Search

Transplantation remains the preferred treatment for end-stage kidney disease but is critically limited by the number of available organs. Xenografts from genetically modified pigs have become a promising solution to the loss of life while waiting for transplantation. However, the current clinical model for xenotransplantation will require off-site procurement, leading to a period of ischemia during transportation. As of today, there is limited understanding regarding the preservation of these organs, including the duration of viability, and the associated molecular changes. Thus, our aim was to evaluate the effects of static cold storage (SCS) on α1,3-galactosyltransferase knockout (GGTA1 KO) kidney. After SCS, viability was further assessed using acellular sub-normothermic ex vivo perfusion and simulated transplantation with human blood. Compared to baseline, tubular and glomerular interstitium was preserved after 2 days of SCS in both WT and GGTA1 KO kidneys. Bulk RNA-sequencing demonstrated that only eight genes were differentially expressed after SCS in GGTA1 KO kidneys. During sub-normothermic perfusion, kidney function, reflected by oxygen consumption, urine output, and lactate production was adequate in GGTA1 KO grafts. During a simulated transplant with human blood, macroscopic and histological assessment revealed minimal kidney injury. However, GGTA1 KO kidneys exhibited higher arterial resistance, increased lactate production, and reduced oxygen consumption during the simulated transplant. In summary, our study suggests that SCS is feasible for the preservation of porcine GGTA1 KO kidneys. However, alternative preservation methods should be evaluated for extended preservation of porcine grafts., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Although rare, infection and vaccination can result in antibodies to human leukocyte antigens (HLA). We analyzed the effect of SARS-CoV-2 infection or vaccination on HLA antibodies in waitlisted renal transplant candidates. Specificities were collected and adjudicated if the calculated panel reactive antibodies (cPRA) changed after exposure. Of 409 patients, 285 (69.7 %) had an initial cPRA of 0 %, and 56 (13.7 %) had an initial cPRA > 80 %. The cPRA changed in 26 patients (6.4 %), 16 (3.9 %) increased, and 10 (2.4 %) decreased. Based on cPRA adjudication, cPRA differences generally resulted from a small number of specificities with subtle fluctuations around the borderline of the participating centers' cutoff for unacceptable antigen listing. All five COVID recovered patients with an increased cPRA were female (p = 0.02). In summary, exposure to this virus or vaccine does not increase HLA antibody specificities and their MFI in approximately 99 % of cases and 97 % of sensitized patients. These results have implications for virtual crossmatching at the time of organ offer after SARS-CoV-2 infection or vaccination, and these events of unclear clinical significance should not influence vaccination programs., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Inc.)

Background: At every stage in the transplantation process for a deceased-donor kidney, time means ischemia. Donation after circulatory death (DCD) kidneys are already subject to warm ischemia in the donor, but another underappreciated component of warm ischemia time is the time required for anastomosis prior to reperfusion. We studied the effect of anastomosis time (AT) on outcomes after DCD kidney transplantation., Study Design: This is a retrospective study of the Scientific Registry of Transplant Recipients, including all US adult DCD kidney transplantation recipients from 2009 to 2015 (N = 6,397). Our exposure was AT (time out of cold storage until reperfusion, quartiles). Outcomes included delayed graft function (DGF), death-censored graft survival, and overall patient survival. Multivariable logistic and Cox regression quantified the association of AT with outcomes, adjusting for donor and recipient factors (including donor warm ischemia time)., Results: AT accounted for 67% of total warm ischemia time on average, with a median AT of 38 minutes (median total warm ischemia 56 minutes). Longer AT (fourth [≥48min] vs first quartile [≤30min]) was associated with increased DGF (odds ratio = 1.19, p = 0.024) and increased graft failure (hazard ratio = 1.21, p = 0.043) but was not associated with patient survival. Comparing patients with the longest vs shortest AT, adjusted DGF incidence was 44.0% vs 36.7% (p = 0.024), and 5-year graft survival was 84.8% vs 88.2% (p = 0.004)., Conclusion: Prolonged AT is associated with worse graft outcomes in DCD kidney transplant recipients. Efforts to minimize rewarming during implantation and optimize AT may improve graft outcomes., (Copyright © 2022 by the American College of Surgeons. Published by Wolters Kluwer Health, Inc. All rights reserved.)

