Diagnostic, Prognostic, and Therapeutic Value of Non-Coding RNA Expression Profiles in Renal Transplantation

Franco-Acevedo, Adriana; Melo, Zesergio; Echavarría, Raquel

doi:10.3390/diagnostics10020060

Cited by 5 publications

(4 citation statements)

References 102 publications

(132 reference statements)

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“…miRNAs, which we already analyzed as donor-derived biomarkers, have been the focus of several studies also in KTx recipients, representing both a biomarker and a potential therapeutic target [ 34 , 35 , 36 ]. MiR 182-5p and miR-21-3p in recipient’s serum and urine correlated with DGF in one study [ 18 ].…”

Section: Iri and Dgfmentioning

confidence: 99%

Recent Advances on Biomarkers of Early and Late Kidney Graft Dysfunction

Quaglia

Merlotti

Guglielmetti

et al. 2020

IJMS

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New biomarkers of early and late graft dysfunction are needed in renal transplant to improve management of complications and prolong graft survival. A wide range of potential diagnostic and prognostic biomarkers, measured in different biological fluids (serum, plasma, urine) and in renal tissues, have been proposed for post-transplant delayed graft function (DGF), acute rejection (AR), and chronic allograft dysfunction (CAD). This review investigates old and new potential biomarkers for each of these clinical domains, seeking to underline their limits and strengths. OMICs technology has allowed identifying many candidate biomarkers, providing diagnostic and prognostic information at very early stages of pathological processes, such as AR. Donor-derived cell-free DNA (ddcfDNA) and extracellular vesicles (EVs) are further promising tools. Although most of these biomarkers still need to be validated in multiple independent cohorts and standardized, they are paving the way for substantial advances, such as the possibility of accurately predicting risk of DGF before graft is implanted, of making a “molecular” diagnosis of subclinical rejection even before histological lesions develop, or of dissecting etiology of CAD. Identification of “immunoquiescent” or even tolerant patients to guide minimization of immunosuppressive therapy is another area of active research. The parallel progress in imaging techniques, bioinformatics, and artificial intelligence (AI) is helping to fully exploit the wealth of information provided by biomarkers, leading to improved disease nosology of old entities such as transplant glomerulopathy. Prospective studies are needed to assess whether introduction of these new sets of biomarkers into clinical practice could actually reduce the need for renal biopsy, integrate traditional tools, and ultimately improve graft survival compared to current management.

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Section: Iri and Dgfmentioning

confidence: 99%

Recent Advances on Biomarkers of Early and Late Kidney Graft Dysfunction

Quaglia

Merlotti

Guglielmetti

et al. 2020

IJMS

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“…miRNA is clearly associated with the immune response during kidney transplantation [ 60 ], and the miRNome of uEV has been well demonstrated before transplantation. In 2013, Gildea and team first reported a miRNome of urinary exosome where less than 21 serum-exosome-derived miRNA were detected in a total measured 1898 miRNA, suggesting that uEV-miRNA might derive mostly from the kidney or urinary tract [ 61 ].…”

Section: Discussionmentioning

confidence: 99%

Urinary Extracellular Vesicles Are a Novel Tool to Monitor Allograft Function in Kidney Transplantation: A Systematic Review

Boer

Woud

et al. 2021

IJMS

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Extracellular vesicles (EVs) are nanoparticles that transmit molecules from releasing cells to target cells. Recent studies link urinary EVs (uEV) to diverse processes such as infection and rejection after kidney transplantation. This, and the unmet need for biomarkers diagnosing kidney transplant dysfunction, has led to the current high level of interest in uEV. uEV provide non-intrusive access to local protein, DNA, and RNA analytics without invasive biopsy. To determine the added value of uEV measurements for detecting allograft dysfunction after kidney transplantation, we systematically included all related literature containing directly relevant information, with the addition of indirect evidence regarding urine or kidney injury without transplantation. According to their varying characteristics, uEV markers after transplantation could be categorized into kidney-specific, donor-specific, and immune response-related (IR-) markers. A few convincing studies have shown that kidney-specific markers (PODXL, ion cotransporters, SYT17, NGAL, and CD133) and IR-markers (CD3, multi-mRNA signatures, and viral miRNA) could diagnose rejection, BK virus-associated nephropathy, and calcineurin inhibitor nephrotoxicity after kidney transplantation. In addition, some indirect proof regarding donor-specific markers (donor-derived cell-free DNA) in urine has been demonstrated. Together, this literature review provides directions for exploring novel uEV markers’ profiling complications after kidney transplantation.

