Factors leading to the discard of deceased donor kidneys in the United States.

The proportion of deceased donor kidneys procured for transplant but subsequently discarded has been growing steadily in the United States, but factors contributing to the rising discard rate remain unclear. To assess the reasons for and probability of organ discard we assembled a cohort of 212,305 deceased donor kidneys recovered for transplant from 2000-2015 in the SRTR registry that included 36,700 kidneys that were discarded. 'Biopsy Findings' (38.2%) was the most commonly reported reason for discard. The median Kidney Donor Risk Index of discarded kidneys was significantly higher than transplanted organs (1.78 vs 1.12), but a large overlap in the quality of discarded and transplanted kidneys was observed. Kidneys of donors who were older, female, Black, obese, diabetic, hypertensive or HCV-positive experienced a significantly increased odds of discard. Kidneys from donors with multiple unfavorable characteristics were more likely to be discarded, whereas unilaterally discarded kidneys had the most desirable donor characteristics and the recipients of their partner kidneys experienced a one-year death-censored graft survival rate over 90%. There was considerable geographic variation in the odds of discard across the United States, which further supports the notion that factors beyond organ quality contributed to kidney discard. Thus, while the discard of a small fraction of organs procured from donors may be inevitable, the discard of potentially transplantable kidneys needs to be avoided. This will require a better understanding of the factors contributing to organ discard in order to remove the disincentives to utilize less-than-ideal organs for transplantation.

Association between Reperfusion Renal Allograft Biopsy Findings and Transplant Outcomes.

Biopsy findings at the time of procurement of deceased donor kidneys remain the most common reason cited for kidney discard. To determine the value of renal allograft histology in predicting outcomes, we evaluated the significance of histologic findings, read by experienced renal pathologists, in 975 postreperfusion biopsy specimens collected from 2005 to 2009 after living donor (n=427) or deceased donor (n=548) renal transplant. We evaluated specimens for the degree of glomerulosclerosis, interstitial fibrosis and tubular atrophy, and vascular disease; specimens with a score of 0 or 1 (scale, 0-3) for each parameter were considered optimal. Overall, 66.3% of living donor kidneys and 50.7% of deceased donor kidneys received an optimal histology score (P<0.001). Irrespective of donor status, suboptimal kidneys came from older donors with a higher incidence of diabetes mellitus, hypertension, and obesity and a higher mean kidney donor risk index (all P<0.001). Death-censored outcomes after transplant differed significantly between optimal and suboptimal kidneys only in the deceased donor transplants (P=0.02). Regardless of histologic classification, outcomes with deceased donor kidneys were inferior to outcomes with living donor kidneys. However, 73.2% of deceased donor kidneys with suboptimal histology remained functional at 5 years. Our findings suggest that histologic findings on postreperfusion biopsy associate with outcomes after deceased donor but not living donor renal transplants, thus donor death and organ preservation-related factors may be of greater prognostic importance. Discarding donated kidneys on the basis of histologic factors may be inappropriate and merits further study.

The weekend effect alters the procurement and discard rates of deceased donor kidneys in the United States.

Factors contributing to the high rate of discard among deceased donor kidneys remain poorly understood and the influence of resource limitations of weekends on kidney transplantation is unknown. To quantify this we used data from the Scientific Registry of Transplant Recipients and assembled a retrospective cohort of 181,799 deceased donor kidneys recovered for transplantation from 2000-2013. We identified the impact of the day of the week on the procurement and subsequent utilization or discard of deceased donor kidneys in the United States, as well as report the geographic variation of the impact of weekends on transplantation. Compared with weekday kidneys, organs procured on weekends were significantly more likely to be discarded than transplanted (odds ratio: 1.16; 95% confidence interval: 1.13-1.19), even after adjusting for organ quality (adjusted odds ratio: 1.13; 95% confidence interval: 1.10-1.17). Weekend discards were of a significantly higher quality than weekday discards (Kidney Donor Profile Index: 76.5% vs. 77.3%). Considerable geographic variation was noted in the proportion of transplants that occurred over the weekend. Kidneys available for transplant over the weekend were significantly more likely to be used at larger transplant centers, be shared without payback, and experienced shorter cold ischemia times. Thus, factors other than kidney quality are contributing to the discard of deceased donor kidneys, particularly during weekends. Policy prescriptions, administrative or organizational solutions within transplant programs may potentially mitigate against the recent increase in kidney discards.

Donor-specific antibodies adversely affect kidney allograft outcomes.

The effect of low titers of donor-specific antibodies (DSAs) detected only by sensitive solid-phase assays (SPAs) on renal transplant outcomes is unclear. We report the results of a systematic review and meta-analysis of rejection rates and graft outcomes for renal transplant recipients with such preformed DSAs, defined by positive results on SPA but negative complement-dependent cytotoxicity and flow cytometry crossmatch results. Our search identified seven retrospective cohort studies comprising a total of 1119 patients, including 145 with isolated DSA-SPA. Together, these studies suggest that the presence of DSA-SPA, despite a negative flow cytometry crossmatch result, nearly doubles the risk for antibody-mediated rejection (relative risk [RR], 1.98; 95% confidence interval [CI], 1.36-2.89; P<0.001) and increases the risk for graft failure by 76% (RR, 1.76; 95% CI, 1.13-2.74; P=0.01). These results suggest that donor selection should consider the presence of antibodies in the recipient, identified by the SPA, even in the presence of a negative flow cytometry crossmatch result.