The risk of adverse outcomes for pediatric renal transplant patients is highest during the transition from pediatric to adult care. While there have been many studies focus on graft failure and death, loss to follow-up likely plays a large role in patient outcomes. We hypothesize patients are lost to follow-up during this transition period and that patients transplanted at pediatric centers with a closely affiliated adult center (AFFs) are less likely to suffer from fragmentation of care and become lost to follow-up. AFFs were defined as those pediatric centers whose transplant surgeons were also on staff at an adult center and were identified using center websites. We included patients undergoing renal transplantation at <=18 years of age and had data for the entire transition period on the Scientific Registry of Transplant Recipients (n = 6,762, 92.3% in 95 AFFs). 32% of patients were lost to follow-up. On regression, patients transplanted at AFF were 33% less likely to be lost to follow-up compared with those from non-AFF (OR 0.67 CI 0.54-0.82, P < 0.01). The proportion of patients lost to follow-up during the transition period is remarkably high, but lower among recipients transplanted at AFFs. Poor follow-up may be mitigated by improving integration of care., (2019 Wiley Periodicals, Inc.)

Background: Direct-acting antivirals have changed the landscape of hepatitis C virus (HCV) care. While transplantation with HCV-positive donor organs is increasing, little is known about providers' attitudes toward this topic. The aim of this study is to determine providers' attitudes toward HCV-positive kidney transplantation., Methods: Willing transplant and nontransplant nephrologists, transplant surgeons, and mid-level providers completed an online survey from April through May 2018. The survey asked about HCV knowledge and willingness to transplant HCV-positive antibody, nucleic acid testing-positive kidneys into HCV-negative recipients. Descriptive analyses including mean and median for continuous variables and frequencies for categorical variables were calculated., Results: Seven-hundred surveys were emailed and 99 providers (62 transplant nephrologists, 28 nontransplant nephrologists, 7 transplant surgeons, and 2 advanced practice providers) completed the survey (participation rate 14.1%). All providers knew that HCV was curable, with 60% believing that it had no effect on transplant success and 32% thinking it reduced transplant success. Providers were significantly more likely to offer a HCV-positive organ to HCV-positive recipients compared to HCV-negative recipients in all queried circumstances (p < 0.005 in all cases), especially with increasing impact on patient's quality of life. While only 39% of providers would offer a HCV-positive organ for transplant to a patient without HCV if it reduced the waitlist time by 1 year, 92% would offer a HCV-positive organ if it reduced the waitlist time by 4 years. However, only 47% thought that the use of HCV-positive kidneys should be for routine care, while 38% believed it should be reserved for research purposes only. There were no significant differences between transplant and nontransplant nephrologists in attitudes toward HCV-positive kidney transplantation. Providers believed that donor organs from those who were obese, >50 years old, or had died from a cardiac arrest were significantly more likely to reduce the likelihood of a successful transplant 1-year posttransplant when compared with a HCV-positive organ (p < 0.005 in all cases). Eighty-six percent of providers had concerns about HCV curability posttransplant., Conclusion: Although 92% of providers were willing to offer a HCV-positive kidney for transplant as patient waitlist time increases, less than half supported offering HCV-positive transplantation for routine care rather than for research. The results underscore the need for further education and data about the efficacy and safety of HCV-positive kidney transplantation., (© 2019 S. Karger AG, Basel.)

