 15.5%–26.0%), respectively. The pooled estimated rate of biopsy proven FD recurrence was 11.1% (95%CI: 3.6%–29.4%), respectively. There are no significant differences in the risks of all-cause graft failure (p = 0.10) or mortality (0.48) among recipients with vs. without FD. Conclusions: Despite possible FD recurrence after transplantation of 11.1%, allograft and patient survival are comparable among kidney transplant recipients with vs. without FD.

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CD56+CD57+ infiltrates as the most predominant subset of intragraft natural killer cells in renal transplant biopsies with antibody-mediated rejection

Scientific Reports ◽

10.1038/s41598-019-52864-5 ◽

2019 ◽

Vol 9 (1) ◽

Author(s):

Hey Rim Jung ◽

Mi Joung Kim ◽

Yu-Mee Wee ◽

Jee Yeon Kim ◽

Monica Young Choi ◽

...

Keyword(s):

Renal Transplant ◽

Nk Cells ◽

Natural Killer ◽

Kidney Transplant ◽

Graft Failure ◽

Nk Cell ◽

Cell Infiltration ◽

Transplant Recipients ◽

Kidney Transplant Recipients ◽

Antibody Mediated Rejection

Abstract Little is known about the characteristics and clinical implications of specific subsets of intragraft natural killer (NK) cells in kidney transplant recipients. We analyzed 39 for-cause renal transplant biopsies performed at our center from May 2015 to July 2017. According to histopathologic reports, 8 patients (20.5%) had no rejection (NR), 11 (28.2%) had T cell-mediated rejections (TCMR) only, and 20 (51.3%) had antibody-mediated rejection (ABMR). NK cells were defined as CD3–CD56+ lymphocytes that are positive for CD57, CD49b, NKG2A, or KIR. The density of NK cells was significantly higher in the ABMR group (2.57 ± 2.58/mm2) than in the NR (0.12 ± 0.22/mm2) or the TCMR (0.25 ± 0.34/mm2) group (P = 0.002). Notably, CD56+CD57+ infiltrates (2.16 ± 1.89) were the most frequently observed compared with CD56+CD49b+ (0.05 ± 0.13), CD56+NKG2A+ (0.21 ± 0.69), and CD56+KIR+ (0.15 ± 0.42) cells in the ABMR group (P < 0.001). Death-censored graft failure was significantly higher in patients with NK cell infiltration than those without (Log-rank test, P = 0.025). In conclusion, CD56+CD57+ infiltrates are a major subset of NK cells in kidney transplant recipients with ABMR and NK cell infiltration is significantly associated with graft failure post-transplant.

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Impact of deceased donor with acute kidney injury on subsequent kidney transplant outcomes–an ANZDATA registry analysis

PLoS ONE ◽

10.1371/journal.pone.0249000 ◽

2021 ◽

Vol 16 (3) ◽

pp. e0249000

Author(s):

Juan Pei ◽

Yeoungjee Cho ◽

Yong Pey See ◽

Elaine M. Pascoe ◽

Andrea K. Viecelli ◽

...

Keyword(s):

Acute Kidney Injury ◽

Kidney Transplantation ◽

Acute Rejection ◽

Kidney Transplant ◽

Graft Failure ◽

Cox Regression ◽

Graft Function ◽

Kidney Injury ◽

Deceased Donor ◽

Hazard Ratio

Background The need for kidney transplantation drives efforts to expand organ donation. The decision to accept organs from donors with acute kidney injury (AKI) can result in a clinical dilemma in the context of conflicting reports from published literature. Material and methods This observational study included all deceased donor kidney transplants performed in Australia and New Zealand between 1997 and 2017. The association of donor-AKI, defined according to KDIGO criteria, with all-cause graft failure was evaluated by multivariable Cox regression. Secondary outcomes included death-censored graft failure, death, delayed graft function (DGF) and acute rejection. Results The study included 10,101 recipients of kidneys from 5,774 deceased donors, of whom 1182 (12%) recipients received kidneys from 662 (11%) donors with AKI. There were 3,259 (32%) all-cause graft failures, which included 1,509 deaths with functioning graft. After adjustment for donor, recipient and transplant characteristics, donor AKI was not associated with all-cause graft failure (adjusted hazard ratio [HR] 1.11, 95% CI 0.99–1.26), death-censored graft failure (HR 1.09, 95% CI 0.92–1.28), death (HR 1.15, 95% CI 0.98–1.35) or graft failure when death was evaluated as a competing event (sub-distribution hazard ratio [sHR] 1.07, 95% CI 0.91–1.26). Donor AKI was not associated with acute rejection but was associated with DGF (adjusted odds ratio [OR] 2.27, 95% CI 1.92–2.68). Conclusion Donor AKI stage was not associated with any kidney transplant outcome, except DGF. Use of kidneys with AKI for transplantation appears to be justified.

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Recurrence of FSGS after Kidney Transplantation in Adults

Clinical Journal of the American Society of Nephrology ◽

10.2215/cjn.08970719 ◽

2020 ◽

Vol 15 (2) ◽

pp. 247-256 ◽

Cited By ~ 6

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.

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Recent Advances and Clinical Outcomes of Kidney Transplantation

Journal of Clinical Medicine ◽

10.3390/jcm9041193 ◽

2020 ◽

Vol 9 (4) ◽

pp. 1193 ◽

Cited By ~ 5

Author(s):

Charat Thongprayoon ◽

Panupong Hansrivijit ◽

Napat Leeaphorn ◽

Prakrati Acharya ◽

Aldo Torres-Ortiz ◽

...

