Impact of Deceased Donor Kidney Procurement Biopsy Technique on Histologic Accuracy.

INTRODUCTION: The factors that influence deceased donor kidney procurement biopsy reliability are not well established. We examined the impact of biopsy technique and pathologist training on procurement biopsy accuracy. METHODS: We retrospectively identified all deceased donor kidney-only transplants at our center from 2006 to 2016 with both procurement and reperfusion biopsies performed and information available on procurement biopsy technique and pathologist (n = 392). Biopsies were scored using a previously validated system, classifying "suboptimal" histology as the presence of at least 1 of the following: glomerulosclerosis ≥11%, moderate/severe interstitial fibrosis/tubular atrophy, or moderate/severe vascular disease. We calculated relative risk ratios (RRR) to determine the influence of technique (core vs. wedge) and pathologist (renal vs. nonrenal) on concordance between procurement and reperfusion biopsy histologic classification. RESULTS: A total of 171 (44%) procurement biopsies used wedge technique, and 221 (56%) used core technique. Results of only 36 biopsies (9%) were interpreted by renal pathologists. Correlation between procurement and reperfusion glomerulosclerosis was poor for both wedge (r 2 = 0.11) and core (r 2 = 0.14) biopsies. Overall, 34% of kidneys had discordant classification on procurement versus reperfusion biopsy. Neither biopsy technique nor pathologist training was associated with concordance between procurement and reperfusion histology, but a larger number of sampled glomeruli was associated with a higher likelihood of concordance (adjusted RRR = 1.12 per 10 glomeruli, 95% confidence interval = 1.04-1.22). CONCLUSIONS: Biopsy technique and pathologist training were not associated with procurement biopsy histologic accuracy in this retrospective study. Prospective trials are needed to determine how to optimize procurement biopsy practices.

Impact of warm ischemia time on outcomes for kidneys donated after cardiac death Post-KAS.

Prolonged warm (WIT) and cold (CIT) ischemia times are often important considerations in the discard of DCD kidneys, but their impact on post-transplant outcomes in the post-KAS era is unclear. We examined the association of ischemia time on delayed graft function (DGF) and death-censored graft failure for DCD kidneys. The 2018 SRTR SAF was utilized to identify post-KAS DCD kidney transplants occurring from 2015 to 2018. Relative risk and Cox regression were used to calculate risk of delayed graft function and hazard of death-censored graft failure, respectively. We identified 4,680 kidneys from DCD donors transplanted from 2015 to 2018 with recorded WIT and CIT times. Median WIT was 21.0 minutes (IQR 14.0-28.0), and CIT was 18.5 hours (IQR 13.9-23.5). The overall incidence of DGF was 42.7%. In a univariable relative risk regression model, extended CIT (24-30 hours:RR 1.37, 95% CI 1.15-1.77; >30 hours:RR 1.47, 95% CI 1.22-1.77) and WIT (20-40 minutes:RR 1.10, 95% CI 1.03-1.17) were associated with increased risk of DGF. When included in a multivariable model, neither prolonged CIT nor WIT were significantly associated with death-censored graft failure. Prolonged WIT and CIT are associated with increased DGF but not death-censored graft failure in recipients of DCD kidney transplants in the post-KAS era. Extended ischemia alone should not be used as a basis for discard or non-utilization of these organs.

Treatment of borderline infiltrates with minimal inflammation in kidney transplant recipients has no effect on allograft or patient outcomes.

In 2005, the Banff committee expanded the "borderline changes" category to include lesions with minimal (<10%) inflammation: "i0" borderline infiltrates. Clinical significance and optimal treatment of i0 borderline infiltrates are not known. Data suggest that i0 borderline infiltrates may have a more favorable prognosis than borderline infiltrates with higher grades of interstitial inflammation. In this single-center, retrospective, observational study, we assessed 90 renal transplant recipients with i0 borderline infiltrates on biopsies indicated for graft dysfunction. We studied the impact of treatment with corticosteroids on allograft function, allograft survival, and patient survival. We found no differences between treated and untreated groups with respect to eGFR at 4 weeks and 6 months after biopsy. Follow-up biopsies, available in 67% of patients, were negative for rejection in almost half of all cases, regardless of treatment status. The frequencies of persistent borderline infiltrates (38%) and higher-grade T cell-mediated rejection (1A or greater, 14%) on follow-up biopsies were similar between the two groups. There were no differences in rejection-free allograft survival, death-censored graft failure, or patient mortality among treated vs non-treated i0 borderline patients. Our findings suggest that the natural history of i0 borderline infiltrates, in relatively low immunologic risk patients, is not affected by corticosteroid treatment.

