scholarly journals Non-invasive screening for sub-clinical antibody-mediated rejection as a new tool for indication of kidney allograft biopsy

EBioMedicine ◽  
2019 ◽  
Vol 46 ◽  
pp. 13-14
Author(s):  
Nicolas Kozakowski
Keyword(s):  
Kidney Allograft ◽  
Antibody Mediated Rejection ◽  
Non Invasive ◽  
Allograft Biopsy

scholarly journals Urinary Cell mRNA Profiles Predictive of Human Kidney Allograft Status

2021 ◽  
pp. CJN.14010820
Author(s):  
Michelle L. Lubetzky ◽  
Thalia Salinas ◽  
Joseph E. Schwartz ◽  
Manikkam Suthanthiran
Keyword(s):  
Clinical Trials ◽  
T Cell ◽  
Acute Rejection ◽  
Biopsy Specimen ◽  
Acute Cellular Rejection ◽  
Kidney Allograft ◽  
Antibody Mediated Rejection ◽  
Biopsy Specimens ◽  
Allograft Biopsy ◽  
Cellular Rejection

Immune monitoring of kidney allograft recipients and personalized therapeutics may help reach the aspirational goal of “one transplant for life.” The invasive kidney biopsy procedure, the diagnostic tool of choice, has become safer and the biopsy classification more refined. Nevertheless, biopsy-associated complications, interobserver variability in biopsy specimen scoring, and costs continue to be significant concerns. The dynamics of the immune repertoire make frequent assessments of allograft status necessary, but repeat biopsies of the kidney are neither practical nor safe. To address the existing challenges, we developed urinary cell mRNA profiling and investigated the diagnostic, prognostic, and predictive accuracy of absolute levels of a hypothesis-based panel of mRNAs encoding immunoregulatory proteins. Enabled by our refinements of the PCR assay and by investigating mechanistic hypotheses, our single-center studies identified urinary cell mRNAs associated with T cell–mediated rejection, antibody-mediated rejection, interstitial fibrosis and tubular atrophy, and BK virus nephropathy. In the multicenter National Institutes of Health Clinical Trials in Organ Transplantation-04, we discovered and validated a urinary cell three-gene signature of T-cell CD3 ε chain mRNA, interferon gamma inducible protein 10 (IP-10) mRNA, and 18s ribosomal RNA that is diagnostic of subclinical acute cellular rejection and acute cellular rejection and prognostic of acute cellular rejection and graft function. The trajectory of the signature score remained flat and below the diagnostic threshold for acute cellular rejection in the patients with no rejection biopsy specimens, whereas a sharp rise was observed during the weeks before the biopsy specimen that showed acute cellular rejection. Our RNA sequencing and bioinformatics identified kidney allograft biopsy specimen gene signatures of acute rejection to be enriched in urinary cells matched to acute rejection biopsy specimens. The urinary cellular landscape was more diverse and more enriched for immune cell types compared with kidney allograft biopsy specimens. Urinary cell mRNA profile–guided clinical trials are needed to evaluate their value compared with current standard of care.

scholarly journals Both absolute and relative quantification of urinary mRNA are useful for non-invasive diagnosis of acute kidney allograft rejection

PLoS ONE ◽  
2017 ◽  
Vol 12 (6) ◽  
pp. e0180045 ◽  
Author(s):  
Jung-Woo Seo ◽  
Haena Moon ◽  
Se-Yun Kim ◽  
Ju-Young Moon ◽  
Kyung Hwan Jeong ◽  
...  
Keyword(s):  
Allograft Rejection ◽  
Relative Quantification ◽  
Kidney Allograft ◽  
Non Invasive ◽  
Kidney Allograft Rejection

scholarly journals P1639DEVELOPMENT OF SELF-LIMITED LOW-LEVEL BK VIREMIA/VIRURIA SUGGESTS IDEAL IMMUNOSUPPRESSION TO SUPPRESS T-CELL AND ANTIBODY-MEDIATED REJECTION AND PRESERVE KIDNEY ALLOGRAFT FUNCTION

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Bettina Näf ◽  
Thomas Müller ◽  
Rudolf Peter Wuthrich ◽  
Thomas Schachtner
Keyword(s):  
Lower Incidence ◽  
De Novo ◽  
Allograft Survival ◽  
Kidney Allograft ◽  
Low Level ◽  
Antibody Mediated Rejection ◽  
Maintenance Immunosuppression ◽  
Allograft Function ◽  
High Level ◽  
Egfr Slope

