Dataset Information

Abnormal time-zero histology is predictive of kidney transplant outcomes.

ABSTRACT:

Introduction

Time-zero biopsies can detect donor-derived lesions at the time of kidney transplantation, but their utility in predicting long-term outcomes is unclear under the updated Kidney Allocation System.

Methods

We conducted a single-center retrospective cohort study of 272 consecutive post-reperfusion time-zero biopsies. We tested the hypothesis that abnormal time-zero histology is a strong indicator of donor quality that increases the precision of the kidney donor profile index (KDPI) score to predict long-term outcomes.

Results

We detected abnormal biopsies in 42% of the cohort, which were independently associated with a 1.2-fold increased hazard for a composite of acute rejection, allograft failure, and death after adjusting for clinical characteristics including KDPI. By Kaplan-Meier analysis, the relationship between abnormal time-zero histology and the composite endpoint was only significant in the subgroup of deceased donor kidney transplants with KDPI scores >35. Abnormal time-zero histology, particularly vascular intimal fibrosis and arteriolar hyalinosis scores, was independently associated with lower 12-month estimated GFR.

Conclusion

In conclusion, abnormal time-zero histology is relatively common and identifies a group of kidney recipients at increased risk for worse long-term outcomes. Further studies are needed to determine the optimal patient population in which to deploy time-zero biopsies as an additional surveillance tool.

SUBMITTER: Raza SS

PROVIDER: S-EPMC9276634 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature

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Publications

Abnormal time-zero histology is predictive of kidney transplant outcomes.

Raza Syed Sikandar SS Agarwal Gaurav G Anderson Douglas D Deierhoi Mark M Fatima Huma H Hanaway Michael M Locke Jayme J MacLennan Paul P Orandi Babak B Young Carlton C Mannon Roslyn B RB Seifert Michael E ME

Clinical transplantation 20220426 7

<h4>Introduction</h4>Time-zero biopsies can detect donor-derived lesions at the time of kidney transplantation, but their utility in predicting long-term outcomes is unclear under the updated Kidney Allocation System.<h4>Methods</h4>We conducted a single-center retrospective cohort study of 272 consecutive post-reperfusion time-zero biopsies. We tested the hypothesis that abnormal time-zero histology is a strong indicator of donor quality that increases the precision of the kidney donor profile ...[more]

PMID: 35437836

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Project description:Zero-time biopsies are taken to determine the quality of the donor organ at the time of transplantation. Histological analyses alone have so far not been able to identify parameters that allow the prediction of subsequent rejection episodes or graft survival. This study investigated whether gene expression analyses of zero-time biopsies might support this prediction. Using a well-characterized cohort of 26 zero-time biopsies from renal transplant patients that include 4 living donor (LD) and 22 deceased donor (DD) biopsies that later developed no rejection (Ctrl, n = 7), delayed graft function (DGF, n = 4), cellular (T-cell mediated rejection; TCMR, n = 8), or antibody-mediated rejection (ABMR, n = 7), we analyzed gene expression profiles for different types of subsequent renal transplant complication. To this end, RNA was isolated from formalin-fixed, paraffin-embedded (FFPE) sections and gene expression profiles were quantified. Results were correlated with transplant data and B-cell, and plasma cell infiltration was assessed by immunofluorescence microscopy. Both principal component analysis and clustering analysis of gene expression data revealed marked separation between LDs and DDs. Differential expression analysis identified 185 significant differentially expressed genes (adjusted p < 0.05). The expression of 68% of these genes significantly correlated with cold ischemia time (CIT). Furthermore, immunoglobulins were differentially expressed in zero-time biopsies from transplants later developing rejection (TCMR + ABMR) compared to non-rejected (Ctrl + DGF) transplants. In addition, immunoglobulin expression did not correlate with CIT but was increased in transplants with previous acute renal failure (ARF). In conclusion, gene expression profiles in zero-time biopsies derived from LDs are markedly different from those of DDs. Pre-transplant ARF increased immunoglobulin expression, which might be involved in triggering later rejection events. However, these findings must be confirmed in larger cohorts and the role of early immunoglobulin upregulation in zero-biopsies needs further clarification.

Project description:Rationale & objectiveAn average of 3,280 recovered deceased donor kidneys are discarded annually in the United States. Increased cold ischemia time is associated with an increased rate of organ decline and subsequent discard. Here we examined the effect of prolonged cold ischemia time on kidney transplant outcomes.Study designRetrospective observational study.Setting & participantsRecipients of deceased donor kidney transplants in the United States from 2000 to 2018.ExposureRecipients of deceased donor kidneys were divided based on documented cold ischemia time: ≤16, 16-24, 24-32, 32-40, and >40 hours.OutcomesThe incidence of delayed graft function, primary nonfunction, and 10-year death-censored graft survival.Analytical approachThe Kaplan-Meier method was used to generate survival curves, and the log rank test was used to compare graft survival.ResultsThe rate of observed delayed graft function increased with cold ischemia time (20.9%, 28.1%, 32.4%, 37.5%, and 35.8%). Primary nonfunction also showed a similar increase with cold ischemia time (0.6%, 0.9%, 1.3%, 2.1%, and 2.3%), During a median follow-up time of 4.6 years, 37,301 recipients experienced death-censored graft failure. Analysis based on kidney donor profile index (KDPI) demonstrated significant differences in 10-year death-censored graft survival, with a death-censored graft survival in recipients of a kidney with a KDPI <85% of 71.0% (95% CI, 70.5%-71.5%), 70.5% (95% CI, 69.9%-71.0%), 69.6% (95% CI, 68.7%-70.4%), 65.5% (95% CI, 63.7%-67.3%), and 67.2% (95% CI, 64.6%-69.6%), compared to 53.5% (95% CI, 51.1%-55.8%), 50.7% (95% CI, 48.3%-53.1%), 50.3% (95% CI, 46.6%-53.8%), 50.7% (95% CI, 45.1%-56.1%), and 48.3% (95% CI, 40.0%-56.1%), for recipients of a kidney with a KDPI >85%.LimitationsHeterogeneity of acceptance patterns among transplant centers, presence of confounding variables leading to acceptance of kidneys with prolonged cold ischemia times.ConclusionsCold ischemia time was associated with an increased risk of delayed graft function and primary nonfunction. However, the effect of increased cold ischemia time is modest and has less impact than the KDPI. Transplant programs should not consider prolonged cold ischemia time alone as a predominant reason to decline an organ, especially with a KDPI <85%.

Dataset Information

Abnormal time-zero histology is predictive of kidney transplant outcomes.

Introduction

Methods

Results

Conclusion

Publications

Abnormal time-zero histology is predictive of kidney transplant outcomes.

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