Pretransplant kidney transcriptome captures intrinsic donor organ quality and predicts 24-month outcomes

Archer, Kellie J.; Bardhi, Elissa; Maluf, Daniel G.; McDaniels, Jennifer; Rousselle, Thomas; King, Anne; Eason, James D.; Gallon, Lorenzo; Akalin, Enver; Mueller, Thomas; Mas, Valeria R.

doi:10.1111/ajt.17127

Cited by 8 publications

(10 citation statements)

References 71 publications

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“…Other researchers focused on molecular investigations with tools such as epigenetics, transcriptomics, proteomics, and metabolomics [ 54 ]. A recent study reported the potential role of pretransplant transcriptomic biomarkers for predicting posttransplant outcome [ 55 ]. However, this promising result should be confirmed by larger studies, and the clinical application remains doubtful.…”

Section: Risk Factors For Dgfmentioning

confidence: 99%

Delayed Graft Function in Kidney Transplant: Risk Factors, Consequences and Prevention Strategies

Ponticelli¹,

Reggiani

Moroni

2022

JPM

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Background. Delayed graft function is a frequent complication of kidney transplantation that requires dialysis in the first week posttransplant. Materials and Methods. We searched for the most relevant articles in the National Institutes of Health library of medicine, as well as in transplantation, pharmacologic, and nephrological journals. Results. The main factors that may influence the development of delayed graft function (DGF) are ischemia–reperfusion injury, the source and the quality of the donated kidney, and the clinical management of the recipient. The pathophysiology of ischemia–reperfusion injury is complex and involves kidney hypoxia related to the duration of warm and cold ischemia, as well as the harmful effects of blood reperfusion on tubular epithelial cells and endothelial cells. Ischemia–reperfusion injury is more frequent and severe in kidneys from deceased donors than in those from living donors. Of great importance is the quality and function of the donated kidney. Kidneys from living donors and those with normal function can provide better results. In the peri-operative management of the recipient, great attention should be paid to hemodynamic stability and blood pressure; nephrotoxic medicaments should be avoided. Over time, patients with DGF may present lower graft function and survival compared to transplant recipients without DGF. Maladaptation repair, mitochondrial dysfunction, and acute rejection may explain the worse long-term outcome in patients with DGF. Many different strategies meant to prevent DGF have been evaluated, but only prolonged perfusion of dopamine and hypothermic machine perfusion have proven to be of some benefit. Whenever possible, a preemptive transplant from living donor should be preferred.

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Section: Risk Factors For Dgfmentioning

confidence: 99%

Delayed Graft Function in Kidney Transplant: Risk Factors, Consequences and Prevention Strategies

Ponticelli¹,

Reggiani

Moroni

2022

JPM

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“…In agreement with this finding, we recently demonstrated that early subclinical kidney injury resulting in defective tubular reabsorption is reflected in protein and metabolic alterations in urine that identified normoalbuminuric subjects within the high-normal range (albumin:creatinine ratio 10–30 mg/g) that have a higher risk of cardiovascular disease and renal function decline [ 42 , 43 ]. The tricarboxylic acid cycle was identified as a key biological pathway in urine of high-risk normoalbuminuric subjects and it is also altered in pre-implantation biopsies taken from kidneys that displayed low function 24 months post-transplantation [ 26 ]. In a similar manner, the levels of plasma donor mitochondrial DNA (dmtDNA), a surrogate marker of tissue damage, correlated with donor AKI and DGF, as well as with 6-month allograft function and 1-year graft survival [ 44 ].…”

Section: Predicting Short- Medium- and Long-term Post-transplant Kidn...mentioning

confidence: 99%

“…Few studies have used donor samples, and even fewer in the context of predicting long-term function (beyond 12 months). Very recently, a transcriptomic profile of pre-implantation biopsies was shown to predict 24-month graft function [ 26 ]. However, novel biological indicators are needed to more accurately rank available kidneys according to long-term outcome potential [ 27–29 ].…”

Section: Introductionmentioning

confidence: 99%

Donor liquid biopsy and outcomes in kidney transplantation

Anfaiha-Sanchez

Calabia

Ortíz

et al. 2022

Clinical Kidney Journal

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Kidney transplantation is the treatment of choice for patients with kidney failure. Priority on the waiting list and optimal donor-recipient matching are guided by mathematical scores, clinical variables and macroscopic observation of the donated organ. Despite the increasing rates of successful kidney transplantation, maximizing the number of available organs while ensuring optimum long-term performance of the transplanted kidney remains both key and challenging, and no unequivocal markers are available for clinical decision-making. Moreover, the majority of studies performed thus far has focused on the risk of primary non-function and delayed graft function and subsequent survival, and have mainly analyzed recipients’ samples. Given the increasing use of donors with expanded criteria and/or cardiac death, predicting whether grafts will provide sufficient kidney function is increasingly more challenging. Here, we compile the available tools for pre-transplant kidney evaluation and summarize the latest molecular data from donors that may predict short-term (immediate or delayed graft function), medium-term (6 months) and long-term (≥12 months) kidney function. The use of liquid biopsy (urine, serum, plasma) to overcome the limitations of the pre-transplant histological evaluation is proposed. Novel molecules and approaches such as the use of urinary extracellular vesicles are also reviewed and discussed, along with directions for future research.

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“…In the current issue, Archer et al describe the development of a transcriptomic tool for evaluating deceased donor organ quality. 3 In their study, a training set of 174 deceased donor pretransplant biopsies was used to assess the utility of pretransplant gene expression profiles in predicting 24-month outcomes after kidney transplantation. Gene expression for a subset of candidate genes was then measured in an independent set of 96 pretransplant biopsies, and a risk calculator was created using 13 genes and three donor characteristics (age, race, BMI), with good predictive performance, outperforming e.g., KDPI.…”

mentioning

confidence: 99%

“…In the current issue, Archer et al describe the development of a transcriptomic tool for evaluating deceased donor organ quality 3 . In their study, a training set of 174 deceased donor pretransplant biopsies was used to assess the utility of pretransplant gene expression profiles in predicting 24‐month outcomes after kidney transplantation.…”

mentioning

confidence: 99%

Gene expression profiling using deceased donor kidney biopsies to predict graft outcomes—We are not there yet

Helanterä

Divard

2022

American Journal of Transplantation

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Gene expression profiling using deceased donor kidney biopsies to predict graft outcomes-We are not there yetThe field of organ transplantation has seen enormous developments in creating and validating new biomarkers or composite risk scores as prognostic tools to predict graft outcomes. 1 Most of these tools rely on findings or events after transplantation, and the field would benefit greatly from a reliable prognostic method to identify highrisk patients already at the time of transplantation. Although risk predictors already exist to evaluate deceased donor quality, most importantly the Kidney Donor Profile Index (KDPI), these predictors fail to categorize all risk donors adequately, with serious consequences in the current context of organ shortage. 2

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Pretransplant kidney transcriptome captures intrinsic donor organ quality and predicts 24-month outcomes

Cited by 8 publications

References 71 publications

Delayed Graft Function in Kidney Transplant: Risk Factors, Consequences and Prevention Strategies

Delayed Graft Function in Kidney Transplant: Risk Factors, Consequences and Prevention Strategies

Donor liquid biopsy and outcomes in kidney transplantation

Gene expression profiling using deceased donor kidney biopsies to predict graft outcomes—We are not there yet

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