Abstract Background and Aims Polyomavirus BK (BKV) viremia has been suggested as a surrogate marker of overimmunosuppression. Due to recent advances in monitoring strategies and pre-emptive therapy, progression to BKV-associated nephropathy (BKVN) has been reduced. Reduction of maintenance immunosuppression during BKVN, however, has been associated with both T-cell mediated rejection (TCMR), antibody-mediated rejection (ABMR), and inferior kidney allograft outcomes. Although the administration of intravenous immunoglobulins (IVIG) failed to treat BKVN, IVIG may have properties to reduce allosensitization. Method We studied 860 kidney transplant recipients (KTRs) predominantly under tacrolimus-based triple-drug maintenance immunosuppression from 2009 to 2018. We identified 130 KTRs (15.1%) with high-level BK viremia >10,000 copies/mL (presumptive BKVN), 180 KTRs (20.9%) with low-level BK viremia <10,000 copies/mL, 85 KTRs (9.9%) with isolated BK viruria, and 465 KTRs (54.1%) with no BK viruria/viremia. Kidney allograft outcomes with respect to TCMR, ABMR, development of de novo donor-specific antibodies (DSA), kidney allograft survival, and estimated glomerular filtration rate (eGFR) slope were analysed. Due to the increased incidence of TCMR and ABMR among KTRs with presumptive BKVN, 48 of 130 KTRs (36.9%) with high-level BK viremia starting from 2015 received IVIG (0.5 g/kg of body weight) on a biweekly basis during BKV replication. Results Very interestingly, KTRs with low-level BK viremia/viruria showed a significantly lower incidence of TCMR compared to KTRs with no BK viremia/viruria and KTRs with high-level BK viremia (p<0.05). In addition, KTRs with low-level BK viremia/viruria showed a significantly lower incidence of ABMR compared to KTRs with high-level BK viremia (p<0.05). No differences were observed with respect to the development of de novo DSA (MFI>5000) between KTRs with low-level BK viremia/viruria, KTRs with no BK viremia/viruria, and KTRs with high-level BK viremia (p>0.05). KTRs with low-level BK viremia/viruria showed superior kidney allograft survival and lower eGFR slope compared to KTRs with no BK viremia/viruria and KTRs with high-level BK viremia (p<0.05). The administration of IVIG during high-level BK viremia didn’t impact the development of TCMR, ABMR, development of de novo DSA, eGFR slope, and kidney allograft survival (p<0.05). Conclusion Our results show that low-level BK viremia/viruria is associated with suppression of TCMR and ABMR in the early period posttransplantation, and preservation of kidney allograft function in the long-term. The administration of IVIG didn’t prove beneficial to reduce allosensitization among KTRs with high-level BK viremia.

scholarly journals Transplant Glomerulopathy, Late Antibody-Mediated Rejection and the ABCD Tetrad in Kidney Allograft Biopsies for Cause

2007 ◽  
Vol 7 (7) ◽  
pp. 1743-1752 ◽  
Author(s):  
B. Sis ◽  
P. M. Campbell ◽  
T. Mueller ◽  
C. Hunter ◽  
S. M. Cockfield ◽  
...  
Keyword(s):  
Kidney Allograft ◽  
Antibody Mediated Rejection ◽  
Transplant Glomerulopathy

Soluble BAFF Cytokine Levels and Antibody-Mediated Rejection of the Kidney Allograft

2016 ◽  
Vol 64 (S1) ◽  
pp. 47-53 ◽  
Author(s):  
Antonij Slavcev ◽  
Jitka Brozova ◽  
Janka Slatinska ◽  
Zuzana Sekerkova ◽  
Eva Honsova ◽  
...  
Keyword(s):  
Kidney Allograft ◽  
Antibody Mediated Rejection ◽  
Cytokine Levels

scholarly journals Histopathological evaluation of renal allograft biopsies in Nepal: interpretation and significance

1970 ◽  
Vol 2 (3) ◽  
pp. 172-179
Author(s):  
G Aryal ◽  
DS Shah
Keyword(s):  
T Cell ◽  
Renal Allograft ◽  
Calcineurin Inhibitor ◽  
Viral Infections ◽  
Ischemic Injury ◽  
Graft Dysfunction ◽  
Post Transplant ◽  
Medical College ◽  
Antibody Mediated Rejection ◽  
Allograft Biopsy

Background:  Renal allograft biopsy remains the gold standard for the diagnosis of graft dysfunction. Protocol renal allograft biopsies have provided insights into pathogenesis of early and late allograft injury and guided clinical management. The aim of this study was to find out the causes of early and late graft dysfunction in renal allograft biopsies taken at different time points after transplantation. Materials and Methods: Between August 2008 and February 2011, a total of 98 renal allograft biopsies from 62 kidney transplants recipients were received in the department of Pathology, KIST Medical College and Teaching Hospital. Renal allograft biopsies were interpreted according to the Schemes of Banff ’09 update. Results: The maximum numbers of recipients were in the age group of 31-40 years. Age ranges from 16 to 61 years. Out of 62 recipients, there were 47(75.8%) males and 15 (24.2%) females. The time of biopsy ranges from 0 hour to 6 years after transplantation. There were 9 (9.18%) cases of acute T cell-mediated rejection, 8 (8.16%) cases of acute antibody-mediated rejection, 6 (6.12%) cases of acute ischemic injury, 6 (6.12%) cases of borderline lesions and 4 (4.08%) cases of chronic calcineurin inhibitor toxicity. Conclusion: In the early post-transplant period (0-6 months), acute antibody-mediated rejection, acute ischemic injury and T cell-mediated rejection are the major causes for graft dysfunction. In the late post transplant period (> 6 months after transplant), transplant glomerulopathy, chronic calcineurin inhibitor toxicity, viral infections and graft senescence including donor derived disease result in poor late graft survival.DOI: http://dx.doi.org/10.3126/jpn.v2i3.6016 JPN 2012; 2(3): 172-179

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