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Jianlei Ji,* Qinghai Wang,* Tao Huang, Ziyu Wang, Pingli He, Chen Guo, Weijia Xu, Yanwei Cao, Zhen Dong, Hongyang Wang Department of Kidney Transplantation, the Affiliated Hospital of Qingdao University, Qingdao, 266000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zhen Dong; Hongyang WangDepartment of Kidney Transplantation, the Affiliated Hospital of Qingdao University, No. 59 Haier Road, Qingdao, 266000, People’s Republic of ChinaTel +8613455263336; +8618661803752Email dong266000@163.com; why19850804@163.comBackground: Trimethoprim/sulfamethoxazole (TMP-SMX) is considered the first-choice treatment for Pneumocystis jirovecii pneumonia (PJP) in recipients of solid organ transplantation. However, this treatment is associated with various severe adverse events that might not be tolerable for some renal transplant recipients, and the optimal dose remains elusive. The present study assessed the efficacy of low-dose TMP-SMX in recipients of a deceased donor kidney.Methods: A total of 37 adult deceased donor kidney recipients who suffered PJP between January 2015 and June 2020 were included. The survival rates of the patients and grafts, the rate of invasive ventilation, and adverse events, including gastrointestinal discomfort, hematologic side effects, hyperkalemia, and renal function impairments, were assessed.Results: The patient and graft survival rates were both 100%. Two patients (5.4%) required invasive ventilation. Eight patients (21.6%) reported gastrointestinal discomfort, but none required dose reduction or discontinued treatment. The frequencies of hematologic side effects, hyperkalemia and impaired kidney function were 5.4% (2/37), 2.7% (1/37), and 2.7% (1/37), respectively.Conclusion: Optimization of TMP-SMX dose may reduce the risk of adverse events without compromising efficacy for the treatment of PJP in deceased donor kidney recipients.Keywords: efficacy, low dose, trimethoprim/sulfamethoxazole, Pneumocystis jirovecii pneumonia, deceased donor kidney recipients

PURPOSE OF REVIEW: There has been an increased emphasis by the transplant community and the federal government to increase the utilization of deceased donor kidneys. Procurement biopsies during allocation are the most common reason for kidney discards. This manuscript reviews the evidence of procurement biopsies practices and utility. RECENT FINDINGS: Procurement biopsies are performed in over half of all the kidneys recovered in the United States and account for more than one third of the kidney discards. However, there is a significant heterogeneity across the organ procurement organizations regarding the indications for biopsy, biopsy techniques and their reporting. Procurement biopsy findings are not reproducible and poorly correlate to post-implantation histology, although reasons for these limitations are not clear. Procurement biopsy findings are not associated with post-transplant outcomes after accounting for readily available donor clinical characteristics. SUMMARY: Procurement biopsies contribute to deceased donor kidney discards but do not predict post-transplant outcomes. Research to establish the best practices for procurement biopsies is needed to improve organ utilization.

For assessing human leukocyte antigen compatibility in deceased donor kidney transplantation, virtual crossmatch is used as an alternative to physical crossmatch and has potential to reduce cold ischemia time. The 2014 United States kidney allocation system prioritized highly sensitized candidates but led to increased shipping of kidneys. Using data from the Scientific Registry of Transplant Recipients, we evaluated changes in virtual crossmatch use with the new allocation policy and the impact of virtual crossmatch use on cold ischemia time and transplant outcomes. This was a retrospective cohort study of adult deceased donor kidney recipients in the United States (2011-2018) transplanted with either 9,632 virtual or 71,839 physical crossmatches. Before allocation change, only 9% of transplants were performed relying on a virtual crossmatch. After the 2014 allocation change, this increased by 2.4%/year so that 18% transplants in 2018 were performed with just a virtual crossmatch. There was significant variation in virtual crossmatch use among transplant regions (range 0.7-36%) and higher use was noted among large volume centers. Compared to physical crossmatches, virtual crossmatches were significantly associated with shorter cold ischemia times (mean 15.0 vs 16.5 hours) and similar death-censored graft loss and mortality (both hazard ratios HR 0.99) at a median follow-up of 2.9 years. Thus, our results show that virtual crossmatch is an attractive strategy for shortening cold ischemia time without negatively impacting transplant outcomes. Hence, strategies to optimize use and reduce practice variation may allow for maximizing benefits from virtual crossmatch.

It is a well-known fact that the demand for kidneys far outpaces our society’s supply. The kidney allocation system (KAS) was created to ensure a fair distribution of a scarce societal resource. In 2014, the KAS was revised to help balance the equity and utility. Here we examine the many inequalities the KAS 2014 overcame, discuss the barriers that still exist, and evaluate the future implications of the new version of the KAS that is set to begin March 14, 2021. With the implementation of KAS 2014, longevity matching was much improved with decrease in number of recipient and donor age mismatch >15 years. There was an increase in highly sensitized transplants, especially those with calculated panel reactive antibody (cPRA) >98% due to a sliding scale of points and local/regional/national priority. Some groups even reported that it may have advantaged the very highly sensitized patients too much and suggested a more gradual sliding scale of points. The racial/ethnic disparities were much improved with allowance of wait time to start at time of dialysis initiation to capture those who did not have adequate and early access to a transplant center. Despite these improvements, there remains a geographic disparity which was not addressed with KAS 2014. KAS 2021 (set to begin March 14, 2021) was created to lessen the geographic barriers without compromising the utility of the organs. By eliminating donor service area (DSA) and instead using 250 nautical mile (nm) concentric circles around donor hospitals, this new system is intended to broaden the sharing. This change to the allocation is another step toward the goal of improving equality, but how this change will affect the utility remains to be seen.

