Corrigendum: Non-Invasive Diagnosis for Acute Rejection Using Urinary mRNA Signature Reflecting Allograft Status in Kidney Transplantation

Urine has been regarded as a good resource based on the assumption that urine can directly reflect the state of the allograft or ongoing injury in kidney transplantation. Previous studies, suggesting the usefulness of urinary mRNA as a biomarker of acute rejection, imply that urinary mRNA mirrors the transcriptional activity of the kidneys. We selected 14 data-driven candidate genes through a meta-analysis and measured the candidate genes using quantitative PCR without pre-amplification in the cross-sectional specimens from Korean kidney transplant patients. Expression of 9/14 genes (CXCL9, CD3ϵ, IP-10, LCK, C1QB, PSMB9, Tim-3, Foxp3, and FAM26F) was significantly different between acute rejection and stable graft function with normal pathology and long-term graft survival in 103 training samples. CXCL9 was also distinctly expressed in allografts with acute rejection in in situ hybridization analysis. This result, consistent with the qPCR result, implies that urinary mRNA could reflect the magnitude of allograft injury. We developed an AR prediction model with the urinary mRNAs by a binary logistic regression and the AUC of the model was 0.89 in the training set. The model was validated in 391 independent samples, and the AUC value yielded 0.84 with a fixed manner. In addition, the decision curve analysis indicated a range of reasonable threshold probabilities for biopsy. Therefore, we suggest the urine mRNA signature could be used as a non-invasive monitoring tool of acute rejection for clinical application and could help determine whether to perform a biopsy in a recipient with increased creatinine.

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Non-Invasive Tool to Distinguish Between Acute Rejection and Stable Graft Function Using Urinary mRNA Signature Reflecting Allograft Status in Kidney Transplantation

10.21203/rs.3.rs-128249/v1 ◽

2020 ◽

Author(s):

Jung-Woo Seo ◽

Yu-Ho Lee ◽

Dong Hyun Tae ◽

Seon Hwa Park ◽

Ju-Young Moon ◽

...

Keyword(s):

Kidney Transplantation ◽

Acute Rejection ◽

Candidate Genes ◽

Large Scale ◽

Scale Validation ◽

Graft Function ◽

Area Under The Curve ◽

Binary Logistic Regression ◽

Cross Sectional ◽

Non Invasive

Abstract Background: Urine has been regarded as the best resource based on the assumption that urine can directly reflect the state of the allograft or ongoing injury in kidney transplantation. Previous studies, suggesting the usefulness of urinary mRNA as a biomarker of acute rejection, imply that urinary mRNA mirrors the transcriptional activity of the kidneys. Methods: We absolutely measured 14 data-driven candidate genes using quantitative PCR without pre-amplification in the cross-sectional specimens collected from Korean kidney transplant patients. We developed a clinical application model adopting urinary mRNAs for allograft rejection using a binary logistic regression and finally verified its usefulness in a large-scale validation group.Results: We measured the candidate genes in 103 training samples. Expression of 8/14 genes were significantly different between acute rejection and stable graft function with normal pathology and long-term graft survival. Also, CXCL9 was distinctly expressed in allografts with acute rejection in in situ hybridization analysis. This result, consistent with the qPCR result, implies that urinary mRNA could reflect the magnitude of allograft injury. We developed AR prediction model by differently combined mRNAs and the area under the curve (AUC) of the model was 0.89 in training set. The model was validated in 391 independent samples, and the AUC of the model was 0.84 with a fixed manner. In addition, the decision curve analysis indicated a range of reasonable threshold probabilities for biopsy. Conclusions. Therefore, we suggest urinary mRNA signature may serve as a non-invasive monitoring tool of acute rejection and intragraft immune injury.

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Monitoring of molecular profiling of regulatory T cell biomarkers by using non- invasive strategies to predict outcome in renal transplantation

10.21203/rs.3.rs-267696/v1 ◽

2021 ◽

Author(s):

Angelica Canossi ◽

Samuele Iesari ◽

Quirino Lai ◽

Simone Ciavatta ◽

Tiziana Del Beato ◽

...

