Assessment of Organ Quality in Kidney Transplantation by Molecular Analysis and Why It May Not Have Been Achieved, Yet

Moos, Seraina von; Akalin, Enver; Mas, Valeria R.; Mueller, Thomas

doi:10.3389/fimmu.2020.00833

Cited by 18 publications

(17 citation statements)

References 80 publications

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“…Various tools to aid decision-making are currently available or under investigation. These include donor risk scores in the setting of DCD kidneys ( 85 ), donor-recipient characteristics ( 86 ), donor-specific features ( 87 ), monitoring of perfusion parameters and assessment of tissue viability function ex situ ( 88 ), molecular diagnostics ( 89 ), and machine learning and artificial intelligence (AI) algorithms ( 90 - 92 ). The latter remains in its infancy, with tremendous potential to augment the decision-making regarding transplantation ( 93 ), but requires more granular data, generalizability, and validation across different population cohorts to enter mainstream use.…”

Section: Decision Challengesmentioning

confidence: 99%

Deceased Donor Characteristics and Kidney Transplant Outcomes

Sharif

2022

Transpl Int

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Kidney transplantation is the therapy of choice for people living with kidney failure who are suitable for surgery. However, the disparity between supply versus demand for organs means many either die or are removed from the waiting-list before receiving a kidney allograft. Reducing unnecessary discard of deceased donor kidneys is important to maximize utilization of a scarce and valuable resource but requires nuanced decision-making. Accepting kidneys from deceased donors with heterogenous characteristics for waitlisted kidney transplant candidates, often in the context of time-pressured decision-making, requires an understanding of the association between donor characteristics and kidney transplant outcomes. Deceased donor clinical factors can impact patient and/or kidney allograft survival but risk-versus-benefit deliberation must be balanced against the morbidity and mortality associated with remaining on the waiting-list. In this article, the association between deceased kidney donor characteristics and post kidney transplant outcomes for the recipient are reviewed. While translating this evidence to individual kidney transplant candidates is a challenge, emerging strategies to improve this process will be discussed. Fundamentally, tools and guidelines to inform decision-making when considering deceased donor kidney offers will be valuable to both professionals and patients.

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Section: Decision Challengesmentioning

confidence: 99%

Deceased Donor Characteristics and Kidney Transplant Outcomes

Sharif

2022

Transpl Int

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“…Donor organ quality is essential for a successful long-term outcome in kidney transplantation. Accurately predicting organ quality remains a major challenge [2,3]. Previously many research projects focused on pathological loss of kidney function, e.g., on renal fibrosis secondary to renal damage.…”

Section: Introductionmentioning

confidence: 99%

“…Therefore, identifying reliable biomarkers of kidney function in old organ donors may help assist the selection of donors but also the management of recipients after transplantation. Several parameters have been investigated to better assess kidney function, notably in relation with ageing [2,3,[7][8][9][10]. Established methods of kidney function assessment are based mainly on histological examination of renal damage and the measurement of conventional markers in blood and urine (e.g., creatinine, albumin, urea) [2,6].…”

Section: Introductionmentioning

confidence: 99%

“…Established methods of kidney function assessment are based mainly on histological examination of renal damage and the measurement of conventional markers in blood and urine (e.g., creatinine, albumin, urea) [2,6]. Furthermore, methods based on transcriptomics or proteomics aim at identifying molecular markers associated with biological age as indicators of organ quality [3]. For instance, expression of genes associated with inflammation and immune activation has been correlated with kidney function and with ageing (so-called inflammaging) [8,[11][12][13][14][15][16].…”

Section: Introductionmentioning

confidence: 99%

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Assessment of Physiological Rat Kidney Ageing—Implications for the Evaluation of Allograft Quality Prior to Renal Transplantation

et al. 2022

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Due to organ shortage and rising life expectancy the age of organ donors and recipients is increasing. Reliable biomarkers of organ quality that predict successful long-term transplantation outcomes are poorly defined. The aim of this study was the identification of age-related markers of kidney function that might accurately reflect donor organ quality. Histomorphometric, biochemical and molecular parameters were measured in young (3-month-old) and old (24-month-old) male Sprague Dawley rats. In addition to conventional methods, we used urine metabolomics by NMR spectroscopy and gene expression analysis by quantitative RT-PCR to identify markers of ageing relevant to allograft survival. Beside known markers of kidney ageing like albuminuria, changes in the concentration of urine metabolites such as trimethylamine-N-oxide, trigonelline, 2-oxoglutarate, citrate, hippurate, glutamine, acetoacetate, valine and 1-methyl-histidine were identified in association with ageing. In addition, expression of several genes of the toll-like receptor (TLR) pathway, known for their implication in inflammaging, were upregulated in the kidneys of old rats. This study led to the identification of age-related markers of biological allograft age potentially relevant for allograft survival in the future. Among those, urine metabolites and markers of immunity and inflammation, which are highly relevant to immunosuppression in transplant recipients, are promising and deserve further investigation in humans.

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“…Several attempts have been made to identify recipient biomarkers that can predict early graft dysfunction ( 7 , 9 , 10 ).However, recipient biomarkers are difficult to assess in the decision to allocate deceased-donor kidneys in current clinical practice. A definition of donor-related biomarkers in kidney transplant biopsies or in serum or urine fluids could be a valuable tool to assess the pre-transplant quality of kidneys and orient early management of risk after transplant surgery ( 11 , 12 ).These biomarkers are limited by the accessibility of donor-derived fluid or procurement biopsies during the clinical transplantation procedure ( 10 , 13 , 14 ).…”

Section: Introductionmentioning

confidence: 99%

An enhanced level of VCAM in transplant preservation fluid is an independent predictor of early kidney allograft dysfunction

et al. 2022

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BackgroundWe aimed to evaluate whether donor-related inflammatory markers found in kidney transplant preservation fluid can associate with early development of kidney allograft dysfunction.MethodsOur prospective study enrolled 74 consecutive donated organs who underwent kidney transplantation in our center between September 2020 and June 2021. Kidneys from 27 standard criteria donors were allocated to static cold storage and kidneys from 47 extended criteria donors to hypothermic machine perfusion. ELISA assessment of inflammatory biomarkers (IL-6, IL6-R, ICAM, VCAM, TNFα, IFN-g, CXCL1 and Fractalkine) was analyzed in view of a primary endpoint defined as the occurrence of delayed graft function or slow graft function during the first week following transplantation.ResultsSoluble VCAM levels measured in transplant conservation fluid were significantly associated with recipient serum creatinine on day 7. Multivariate stepwise logistic regression analysis identified VCAM as an independent non-invasive predictor of early graft dysfunction, both at 1 week (OR: 3.57, p = .04, 95% CI: 1.06-12.03) and 3 Months (OR: 4.039, p = .034, 95% CI: 1.11-14.73) after transplant surgery.ConclusionsThis prospective pilot study suggests that pre-transplant evaluation of VCAM levels could constitute a valuable indicator of transplant health and identify the VCAM-CD49d pathway as a target to limit donor-related vascular injury of marginal transplants.

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Assessment of Organ Quality in Kidney Transplantation by Molecular Analysis and Why It May Not Have Been Achieved, Yet

Cited by 18 publications

References 80 publications

Deceased Donor Characteristics and Kidney Transplant Outcomes

Deceased Donor Characteristics and Kidney Transplant Outcomes

Assessment of Physiological Rat Kidney Ageing—Implications for the Evaluation of Allograft Quality Prior to Renal Transplantation

An enhanced level of VCAM in transplant preservation fluid is an independent predictor of early kidney allograft dysfunction

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