Biomarkers to detect rejection after kidney transplantation

Dharnidharka, Vikas R.; Malone, Andrew F.

doi:10.1007/s00467-017-3712-6

Cited by 15 publications

(15 citation statements)

References 75 publications

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“…However, in consideration of its side effects, performing serial renal biopsies are impractical at the same periodicity as blood or urine examination. Besides, Dharnidharka and his colleagues found that cellular and molecular events of AR occur before the rise of the clinical biomarker like serum creatinine as well as according to serum creatinine elevated, clinical doctors can't distinguished a superimposed AR from chronic allograft injury progression, which suggests that functional markers like serum creatinine for glomerular ltration are not as speci c as injury markers [20] .…”

Section: Discussionmentioning

confidence: 99%

Noninvasive Identification of Core Gene Biomarkers in Patients with Acute Kidney Transplant Rejection

Zhao

2020

Preprint

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Background: Acute rejection (AR) is one of common and critical complications after kidney transplantation, which gives rise to an increasing of allograft loss and even death. However, the potential mechanisms of AR remain incompletely understood at present. This study aimed to reveal the underlying mechanisms and identify core biomarkers of AR.Methods: The AR gene expression profile GSE1563 involving 6 renal transplant patients undergoing AR and 9 patients with well-functioning transplant with no clinical evidence of rejection was selected to analyze the differentially expressed genes (DEGs) from purified RNA of peripheral blood lymphocytes. DAVID was used to carry out Gene ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. A protein-protein interaction (PPI) network was built to display the interactions among these DEGs. To get further reliable significant genes and mechanisms, gene set enrichment analysis (GSEA) was applied to evaluate the hub gene analyzing via PPI network.Results: A total of 347 DEGs were captured, including 301 upregulated genes and 46 downregulated genes. Go and KEGG pathway analysis showed the DEGs were particularly enriched in immune response, inflammatory response to antigenic stimulus, RNA transport and protein stabilization. The PPI network indicated 3 modules were also mainly involved in immune response and RNA transport. 18 hub genes were selected in PPI network, among which there were 6 core genes evaluated by DAVID. By the way of GSEA, Oxidative stress was another potential mechanism besides immunity and ncRNA transport. Conclusion: Our analysis uncovered the immune response including humoral and cellular immunity, ncRNA transport as well as oxidative stress was the major mechanisms of AR associated respectively with MAPK8, CCL5, HMGB1, NCBP2, XPO1 and APP, which could be novel noninvasive biomarkers in peripheral blood for early diagnosis and could be helpful to the treatment of AR.

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Section: Discussionmentioning

confidence: 99%

Noninvasive Identification of Core Gene Biomarkers in Patients with Acute Kidney Transplant Rejection

Zhao

2020

Preprint

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“…A non-invasive biomarker for ABMR should be easy to obtain, fast and inexpensive. In addition, it should enable early prediction of the occurrence of ABMR and possess high positive predictive value (PPV), negative predictive values (NPV), and specificity to diagnose rejection and predict prognosis (Dharnidharka and Malone, 2018). Serum creatinine of more than 3 mg/dL and spot urine protein to creatinine ratio of more than 1 g/g were associated with increased risk of allograft loss (Redfield et al, 2016).…”

Section: Monitoring Of Renal Allograftmentioning

confidence: 99%

“…A variety of promising non-invasive biomarkers have been identified that can be used to monitor the immune status of KT patients: the IFN-γ enzyme-linked immunosorbent spot assay evaluating circulating antidonor T cell alloreactivity, gene expression analysis including Allomap (CareDx, Brisbane, CA), kSORT (ImmuCor, Grand Rapids, MI), Trugraf (ViraCor EuroFins, Lee Summit, MO), urine gene signature panels including Quest Laboratories Renal Transplant Monitoring panel, urinary chemokine including CXCL9 and CXCL10, mircroRNA, and donor-derived cell-free DNA (dd-cfDNA) Allosure (CareDx, Brisbane, CA), Prosepera (Natera, San Carlos, CA) (Dharnidharka and Malone, 2018). Most of these biomarkers are useful for diagnosing or predicting acute rejection or TCMR but still require validation in a large, well-controlled cohort.…”