HLA-incompatible living donor kidney transplantation (LDKT) is one of efforts to increase kidney transplantation opportunity for sensitized patients with kidney failure. However, there are conflicting reports for outcomes of HLA-incompatible kidney transplantation compared to patients who wait for HLA-compatible deceased donor kidney transplantation (DDKT) in the United States and United Kingdom. Waiting for an HLA-compatible DDKT is relatively disadvantageous in Korea, because the average waiting time is more than five years. To study this further, we compared outcomes of HLA-incompatible LDKT with those who wait for HLA-compatible DDKT in Korea. One hundred eighty nine patients underwent HLA-incompatible LDKT after desensitization between 2006 and 2018 in two Korean hospitals (42 with a positive complement-dependent cytotoxicity cross-match, 89 with a positive flow cytometric cross-match, and 58 with a positive donor-specific antibody with negative cross-match). The distribution of matched variables was comparable between the HLA-incompatible LDKT group and the matched control groups (waiting-list-only group; and the waiting-list-or-HLA-compatible-DDKT groups; 930 patients each). The HLA-incompatible LDKT group showed a significantly better patient survival rate compared to the waiting-list-only group and the waiting-list-or-HLA-compatible-DDKT groups. Furthermore, the HLA-incompatible LDKT group showed a significant survival benefit as compared with the matched groups at all strength of donor-specific antibodies. Thus, HLA-incompatible LDKT could have a survival benefit as compared with patients who were waitlisted for HLA-compatible DDKT or received HLA-compatible DDKT in Korea. This suggests that HLA-incompatible LDKT as a good option for sensitized patients with kidney failure in countries with prolonged waiting times for DDKT.

Unfavourable procurement biopsy findings are the most common reason for deceased donor kidney discard in the United States. We sought to assess the association between biopsy findings and post-transplant outcomes when donor characteristics are accounted for. We used registry data to identify 1566 deceased donors of 3132 transplanted kidneys (2015-2020) with discordant right/left procurement biopsy classification and performed time-to-event analyses to determine the association between optimal histology and hazard of death-censored graft failure or death. We then repeated all analyses using a local cohort of 147 donors of kidney pairs with detailed procurement histology data available (2006-2016). Among transplanted kidney pairs in the national cohort, there were no significant differences in incidence of delayed graft function or primary nonfunction. Time to death-censored graft failure was not significantly different between recipients of optimal versus suboptimal kidneys. Results were similar in analyses using the local cohort. Regarding recipient survival, analysis of the national, but not local, cohort showed optimal kidneys were associated with a lower hazard of death (adjusted HR 0.68, 95% CI 0.52-0.90, P = 0.006). In conclusion, in a large national cohort of deceased donor kidney pairs with discordant right/left procurement biopsy findings, we found no association between histology and death-censored graft survival.

BACKGROUND In March 2016, Australia's deceased donor kidney allocation program introduced calculated panel reactive antibody (cPRA) based on antibody exclusions using multiplex assays to define sensitization for waitlisted candidates. We aimed to assess the impact of this change and review access to transplantation for highly sensitized patients under the current allocation rules. METHODS Registry data were used to reconstruct changes in panel reactive antibody (PRA)/cPRA for all patients active on the waiting list between 2013 and 2018. A multilevel, mixed-effects negative binomial regression model was used to determine the association between sensitization and transplantation rate in the cPRA era. RESULTS Following the introduction of cPRA, there was an increase in the percentage of the waiting list classified as highly sensitized (PRA/cPRA ≥80%) from 7.2% to 27.8% and very highly sensitized (PRA/cPRA ≥99%) from 2.7% to 15.3%. Any degree of sensitization was associated with a decreased rate of transplantation with a marked reduction for those with cPRA 95%-98% (adjusted incidence rate ratio, 0.36 [95% confidence interval, 0.28-0.47], P < 0.001) and cPRA ≥99% (adjusted incidence rate ratio, 0.09 [95% confidence interval, 0.07-0.12], P < 0.001). CONCLUSIONS The proportion of the waiting list classified as highly sensitized increased substantially following the introduction of cPRA, and despite current prioritization, very highly sensitized patients have markedly reduced access to deceased donor transplantation.

COVID-19 has been sweeping the globe, hitting the United States particularly hard with a state of emergency declared on March 13, 2020. Transplant hospitals have taken various precautions to protect patients from potential exposure. OPTN donor, candidate, and transplant data were analyzed from January 5, 2020 to September 5, 2020. The number of new waiting list registrations decreased, with the Northeast seeing over a 50% decrease from the week of 3/8 versus the week of 4/5. The national transplant system saw near cessation of living donor transplantation (-90%) from the week of 3/8 to the week of 4/5. Similarly, deceased donor kidney transplant volume dropped from 367 to 202 (-45%), and other organs saw similar decreases: lung (-70%), heart (-43%), and liver (-37%). Deceased donors recovered dropped from 260 to 163 (-45%) from 3/8 compared to 4/5, including a 67% decrease for lungs recovered. The magnitude of this decrease varied by geographic area, with the largest percent change (-67%) in the Northeast. Despite the pandemic, discard rates across organ has remained stable. Although the COVID-19 pandemic continues to evolve, OPTN data show recent evidence of stabilization, an indication that an early recovery of the number of living and deceased donors and transplants has ensued.