Keyword(s):

Kidney Transplantation ◽

T Cell ◽

Acute Rejection ◽

Regulatory T Cell ◽

Peripheral Blood ◽

De Novo ◽

Mrna Levels ◽

Healthy Controls ◽

Non Invasive ◽

One Year

Abstract Background. T-cell mediated acute rejection (aTCMR) is still an issue in kidney transplantation for it is associated with chronic rejection, graft loss, and overall worse outcomes. For these reasons, a standard non-invasive molecular tool to detect is desirable to offer a simpler monitoring of kidney transplant recipients (KTRs). The purpose of our study was to examine, in peripheral blood before and after transplantation, the expression patterns of regulatory T cell (Treg)-related genes: the forkhead box P3 (FOXP3) and the two CTLA-4 isoforms (full-length and soluble) to predict aTCMR onset, de novo donor-specific antibodies (DSA) development and renal dysfunction one year after transplantation. Methods. We profiled by using a relative quantification analysis (qRT-PCR 2-∆∆CT) the circulating mRNA levels of these biomarkers in peripheral blood of 89 KTRs within the first post-transplant year (at baseline and 15, 60, 365 days after transplantation and when possible at acute rejection) and compared the results with 24 healthy controls. Results. The three mRNA levels drastically reduced 15 days after transplantation and gradually recovered at one year in comparison with baseline, with very low levels by the time of aTCMR for FOXP3 (RQ=0.445, IQR=0.086-1.264, p=0.040). Healthy controls exhibited higher FOXP3 levels than patients at baseline (median RQ: 2.132, IQR=1.664-2.895 vs. p=0.005). Noteworthy, solCTLA-4 displayed a dual profile: on the one hand, at multivariate analysis solCTLA-4 transcripts at 15 days were associated with an increased risk of aTCMR over time (HR=3.905, 95%CI: 0.958-15.916, p=0.050), and graft dysfunction at one year (AOR=3.683, 95%CI=1.165-12.079, p=0.027); on the other hand, pre-transplant levels showed a protective association with de novo DSAs development (HR=0.189, 95%CI=0.078-0.459, p<0.001). Conclusions. Peripheral blood mRNA levels of Treg-associated molecules might help shape immunosuppression, tailor monitoring and achieve a better long-term clinical course of kidney transplantation in the wake of “precision medicine”. While the potential of these molecules as a therapeutic target needs further investigation, we found out preliminary evidence that solCTLA-4 can qualify as a candidate non-invasive biomarker of cellular and humoral alloreactivity in clinical transplantation.

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1872: The Efficacy of Deoxyspergualin and Plasmapheresis for Antibody-Mediated Acute Rejection After Kidney Transplantation

The Journal of Urology ◽

10.1016/s0022-5347(18)39064-5 ◽

2004 ◽

Vol 171 (4S) ◽

pp. 494-494

Author(s):

Michio Michio Nojima ◽

Tetsuro Yoshimoto ◽

Atsushi Nakao ◽

Takuo Maruyama ◽

Hidekazu Takiuchi ◽

...

Keyword(s):

Kidney Transplantation ◽

Acute Rejection

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Acute Rejection Following Kidney Transplantation: State-of-the-Art and Future Perspectives

Current Pharmaceutical Design ◽

10.2174/1381612826666200610184433 ◽

2020 ◽

Vol 26 (28) ◽

pp. 3468-3496

Author(s):

Emilio Rodrigo ◽

Marcio F. Chedid ◽

David San Segundo ◽

Juan C.R. San Millán ◽

Marcos López-Hoyos

Keyword(s):

Kidney Transplantation ◽

Acute Rejection ◽

Rescue Therapy ◽

Standard Of Care ◽

Rejection Rate ◽

New Drugs ◽

High Dose ◽

Current Standard ◽

Antibody Mediated Rejection ◽

Cellular Rejection

: Although acute renal graft rejection rate has declined in the last years, and because an adequate therapy can improve graft outcome, its therapy remains as one of the most significant challenges for pharmacists and physicians taking care of transplant patients. Due to the lack of evidence highlighted by the available metaanalyses, we performed a narrative review focused on the basic mechanisms and current and future therapies of acute rejection in kidney transplantation. : According to Kidney Disease/Improving Global Outcomes (KDIGO) guidelines, both clinical and subclinical acute rejection episodes should be treated. Usually, high dose steroids and basal immunosuppression optimization are the first line of therapy in treating acute cellular rejection. Rabbit antithymocytic polyclonal globulins are used as rescue therapy for recurrent or steroid-resistant cellular rejection episodes. Current standard-of-care (SOC) therapy for acute antibody-mediated rejection (AbMR) is the combination of plasma exchange with intravenous immunoglobulin (IVIG). Since a significant rate of AbMR does not respond to SOC, different studies have analyzed the role of new drugs such as Rituximab, Bortezomib, Eculizumab and C1 inhibitors. Lack of randomized controlled trials and heterogenicity among performed studies limit obtaining definite conclusions. Data about new direct and indirect B cell and plasma cell depleting agents, proximal and terminal complement blockers, IL-6/IL-6R pathway inhibitors and antibody removal agents, among other promising drugs, are reviewed.

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