Background: Hepatitis C virus (HCV)-infected organs are being transplanted in patients with and without HCV in the direct-acting antiviral era. Little is known about patient attitudes towards receiving an HCV-positive organ., Objectives: The aim of this study is to determine transplant candidates' attitudes towards receiving HCV-positive organs., Methods: Adult solid organ transplant candidates were identified during a clinic visit or during outpatient hemodialysis from May to December 2017. Willing participants completed a survey. Descriptive analysis including mean and median for continuous variables and frequencies for categorical variables were calculated by the appropriate statistical method and compared across willing, unsure, and unwilling patients and between willing and unsure/unwilling patients., Results: Fifty patients were surveyed with median age 54.5 years (range 32-77). Eighty-eight percent were awaiting kidney transplant, and 12% were awaiting other organs. Median waitlist time was 39.8 months (range 1.7-203 months). Most patients (90%) had prior knowledge of HCV, but only 60% knew it was curable. Forty-six percent were willing, 30% were unsure, and 24% were unwilling to receive an HCV-positive organ. Those willing to accept an HCV-positive organ were significantly older, Caucasian, had shorter waitlist times, and had greater physician trust than those that were unsure/unwilling. Similar worries, such as HCV incurability, insurance coverage, fears over the organ not working, and post-transplant death, were expressed in both the willing and unsure/unwilling patients., Conclusions: The availability of HCV-positive organs may expand the donor pool and decrease waitlist times and mortality. These data highlight the need for patient education towards use of these organs., (© 2018 S. Karger AG, Basel.)

Distance from pediatric kidney transplant centers may be a significant barrier in accessing care for patients and families, particularly due to the lower number of pediatric kidney transplant centers compared with the number of adult centers. We performed a retrospective cohort study using data from the Scientific Registry of Transplant Recipients to determine the effect of distance on pediatric kidney transplant waitlist outcomes. We found that distance did not play a role in the likelihood of transplantations for patients who were placed on the waitlist. However, living a greater distance from the transplant center was associated with a greater risk of death while on the waitlist. Larger volume centers attracted patients from greater distances, many of whom had other centers closer to their home. Further investigation on the role of distance to transplant center and the likelihood of being evaluated and listed for a kidney transplant would elucidate whether there are additional barriers these patients face., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Although residential segregation has been implicated in various negative health outcomes, its association with kidney transplantation has not been examined., Methods: Age- and sex-standardized kidney transplantation rates were calculated from the Scientific Registry of Transplant Recipients, 2000-2013. Population characteristics including segregation indices were derived from the 2010 U.S. Census data and the U.S. Renal Data System. Separate multivariable Poisson regression models were constructed to identify factors independently associated with kidney transplantation among Blacks and Whites., Results: Median age- and sex-standardized kidney transplantation rates were 114 per 100,000 for Blacks and 38 per 100,000 for Whites. 16.1% of the U.S. population lived in counties with high segregation. There was no difference in the kidney transplantation rates across the levels of segregation among Blacks and Whites., Conclusion: Factors other than residential segregation may play roles in kidney transplantation disparities. Continued efforts to identify these factors may be beneficial in reducing transplantation disparities across the U.S., Summary: Using the Scientific Registry of Transplant Recipients and U.S. census data, we aimed to determine whether residential segregation was associated with kidney transplantation rates. We found that there was no association between residential segregation and kidney transplantation rates., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Introduction: Early allograft thrombosis is a devastating complication that often leads to graft loss after living donor kidney transplantation. In addition to the psychological effects on donor and recipient, it could make future kidney matches challenging due to sensitization., Patients and Methods: The Scientific Registry of Transplant Recipients (SRTR) was queried for adult patients undergoing living donor renal transplantation from 2001 to 2010. Sensitization was defined as a panel reactive antibody of ≥50%. Early allograft thrombosis included events within 30 d of transplantation., Results: In multivariable logistic regression, recipient female gender (odds ratio [OR] 2.24, p < 0.001) and right kidneys (OR 1.46, p < 0.001) were associated with increased risk of thrombosis, while increasing recipient age per 10 yr (OR 0.62, p < 0.001) and recipient Asian race/ethnicity (OR 0.34, p = 0.02) were protective. In a time-varying Cox model examining factors affecting the likelihood of retransplantation, the chance of retransplantation was 37% lower (p = 0.01) once patients became sensitized. The median time to sensitization after transplantation was 288 d., Conclusions: Even with relatively brief exposure to foreign antigen, sensitization occurs and delays retransplantation for recipients of living donor kidneys with early allograft thrombosis., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Organ procurement organizations (OPOs) are currently evaluated on donation rates and number of organs per donor. However, there is significant variability in market characteristics which affect transplant programs' donor organ acceptance practices and OPOs' ability to successfully place higher risk organs. The impact of transplant market characteristics on OPO performance metrics has not been evaluated., Methods: The OPO performance measures were correlated annually with the Herfindahl Hirschman Index, a standard measure of market competition for centers within the OPO donor service areas from 2003 to 2011., Results: More competitive donor service areas were associated with increased number of donors (P = 0.01) and eligible deaths (P < 0.001). Market competition was associated with increased use of high Donor Risk Index for kidney (P = 0.03) and liver (P = 0.01) allografts. The OPOs with increased competition in liver transplant also were noted to have a higher donor conversion rate (P < 0.001), more donors per million population (P < 0.001), and a higher utilization rate for liver allografts (P = 0.007)., Conclusions: These data suggest that proposals to increase district size to increase competition among transplant programs could result in improved organ utilization over time by incentivizing the use of marginal donor organs and increasing access to transplantation.