BACKGROUND There is an abundant need to increase the availability of deceased donor kidney transplantation (DDKT) to address the high incidence of kidney failure. Challenges exist in the utilization of higher risk donor organs into what appears to be increasingly complex recipients; thus the identification of modifiable risk factors associated with poor outcomes is paramount. AIM To identify risk factors associated with delayed graft function (DGF). METHODS Consecutive adults undergoing DDKT between January 2016 and July 2017 were identified with a study population of 294 patients. The primary outcome was the occurrence of DGF. RESULTS The incidence of DGF was 27%. Under logistic regression, eight independent risk factors for DGF were identified including recipient body mass index ≥ 30 kg/m2, baseline mean arterial pressure < 110 mmHg, intraoperative phenylephrine administration, cold storage time ≥ 16 h, donation after cardiac death, donor history of coronary artery disease, donor terminal creatinine ≥ 1.9 mg/dL, and a hypothermic machine perfusion (HMP) pump resistance ≥ 0.23 mmHg/mL/min. CONCLUSION We delineate the association between DGF and recipient characteristics of pre-induction mean arterial pressure below 110 mmHg, metabolic syndrome, donor-specific risk factors, HMP pump parameters, and intraoperative use of phenylephrine.

In December 2014, the Kidney Donor Profile Index (KDPI) was developed to give more precise information on donor kidney quality. Kidneys with KDPI scores ≥ 85 (K ≥ 85) have been reported to have inferior outcomes to kidneys with KDPI scores 85.After the implementation of the new Kidney Allocation System, we developed a protocol to evaluate K ≥ 85 use. We analyzed the safety and efficacy of our institutional criteria and evaluated post-transplant outcomes. K ≥ 85 recipients were stratified based on their 1-year creatinine and estimated glomerular filtration rates to elucidate characteristics associated with serum creatinine 1.7 mg/dL or estimated glomerular filtration rates ≤ 45 mL/min/1.73 mFrom December 2014 to December 2019, 304 deceased donor kidney transplants were performed at Hartford Hospital; 58 (19%) were K ≥ 85 with an average KDPI of 91%. There were 4 graft losses; 2 were death censored. Prolonged cold ischemia time and black recipient race were associated with inferior recipient graft function at 1 year.High KDPI kidney use requires a multifaceted evaluation that takes into account donor and recipient characteristics for an ideal match. We have identified several characteristics that may predict optimal post-transplant kidney function.

Implementation of the HIV Organ Policy Equity (HOPE) Act marks a new era in transplantation, allowing organ transplantation from HIV+ donors to HIV+ recipients (HIV D+/R+ transplantation). In this review, we discuss major milestones in HIV and transplantation which paved the way for this landmark policy change, including excellent outcomes in HIV D–/R+ recipient transplantation and success in the South African experience of HIV D+/R+ deceased donor kidney transplantation. Under the HOPE Act, from March 2016 to December 2018, there were 56 deceased donors, and 102 organs were transplanted (71 kidneys and 31 livers). In 2019, the first HIV D+/R+ living donor kidney transplants occurred. Reaching the full estimated potential of HIV+ donors will require overcoming challenges at the community, organ procurement organization, and transplant center levels. Multiple clinical trials are ongoing, which will provide clinical and scientific data to further extend the frontiers of knowledge in this field.

Donor-recipient age difference (DRAD) is one of the reasons why patients on kidney waiting lists refuse to receive the offered organ. However, its impact on deceased donor kidney transplantation (DDKT) outcomes is still controversial.One hundred fifty-three kidney transplant recipients (KTRs) who received their first-time DDKT were enrolled. The KTRs were divided into groups by DRAD: group 1 (n = 74) (DRAD 0) and group 2 (n = 79) (DRAD ≥ 0). The KTRs in group 2 were divided into 3 subgroups: DRAD 0 to 10 (n = 35), 10 to 20 (n = 32), and ≥ 20 (n = 12). The outcome measures included estimated glomerular filtration rate (eGFR), delayed graft function (DGF), acute rejection (AR), and graft and patient survival.There were no significant differences in clinical outcomes between group 1 and 2 except eGFR until 5 years after DDKT. Among the subgroups of group 2, DGF, AR, patient survival, and eGFR until 5 years showed no significant differences. However, graft survival was significantly different (P = .015); in addition, in the DRAD ≥ 20 subgroup, graft survival decreased compared with that in the DRAD 10 to 20 subgroup and DRAD 0 to 10 subgroup (P = .020, P = .012, respectively). In a multivariate Cox proportional hazards analysis, the DRAD ≥ 20 subgroup showed a higher risk for graft failure than the DRAD 0 to 10 subgroup.Although donors were of the same age or older than recipients, DDKT showed acceptable graft outcomes. However, because donors over 20 years older than recipients showed a decreased graft survival, it might be important to consider this point in donor-recipient matching of DDKT.

