Dataset Information

Subclinical Changes in Deceased Donor Kidney Proteomes Are Associated With 12-month Allograft Function Posttransplantation-A Preliminary Study.

ABSTRACT:

Background

Cerebral injury during donation after brain death may induce systemic damage affecting long-term kidney function posttransplantation. Conventional evaluation of donor organ quality as a triage for transplantation is of limited utility.

Methods

We compared donor kidneys yielding opposing extremes of the continuum of posttransplantation outcomes by several common kidney biopsy evaluation techniques, including Kidney Donor Profile Index and Remuzzi scoring, and analyzed tissue from a minimal sample cohort using label-free quantitation mass spectrometry. Further assessment of the proteomic results was performed by orthogonal quantitative comparisons of selected key proteins by immunoblotting.

Results

We show that common evaluation techniques of kidney biopsies were not predictive for posttransplantation outcomes. In contrast, despite the limited cohort size, the proteomic analysis was able to clearly differentiate between kidneys yielding extreme posttransplantation outcome differences. Pathway analysis of the proteomic data suggested that outcome-related variance in protein abundance associated with profibrotic, apoptosis, and antioxidant proteins. Immunoblotting confirmation further supported this observation.

Conclusions

We present preliminary data indicating that there is scope for existing evaluation approaches to be supplemented by the analysis of proteomic differences. Furthermore, the observed outcome-related variance in a limited cohort was supported by immunoblotting and is consistent with mechanisms previously implicated in the development of injury and cytoprotection in kidney transplantation.

SUBMITTER: Kaisar M

PROVIDER: S-EPMC6365243 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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Publications

Subclinical Changes in Deceased Donor Kidney Proteomes Are Associated With 12-month Allograft Function Posttransplantation-A Preliminary Study.

Kaisar Maria M van Dullemen Leon L Charles Philip P Akhtar Zeeshan M ZM Thézénas Marie L ML Huang Honglei H Klooster Astrid A Watkins Nicholas A NA Kessler Benedikt B Ploeg Rutger J RJ

Transplantation 20190201 2

<h4>Background</h4>Cerebral injury during donation after brain death may induce systemic damage affecting long-term kidney function posttransplantation. Conventional evaluation of donor organ quality as a triage for transplantation is of limited utility.<h4>Methods</h4>We compared donor kidneys yielding opposing extremes of the continuum of posttransplantation outcomes by several common kidney biopsy evaluation techniques, including Kidney Donor Profile Index and Remuzzi scoring, and analyzed ti ...[more]

PMID: 30157158

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Project description:Rationale & objectiveThere is debate on whether weight loss, a hallmark of frailty, signals higher risk for adverse outcomes among recipients of deceased donor kidney transplantation (DDKT).Study designRetrospective cohort study.Setting & participantsUsing national Organ Procurement and Transplantation Network data, we included all DDKT recipients in the United States between December 4, 2004, and December 3, 2014, who were adults (aged ≥ 18 years) when listed for DDKT.ExposuresRelative pre-DDKT weight change as a continuous predictor and categorized as <5% weight change from listing to DDKT, ≥5% to <10% weight loss, ≥10% weight loss, ≥5% to <10% weight gain, and ≥10% weight gain.OutcomesWe examined 3 post-DDKT outcomes: (1) transplant hospitalization length of stay (LOS) in days, (2) all-cause graft failure, and (3) mortality.Analytic approachUnadjusted fractional polynomial methods, multivariable log-gamma models, and multivariable Cox proportional hazards models.ResultsAmong 94,465 recipients of DDKT, median pre-DDKT weight change was 0 (interquartile range, -3.5 to +3.9) kg. There were nonlinear unadjusted associations between relative pre-DDKT weight loss and longer transplant hospitalization LOS, higher all-cause graft loss, and higher mortality. Compared with recipients with <5% pre-DDKT weight change (n = 49,366; 52%), recipients who lost ≥10% of their listing weight (n = 10,614; 11%) had 0.66 (95% CI, 0.23-1.09) days longer average transplant hospitalization LOS (P = 0.003), 1.11-fold higher graft loss (adjusted HR [aHR], 1.11; 95% CI, 1.06-1.17; P < 0.001), and 1.18-fold higher mortality (aHR, 1.18; 95% CI, 1.11-1.25; P < 0.001) independent of recipient, donor, and transplant factors. Pre-DDKT dialysis exposure, listing body mass index category, and waiting time modified the association of pre-DDKT weight change with hospital LOS (interaction P < 0.10), but not with all-cause graft loss and mortality.LimitationsUnmeasured confounders and inability to identify volitional weight change. Also, the higher significance level set to increase the power of detecting interactions with the fixed sample size may have resulted in increased risk for type 1 error.ConclusionsDDKT recipients with ≥10% pre-DDKT weight loss are at increased risk for adverse outcomes and may benefit from augmented support post-DDKT.

