Pilot Randomized Trial Exploring the Impacts of Deceased Donor Kidney Procurement Biopsies on Organ Evaluation and Transplant Outcomes.

Abstract

Background: Kidney biopsies obtained at the time of organ procurement are often used in evaluating deceased donor (DD) kidneys. We conducted a pilot randomized controlled trial (RCT) to help assess the feasibility and impact of deferring procurement biopsy information at the time of organ offer.

Methodology: This pilot RCT involved one Midwestern Organ Procurement Organization (OPO) and two local transplant centers in the United States. Waitlisted transplant candidates were approached between July 01, 2019, and May 31, 2022, for consent to receive a kidney from a randomized DD if an offer arose. Criteria for DD randomization to immediate frozen biopsy or permanent section processing (delayed biopsy information) were based on factors used for routine biopsy at the time. Outcomes were assessed through linked registry data.

Results:  Of 408 transplant candidates approached, 85 (20.1%) consented to receive a kidney from a randomized DD, if available. Substantial effort was invested in candidate recruitment and consent. Consented candidates disenrolled for reasons including living donor transplantation (9/85, 10.5%), receiving an imported, previously biopsied kidney (11/85, 12.9%), DD outside biopsy criteria (18/85, 21.2%), or immediate frozen biopsy requested (5/85, 5.9%). Eleven randomized DD yielded 12 transplants (6 kidneys from 5 donors in each arm), with a median kidney donor profile index of 49 in the frozen section arm and 54 in the permanent section arm. Biopsy results were similar between arms (median glomerulosclerosis 3.4% vs. 9.9%; P = 0.09), with no kidneys exhibiting more than mild interstitial fibrosis or tubular atrophy. Only one biopsy (frozen section arm: 1/7, 14.3%) showed moderate chronic arteriosclerosis. Five frozen biopsies were compared to their post-transplantation permanent section processing, and the median percentage of glomerulosclerosis was similar between reports (1.2% vs.1.2%; P = 0.74). None of the frozen biopsies were read as having more severe changes on permanent processing, while two (2/5, 40.0%) showed less severe changes. A single kidney from a randomized donor was unused in the frozen section arm. Unadjusted kidney yield was similar in both groups. Delayed graft function (DGF) after transplant in the frozen vs. permanent processing arms was 50% (3/6) vs. 33.3% (2/6) (P > 0.05). Within one year, one recipient from a DD in the frozen section arm died (also with primary non-function), and another experienced graft failure, whereas no events occurred after permanent processing. An RCT designed to detect the observed difference in DGF with power = 0.80 and alpha = 0.05 would require 136 transplants in each arm (272 transplants total). If a similar study achieved the same proportional reduction from consented candidates to randomized transplants, 1,926 consented candidates would be needed.

Conclusions: This pilot RCT did not suggest concerns for delayed DD kidney biopsy information on organ use or transplant outcomes. However, the randomized sample was small, underpowered, and comprised intermediate-risk donors. Trial conduct required considerable effort and faced a high disenrollment rate. Substantial expansion would be required to detect clinically significant differences in outcomes in future trials. Building evidence on the role of kidney procurement biopsies may require national collaboration and consideration of opt-out consent models for waiting candidates.