The dialysis-based definition of Delayed Graft Function (dDGF) is not necessarily objective as it depends on the individual physician's decision. The functional definition of DGF (fDGF, the failure of serum creatinine to decrease by at least 10% daily on 3 consecutive days during the first week post-transplant), may be more sensitive to reflect recovery after the ischemia-reperfusion injury. We retrospectively analyzed both definitions in 253 deceased donor kidney transplant recipients for predicting death-censored graft failure as primary outcome, using eGFR < 25 ml/min/1.73 m2 as a surrogate end-point for graft failure. Secondary outcome was a composite outcome that included graft failure as above and also patient's death. Median follow-up was 3.22 [2.38-4.21] years. Seventy-nine patients developed dDGF (31.2%) and 127 developed fDGF (50.2%). Sixty-three patients fulfilled criteria for both definitions (24.9%). At multivariable analysis, the two definitions were significantly associated with the primary [HR (95%CI) 2.07 (1.09-3.94), P = 0.026 for fDGF and HR (95%CI) 2.41 (1.33-4.37), P = 0.004 for dDGF] and the secondary composite outcome [HR (95%CI) 1.58 (1.01-2.51), P = 0.047 for fDGF and HR (95%CI) 1.67 (1.05-2.66), P = 0.028 for dDGF]. Patients who met criteria for both definitions had the worst prognosis, with a three-year estimates (95%CI) of survival from the primary and secondary outcomes of 2.31 (2.02-2.59) and 2.20 (1.91-2.49) years for fDGF+/dDGF+, in comparison with the other groups (P < 0.01 for trend). fDGF provides supplementary information about graft outcomes on top of the dDGF definition in a modern series of kidney transplantation.

Kidneys from very small donors have the potential to significantly expand the donor pool. We describe the collective experience of transplantation using kidneys from donors aged ≤1 year in Australian and New Zealand. The ANZDATA registry was analysed on all deceased donor kidney transplants from donors aged ≤1 year. We compared recipient characteristics and outcomes between 1963-1999 and 2000-2018. From 1963 to 1999, 16 transplants were performed [9 (56%) adults, 7 (44%) children]. Death-censored graft survival was 50% and 43% at 1 and 5 years, respectively. Patient survival was 90% and 87% at 1 and 5 years, respectively. From 2000 to 2018, 26 transplants were performed [25 (96%) adults, 1 (4%) children]. Mean creatinine was 73 µmol/l ±49.1 at 5 years. Death-censored graft survival was 85% at 1 and 5 years. Patient survival was 100% at 1 and 5 years. Thrombosis was the cause of graft loss in 12% of recipients in the first era from 1963 to 1999, and 8% of recipients in the second era from 2000 to 2018. We advocate the judicious use of these small paediatric grafts from donors ≤1 year old. Optimal selection of donor and recipients may lead to greater acceptance and success of transplantation from very young donors.

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 (r2 = 0.11) and core (r2 = 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., Graphical abstract

Objectives Gujarat, Tamil Nadu, Telangana, Maharashtra, Kerala, Chandigarh, and Karnataka are states in India with active programs for deceased donor kidney transplant. We report our experience of 2 decades of deceased donor kidney transplant at the Institute of Kidney Diseases and Research Center, Dr. H. L. Trivedi Institute of Transplantation Sciences, Ahmedabad, Gujarat, India. Materials and methods This single-center retrospective study comprised data from 831 deceased donor kidney transplant recipients between January 1, 1997 and December 31, 2018. Mean recipient age was 38 ± 14 years; 564 were male, and 267 were female. Mean donor age was 45.3 ± 17.13 years; 565 were men, and 266 were women. Results Between January 1, 1997 and March 15, 2020, 5838 kidney transplants were completed, including 4895 living donor kidney transplants, 943 deceased donor kidney transplants, and 440 kidney paired donation transplants. Over the mean follow-up time of 8 ± 5.4 years, patient survival rate was 70% (n = 581) and death-censored graft survival rate was 84% (n = 698). Delayed graft function was shown in 210 patients (25%) and biopsy-proven acute rejection rate in 180 patients (21%). Our experience of favorable outcomes with deceased donor kidney transplants has expanded the donor pool in many ways, including transplant from expanded criteria donors to younger recipients; transplant from older donors to older recipients; donation after cardiac death; successful intercity organ procurement; dual-kidney transplant; en bloc transplant from a pediatric deceased donor; and transplant from brain death deceased donors who died from neurotoxic snakebite, recurrent primary brain tumor, bacterial meningitis, or head injury, or with disseminated intravascular coagulation and deranged renal functions. The pathway to increase organ donation was investigated. Conclusions Deceased donor kidney transplant can achieve acceptable graft function with patient/graft survival, which may encourage the use of this approach to increase the number of available organs.

