Associations of Perfusate Biomarkers and Pump Parameters With Delayed Graft Function and Deceased Donor Kidney Allograft Function

Parikh, Chirag R.; Hall, Isaac E.; Bhangoo, R.S.; Ficek, Joseph; Abt, Peter L.; Thiessen‐Philbrook, Heather; Lin, Haiqun; Bimali, Milan; Murray, Patrick; Rao, Veena S.; Schröppel, Bernd; Doshi, Mona D.; Weng, Francis L.; Reese, Peter P.

doi:10.1111/ajt.13655

Cited by 76 publications

(93 citation statements)

References 35 publications

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“…Consequently, kidneys from NHBDs should not be discarded because of high concentration of a perfusate biomarker. Similar conclusions were reached by Parikh et al (57) in the largest prospective multicenter cohort study, which investigated associations among perfusate biomarkers (NGAL, KIM-1, IL-18, L-FABP ) and pump parameters (resistance and flow) with DGF and allograft eGFR at six months. Recently Guy et al (58) effectuated one-dimensional proton-nuclear magnetic resonance spectroscopy on 45-min and 4-h perfusate samples from 26 kidneys to demonstrate that 28 different metabolites varied in concentration during HMP, while specific metabolites (leucine, inosine, gluconate, and glucose) predicted DGF.…”

Section: Perfusate Biomarkerssupporting

confidence: 80%

Pre-transplant biomarkers and prediction of post-transplant outcomes in kidney transplantation

Salvadori¹,

Tsalouchos²

2017

J Renal Inj Prev

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New findings in "omics" and genomics allowed us to find out new robust biomarkers that may allow a diagnosis avoiding invasive and dangerous procedures. This could be of particular importance if applied on transplant clinical practice. In kidney transplantation several pre-transplant biomarkers revealed useful either for a better renal allocation and as predictive of future outcomes as delayed graft function, rejections and long term outcome. Different biomarkers have been recently described bringing interesting results regarding predictive outcomes in the field of kidney transplantation. In this setting, an evaluation for pre-transplant biomarkers especially in the era of expanded criteria donors (ECDs) and non-heart-beating donors (NHBDs) could help transplant physicians to make decisions on allocation or even on discharge of the allograft. Furthermore, identify pre-transplant biomarkers is useful for a risk stratification of delayed graft function (DGF), acute rejection (AR) episodes and chronic allograft dysfunction (CAD) after kidney transplantation (KT). In this review, we report recent findings on pre-transplant biomarkers from various biological samples from donors or recipients. Please cite this paper as:

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Section: Perfusate Biomarkerssupporting

confidence: 80%

Pre-transplant biomarkers and prediction of post-transplant outcomes in kidney transplantation

Salvadori¹,

Tsalouchos²

2017

J Renal Inj Prev

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“…In spite of the poor predictivity of the selected perfusate biomarkers for short‐term graft outcomes, perfusate NGAL and L‐FABP measured near the end of machine perfusion as well as pump parameters (resistance and flow) were modestly associated with six‐month eGFR. Although the study found lacking or weak prognostic utility of the most known biomarkers of ischemia‐reperfusion injury in the perfusate, additional candidate molecules involved in other pathways might deserve further research, especially in view of the growing organ shortage and the critical issue relative to kidney allocation acceptance or refusal decisions 55.…”

Section: Ngal As a Perfusion Marker In Kidney Preserved By Hypothermimentioning

confidence: 91%

“…NGAL has been also evaluated as a hypothermic machine perfusion biomarker for assessing organ quality in deceased donor kidney transplantation 53, 54, 55.…”

Section: Ngal As a Perfusion Marker In Kidney Preserved By Hypothermimentioning

confidence: 99%

Neutrophil Gelatinase‐Associated Lipocalin as a Biomarker of Allograft Function After Renal Transplantation: Evaluation of the Current Status and Future Insights

et al. 2017

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Neutrophil gelatinase‐associated lipocalin (NGAL), a protein belonging to the lipocalin superfamily initially found in activated neutrophils, is expressed by several cell types, including kidney tubule. The increase in NGAL production and release from tubular cells in response to various insults has been proven to predict acute kidney injury (AKI). For this reason, it has emerged as a valuable noninvasive biomarker of AKI in clinical nephrology. Also in the renal transplant setting, different studies have indicated NGAL as a valuable tool, especially in the early postoperative period, since the currently available clinical and laboratory parameters remain poorly sensitive to monitor immediate posttransplant graft function. This is an analysis of the recent literature to assess the utility of plasma and urinary NGAL, exosomal mRNA for NGAL, and NGAL levels in the perfusate of machine‐perfused kidneys for the prediction of graft function recovery in the early postsurgery phase after renal transplantation. We found that NGAL appears as a promising troponin‐like biomarker to detect short‐term impairment of graft function after renal transplant, but there are still some limitations in its clinical application, essentially related to its low specificity. Moreover, comparing NGAL assayed in serum, urine, machine‐perfusate, or as exosomal mRNA, each one has shown limitations and benefits in terms of predictive performance for DGF, according to various existing studies, feasibly due to different cut‐off levels, designs and patient sample sizes.

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“…Recently, Parikh et al demonstrated an association between DGF and several markers in cold machine-perfused donor kidney perfusates, including KIM-1, IL-18, and liver fatty acid binding protein (L-FABP) (29), none of which associated with DGF in our discovery panel. Similarly, YKL-40 (in serum and urine) could be detected, but showed no association with DGF.…”

Section: Discussionmentioning

confidence: 65%

“…Urinary NGAL has been demonstrated to predict DGF with reasonable accuracy (AUC approximately 0.8) (27), and also plasma and serum NGAL levels at day 1 after transplantation are higher in recipients that develop DGF (16,17,28). An association between DGF and NGAL levels in donor kidney perfusate has been described for machine-perfused kidneys (29).…”

Section: Discussionmentioning

confidence: 95%

Proteins in Preservation Fluid as Predictors of Delayed Graft Function in Kidneys from Donors after Circulatory Death

Balkom¹,

Gremmels²,

Ooms

et al. 2017

CJASN

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Background and objectives Kidney transplantation is the preferred treatment for ESRD, and donor kidney shortage urges proper donor-recipient matching. Zero-hour biopsies provide predictive values for short-and long-term transplantation outcomes, but are invasive and may not reflect the entire organ. Alternative, more representative methods to predict transplantation outcome are required. We hypothesized that proteins accumulating in preservation fluid during cold ischemic storage can serve as biomarkers to predict posttransplantation graft function. Conclusions We demonstrate that donor kidney preservation fluid harbors biomarkers that, together with information on recipient BMI, predict short-term post-transplantation kidney function. Our approach is safe, easy, and performs better than current prediction algorithms, which are only on the basis of clinical parameters.

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Associations of Perfusate Biomarkers and Pump Parameters With Delayed Graft Function and Deceased Donor Kidney Allograft Function

Cited by 76 publications

References 35 publications

Pre-transplant biomarkers and prediction of post-transplant outcomes in kidney transplantation

Pre-transplant biomarkers and prediction of post-transplant outcomes in kidney transplantation

Neutrophil Gelatinase‐Associated Lipocalin as a Biomarker of Allograft Function After Renal Transplantation: Evaluation of the Current Status and Future Insights

Proteins in Preservation Fluid as Predictors of Delayed Graft Function in Kidneys from Donors after Circulatory Death

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