Kidney allograft fibrosis: what we learned from latest translational research studies

Granata, Simona; Benedetti, Claudia; Gambaro, Giovanni; Zaza, Gianluigi

doi:10.1007/s40620-020-00726-z

Cited by 17 publications

(18 citation statements)

References 128 publications

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“…Recent studies have focused on upregulation of genes involved in IFTA. Inflammation in IFTA areas (“inflammatory IFTA”, i-IFTA) has been identified as pivotal element in prompting development of chronic renal damage, further underlying the relationship between chronic, subclinical immunological activity and irreversible fibrosis [ 161 , 162 ].…”

Section: Chronic Allograft Dysfunction (Cad)mentioning

confidence: 99%

“…Halloran et al employed the “molecular microscope” approach (already discussed in the paragraph on AR) and demonstrated a progressively higher prevalence of IFTA lesions over time and its association with transcripts related to rejection and glomerulonephritis in late biopsies. This suggests a continuing, active tissue response rather than autonomous fibrogenesis and that early abrogation of the immunological process may be critical to block this evolution and preserve long-term graft function [ 93 , 161 ].…”

Section: Chronic Allograft Dysfunction (Cad)mentioning

confidence: 99%

“…Both EMT and EndMT lead to abnormal production of EM and consequently play a key role in the pathogenesis of allograft IFTA [ 161 ]. Several histological and urinary EMT biomarkers have been proposed ( Table 8 ), whereas more recent, initial evidence on potential EndMT biomarkers in KTx is available.…”

Section: Chronic Allograft Dysfunction (Cad)mentioning

confidence: 99%

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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: Chronic Allograft Dysfunction (Cad)mentioning

confidence: 99%

Section: Chronic Allograft Dysfunction (Cad)mentioning

confidence: 99%

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Recent Advances on Biomarkers of Early and Late Kidney Graft Dysfunction

Quaglia

Merlotti

Guglielmetti

et al. 2020

IJMS

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“…Particularly in renal cells, TGF-β amplifies apoptosis under stress conditions [ 26 ]. Of note, TGF-β has also been shown to promote fibrosis, a common complication after kidney transplantation [ 27 ].…”

Section: Discussionmentioning

confidence: 99%

Low Pre-Transplant Caveolin-1 Serum Concentrations Are Associated with Acute Cellular Tubulointerstitial Rejection in Kidney Transplantation

et al. 2021

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Acute and chronic transplant rejections due to alloreactivity are essential contributors to graft loss. However, the strength of alloreactivity is biased by non-immunological factors such as ischemia reperfusion injury (IRI). Accordingly, protection from IRI could be favorable in terms of limiting graft rejection. Caveolin-1 (Cav-1) is part of the cell membrane and an important regulator of intracellular signaling. Cav-1 has been demonstrated to limit IRI and to promote the survival of a variety of cell types including renal cells under stress conditions. Accordingly, Cav-1 could also play a role in limiting anti-graft immune responses. Here, we evaluated a possible association between pre-transplant serum concentrations of Cav-1 and the occurrence of rejection during follow-up in a pilot study. Therefore, Cav-1-serum concentrations were analyzed in 91 patients at the time of kidney transplantation and compared to the incidence of acute and chronic rejection. Higher Cav-1 levels were associated with lower occurrence of acute cellular tubulointerstitial rejection episodes.

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“…They secrete proinflammatory chemokines and cytokines, which accelerate graft fibrosis. There is a global interest in the development of senolytic agents and evidence exists that they may promote the survival of organs after transplantation [69]. Amor et al [70] investigated whether CAR-T based technologies could serve as senolytic agents.…”

Section: Car-t Cells To Reverse Fibrosismentioning

confidence: 99%

Pushing the boundaries of organs before it’s too late: pre‐emptive regeneration

Maanaoui

Kerr–Conte

2021

Transpl Int

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Solid organ transplantation is marked by accelerated aging and inexorable fibrosis. It is crucial to promote strategies to attenuate, or to reverse, damage before organ failure. Hence, the objective of this article is to provide insight into strategies, which aim to regenerate or rejuvenate the transplanted organs. Cell therapy with mesenchymal stromal cells is currently under investigation because of their antifibrotic properties. Their ability to promote mitochondrial biogenesis, and to transfer mitochondria to wounded cells, is another approach to boost the organ regeneration. Other teams have investigated bioengineered organs, which consists of decellularization of the damaged organ followed by recellularization. Lastly, the development of CAR-T cell-based technologies may revolutionize the field of transplantation, as recent preclinical studies showed that CAR-T cells could efficiently clear senescent cells from an organ and reverse fibrosis. Ultimately, these cutting-edge strategies may bring the holy grail of a preemptive regenerated organ closer to reality.

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Kidney allograft fibrosis: what we learned from latest translational research studies

Cited by 17 publications

References 128 publications

Recent Advances on Biomarkers of Early and Late Kidney Graft Dysfunction

Recent Advances on Biomarkers of Early and Late Kidney Graft Dysfunction

Low Pre-Transplant Caveolin-1 Serum Concentrations Are Associated with Acute Cellular Tubulointerstitial Rejection in Kidney Transplantation

Pushing the boundaries of organs before it’s too late: pre‐emptive regeneration

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