Background: Kidney transplant centers are distributed unevenly throughout 58 donor service areas (DSAs) in the United States. Market competition and transplant center density may affect transplantation access and outcomes. We evaluated the role of spatial organization of transplant centers in conjunction with market competition in the conduct of kidney transplantation., Methods: The Scientific Registry of Transplant Recipients was queried for market characteristics associated with kidney transplantation between 2003 and 2012. Market competition was calculated using the Herfindahl Hirschman Index. Kidney transplant centers were geocoded to measure spatial organization by the average nearest neighbor (ANN) method. Kidney quality was assessed by kidney donor risk index. A hierarchical negative binomial mixed effects model tested the relationship between market characteristics and annual kidney transplants by DSA., Results: About 152,071 kidney transplants were performed at 229 adult kidney transplant centers in 58 DSAs. Greater market competition was associated with kidney transplant center spatial clustering (P < 0.001). In multivariable analysis, more kidney transplant centers (incidence rate ratio [IRR], 1.04; P = 0.005), 100 more new listings (IRR, 1.02; P = 0.003), 100 more deceased donors (IRR, 1.23; P < 0.001), 100 more new dialysis registrants (IRR, 1.01; P < 0.001), and higher kidney donor risk index (IRR, 1.98; P < 0.001) were associated with increased kidney transplants., Conclusions: After controlling for market characteristics, larger numbers of kidney transplant centers were associated with more kidney transplants and increased utilization of deceased donor kidneys. This underlines the importance of understanding geography as well as competition in improving access to kidney transplantation.

Objective: To evaluate the impact of market competition on patient mortality and graft failure after kidney transplantation., Background: Kidneys are initially allocated within 58 donation service areas (DSAs), which have varying numbers of transplant centers. Market competition is generally considered beneficial., Methods: The Scientific Registry of Transplant Recipients database was queried and the Herfindahl-Hirschman index (HHI), a measure of market competition, was calculated for each DSA from 2003 to 2012. Receipt of low-quality kidneys (Kidney Donor Profile Index ≥ 85) was modeled with multivariable logistic regression, and Cox proportional hazards models were created for graft failure and patient mortality., Results: A total of 127,355 adult renal transplants were performed. DSAs were categorized as 7 no (HHI = 1), 17 low (HHI = 0.52-0.97), 17 medium (HHI = 0.33-0.51), or 17 high (HHI = 0.09-0.32) competition. For deceased donor kidney transplantation, increasing market competition was significantly associated with mortality [hazard ratio (HR): 1.11, P = 0.01], graft failure (HR: 1.18, P = 0.0001), and greater use of low-quality kidneys (odds ratio = 1.39, P < 0.0001). This was not true for living donor kidney transplantation (mortality HR: 0.94, P = 0.48; graft failure HR: 0.99, P = 0.89). Competition was associated with longer waitlists (P = 0.04) but not with the number of transplants per capita in a DSA (P = 0.21)., Conclusions: Increasing market competition is associated with increased patient mortality and graft failure and the use of riskier kidneys. These results may represent more aggressive transplantation and tolerance of greater risk for patients who otherwise have poor alternatives. Market competition should be better studied to ensure optimal outcomes.

