Risk for graft loss in pediatric and young adult kidney transplant recipients due to recurrent IgA nephropathy.

IgA nephropathy (IgAN) is associated with a risk for posttransplant recurrence. Data are limited regarding graft loss attributable to recurrence of IgAN among pediatric and young adult kidney transplant (KT) recipients. This was a retrospective cohort study of patients aged 0 to 25 years from the Scientific Registry of Transplant Recipients who received a primary KT for IgAN. Patients with history of KT attributable to renal dysplasia were comparators. Outcomes included the incidence of graft loss attributable to IgAN recurrence, association with donor type, and posttransplant corticosteroid use. In total, 5475 transplant recipients were included, with 1915 patients with IgAN and 3560 patients with renal dysplasia. In a multivariable Cox proportional hazards model, IgAN was associated with higher risk of graft loss (adjusted hazard ratio [aHR], 1.35; 95% CI, 1.21-1.50; P < .001) compared with dysplasia. Graft loss was attributed to recurrent disease in 5.4% of patients with IgAN. In a multivariable competing risks analysis, patients with IgAN receiving a parental living-donor kidney were more likely to report graft loss from recurrent disease compared with patients with a nonparental living donor (aHR, 0.52; 95% CI, 0.31-0.91; P = .02). Posttransplant prednisone use was not associated with improved graft survival (P = .2). These data challenge existing paradigms in posttransplant management of patients with IgAN.

A retrospective cohort study of socioeconomic deprivation and post-liver transplant survival in adults.

The Area Deprivation Index is a granular measure of neighborhood socioeconomic deprivation. The relationship between neighborhood socioeconomic deprivation and recipient survival following liver transplantation (LT) is unclear. To investigate this, the authors performed a retrospective cohort study of adults who underwent LT at the University of Washington Medical Center from January 1, 2004, to December 31, 2020. The primary exposure was a degree of neighborhood socioeconomic deprivation as determined by the Area Deprivation Index score. The primary outcome was posttransplant recipient mortality. In a multivariable Cox proportional analysis, LT recipients from high-deprivation areas had a higher risk of mortality than those from low-deprivation areas (HR: 1.81; 95% CI: 1.03-3.18, p =0.04). Notably, the difference in mortality between area deprivation groups did not become statistically significant until 6 years after transplantation. In summary, LT recipients experiencing high socioeconomic deprivation tended to have worse posttransplant survival. Further research is needed to elucidate the extent to which neighborhood socioeconomic deprivation contributes to mortality risk and identify effective measures to improve survival in more socioeconomically disadvantaged LT recipients.

Kidney retransplantation outcomes in adults aged 70 and older: Analysis of risk factors and survival.

BACKGROUND: An increasing number of older patients are undergoing kidney transplant. Because of a finite longevity, more patients will be faced with failing allografts. At present there is a limited understanding of the benefits and risks associated with kidney retransplantation in this challenging population. METHODS: We performed a retrospective analysis of the Organ Procurement and Transplantation Network database of all adults ≥70 undergoing kidney retransplant from January 1, 2014 to December 31, 2022. We examined patient and graft survival of retransplanted patients compared to first time transplants. We also analyzed the risk factors that impacted the survival. RESULTS: During the study period there has been a significant rise in the number of retransplants performed, with 631 patients undergoing the procedure. Although clinically insignificant, overall graft, and patient survival rates were slightly lower in the retransplant group compared to the primary transplant group. With retransplant, patient survival was 91.3%, 75.6%, and 56.9% compared to 93.4%, 81.4%, and 64.4% with primary transplant at 1, 3, and 5 years, respectively. With retransplant, graft survival was 89.5%, 73.5%, 57.4% compared to 91.5%, 79.0%, and 63.6% in a primary transplant group at 1, 3, and 5 years, respectively. Multivariable analysis showed that factors predicting poor survival included longer time on dialysis before retransplantation and decreased functional capacity. No survival difference was noted between recipients of deceased versus living donor kidneys. Patients who underwent retransplantation before initiating dialysis had better patient and graft survival. CONCLUSION: Patients aged ≥70 achieve satisfactory outcomes following kidney retransplantation, highlighting that chronologic age should not preclude this medically complex population from this life-saving procedure. Improvement in functional status and timely retransplantation are the key factors to successful outcome.

Optimizing pediatric liver transplantation: Evaluating the impact of donor age and graft type on patient survival outcome.

BACKGROUND: We examined the combined effects of donor age and graft type on pediatric liver transplantation outcomes with an aim to offer insights into the strategic utilization of these donor and graft options. METHODS: A retrospective analysis was conducted using a national database on 0-2-year-old (N = 2714) and 3-17-year-old (N = 2263) pediatric recipients. These recipients were categorized based on donor age (≥40 vs <40 years) and graft type. Survival outcomes were analyzed using the Kaplan-Meier and Cox proportional hazards models, followed by an intention-to-treat (ITT) analysis to examine overall patient survival. RESULTS: Living and younger donors generally resulted in better outcomes compared to deceased and older donors, respectively. This difference was more significant among younger recipients (0-2 years compared to 3-17 years). Despite this finding, ITT survival analysis showed that donor age and graft type did not impact survival with the exception of 0-2-year-old recipients who had an improved survival with a younger living donor graft. CONCLUSIONS: Timely transplantation has the largest impact on survival in pediatric recipients. Improving waitlist mortality requires uniform surgical expertise at many transplant centers to provide technical variant graft (TVG) options and shed the conservative mindset of seeking only the "best" graft for pediatric recipients.