In order to counter the lack of sufficient kidney donors, there has been interest in expanding the utilization of organs from increased infectious-risk donors. Negative nucleic acid testing of increased infectious-risk organs has been shown to increase their use as compared to only enzyme-linked immunosorbent assay negativity. However, it is not known how the expanded use of nucleic acid testing on a national scale might affect total donor utilization. The objective of this paper was to determine if a national screening policy requiring the use of nucleic acid testing in both increased infectious-risk and non-increased infectious-risk renal transplant donors would increase the donor organ pool. This study used decision-tree analysis to determine the cost-effectiveness of four US national screening policies based on an increasingly expansive use of nucleic acid testing for increased infectious-risk and non-increased infectious-risk kidneys. Parameters were taken from the literature. All costs were reported in 2020 US dollars using a Medicare payer perspective and a life-time horizon. The use of nucleic acid screening solely for increased infectious-risk organs was the dominant strategy. Our results were robust to deterministic and probabilistic sensitivity analyses. One of the main driving factors of cost-effectiveness was the false-positive rate of nucleic acid testing. Before implementing nucleic acid screening outside of increased infectious-risk organs, its false-positivity rate should be directly studied to ensure that its use does not detrimentally affect transplantation numbers, quality-adjusted life-years, and costs.

This registry-based study evaluated the contribution of center characteristics to kidney transplant outcomes in adult first kidney transplant recipients in Australia and New Zealand between 2004 and 2014. Primary outcomes were mortality and graft failure, and secondary outcomes were transplant complications. Overall, 6970 transplants from 17 centers were included. For deceased donor transplants, 5-year patient and graft survival rates varied considerably (81.0-93.9% and 72.2-88.3%, respectively). Variations in mortality and graft failure were partially reduced after adjustment for patient characteristics (1% and 20% reductions) and more markedly reduced after adjustment for center characteristics (41% and 55% reductions). For living donor transplants, 5-year patient and graft survival rates varied (89.7-100% and 79.2-96.9%, respectively). Centers with high average total ischemic times (>14 h) were associated with higher mortality for both deceased (adjusted hazard ratio [(AHR] 2.24, 95% CI 1.21-4.13) and living donor transplants (AHR 1.76, 95% CI 1.02-3.04). Small center size (

The consequences of prolonging cold ischemia time (CIT) to facilitate HLA matching in kidney transplantation are not known.Patients with a history of kidney transplant in the United States (2000-2016) with 0 HLA mismatch (MM) were categorized based on CIT (10; 10 to 15; 15 to 20; 20 to 25; 25 to 30; and ≥ 30 hours). Time to graft loss was compared for each CIT category to a reference group of individuals with0 HLA MM and short CIT (10 hours) using a multivariable Cox proportional hazards model.The adjusted risk of graft failure was significantly lower for 0 HLA MM with the shortest CIT compared to the reference group (hazard ratio, 0.82; 95% confidence interval, 0.72-0.94), and this survival advantage persisted to a threshold of 20 hours of CIT. No survival advantage was observed for the 0 HLA MM group once CIT was20 hours. This trend persisted after excluding highly sensitized recipients (panel reactive antibody98%) where shipping of organs occurs to achieve more equitable access to organs rather than optimize HLA match.CIT20 hours offsets the benefit of 0 HLA MM in kidney transplantation. This may have implications in organ shipping to facilitate immunologic match.

Objective To evaluate the clinical effect of hypothermic machine perfusion (HMP) in the storage of renal grafts from deceased donor (DD) with high-risk delayed graft function (DGF). Methods Clinical data of 52 donors with high-risk DGF were collected in this prospective randomized controlled study. Two renal grafts from each donor were randomly divided into the HMP group (n=52) and static cold storage (SCS) group (n=52). In the HMP group, the renal grafts were stored by LifePort under HMP, whereas the renal grafts in the SCS group were preserved in University of Wisconsin solution (UW solution). The incidence of DGF and primary nonfunction (PNF) after renal transplantation was statistically compared between two groups. The recovery of renal graft function, the survival rates of the recipients and renal grafts within postoperative 1 year were observed in two groups. Results The incidence of DGF in the HMP group was 4%(2/52), significantly lower than 17% (9/52) in the SCS group (P < 0.05). No PNF was reported in the HMP group and 1 case of PND was noted in the SCS group, the difference was not statistically significant (P > 0.05). The recovery time of graft function of the recipients in the HMP and SCS groups were (7.2±0.6) d and (7.7±1.0) d with no statistical significance (P > 0.05). In the HMP group, the urine volume of the recipients on the day of operation, postoperative 1 and2 d was significantly larger than that in the SCS group (all P < 0.05). In the HMP group, the levels of serum creatinine at each time point after operation were significantly lower than those in the SCS group (all P < 0.05). The 1-year survival rates of the recipient and kidney were 98.1%, 92.3% and 100%, 96.2% in the HMP and SCS groups with no statistical significance (all P > 0.05). Conclusions HMP can significantly reduce the incidence of DGF after renal transplantation from DD with high-risk DGF and promote the early recovery of graft function.