Section: Monitoring Of Renal Allograftmentioning

confidence: 99%

“…Most of these biomarkers are useful for diagnosing or predicting acute rejection or TCMR but still require validation in a large, well-controlled cohort. To date, kSORT and dd-cfDNA are commercially available for acute rejection (Dharnidharka and Malone, 2018). In particular, dd-cfDNA was validated in the Diagnosing Acute Rejection in Kidney Transplant Recipients (DART) study which included patients with active ABMR, chronic active ABMR, or TCMR (Bloom et al, 2017).…”

Section: Monitoring Of Renal Allograftmentioning

confidence: 99%

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Therapies for Chronic Allograft Rejection

Kim

Brennan

2021

Front. Pharmacol.

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Remarkable advances have been made in the pathophysiology, diagnosis, and treatment of antibody-mediated rejection (ABMR) over the past decades, leading to improved graft outcomes. However, long-term failure is still high and effective treatment for chronic ABMR, an important cause of graft failure, has not yet been identified. Chronic ABMR has a relatively different phenotype from active ABMR and is a slowly progressive disease in which graft injury is mainly caused by de novo donor specific antibodies (DSA). Since most trials of current immunosuppressive therapies for rejection have focused on active ABMR, treatment strategies based on those data might be less effective in chronic ABMR. A better understanding of chronic ABMR may serve as a bridge in establishing treatment strategies to improve graft outcomes. In this in-depth review, we focus on the pathophysiology and characteristics of chronic ABMR along with the newly revised Banff criteria in 2017. In addition, in terms of chronic ABMR, we identify the reasons for the resistance of current immunosuppressive therapies and look at ongoing research that could play a role in setting better treatment strategies in the future. Finally, we review non-invasive biomarkers as tools to monitor for rejection.

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“…The ability to identify AMR, and perhaps even characterize AMR phenotypes based on gene expression profiles in biopsy tissue [128,129] should allow a clearer determination of AMR severity and ultimately help guide therapy. The identification of serum and/or urinary biomarkers [130][131][132][133] should enable better surveillance, earlier diagnosis of AMR, and prompt treatment to prevent irreversible tissue injury. Ultimately, optimizing the diagnosis and treatment of AMR will lead to greater graft longevity and thus, better utilization of this vastly limited resource.…”

Section: Outcomes and Unanswered Questionsmentioning

confidence: 99%

Diagnosis, Treatment, and Outcomes of Antibody-Mediated Rejection in Kidney Transplantation

Tatapudi¹,

Lonze²

2018

Organ Donation and Transplantation - Current Status and Future Challenges

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Antibody mediated rejection remains an important barrier to optimal long-term outcomes after kidney transplantation. Donor specific antibody, while not the formidable barrier to transplantation it once was, remains a major risk factor for antibody mediated rejection and its consequences of premature graft failure. Recent advances in understanding of the cellular and molecular mechanisms of antibody production and antibodymediated injury have led to refinements in diagnostic techniques, and have paved the way for the development of novel therapies to treat rejection and prolong allograft function. The purpose of this chapter is to review the current level at which we understand the pathophysiology of antibody mediated rejection, describe the current diagnostic criteria for antibody mediated rejection, and discuss available and emerging treatments as well as their outcomes.

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Biomarkers to detect rejection after kidney transplantation

Cited by 15 publications

References 75 publications

Noninvasive Identification of Core Gene Biomarkers in Patients with Acute Kidney Transplant Rejection

Noninvasive Identification of Core Gene Biomarkers in Patients with Acute Kidney Transplant Rejection

Therapies for Chronic Allograft Rejection

Diagnosis, Treatment, and Outcomes of Antibody-Mediated Rejection in Kidney Transplantation

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