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“…A recent integrative omics analysis of kidney allograft biopsies demonstrated several miRNA associated with microvascular inflammation-related pathways, in particular miRNA such as miR-142-3p/150-5p/155-5p/222-3p/223-3p ( 150 ). Earlier studies from our lab, and others, in organ transplantation have shown miRNA such as miR142-3p/5p (AMR) ( 153 ), miR155 (T cell activation and fibrosis) ( 154 ), miR223 (inflammation and aggravation of renal dysfunction) ( 151 ), miR10a (acute rejection) ( 155 ), let-7c (inflammation, cell migration, and proliferation) ( 156 ) can predict allograft status ( 157 ).…”

Section: Microrna’s In Evs and Their Role In Immune Responsementioning

confidence: 99%

Extracellular Vesicles Mediate Immune Responses to Tissue-Associated Self-Antigens: Role in Solid Organ Transplantations

et al. 2022

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Transplantation is a treatment option for patients diagnosed with end-stage organ diseases; however, long-term graft survival is affected by rejection of the transplanted organ by immune and nonimmune responses. Several studies have demonstrated that both acute and chronic rejection can occur after transplantation of kidney, heart, and lungs. A strong correlation has been reported between de novo synthesis of donor-specific antibodies (HLA-DSAs) and development of both acute and chronic rejection; however, some transplant recipients with chronic rejection do not have detectable HLA-DSAs. Studies of sera from such patients demonstrate that immune responses to tissue-associated antigens (TaAgs) may also play an important role in the development of chronic rejection, either alone or in combination with HLA-DSAs. The synergistic effect between HLA-DSAs and antibodies to TaAgs is being established, but the underlying mechanism is yet to be defined. We hypothesize that HLA-DSAs damage the transplanted donor organ resulting in stress and leading to the release of extracellular vesicles, which contribute to chronic rejection. These vesicles express both donor human leukocyte antigen (HLA) and non-HLA TaAgs, which can activate antigen-presenting cells and lead to immune responses and development of antibodies to both donor HLA and non-HLA tissue-associated Ags. Extracellular vesicles (EVs) are released by cells under many circumstances due to both physiological and pathological conditions. Primarily employing clinical specimens obtained from human lung transplant recipients undergoing acute or chronic rejection, our group has demonstrated that circulating extracellular vesicles display both mismatched donor HLA molecules and lung-associated Ags (collagen-V and K-alpha 1 tubulin). This review focuses on recent studies demonstrating an important role of antibodies to tissue-associated Ags in the rejection of transplanted organs, particularly chronic rejection. We will also discuss the important role of extracellular vesicles released from transplanted organs in cross-talk between alloimmunity and autoimmunity to tissue-associated Ags after solid organ transplantation.

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Diagnostic, Prognostic, and Therapeutic Value of Non-Coding RNA Expression Profiles in Renal Transplantation

Cited by 5 publications

References 102 publications

Recent Advances on Biomarkers of Early and Late Kidney Graft Dysfunction

Recent Advances on Biomarkers of Early and Late Kidney Graft Dysfunction

Urinary Extracellular Vesicles Are a Novel Tool to Monitor Allograft Function in Kidney Transplantation: A Systematic Review

Extracellular Vesicles Mediate Immune Responses to Tissue-Associated Self-Antigens: Role in Solid Organ Transplantations

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