The outcomes of lymphocyte-depleting antibody induction therapy (LDAIT), [thymoglobulin (ATG) or alemtuzumab (ALM)] versus interleukin-2 receptor antagonist (IL-2RA) in the nonbroadly-sensitized [pretransplant calculated panel reactive antibody (cPRA)

BACKGROUND: Organ scarcity continues in solid organ transplantation, such that the availability of organs limits the number of people able to benefit from transplantation. Medical advancements in managing end-stage organ disease have led to an increasing demand for multi-organ transplant, wherein a patient with multi-organ disease receives more than one organ from the same donor. Current allocation schemes give priority to multi-organ recipients over single-organ transplant recipients, which raises ethical questions regarding equity and utility. METHODS: We use simultaneous liver-kidney (SLK) transplant, a type of multi-organ transplant, as a case study to examine the tension between equity and utility in multi-organ allocation. We adapt the health economics willingness-to-pay threshold to a solid organ transplant setting by coining a new metric: the willingness-to-transplant (WTT) threshold. RESULTS: We demonstrate how the WTT threshold can be used to evaluate different SLK allocation strategies by synthesizing utility and equity perspectives. CONCLUSIONS: We submit that this new framework enables us to distill the question of SLK allocation down to: what is the minimum amount of benefit we require from a deceased donor kidney to allocate it for a particular indication? Addressing the above question will prove helpful to devising a rational system of SLK allocation and is applicable to other transplant settings.

Background. Long cold ischemia time (CIT) is the most important factor contributing to delayed graft function (DGF) after kidney transplant. Improvements in pretransplant procedures may reduce CIT and improve clinical outcome. Materials and Methods. Pretransplant histocompatibility tests were modernized at our laboratory in 2015, leading to significant decrease of time consumed for these enabling earlier surgery. The effects of this on kidney transplant CIT, DGF, and other clinical outcomes were studied. The study population consisted of 896 consecutive deceased donor kidney recipients, of which 442 patients received a transplant with the old crossmatch and 454 received a transplant with the new crossmatch. Results. CIT shortened from mean 20 hours 6 minutes to 15 hours 52 minutes (P

There is an increasing gulf between demand and supply for kidneys in end-stage renal failure patients worldwide, especially Asia. Renal transplantation is often the treatment of choice for long-suffering patients who have to undergo dialysis on a regular basis. The utilization of expanded criteria donors (ECDs) to address the donor pool shortage has been proven to be a legitimate solution. Metzger first described the classification of standard criteria donor and ECD in 2002. Since then, the criterion has undergone various modifications, with the key aims of optimizing organ procurement rate while minimizing discard and rejection rates. We review the methods to improve selection, characterization of risks, and surgical techniques. Although the ECD kidneys have a higher risk of impaired donor and recipient outcome than the “standard criteria” transplants, it may be justified by the improved overall survival of these patients compared to those who remained on dialysis. It is, therefore, crucial that we perform meticulous selection, along with state of the art surgical techniques to maximize the use of this scarce resource. In this article, we review the pre-procurement and post-procurement processes implemented to preserve outcomes.

Objective We aimed to evaluate the effect of prolonged recovery from DGF on outcomes, using a new definition of DGF recovery time, among deceased donor kidney transplant recipients with DGF, and to examine the risk factors for prolonged recovery. Methods From 2007 to 2016, 91 deceased donor kidney transplant recipients with DGF were retrospectively analyzed. DGF recovery time was defined as the time from transplantation to achieve a stable estimated glomerular filtration rate (eGFR). Recipients with a DGF recovery time greater than or equal to the median were assigned to the prolonged recovery group, while the others were assigned to the rapid recovery group. Result The median DGF recovery time was 27 days. Donor terminal eGFR was significantly lower in the prolonged recovery group (n = 46) compared with the rapid recovery group (n = 45) (median 24.9 vs. 65.4 ml/min/1.73m2, p = 0.004). The eGFR at 1 year post-transplant in the prolonged recovery group was significantly lower than that in the rapid recovery group (50.6 ± 20.0 vs. 63.5 ± 21.4 ml/min/1.73m2, p = 0.005). The risk of adverse outcomes (acute rejection, pneumonia, graft failure, and death) was significantly greater in the prolonged recovery group (hazard ratio 2.604, 95% confidence interval 1.102–6.150, p = 0.029) compared with the rapid recovery group. Conclusion Decreased donor terminal eGFR is a risk factor for prolonged recovery from DGF after deceased kidney transplantation. Prolonged DGF recovery time is associated with reduced graft function at 1-year post-transplant, and poor transplant outcome.

BACKGROUND: Early steroid withdrawal (ESW) is associated with acceptable outcomes in kidney transplant (KT) recipients. Recipients with delayed graft function (DGF), however, often have a suboptimal allograft milieu, which may alter the risk/benefit equation for ESW. This may contribute to varying practices across transplant centers. METHODS: Using the Scientific Registry of Transplant Recipients, we studied 110,019 adult deceased-donor KT recipients between 2005 and 2017. We characterized the association of DGF with the use of ESW versus continued steroid maintenance across KT centers, and quantified the association of ESW with acute rejection, graft failure, and mortality using multivariable logistic and Cox regression with DGF-ESW interaction terms. RESULTS: Overall 29.2% of KT recipients underwent ESW. Recipients with DGF had lower odds of ESW (aOR=(0.60)0.67(0.75)). The strength of this association varied across 261 KT centers, with center-specific aOR of 1.0 at 22 (8.4%) centers. ESW was associated with benefits and harms among recipients with immediate graft function (IGF), but only with harms among recipients with DGF. ESW was associated with increased acute rejection (aOR=(1.09)1.16(1.23)), slightly increased graft failure (aHR=(1.01)1.06(1.12)), but decreased mortality (aHR=(0.86)0.89(0.93)) among recipients with IGF. Among recipients with DGF, ESW was associated with a similar increase in rejection (aOR=1.12; 95% CI, 1.02 to 1.23), a more pronounced increase in graft failure (aHR=1.16; 95% CI, 1.08 to 1.26), and no improvement in mortality (aHR=1.00; 95% CI, 0.94 to 1.07). DGF-ESW interaction was statistically significant for graft failure (P=0.04) and mortality (P=0.003), but not for rejection (P=0.6). CONCLUSIONS: KT centers in the United States use ESW inconsistently in recipients with DGF. Our findings suggest ESW may lead to worse KT outcomes in recipients with DGF.