Keyword(s):

Kidney Transplantation ◽

Cardiovascular Diseases ◽

Kidney Disease ◽

Kidney Transplant ◽

Molecular Techniques ◽

Kidney Allograft ◽

Antibody Mediated Rejection ◽

Recent Advances ◽

Monitoring Protocols

Recent advances in surgical, immunosuppressive and monitoring protocols have led to the significant improvement of overall one-year kidney allograft outcomes. Nonetheless, there has not been a significant change in long-term kidney allograft outcomes. In fact, chronic and acute antibody-mediated rejection (ABMR) and non-immunological complications following kidney transplantation, including multiple incidences of primary kidney disease, as well as complications such as cardiovascular diseases, infections, and malignancy are the major factors that have contributed to the failure of kidney allografts. The use of molecular techniques to enhance histological diagnostics and noninvasive surveillance are what the latest studies in the field of clinical kidney transplant seem to mainly focus upon. Increasingly innovative approaches are being used to discover immunosuppressive methods to overcome critical sensitization, prevent the development of anti-human leukocyte antigen (HLA) antibodies, treat chronic active ABMR, and reduce non-immunological complications following kidney transplantation, such as the recurrence of primary kidney disease and other complications, such as cardiovascular diseases, infections, and malignancy. In the present era of utilizing electronic health records (EHRs), it is strongly believed that big data and artificial intelligence will reshape the research done on kidney transplantation in the near future. In addition, the utilization of telemedicine is increasing, providing benefits such as reaching out to kidney transplant patients in remote areas and helping to make scarce healthcare resources more accessible for kidney transplantation. In this article, we discuss the recent research developments in kidney transplants that may affect long-term allografts, as well as the survival of the patient. The latest developments in living kidney donation are also explored.

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Acute Kidney Injury and Long-Term Risk for Cardiovascular Events in Patients after Kidney Transplantation

Kidney & Blood Pressure Research ◽

10.1159/000502523 ◽

2019 ◽

Vol 44 (5) ◽

pp. 1149-1157

Author(s):

Ruth Rahamimov ◽

Tuvia Y. van Dijk ◽

Maya Molcho ◽

Itay Vahav ◽

Eytan Mor ◽

...

Keyword(s):

Acute Kidney Injury ◽

Kidney Transplantation ◽

Kidney Transplant ◽

Cardiovascular Events ◽

Kidney Injury ◽

Time Varying ◽

Cox Regression Analysis ◽

Increased Risk ◽

All Cause Mortality ◽

Cv Disease

Background: Acute kidney injury (AKI) was found to be associated with an increased risk of major adverse cardiovascular events (MACE) in the general population. Patients after kidney transplantation are prone to AKI events and are also at an increased risk of cardiovascular (CV) disease. The association between AKI and MACE in kidney transplant patients is yet to be studied. Methods: This retrospective single-center cohort study reviewed 416 adult renal allograft recipients transplanted between 2005 and 2010. AKI events were recorded starting 2 weeks after transplantation, or following discharge with a functioning graft. AKI was defined, according to the KDIGO criteria. The primary outcome was the composite of MACE starting 6 months after transplantation and all-cause mortality. For survival analysis, we used univariate and multivariate time varying Cox proportional hazard model. Results: One hundred and twenty-four patients (29.8%) had at least one episode of AKI. During the median follow-up time of 7.2 years (interquartile range 4.3–9.1), 144 outcome events occurred. By time varying Cox regression analysis, AKI was associated with an increased rate of CV outcomes or death (hazard ratio [HR] 1.96, 95% CI 1.36–2.81, p < 0.001), and the association remained significant by multivariate adjusted model (HR 1.76, 95% CI 1.18–2.63, p = 0.005). As for the different components of MACE, all-cause mortality and CV mortality were the only outcomes that were significantly associated with AKI. No interaction between AKI timing and MACE was found. Conclusion: AKI in kidney transplant recipient is associated with an increased risk of CV disease.

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P203 Late antibody-mediated rejection (ABMR) after kidney transplantation – Role of the eGFR slope within the first year after biopsy as a surrogate endpoint predicting graft failure

Human Immunology ◽

10.1016/j.humimm.2019.07.256 ◽

2019 ◽

Vol 80 ◽

pp. 214

Author(s):

Farsad Eskandary ◽

Anita Dumler ◽

Heinz Regele ◽

Alexander Kainz ◽

Konstantin Doberer ◽

...

Keyword(s):

Kidney Transplantation ◽

Graft Failure ◽

Surrogate Endpoint ◽

First Year ◽

Antibody Mediated Rejection ◽

Egfr Slope

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

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfaa142.p1738 ◽

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.

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P1776HLA TYPING BY NGS ENHANCES MISMATCH DETECTION IN LIVING KIDNEY TRANSPLANTATION

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfaa142.p1776 ◽

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.

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Parvovirus: Uncommon Causes of Anemia and Kidney Failure in a Kidney Transplant Patient

Nephro-Urology Monthly ◽

10.5812/numonthly.112713 ◽

2021 ◽

Vol In Press (In Press) ◽

Author(s):

Maliheh Yarmohamadi ◽

Fatemeh Yaghoubi

Keyword(s):

Kidney Transplantation ◽

Renal Transplant ◽

Kidney Transplant ◽

Kidney Failure ◽

Graft Failure ◽

Transplant Patient ◽

Parvovirus B19 ◽

Kidney Transplant Patient ◽

Severe Anemia ◽

Parvovirus B19 Infection

: Parvovirus is one of the uncommon causes of anemia in a kidney transplant patient. We reported a kidney transplant patient with parvovirus infection who developed severe anemia three weeks after kidney transplantation. Suspicion of infections increased due to the decrease in erythrocyte level. The patient's anemia became normal with a decrease in the amount of immunosuppressant and treatment with intravenous immunoglobulin (IVIG). Parvovirus B19 infection should be considered in all patients with persistent anemia with or without graft failure after renal transplant.

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