Biological pathways and comparison with biopsy signals and cellular origin of peripheral blood transcriptomic profiles during kidney allograft pathology

Loon, Elisabet Van; Lamarthée, Baptiste; Loor, Henriëtte de; Craenenbroeck, Amaryllis H. Van; Brouard, Sophie; Danger, Richard; Giral, Magali; Callemeyn, Jasper; Tinel, Claire; Calabuig, Álvaro Cortés; Koshy, Priyanka; Sprangers, Ben; Kuypers, Dirk; Gwinner, Wilfried; Anglicheau, Dany; Marquet, Pierre; Naesens, Maarten

doi:10.1016/j.kint.2022.03.026

Cited by 13 publications

(9 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In the early stages of diabetes, proximal tubular epithelial cells proliferate in response to a variety of stimuli, including AMPK inhibition and mTORC1 of activation (Vallon and Thomson, 2020). Then, the cell cycle stagnates, hypertrophy occurs, and finally cell senescence is observed (Verzola et al, 2008;Satriano et al, 2010).…”

Section: Proximal Tubulementioning

confidence: 99%

See 1 more Smart Citation

Single-cell transcriptomics: A new tool for studying diabetic kidney disease

et al. 2023

View full text Add to dashboard Cite

The kidney is a complex organ comprising various functional partitions and special cell types that play important roles in maintaining homeostasis in the body. Diabetic kidney disease (DKD) is the leading cause of end-stage renal disease and is an independent risk factor for cardiovascular diseases. Owing to the complexity and heterogeneity of kidney structure and function, the mechanism of DKD development has not been fully elucidated. Single-cell sequencing, including transcriptomics, epigenetics, metabolomics, and proteomics etc., is a powerful technology that enables the analysis of specific cell types and states, specifically expressed genes or pathways, cell differentiation trajectories, intercellular communication, and regulation or co-expression of genes in various diseases. Compared with other omics, RNA sequencing is a more developed technique with higher utilization of tissues or samples. This article reviewed the application of single-cell transcriptomics in the field of DKD and highlighted the key signaling pathways in specific tissues or cell types involved in the occurrence and development of DKD. The comprehensive understanding of single-cell transcriptomics through single-cell RNA-seq and single-nucleus RNA-seq will provide us new insights into the pathogenesis and treatment strategy of various diseases including DKD.

show abstract

Section: Proximal Tubulementioning

confidence: 99%

“…Furthermore, donor leukocytes play a role in rejection ( Malone et al, 2020 ). Overexpressed genes in antibody-mediated rejection were demonstrated in peripheral blood scRNA-seq from kidney transplant patients and kidney allograft biopsies scRNA-seq analysis ( Van Loon et al, 2022 ).…”

Section: Single-cell Transcriptomics Studies In Nephrologymentioning

confidence: 99%

Single-cell transcriptomics: A new tool for studying diabetic kidney disease

et al. 2023

View full text Add to dashboard Cite

show abstract

“…An important practical question is whether the transcripts in peripheral blood cells (PBC) reflect transcripts in the graft, and if so, whether a less invasive test could be used instead of a biopsy. Van Loon et al [25 ▪ ] analyzed differential gene expression in 384 PBC samples using Illumina sequencing and compared transcripts with a simultaneous kidney biopsy. The top five DE genes in PBC from patients with rejection versus no rejection were ZEB2, DGKH, PATL2, IL18R1, and SLAMF7 .…”

Section: Transcript Analysis Of Biopsiesmentioning

confidence: 99%

Histologic and molecular features of antibody-mediated rejection

Rosales

Smith

Colvin

2023

Current Opinion in Organ Transplantation

View full text Add to dashboard Cite

Purpose of review This review aims to summarize the highlights from recent research that involved pathological and molecular analysis of kidney allografts. Recent findings As the research on antibody-mediated rejection (AMR) continues to evolve, studies are focused on identification through transcript studies of pathogenetic pathways involved in the development of AMR as well as refinement of diagnostic methods either by correlating Banff pathologic lesions with clinical and molecular data or by machine learning. Of note, the past year has generated high impact research that underscore the importance of pathologic and molecular correlations and detection of transcripts or gene sets that would aid prognostication. The studies involving refinement of pathologic criteria also highlight the continuous efforts to achieve diagnostic accuracy and standardization. Summary Research involving histologic and molecular characteristics that define AMR are central to identification and understanding of pathogenetic pathways and remain critical in the development of diagnostic criteria.

show abstract

“…BK polyomavirus, known to persist latently in the urothelial cells of immunocompetent individuals, is responsible for prevalent infections related to kidney transplantation [ 4 ]. A recent study utilizing single-cell RNA sequencing revealed that pathways resulting in mitochondrial dysfunction are upregulated in polyomavirus infection [ 5 ]. Specifically, the alterations in mitochondrial functions were associated with the expression of agnoprotein.…”

Section: Introductionmentioning

confidence: 99%

“…A recent study utilizing single-cell RNA sequencing revealed that pathways resulting in mitochondrial dysfunction are upregulated in polyomavirus infection [5]. Specifically, the alterations in mitochondrial functions were associated with the expression of agnoprotein.…”

Section: Introductionmentioning

confidence: 99%

Cell-Free Mitochondrial DNA: An Upcoming Non-Invasive Tool for Diagnosis of BK Polyomavirus-Associated Nephropathy

Guo,

Luo,

Wang

et al. 2024

Biomolecules

View full text Add to dashboard Cite

Mitochondria are essential organelles that possess their own DNA. Mitochondrial dysfunction has been revealed in many kidney diseases, including BK polyomavirus-associated nephropathy (BKPyVAN). In this study, we introduce an innovative approach for non-invasive monitoring of mitochondrial impairment through urinary donor-derived cell-free mitochondrial DNA (ddcfmtDNA), addressing the crucial challenge of BKPyVAN diagnosis. Urinary samples were collected at the time of biopsy from a total of 60 kidney transplant recipients, comprising 12 with stable function, 22 with T cell-mediated rejection, and 21 with biopsy-proven BKPyVAN. Our findings reveal that the ddcfmtDNA-to-ddcfDNA ratio exhibits superior capability in distinguishing BKPyVAN from other conditions, with a cutoff value of 4.96% (area under curve = 0.933; sensitivity: 71.4%; and specificity: 97.1%). Notably, an elevation of ddcfmtDNA levels is associated with mitochondrial damage, as visualized through electron microscopy. These results underscore the promise of non-invasive monitoring for detecting subtle mitochondrial damage and its potential utility in BKPyVAN diagnosis. Further investigations are required to advance this field of research.

show abstract

Biological pathways and comparison with biopsy signals and cellular origin of peripheral blood transcriptomic profiles during kidney allograft pathology

Cited by 13 publications

References 32 publications

Single-cell transcriptomics: A new tool for studying diabetic kidney disease

Single-cell transcriptomics: A new tool for studying diabetic kidney disease

Histologic and molecular features of antibody-mediated rejection

Cell-Free Mitochondrial DNA: An Upcoming Non-Invasive Tool for Diagnosis of BK Polyomavirus-Associated Nephropathy

Contact Info

Product

Resources

About