Reproducibility of Deceased Donor Kidney Procurement Biopsies.

BACKGROUND AND OBJECTIVES: Unfavorable histology on procurement biopsies is the most common reason for deceased donor kidney discard. We sought to assess the reproducibility of procurement biopsy findings. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We compiled a continuous cohort of deceased donor kidneys transplanted at our institution from 1/1/2006 to 12/31/2016 that had at least one procurement biopsy performed, and excluded cases with missing biopsy reports and those used in multiorgan transplants. Suboptimal histology was defined as the presence of advanced sclerosis in greater than or equal to one biopsy compartment (glomeruli, tubules/interstitium, vessels). We calculated κ coefficients to assess agreement in optimal versus suboptimal classification between sequential biopsy reports for kidneys that underwent multiple procurement biopsies and used time-to-event analysis to evaluate the association between first versus second biopsies and patient and allograft survival. RESULTS: Of the 1011 kidneys included in our cohort, 606 (60%) had multiple procurement biopsies; 98% had first biopsy performed at another organ procurement organization and their second biopsy performed locally. Categorical agreement was highest for vascular disease (κ=0.17) followed by interstitial fibrosis and tubular atrophy (κ=0.12) and glomerulosclerosis (κ=0.12). Overall histologic agreement (optimal versus suboptimal) was κ=0.15. First biopsy histology had no association with allograft survival in unadjusted or adjusted analyses. However, second biopsy optimal histology was associated with a higher probability of death-censored allograft survival, even after adjusting for donor and recipient factors (adjusted hazard ratio, 0.50; 95% confidence interval, 0.34 to 0.75; P=0.001). CONCLUSIONS: Deceased donor kidneys that underwent multiple procurement biopsies often displayed substantial differences in histologic categorization in sequential biopsies, and there was no association between first biopsy findings and post-transplant outcomes.

A Donor Utilization Index to Assess the Utilization and Discard of Deceased Donor Kidneys Perceived as High Risk.

BACKGROUND AND OBJECTIVES: An increasing number of patients on the waitlist for a kidney transplant indicates a need to effectively utilize as many deceased donor kidneys as possible while ensuring acceptable outcomes. Assessing regional and center-level organ utilization with regards to discard can reveal regional variation in suboptimal deceased donor kidney acceptance patterns stemming from perceptions of risk. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We created a weighted donor utilization index from a logistic regression model using high-risk donor characteristics and discard rates from 113,640 deceased donor kidneys procured for transplant from 2010 to 2016, and used it to examine deceased donor kidney utilization in 182 adult transplant centers with >15 annual deceased donor kidney transplants. Linear regression and correlation were used to analyze differences in donor utilization indexes. RESULTS: The donor utilization index was found to significantly vary by Organ Procurement and Transplantation Network region (P<0.001), revealing geographic trends in kidney utilization. When investigating reasons for this disparity, there was no significant correlation between center volume and donor utilization index, but the percentage of deceased donor kidneys imported from other regions was significantly associated with donor utilization for all centers (rho=0.39; P<0.001). This correlation was found to be particularly strong for region 4 (rho=0.83; P=0.001) and region 9 (rho=0.82; P=0.001). Additionally, 25th percentile time to transplant was weakly associated with the donor utilization index (R2=0.15; P=0.03). CONCLUSIONS: There is marked center-level variation in the use of deceased donor kidneys with less desirable characteristics both within and between regions. Broader utilization was significantly associated with shorter time to transplantation.

Trends in Disparities in Preemptive Kidney Transplantation in the United States.

