Dataset Information

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

ABSTRACT: 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 post-transplantation graft function.Levels of 158 proteins were measured in preservation fluids from kidneys donated after circulatory death (Maastricht category III) collected in two Dutch centers (University Medical Center Utrecht and Erasmus Medical Center Rotterdam) between 2013 and 2015. Five candidate biomarkers identified in a discovery set of eight kidneys with immediate function (IF) versus eight with delayed graft function (DGF) were subsequently analyzed in a verification set of 40 additional preservation fluids to establish a prediction model.Variables tested for their contribution to a prediction model included five proteins (leptin, periostin, GM-CSF, plasminogen activator inhibitor-1, and osteopontin) and two clinical parameters (recipient body mass index [BMI] and dialysis duration) that distinguished between IF and DGF in the discovery set. Stepwise multivariable logistic regression provided a prediction model on the basis of leptin and GM-CSF. Receiver operating characteristic analysis showed an area under the curve (AUC) of 0.87, and addition of recipient BMI generated a model with an AUC of 0.89, outperforming the Kidney Donor Risk Index and the DGF risk calculator, showing AUCs of 0.55 and 0.59, respectively.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.

SUBMITTER: van Balkom BWM

PROVIDER: S-EPMC5477220 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature

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

van Balkom Bas W M BWM Gremmels Hendrik H Ooms Liselotte S S LSS Toorop Raechel J RJ Dor Frank J M F FJMF de Jong Olivier G OG Michielsen Laura A LA de Borst Gert J GJ de Jager Wilco W Abrahams Alferso C AC van Zuilen Arjan D AD Verhaar Marianne C MC

Clinical journal of the American Society of Nephrology : CJASN 20170501 5

<h4>Background and objectives</h4>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 se ...[more]

PMID: 28476951

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Project description:ObjectiveDespite growing evidence of comparable outcomes in recipients of donation after circulatory death and donation after brain death donor lungs, donation after circulatory death allografts continue to be underused nationally. We examined predictors of nonuse.MethodsAll donors who donated at least 1 organ for transplantation between 2005 and 2019 were identified in the United Network for Organ Sharing registry and stratified by donation type. The primary outcome of interest was use of pulmonary allografts. Organ disposition and refusal reasons were evaluated. Multivariable regression modeling was used to assess the relationship between donor factors and use.ResultsA total of 15,458 donation after circulatory death donors met inclusion criteria. Of 30,916 lungs, 3.7% (1158) were used for transplantation and 72.8% were discarded primarily due to poor organ function. Consent was not requested in 8.4% of donation after circulatory death offers with donation after circulatory death being the leading reason (73.4%). Nonuse was associated with smoking history (P < .001), clinical infection with a blood source (12% vs 7.4%, P = .001), and lower PaO2/FiO2 ratio (median 230 vs 423, P < .001). In multivariable regression, those with PaO2/FiO2 ratio less than 250 were least likely to be transplanted (adjusted odds ratio, 0.03; P < .001), followed by cigarette use (0.28, P < .001), and donor age >50 (0.75, P = .031). Recent transplant era was associated with significantly increased use (adjusted odds ratio, 2.28; P < .001).ConclusionsNontransplantation of donation after circulatory death lungs was associated with potentially modifiable predonation factors, including organ procurement organizations' consenting behavior, and donor factors, including hypoxemia. Interventions to increase consent and standardize donation after circulatory death donor management, including selective use of ex vivo lung perfusion in the setting of hypoxemia, may increase use and the donor pool.

Dataset Information

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

Publications

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

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