Background: Isolated islet transplantation with infusions from two to three donor pancreata and Edmonton immunosuppression consistently achieves insulin independence in patients with type 1 diabetes. The success of this protocol has been attributed to a novel combination of immunosuppressive agents and avoidance of steroids; however, the outcome of islet transplantation may differ in kidney transplant recipients who are already immunosuppressed., Methods: We compared the metabolic outcomes and graft survival of islet transplantation in our program where nine patients underwent islet transplantation alone treated with Edmonton immunosuppression and eight patients received islet after kidney (IAK) transplants under standard kidney transplant immunosuppression often including steroids., Results: Transplants in the IAK and islet transplantation alone setting demonstrated similar islet potency (islet equivalents/unit insulin reduction) and recipients from both groups routinely gained insulin independence, functional islet mass, and duration of graft survival, however, seemed superior in the IAK group., Conclusions: These results suggest that better islet graft function and survival may be attained using non-Edmonton rather than Edmonton immunosuppression and can include maintenance steroid therapy.

Gradual rewarming from hypothermic to normothermic is a novel perfusion modality with superior outcome to sudden rewarming to normothermic. However, the identification of an oxygen carrier that could function at a temperature range from 4 to 7°C or whether it is necessary to use oxygen carrier during kidney rewarming, remains unresolved. This study was designed to test the use of a hemoglobin‐based oxygen carrier (HBOC) during gradual kidney rewarming as an alternative to simple dissolved oxygen. In this study, 10 rat kidneys were randomly divided into the control and the HBOC group. In the control group, no oxygen carrier was used during rewarming perfusion and the perfusion solution was oxygenated only by applying diffused carbogen flow. The protocol mimicked a donor after circulatory death (DCD) kidney transplantation, where after 30 minutes warm ischemia and 120 minutes cold storage in University of Wisconsin solution, the DCD kidneys underwent gradual rewarming from 10 to 37°C during 90 minutes with or without HBOC. This was followed by 30 minutes of warm ischemia in room temperature to mimic the anastomosis time and 120 minutes of reperfusion at 37°C to mimic the early post‐transplant state of the graft. The HBOC group demonstrated superior kidney function which was highlighted by higher ultrafiltrate production, better glomerular filtration rate and improved sodium reabsorption. There was no significant difference between the 2 groups regarding the hemodynamics, tissue injury, and adenosine triphosphate levels. In conclusion, this study suggests better renal function recovery in DCD kidneys after rewarming with HBOC compared to rewarming without an oxygen carrier. [ABSTRACT FROM AUTHOR]

Abstract: Distance from pediatric kidney transplant centers may be a significant barrier in accessing care for patients and families, particularly due to the lower number of pediatric kidney transplant centers compared with the number of adult centers. We performed a retrospective cohort study using data from the Scientific Registry of Transplant Recipients to determine the effect of distance on pediatric kidney transplant waitlist outcomes. We found that distance did not play a role in the likelihood of transplantations for patients who were placed on the waitlist. However, living a greater distance from the transplant center was associated with a greater risk of death while on the waitlist. Larger volume centers attracted patients from greater distances, many of whom had other centers closer to their home. Further investigation on the role of distance to transplant center and the likelihood of being evaluated and listed for a kidney transplant would elucidate whether there are additional barriers these patients face. [ABSTRACT FROM AUTHOR]

Many potential and willing living kidney donors are excluded from donating for a history of malignancy. There is appropriate caution toward patients with a history of malignancy because of concern for transmission of donor-derived malignancy. Thyroid cancer is common and increasing in incidence, and outcomes are very good in otherwise young, healthy potential donors. We review the evidence and guidelines regarding recurrence and transmission risk of thyroid cancer, and then we suggest a standardized guideline for otherwise healthy donors with a history of thyroid malignancy. [ABSTRACT FROM AUTHOR]