Perirenal Adipose Tissue Displays an Age-Dependent Inflammatory Signature Associated With Early Graft Dysfunction of Marginal Kidney Transplants

Boissier, Romain; François, Pauline; Tellier, B. Gondran; Meunier, M.; Lyonnet, Luc; Simoncini, Stéphanie; Magalon, Jérémy; Legris, Tristan; Laurent, Alexis; Guy, Laurent; Dignat-George, Françoise; Karsenty, G.; Burtey, Stéphane; Lechevallier, É.; Sabatier, Florence; Paul, Pascale

doi:10.3389/fimmu.2020.00445

Cited by 9 publications

(9 citation statements)

References 48 publications

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“…The upregulated genes demonstrated a strong association with the inflammatory response, cytokine secretion, and circulatory system development, while the downregulated genes were associated with regulating metabolic processes and circulatory system development. Importantly, Bossier et al's findings provide new evidence that PRAT-SVF serves as a non-invasive source of donor material that can be highly valuable in the assessment of inflammatory features affecting the quality and function of the graft [56].…”

Section: Transcriptomics/genomicsmentioning

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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Section: Transcriptomics/genomicsmentioning

confidence: 99%

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

Warmuzińska

Łuczykowski

Bojko

2022

JCM

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“…An important recent study has demonstrated a direct correlation between age and inflammatory phenotype of donor-derived stromal vascular fraction of perirenal adipose tissue (PRAT-SVF), expressed by a local recruitment of natural killer (NK) cells, which display a CD45+CD3-CD56+ phenotype. The proportion of NK cells in PRAT-SVF is associated with NKG2D receptor activation and transcripts encoding INFγ, suggesting that NK cells may be actively involved in pro-inflammatory mechanisms leading to functional impairment in elderly transplanted patients [ 45 ].…”

Section: Prat In Chronic Renal Pathologymentioning

confidence: 99%

Perirenal Adipose Tissue—Current Knowledge and Future Opportunities

Grigoraș

Bălan

Căruntu

et al. 2021

JCM

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The perirenal adipose tissue (PRAT), a component of visceral adipose tissue, has been recently recognized as an important factor that contributes to the maintenance of the cardiovascular system and kidney homeostasis. PRAT is a complex microenvironment consisting of a mixture of white adipocytes and dormant and active brown adipocytes, associated with predipocytes, sympathetic nerve endings, vascular structures, and different types of inflammatory cells. In this review, we summarize the current knowledge about PRAT and discuss its role as a major contributing factor in the pathogenesis of hypertension, obesity, chronic renal diseases, and involvement in tumor progression. The new perspectives of PRAT as an endocrine organ and recent knowledge regarding the possible activation of dormant brown adipocytes are nowadays considered as new areas of research in obesity, in close correlation with renal and cardiovascular pathology. Supplementary PRAT complex intervention in tumor progression may reveal new pathways involved in carcinogenesis and, implicitly, may identify additional targets for tailored cancer therapy.

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“…Importantly, excessive PRAT inflammation is believed to exacerbate renal vascular and endothelial damage ( 12 , 59 , 158 , 159 ). Moreover, it was recently shown that PRAT exhibits an age-dependent inflammatory signature that is characterized by an increased peri-organ recruitment of macrophages and inflammatory natural killer (NK) cells in the vascular stromal fraction that was associated with a deleterious impact on the microenvironment of renal transplants ( 160 , 161 ). Nevertheless, another study failed to arrive at such association, where PRAT inflammation did not correlate with the reduced early renal graft function observed in obese kidney donors ( 162 ).…”

Section: Perirenal Adipose Tissue and Renal Diseasesmentioning

confidence: 99%

“…Concomitantly, TNF- α induces direct renal endothelial dysfunction thus modulating GFR ( 67 , 158 ). Leptin secretion could also stimulate the sympathetic nervous activity via altering the proopiomelanocortin-melanocortin 4 receptor pathway in the central nervous system ( 160 ). Interestingly, our recent study on non-obese prediabetic rats has shown that a localized PRAT inflammation, presenting as higher IL-1β expression, evoked renal structural and functional deterioration associated with an altered renovascular endothelial function ( 9 ).…”

Section: Perirenal Adipose Tissue and Renal Diseasesmentioning

confidence: 99%

“…Importantly, a recent study reported a direct correlation between age and inflammatory profile of donor-derived stromal vascular fraction of PRAT (PRAT-SVF), expressed by a local recruitment of NK cells. These NK cells are associated with NKG2D receptor activation and encodes for INFγ, indicating that NK cells derived could be involved in the pro-inflammatory pathway leading to renal dysfunction in elderly patients with transplants ( 160 ).…”

Section: Perirenal Adipose Tissue and Renal Diseasesmentioning

confidence: 99%

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Perirenal Adipose Tissue Inflammation: Novel Insights Linking Metabolic Dysfunction to Renal Diseases

et al. 2021

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A healthy adipose tissue (AT) is indispensable to human wellbeing. Among other roles, it contributes to energy homeostasis and provides insulation for internal organs. Adipocytes were previously thought to be a passive store of excess calories, however this view evolved to include an endocrine role. Adipose tissue was shown to synthesize and secrete adipokines that are pertinent to glucose and lipid homeostasis, as well as inflammation. Importantly, the obesity-induced adipose tissue expansion stimulates a plethora of signals capable of triggering an inflammatory response. These inflammatory manifestations of obese AT have been linked to insulin resistance, metabolic syndrome, and type 2 diabetes, and proposed to evoke obesity-induced comorbidities including cardiovascular diseases (CVDs). A growing body of evidence suggests that metabolic disorders, characterized by AT inflammation and accumulation around organs may eventually induce organ dysfunction through a direct local mechanism. Interestingly, perirenal adipose tissue (PRAT), surrounding the kidney, influences renal function and metabolism. In this regard, PRAT emerged as an independent risk factor for chronic kidney disease (CKD) and is even correlated with CVD. Here, we review the available evidence on the impact of PRAT alteration in different metabolic states on the renal and cardiovascular function. We present a broad overview of novel insights linking cardiovascular derangements and CKD with a focus on metabolic disorders affecting PRAT. We also argue that the confluence among these pathways may open several perspectives for future pharmacological therapies against CKD and CVD possibly by modulating PRAT immunometabolism.

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Perirenal Adipose Tissue Displays an Age-Dependent Inflammatory Signature Associated With Early Graft Dysfunction of Marginal Kidney Transplants

Cited by 9 publications

References 48 publications

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

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

Perirenal Adipose Tissue—Current Knowledge and Future Opportunities

Perirenal Adipose Tissue Inflammation: Novel Insights Linking Metabolic Dysfunction to Renal Diseases

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