BACKGROUND AND OBJECTIVES: Long wait times for deceased donor kidneys and low rates of preemptive wait-listing have limited preemptive transplantation in the United States. We aimed to assess trends in preemptive deceased donor transplantation with the introduction of the new Kidney Allocation System (KAS) in 2014 and identify whether key disparities in preemptive transplantation have changed. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We identified adult deceased donor kidney transplant recipients in the United States from 2000 to 2018 using the Scientific Registry of Transplant Recipients. Preemptive transplantation was defined as no dialysis before transplant. Associations between recipient, donor, transplant, and policy era characteristics and preemptive transplantation were calculated using logistic regression. To test for modification by KAS policy era, an interaction term between policy era and each characteristic of interest was introduced in bivariate and adjusted models. RESULTS: The proportion of preemptive transplants increased after implementation of KAS from 9.0% to 9.8%, with 1.10 (95% confidence interval [95% CI], 1.06 to 1.14) times higher odds of preemptive transplantation post-KAS compared with pre-KAS. Preemptive recipients were more likely to be white, older, female, more educated, hold private insurance, and have ESKD cause other than diabetes or hypertension. Policy era significantly modified the association between preemptive transplantation and race, age, insurance status, and Human Leukocyte Antigen zero-mismatch (interaction P<0.05). Medicare patients had a significantly lower odds of preemptive transplantation relative to private insurance holders (pre-KAS adjusted OR, [aOR] 0.26; [95% CI, 0.25 to 0.27], to 0.20 [95% CI, 0.18 to 0.22] post-KAS). Black and Hispanic patients experienced a similar phenomenon (aOR 0.48 [95% CI, 0.45 to 0.51] to 0.41 [95% CI, 0.37 to 0.45] and 0.43 [95% CI, 0.40 to 0.47] to 0.40 [95% CI, 0.36 to 0.46] respectively) compared with white patients. CONCLUSIONS: Although the proportion of deceased donor kidney transplants performed preemptively increased slightly after KAS, disparities in preemptive kidney transplantation persisted after the 2014 KAS policy changes and were exacerbated for racial minorities and Medicare patients.

Outcomes of kidney transplant from deceased donors with acute kidney injury and prolonged cold ischemia time - a retrospective cohort study.

While deceased donor renal transplants (DDRT) from donors with either acute kidney injury (AKI) or long cold ischemia time (CIT) are associated with increased risk of delayed graft function (DGF), recipients of these kidneys have good patient and allograft survival. There are limited data on whether kidneys with both AKI and long CIT have outcomes similar to kidneys with only one of these insults. Using data from the Scientific Registry of Transplant Recipients, we analyzed transplant outcomes in patients (2005-2015) receiving kidneys with AKI (terminal creatinine ≥2.0 mg/dl) and CIT 24-30 h (n = 1289), 30-36 h (n = 734), and >36 h (n = 614), using kidneys with AKI and CIT <24 h (n = 5434) as a reference. DGF was more common with increasing CIT up to 36 h, then decreased slightly (41.2% vs. 46.8% vs. 52.5% vs. 50.2%, P < 0.001). Death-censored graft survival (DCGS) at 3 years was better with CIT <24 h compared with other groups (92.5% vs. 90.8% vs. 92% vs. 89.2%, P = 0.018). On multivariable analysis, donor creatinine was predictive of DCGS, whereas only CIT >36 h was predictive of DCGS (aHR 1.27, P = 0.03). Recipients transplanted with kidneys with both AKI and long CIT have excellent intermediate-term outcomes.

Procurement Biopsies in the Evaluation of Deceased Donor Kidneys.