Home Care Delivery and Remote Patient Monitoring of Kidney Transplant Recipients During COVID-19 Pandemic.

Telehealth plays a critical role in the response of healthcare organizations during the COVID-19 pandemic. While telemedicine offers a real-time patient-provider encounter, the inability to obtain vital signs during virtual visits is a potential limitation. Remote patient monitoring (RPM) uses portable devices in the patient's home to collect and electronically transmit physiological data to clinicians. Two kidney transplant recipients were enrolled in RPM in their immediate post-transplant period. Real-time monitoring of their physiological data at home through the RPM in combination with the ability to titrate medications resulted in normalization of the blood pressure and blood glucose measurements by six weeks. Our initial experience demonstrates that RPM is feasible and effective in the post-transplant period and can expand care opportunities on the remote care model. This is more relevant than ever as remote monitoring can facilitate the care of COVID-19-positive transplant patients who require close monitoring while isolated at home.

Association Between Donor-Recipient Biological Relationship and Allograft Outcomes After Living Donor Kidney Transplant.

Importance: The proportion of living donor kidney transplants from donors unrelated to their recipients is increasing in the US. Objective: To examine the association between donor-recipient biological relationship and allograft survival after living donor kidney transplant. Design, Setting, and Participants: This retrospective cohort study used Organ Procurement and Transplantation Network data on US adult living donor kidney transplants (n = 86 154) performed from January 1, 2000, to December 31, 2014, excluding cases in which recipients previously received a kidney transplant (n = 10 342) or key data were missing (n = 2832). Last follow-up was March 20, 2020. Exposures: Donor-recipient biological relationship. Main Outcomes and Measures: The primary outcome was death-censored allograft failure. Univariate and multivariable time-to-event analyses were performed for death-censored allograft failure for the overall cohort, then separately for recipients with and without primary diagnoses of cystic kidney disease and for transplants from African American and non-African American donors. Results: Among the 72 980 transplant donor and recipients included in the study (median donor age, 41 years; interquartile range [IQR], 32-50 years; 43 990 [60%] female; 50 014 [69%] White), 43 174 (59%) donors and recipients were biologically related and 29 806 (41%) were unrelated. Donors related to their recipients were younger (median [IQR] age, 39 [31-48] vs 44 [35-52] years) and less likely to be female (24 848 [58%] vs 19 142 [64%]) or White (26 933 [62%] vs 23 081 [77%]). Recipients related to their donors were younger (median [IQR] age, 48 [34-58] vs 50 [40-58] years), more likely to be female (18 035 [42%] vs 10 530 [35%]), and less likely to have cystic kidney disease (2530 [6%] vs 4600 [15%]). Related pairs had fewer HLA mismatches overall (median [IQR], 3 [2-3] vs 5 [4-5]). After adjustment for HLA mismatches, donor and recipient characteristics, and transplant era, donor-recipient biological relationship was associated with higher death-censored allograft failure (hazard ratio, 1.05; 95% CI, 1.01-1.10; P = .03). When stratified by primary disease, this association persisted only for recipients without cystic kidney disease. When stratified by donor race, this association persisted only for transplants from African American donors. Conclusions and Relevance: In this cohort study, living donor kidney transplants from donors biologically related to their recipients had higher rates of allograft failure than transplants from donors unrelated to their recipients after HLA matching was accounted for. Further study is needed to determine which genetic or socioenvironmental factors are associated with this finding.

Early Outcomes of Outpatient Management of Kidney Transplant Recipients with Coronavirus Disease 2019.

BACKGROUND AND OBJECTIVES: Outcomes of kidney transplant recipients diagnosed with coronavirus disease 2019 as outpatients have not been described. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We obtained clinical data for 41 consecutive outpatient kidney transplant recipients with known or suspected coronavirus disease 2019. Chi-squared and Wilcoxon rank sum tests were used to compare characteristics of patients who required hospitalization versus those who did not. RESULTS: Of 41 patients, 22 (54%) had confirmed coronavirus disease 2019, and 19 (46%) were suspected cases. Patients most commonly reported fever (80%), cough (56%), and dyspnea (39%). At the end of follow-up, 13 patients (32%) required hospitalization a median of 8 days (range, 1-16) after symptom onset, and 23 (56%) had outpatient symptom resolution a median of 12 days (4-23) after onset. Patients who required hospitalization were more likely to have reported dyspnea (77% versus 21%, P=0.003) and had higher baseline creatinine (median, 2.0 versus 1.3 mg/dl, P=0.02), but there were no other differences between groups. CONCLUSIONS: In an early cohort of outpatient kidney transplant recipients with known or suspected coronavirus disease 2019, many had symptomatic resolution without requiring hospitalization.