BK polyomavirus (BKV) is a common infection among kidney transplant recipients (KTR). Risk factors and outcomes based on donor characteristics remain largely unknown.In this study, we aimed to analyze the impact of donor factors through a paired kidney analysis. We included 289 pairs of adult deceased donor transplants (578 KTRs total); each pair had received kidneys from the same donor. Recipient pairs were divided into three groups: "no BK group" if neither KTR developed BK viremia (n = 336), "discordant" if the only one did (n = 176), and "concordant" if both did (n = 66). Acute rejection (AR), graft failure, and BK nephropathy (BKN) were outcomes of interest.Donors in the concordant group were younger, had lower kidney donor profile index (KDPI), and were less likely to be donor after circulatory death (DCD). In multivariate analyses, KTRs who had a donor with a higher body mass index (BMI) (hazard ratio (HR): 0.97; 95% confidence interval (CI): 0.95-0.99; p = .009) were less likely to develop BKV. Concordance was not associated with AR (HR: 0.83; 95% CI: 0.51-1.34; p = .45), graft failure (HR: 1.77; 95% CI: 0.42-7.50; p = .43), or BKN (HR: 1.02; 95% CI: 0.51-2.03; p = .96).Our study suggests lower donor BMI is associated with BKV infection, and concordance or discordance between paired kidney recipients is not associated with poor outcomes.

Kidney transplantation is the preferred method for selected patients with kidney failure. Despite major improvements over the last decades, a significant proportion of organs are still lost every year. Causes of graft loss and impaired graft function are incompletely understood and prognostic tools are lacking. Here, we describe baseline characteristics and outcomes of the non-interventional Transplant Outcome Prediction Validation Study (TOPVAS). A total of 241 patients receiving a non-living kidney transplant were recruited in three Austrian transplantation centres and treated according to local practices. Clinical information as well as blood and urine samples were obtained at baseline and consecutive follow-ups up to 24 months. Out of the overall 16 graft losses, 11 occurred in the first year. The patient survival rate was 96.7% (95% CI: 94.3–99.1%) in the first year and 94.3% (95% CI: 91.1–97.7%) in the second year. Estimated glomerular filtration rate (eGFR) improved from 37.1 ± 14.0 mL/min/1.73 m2 at hospital discharge to 45.0 ± 14.5 mL/min/1.73 m2 at 24 months. The TOPVAS study provides information on current kidney graft and patient survival, eGFR trajectories, and rejection rates, as well as infectious and surgical complication rates under different immunosuppressive drug regimens. More importantly, it provides an extensive and well-characterized biobank for the future discovery and validation of prognostic methods.

Deceased donor kidneys are a scarce community resource; therefore, the principles underpinning organ allocation should reflect societal values. This study aimed to elicit community and healthcare professional preferences for principles guiding the allocation of kidneys from deceased donors and compare how these differed across the populations. A best-worst scaling survey including 29 principles in a balanced incomplete block design was conducted among a representative sample of the general community (n = 1237) and healthcare professionals working in transplantation (n = 206). Sequential best-worst multinomial logistic regression was used to derive scaled preference scores (PS) (range 0-100). Thematic analysis of free text responses was performed. Five of the six most valued principles among members of the community related to equity, including priority for the longest waiting (PS 100), difficult to transplant (PS 94.5) and sickest (PS 93.9), and equitable access for men and women (PS 94.0), whereas the top four principles for healthcare professional focused on maximizing utility (PS 89.9-100). Latent class analysis identified unmeasured class membership among community members. There are discordant views between community members and healthcare professionals. These should be considered in the design, evaluation, and implementation of deceased donor kidney allocation protocols.

Background: African American (AA) recipients of deceased-donor (DD) kidney transplants (KT) have shorter allograft survival than recipients of other ethnic groups. Reasons for this disparity encompass complex interactions between donors and recipients characteristics. Methods: Outcomes from 3,872 AA and 19,719 European American (EA) DDs who had one kidney transplanted in an AA recipient and one in an EA recipient were analyzed. Four donor/recipient pair groups (DRP) were studied, AA/AA, AA/EA, EA/AA, and EA/EA. Survival random forests and Cox proportional hazard models were fitted to rank and evaluate modifying effects of DRP on variables associated with allograft survival. These analyses sought to identify factors contributing to the observed disparities in transplant outcomes among AA and EA DDKT recipients. Results: Transplant era, discharge serum creatinine, delayed graft function, and DRP were among the top predictors of allograft survival and mortality among DDKT recipients. Interaction effects between DRP with the kidney donor risk index and transplant era showed significant improvement in allograft survival over time in EA recipients. However, AA recipients appeared to have similar or poorer outcomes for DDKT performed after 2010 versus before 2001; allograft survival hazard ratios (95% CI) were 1.15 (0.74, 1.76) and 1.07 (0.8, 1.45) for AA/AA and EA/AA, compared to 0.62 (0.54, 0.71) and 0.5 (0.41, 0.62) for EA/EA and AA/EA DRP, respectively. Recipient mortality improved over time among all DRP, except unemployed AA/AAs. Relative to DDKT performed pre-2001, employed AA/AAs had HR=0.37 (0.2, 0.69) versus 0.59 (0.31, 1.11) for unemployed AA/AA after 2010. Conclusion: Relative to DDKT performed before 2001, similar or worse overall DCAS was observed among AA/AAs, while EA/EAs experienced considerable improvement regardless of employment status, KDRI, and EPTS. AA recipients of an AA DDKT, especially if unemployed, had worse allograft survival and mortality and did not appear to benefit from advances in care over the past 20 years.

