Emerging biomarkers of delayed graft function in kidney transplantation

Mezzolla, Valeria; Pontrelli, Paola; Fiorentino, Marco; Stasi, Alessandra; Pesce, Francesco; Franzin, Rossana; Rascio, Federica; Grandaliano, Giuseppe; Stallone, Giovanni; Infante, Barbara; Gesualdo, Loreto; Castellano, Giuseppe

doi:10.1016/j.trre.2021.100629

Cited by 23 publications

(17 citation statements)

References 47 publications

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“…Taken together, these findings supported an intriguing role for urinary metabolites as a noninvasive tool for rejection and NRKI identification; nevertheless, their use in clinical practice is hindered by some critical issues, such as the lack of universal procedures for study design (i.e., handling and processing of biological samples), the lack of standard guidance for method validation, and the absence of adequate prospective and retrospective cohort studies to allow interlaboratory reproducibility in a large population [ 67 ].…”

Section: Metabolomics In Kidney Transplantationmentioning

confidence: 94%

New Insights from Metabolomics in Pediatric Renal Diseases

Riccio¹,

Valentino²,

Passaro³

et al. 2022

Children

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Renal diseases in childhood form a spectrum of different conditions with potential long-term consequences. Given that, a great effort has been made by researchers to identify candidate biomarkers that are able to influence diagnosis and prognosis, in particular by using omics techniques (e.g., metabolomics, lipidomics, genomics, and transcriptomics). Over the past decades, metabolomics has added a promising number of ‘new’ biomarkers to the ‘old’ group through better physiopathological knowledge, paving the way for insightful perspectives on the management of different renal diseases. We aimed to summarize the most recent omics evidence in the main renal pediatric diseases (including acute renal injury, kidney transplantation, chronic kidney disease, renal dysplasia, vesicoureteral reflux, and lithiasis) in this narrative review.

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Section: Metabolomics In Kidney Transplantationmentioning

confidence: 94%

New Insights from Metabolomics in Pediatric Renal Diseases

Riccio¹,

Valentino²,

Passaro³

et al. 2022

Children

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“…A potential explanation for the different conclusions of these studies may be that Koo et al, used RGF as an outcome in their study, while Reese et al, used DGF due to different donor characteristics. Furthermore, it is worth emphasizing that, while these proteins are upregulated and secreted in urine in response to tubular injury, they were reported to have low specificity for tubular epithelial cell injury and were observed to increase in patients with urinary tract infections and sepsis [78,79].…”

Section: Proteomicsmentioning

confidence: 99%

“…Hence, urinary biomarkers on day 1 post-transplant may not only be useful in predicting who will need dialysis within one week, but they may also allow clinicians to discriminate between more subtle allograft recovery patterns [88]. However, as mentioned above, NGAL is characterized by low specificity; hence, its clinical application is limited due to inconclusive results [78,79]. Williams et al, used a Targeted Urine Proteome Assay (TUPA) to identify biomarkers of DGF following kidney transplantation.…”

Section: Proteomicsmentioning

confidence: 99%

A Review of Current and Emerging Trends in Donor Graft-Quality Assessment Techniques

Warmuzińska

Łuczykowski

Bojko

2022

JCM

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The number of patients placed on kidney transplant waiting lists is rapidly increasing, resulting in a growing gap between organ demand and the availability of kidneys for transplantation. This organ shortage has forced medical professionals to utilize marginal kidneys from expanded criteria donors (ECD) to broaden the donor pool and shorten wait times for patients with end-stage renal disease. However, recipients of ECD kidney grafts tend to have worse outcomes compared to those receiving organs from standard criteria donors (SCD), specifically increased risks of delayed graft function (DGF) and primary nonfunction incidence. Thus, representative methods for graft-quality assessment are strongly needed, especially for ECDs. Currently, graft-quality evaluation is limited to interpreting the donor’s recent laboratory tests, clinical risk scores, the visual evaluation of the organ, and, in some cases, a biopsy and perfusion parameters. The last few years have seen the emergence of many new technologies designed to examine organ function, including new imaging techniques, transcriptomics, genomics, proteomics, metabolomics, lipidomics, and new solutions in organ perfusion, which has enabled a deeper understanding of the complex mechanisms associated with ischemia-reperfusion injury (IRI), inflammatory process, and graft rejection. This review summarizes and assesses the strengths and weaknesses of current conventional diagnostic methods and a wide range of new potential strategies (from the last five years) with respect to donor graft-quality assessment, the identification of IRI, perfusion control, and the prediction of DGF.

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“…Several predictive biomarkers ( 11 , 12 ) and predictive models have been proposed to quantify the risk of DGF using different methods such as logistic regression or machine learning ( 13 ). These methods comprise a combination of donor risk factors, including age, body weight, and kidney function, variables related to the surgical procedure (for example, cold ischemia time), and recipient risk factors, such as obesity, diabetes, and dialysis-related variables ( 2 , 14 ).…”

Section: Introductionmentioning

confidence: 99%

Pre-Transplant Expression of CCR-2 in Kidney Transplant Recipients Is Associated With the Development of Delayed Graft Function

et al. 2022

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BackgroundDelayed graft function (DGF) leads to a reduced graft survival. Donors’ features have been always considered as key pathogenic factors in this setting. The aim of our study was to evaluate the recipients’ characteristics in the development of DGF.MethodsWe enrolled 932 kidney graft recipients from 466 donors; 226 recipients experienced DGF. In 290 donors, both recipients presented with early graft function (EGF, group A), in 50 both recipients experienced DGF (group B), and in 126 one recipient presented with DGF and the other with EGF (group C). In group C, we selected 7 couples of DGF/EGF recipients and we evaluated the transcriptomic profile by microarray on circulating mononuclear cells harvested before transplantation. Results were validated by qPCR in an independent group of 25 EGF/DGF couples.FindingsIn the whole study group, DGF was associated with clinical characteristics related to both donors and recipient. In group C, DGF was significantly associated with body mass index, hemodialysis, and number of mismatches. In the same group, we identified 411 genes differently expressed before transplantation between recipients discordant for the transplant outcome. Those genes were involved in immune dysfunction and inflammation. In particular, we observed a significant increase in DGF patients in the expression of C–C chemokine receptor type 2 (CCR2), the monocyte chemoattractant protein-1 (MCP-1) receptor. CCR-2 upregulation was confirmed in an independent cohort of patients.ConclusionsOur results suggest that recipients’ clinical/immunological features, potentially modulated by dialysis, are associated with the development of DGF independently of donors’ features.

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Emerging biomarkers of delayed graft function in kidney transplantation

Cited by 23 publications

References 47 publications

New Insights from Metabolomics in Pediatric Renal Diseases

New Insights from Metabolomics in Pediatric Renal Diseases

A Review of Current and Emerging Trends in Donor Graft-Quality Assessment Techniques

Pre-Transplant Expression of CCR-2 in Kidney Transplant Recipients Is Associated With the Development of Delayed Graft Function

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