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.

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.

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.

Preformed donor-specific antibodies and risk of antibody-mediated rejection in repeat renal transplantation.

BACKGROUND: Allograft outcomes in patients undergoing repeat renal transplantation are inferior compared to first-time transplant recipient outcomes. Donor-specific antibodies detected by solid-phase assays (DSA-SPA) may contribute to the worse prognosis. The influence of DSA-SPA on repeat renal transplantation outcomes has not been previously studied in detail. DESIGN: This study reports the findings in 174 patients who underwent repeat renal transplantation between years 2007 and 2012. These included 62 patients with preformed DSA-SPA detected by Luminex at the time of transplantation. Patients received standard and consistent immunosuppression and were monitored closely for evidence of rejection. Recipients who underwent desensitization were excluded from this analysis. Endpoints included development of biopsy-proven acute rejection and analysis of graft survival and function. RESULTS: Patients in the DSA-SPA-positive and DSA-SPA-negative groups received similar immunosuppression, and a similar proportion of recipients had a peak panel reactive antibody greater than 20%; the two groups differed with respect to human leukocyte antigen mismatches (4.7 ± 1.1 vs. 4.1 ± 1.7, P=0.024). Recipients with preformed DSA-SPA had higher rejection rates (54.8% vs. 34.8%, P=0.01), including higher rates of antibody-mediated rejection (AMR) (32.3% vs. 7.1%, P<0.001). Recipients who were DSA-SPA-positive and flow cytometry crossmatch (FCXM)-positive had a higher incidence of both AMR (OR 4.6, P=0.009) and of acute rejection (OR 3.57, P=0.02) as compared to those who were DSA-SPA-positive and FCXM-negative. Overall allograft survival was similar in the DSA-SPA-positive and DSA-SPA-negative groups (log-rank test=0.63, P=0.428). Differences in allograft function were detectable after 2 years (32.8 ± 13.1 vs. 47 ± 20.2 mL/min/1.73 m(2), P=0.023) and may be reflective of more AMR among DSA-SPA-positive patients. CONCLUSIONS: This analysis suggests that DSA-SPA increases the overall risk of acute rejection but does not appear to adversely impact allograft survival during the early follow-up period. Close monitoring of renal function and early biopsy for AMR detection appear to allow for satisfactory short-term allograft outcomes in repeat transplant recipients.

Impact of small variations in the delivered dose of rabbit antithymocyte induction therapy in kidney transplantation with early corticosteroid withdrawal.

BACKGROUND: Optimal dosing of rabbit antithymocyte globulin (rATG) induction therapy in kidney transplantation is not well defined. The impact of dosing from variations in dose rounding or single dose limits has not been studied. METHODS: This retrospective study of 242 adult renal transplant recipients receiving rATG induction and steroid-sparing maintenance therapy evaluates the effect of small changes in rATG induction dosing. The local protocol calls for four doses of rATG 1.5 mg/kg, approximated to the nearest 25 mg and limited to a max of 150 mg. Patients were stratified by total rATG dose received 5 to 6 mg/kg (n=151) and 6 mg/kg (n=91) or more. Incidence of biopsy-proven acute rejection, patient and graft survival, and allograft function were examined. RESULTS: Baseline and transplantation characteristics were similar between groups except for differences in mean weight (SD) (81 [17.3] vs. 76.3 [15.6]) and cumulative rATG dose received (451.8 [96.2] vs. 481.1 [93]) for patients in the 5- to 6-mg/kg group and 6-mg/kg or more group, respectively. Patients who received more rATG showed a significantly lower incidence of biopsy-proven acute rejection at last follow-up 11% (32/151) vs. 21.2% (10/91) among those who received only 5 to 6 mg/kg (P<0.042). Renal function (mean serum creatinine level) was similar at both 90 days and time of last follow-up. Safety review of leukopenia or thrombocytopenia did not differ. CONCLUSION: Small changes in total rATG induction administered seem to significantly impact the incidence of rejection. Adequate rATG dosing is associated with improved rejection-free graft survival and should be achieved for all patients; doses should be rounded up when appropriate or additional doses should be administered if necessary.

Combined heart-kidney transplantation: a review of recipient selection and patient outcomes.

Elevated serum creatinine is a common finding among patients awaiting heart transplantation because of reduced renal perfusion in the setting of severe heart failure as well as overlapping risk factors for chronic kidney disease and heart disease. Patients with significant renal dysfunction preoperatively have worse outcomes with heart transplantation alone compared with those with normal renal function or those with renal dysfunction who undergo combined heart-kidney transplantation. Optimizing organ distribution and patient outcomes after cardiac transplantation requires appropriate recipient selection, including deciding which patients will benefit from combined heart-kidney transplantation. This review focuses on the evaluation of patients with chronic kidney disease awaiting heart transplantation and the outcomes of combined heart-kidney transplantation.