Project description:ImportanceIn the United States, substantial disparities in access to kidney transplant exist for wait-listed candidates with end-stage renal disease. The implications of transplant centers' willingness to accept kidney offers for access to transplant and mortality outcomes are unknown.ObjectiveTo determine the outcomes for wait-listed kidney transplant candidates after the transplant center's refusal of a deceased donor kidney offer.Design, setting, and participantsThis cohort study obtained data from the United Network for Organ Sharing Potential Transplant Recipient data set on all deceased donor kidney offers in the United States made between January 1, 2008, and December 31, 2015. The final study cohort included adult patients who were wait-listed for kidney transplant and received at least 1 allograft offer during the study period (N?=?280?041). Data analysis was conducted from June 1, 2018, to March 30, 2019.ExposureCandidate state of residence.Main outcomes and measuresWaiting list outcome event groups included received deceased donor allograft, received living donor allograft, died while on the waiting list, removed from the waiting list without a transplant, or still on the waiting list at the end of follow-up.ResultsAmong the 280?041 kidney transplant candidates included in the study, the mean (SD) age at wait-listing was 51.1 (13.1) years, and male patients were predominant (171 517 [61.2%]). In this cohort, 81 750 candidates (29.2%) received a deceased donor kidney allograft, 30 870 (11.0%) received a living donor allograft, 25 967 (9.3%) died while on the waiting list, and 59 359 (21.2%) were removed from the waiting list. Overall, 10 candidates with at least 1 previous allograft offer died each day during the study period. Time to first offer was similar for candidates who received deceased donor kidney allograft compared with those who died while waiting (median [interquartile range {IQR}] time, 79 [16-426] days vs 78 [17-401] days, respectively). Deceased donor allograft recipients had a median of 17 offers (IQR, 6-44) over 422 days (IQR, 106-909 days), whereas candidates who died while waiting received a median of 16 offers (IQR, 6-41) over 651 days (IQR, 304-1117 days). Most kidneys (84%) were declined on behalf of at least 1 candidate before being accepted for transplant. As reported by centers, organ or donor quality concerns accounted for 8 416 474 (92.6%) of all declined offers, whereas offers were infrequently refused because of patient-related factors (232 193 [2.6%]), logistical limitations (49 492 [0.5%]), or other concerns. The odds of death after an offer and the median number of offers received prior to death varied considerably by state.Conclusions and relevanceThis study found that transplant candidates appeared to receive a large number of viable deceased donor kidney offers that were refused on their behalf by transplant centers, potentially exacerbating the detrimental consequences of the organ shortage; increased transparency in organ allocation process and decisions may improve patient-centered care and access to kidney transplant.

Dataset Information

Subclinical Changes in Deceased Donor Kidney Proteomes Are Associated With 12-month Allograft Function Posttransplantation-A Preliminary Study.

Background

Methods

Results

Conclusions

Publications

Subclinical Changes in Deceased Donor Kidney Proteomes Are Associated With 12-month Allograft Function Posttransplantation-A Preliminary Study.

Similar Datasets

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