BACKGROUND AND OBJECTIVES: Biopsies taken at deceased donor kidney procurement continue to be cited as a leading reason for discard; however, the reproducibility and prognostic capability of these biopsies are controversial. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We compiled a retrospective, single-institution, continuous cohort of deceased donor kidney transplants performed from 2006 to 2009. Procurement biopsy information-percentage of glomerulosclerosis, interstitial fibrosis/tubular atrophy, and vascular disease-was obtained from the national transplant database. Using univariable, multivariable, and time-to-event analyses for death-censored graft survival, we compared procurement frozen section biopsy reports with reperfusion paraffin-embedded biopsies read by trained kidney pathologists (n=270). We also examined agreement for sequential procurement biopsies performed on the same kidney (n=116 kidneys). RESULTS: For kidneys on which more than one procurement biopsy was performed (n=116), category agreement was found in only 64% of cases (κ=0.14). For all kidneys (n=270), correlation between procurement and reperfusion biopsies was poor: overall, biopsies were classified into the same category (optimal versus suboptimal) in only 64% of cases (κ=0.25). This discrepancy was most pronounced when categorizing percentage of glomerulosclerosis, which had 63% agreement (κ=0.15). Interstitial fibrosis/tubular atrophy and vascular disease had agreement rates of 82% (κ=0.13) and 80% (κ=0.15), respectively. Ninety-eight (36%) recipients died, and 56 (21%) allografts failed by the end of follow-up. Reperfusion biopsies were more prognostic than procurement biopsies (hazard ratio for graft failure, 2.02; 95% confidence interval, 1.09 to 3.74 versus hazard ratio for graft failure, 1.30; 95% confidence interval, 0.61 to 2.76), with procurement biopsies not significantly associated with graft failure. CONCLUSIONS: We found that procurement biopsies are poorly reproducible, do not correlate well with paraffin-embedded reperfusion biopsies, and are not significantly associated with transplant outcomes.

Association between the "Timed Up and Go Test" at transplant evaluation and outcomes after kidney transplantation.

BACKGROUND: Studies have demonstrated the Timed Up and Go Test's (TUGT) ability to forecast postoperative outcomes for several surgical specialties. Evaluations of the TUGT for waitlist and posttransplant outcomes have yet to be examined in kidney transplantation. OBJECTIVE: To assess the prognostic utility of the TUGT and its associations with waitlist and posttransplant outcomes for kidney transplant candidates. DESIGN AND METHODS: Single-center, prospective study of 518 patients who performed TUGT during their transplant evaluation between 9/1/2013-11/30/2014. TUGT times were evaluated as a continuous variable or 3-level discrete categorical variable with TUGT times categorized as long (>9 seconds), average (8-9 seconds), or short (5-8 seconds). RESULTS: Transplanted individuals had shorter TUGT times than those who remained on the waitlist (8.99 vs 9.79 seconds, P < 0.001). Bivariable and multivariable logistic regression showed that after adjusting for age, there was no association between TUGT times and probability of waitlist removal (OR 0.997 [0.814-1.221]), prolonged length of stay posttransplant (OR 1.113 [0.958-1.306] for deceased donor, OR 0.983 [0.757-1.277] for living donor), and 30-day readmissions (OR 0.984 [0.845-1.146] for deceased donor, OR 1.254 [0.976-1.613] for living donor). CONCLUSIONS: The TUGT was not associated with waitlist removal or prolonged hospitalization for kidney transplant candidates. Alternative assessments of global health, such as functional status or frailty, should be considered for evaluation of potential kidney transplant candidates.

Patients prioritize waitlist over posttransplant outcomes when evaluating kidney transplant centers.

Factors that patients value when choosing a transplant center have not been well studied. In order to guide the improvement of patient-facing materials, we conducted an anonymous electronic survey of patients that assessed the relative importance of patient experience, practical considerations, transplant center reputation, center experience, and waitlist when selecting a transplant center. A total of 409 respondents completed the survey, of whom 68% were kidney transplant recipients and 32% had chronic kidney disease or were on dialysis. Participants had mean age 56 ± 12 years and were predominantly female (61%), white (79%), and had an associate's degree or higher (68%). Participants most often prioritized waitlist when evaluating transplant centers (transplanted 26%, chronic kidney disease 40%), and waitlist was almost twice as likely as outcomes to be ranked most important (30% vs 17%). Education level and transplant status were significantly associated with factors used for center prioritization. Waitlisted respondents most commonly (48%) relied on physicians for information when selecting a center, while a minority cited transplant-specific organizations. In order to improve shared decision-making, materials outlining center-specific waitlist features should be prioritized. Novel patient-oriented metrics for measuring transplant center quality that align with patient priorities must be explored.