All UK H&I laboratories and transplant units operate under a single national kidney offering policy, but there have been variations in approach regarding when to undertake the pre-transplant crossmatch test. In order to minimize cold ischaemia times for deceased donor kidney transplantation we sought to find ways to be able to report a crossmatch result as early as possible in the donation process. A panel of experts in transplant surgery, nephrology, specialist nursing in organ donation and H&I (all relevant UK laboratories represented) assessed evidence and opinion concerning five factors that relate to the effectiveness of the crossmatch process, as follows: when the result should be ready for reporting; what level of donor HLA typing is needed; crossmatch sample type and availability; fairness and equity; risks and patient safety. Guidelines aimed at improving practice based on these issues are presented, and we expect that following these will allow H&I laboratories to contribute to reducing CIT in deceased donor kidney transplantation.

BACKGROUND: Anatomic abnormalities increase the risk of deceased donor kidney discard, but their effect on transplant outcomes is understudied. We sought to determine the effect of multiple donor renal arteries on early outcomes after deceased donor kidney transplantation. METHODS: For this retrospective cohort study, we identified 1443 kidneys from 832 deceased donors with ≥1 kidney transplanted at our center (2006–2016). We compared the odds of delayed graft function and 90-day graft failure using logistic regression. To reduce potential selection bias, we then repeated the analysis using a paired-kidney cohort, including kidney pairs from 162 donors with one single-artery kidney and one multiartery kidney. RESULTS: Of 1443 kidneys included, 319 (22%) had multiple arteries. Multiartery kidneys experienced longer cold ischemia time, but other characteristics were similar between groups. Delayed graft function (50% multiartery versus 45% one artery, P=0.07) and 90-day graft failure (3% versus 3%, P=0.83) were similar between groups before and after adjusting for donor and recipient characteristics. In the paired kidney analysis, cold ischemia time was significantly longer for multiartery kidneys compared with single-artery kidneys from the same donor (33.5 versus 26.1 hours, P

We investigated whether the development of delayed graft function (DGF) in pre-sensitized patients affects the clinical outcomes after deceased-donor kidney transplantation (DDKT).The study included 709 kidney transplant recipients (KTRs) from three transplant centers. We divided KTRs into four subgroups (highly sensitized DGF, highly sensitized non-DGF, low-sensitized DGF, and low-sensitized non-DGF) according to panel reactive antibody level of 50%, or DGF development. We compared post-transplant clinical outcomes among the four subgroups.Incidence of biopsy-proven acute rejection (BPAR) was higher in two highly sensitized subgroups than in low-sensitized subgroups. It tended to be higher in highly sensitized DGF subgroups than in the highly sensitized non-DGF subgroups. In addition, the highly sensitized DGF subgroup showed the highest risk for BPAR (hazard ratio, 3.051; P=0.005) and independently predicted BPAR. Allograft function was lower in the two DGF subgroups than in the non-DGF subgroup until one month after transplantation, but thereafter it was similar. Death-censored graft loss rates and patient mortality tended to be low when DGF developed, but it did not reach statistical significance.DGF development in highly sensitized patients increases the risk for BPAR in DDKT compared with patients without DGF, suggesting the need for strict monitoring and management of such cases.

Background Procurement biopsies have become a common practice in the evaluation and allocation of deceased donor kidneys in the United States despite questions about their value and reproducibility. We sought to determine the extent of OPO-level differences in criteria used to decide which deceased donor kidneys undergo a procurement biopsy and to assess the degree of variability in procurement biopsy technique and interpretation across OPOs. Methods Each of the country's 58 OPOs were invited to participate in the survey. OPOs were divided into two groups based on organ availability ratio and deceased donor kidney discard rate. Results and conclusions Fifty-out-of-fifty-eight invited OPOs (86% response rate) responded to the survey between November 2020 and December 2020. Thirty (60%) OPOs reported that they have formal criteria for performing kidney procurement biopsy, but for 29 of these OPOs, transplant centers can request biopsy on kidneys that do not meet criteria. OPOs used a total of seven different variables and 12 different numerical thresholds to define impaired kidney function that would prompt a procurement biopsy. Additionally, wide variability was seen in biopsy technique and procedures for biopsy interpretation and reporting of findings to transplant programs. These findings identify a clear opportunity for standardization of procurement biopsies to best practices.