Deceased donor kidneys are discarded at higher rates when labeled as high kidney donor profile index.

The kidney donor risk index (KDRI) and percentile conversion, kidney donor profile index (KDPI), provide a continuous measure of donor quality. Kidneys with a KDPI >85% (KDPI85 ) are referred to as "high KDPI." The KDPI85 cutoff changes every year, impacting which kidneys are labeled as KDPIHIGH . We examine kidney utilization around the KDPI85 cutoff and explore the "high KDPI" labeling effect. KDRI to KDPI Mapping Tables from 2012 to 2020 were used to determine the yearly KDRI85 value. Organ Procurement and Transplantation Network data was used to calculate discard rates and model organ use. KDRI85 varied between 1.768 and 1.888. In a multivariable analysis, kidney utilization was lower for KDPI 86% compared with KDPI 85% kidneys (p = .046). Kidneys with a KDRI between 1.785-1.849 were classified as KDPIHIGH in the years 2015-2017 and KDPILOW in the years 2018-2020. The discard rate was 44.9% when labeled as KDPIHIGH and 39.1% when labeled as KDPILOW (p < .01). For kidneys with the same KDRI, the high KDPI label is associated with increased discard. We should reconsider the appropriateness of the "high KDPI" label.

Acute Graft-Versus-Host Disease After Orthotopic Liver Transplantation: Predicting This Rare Complication Using Machine Learning.

Acute graft-versus-host disease (GVHD) is a rare complication after orthotopic liver transplantation (OLT) that carries high mortality. We hypothesized that machine-learning algorithms to predict rare events would identify patients at high risk for developing GVHD. To develop a predictive model, we retrospectively evaluated the clinical features of 1938 donor-recipient pairs at the time they underwent OLT at our center; 19 (1.0%) of these recipients developed GVHD. This population was divided into training (70%) and test (30%) sets. A total of 7 machine-learning classification algorithms were built based on the training data set to identify patients at high risk for GVHD. The C5.0, heterogeneous ensemble, and generalized gradient boosting machine (GGBM) algorithms predicted that 21% to 28% of the recipients in the test data set were at high risk for developing GVHD, with an area under the receiver operating characteristic curve (AUROC) of 0.83 to 0.86. The 7 algorithms were then evaluated in a validation data set of 75 more recent donor-recipient pairs who underwent OLT at our center; 2 of these recipients developed GVHD. The logistic regression, heterogeneous ensemble, and GGBM algorithms predicted that 9% to 11% of the validation recipients were at high risk for developing GVHD, with an AUROC of 0.93 to 0.96 that included the 2 recipients who developed GVHD. In conclusion, we present a practical model that can identify patients at high risk for GVHD who may warrant additional monitoring with peripheral blood chimerism testing.

Do funding sources influence long-term patient survival in pediatric liver transplantation?

BACKGROUND: Socioeconomic status has been associated with inferior outcomes after multiple surgical procedures, but has not been well studied with respect to pediatric liver transplantation. This study evaluated the impact of insurance status (as a proxy for socioeconomic status) on patient and allograft survival in pediatric first-time liver transplant recipients. METHODS: Our retrospective analysis of the UNOS data base from January 2002 through September 2017 revealed 6997 pediatric patients undergoing first-time isolated liver transplantation. A mixed Cox proportional hazards model adjusted for donor, recipient, and program characteristics determined the RR of insurance status on allograft and patient survival. All results were considered significant at P < .05. All statistical results were obtained using R version 3.5.1 and coxme version 2.2-10. RESULTS: Medicaid status had a significant negative impact on long-term survival after controlling for multiple covariates. Pediatric patients undergoing first-time isolated liver transplantation with Medicaid insurance had a RR of 1.42 [confidence interval: 1.18-1.60] of post-transplant death. CONCLUSION: Pediatric patients undergoing first-time isolated liver transplantation have multiple risk factors that may impact long-term survival. Having Medicaid insurance almost doubles the chances of dying post-liver transplant. This patient population may require more global support post-transplant to improve long-term survival.

End-of-Life Care among US Adults with ESKD Who Were Waitlisted or Received a Kidney Transplant, 2005-2014.

BACKGROUND: The care of patients in the United States who have ESKD is often shaped by their hopes and prognostic expectations related to kidney transplant. Little is known about how patients' engagement in the transplant process might relate to patterns of end-of-life care. METHODS: We compared six measures of intensity of end-of-life care among adults in the United States with ESKD who died between 2005 and 2014 after experiencing differing exposure to the kidney transplant process. RESULTS: Of 567,832 decedents with ESKD, 27,633 (5%) had a functioning kidney transplant at the time of death, 14,653 (3%) had a failed transplant, 16,490 (3%) had been removed from the deceased donor waitlist, 17,010 (3%) were inactive on the waitlist, 11,529 (2%) were active on the waitlist, and 480,517 (85%) had never been waitlisted for or received a transplant (reference group). In adjusted analyses, compared with the reference group, patients exposed to the transplant process were significantly more likely to have been admitted to an intensive care unit and to have received an intensive procedure in the last 30 days of life; they were also significantly more likely to have died in the hospital. Those who died on the transplant waitlist were also less likely than those in the reference group to have been enrolled in hospice and to have discontinued dialysis before death. CONCLUSIONS: Patients who had engaged in the kidney transplant process received more intensive patterns of end-of-life care than other patients with ESKD. These findings support the relevance of advance care planning, even for this relatively healthy segment of the ESKD population.

Livers From Pediatric Donation After Circulatory Death Donors Represent a Viable and Underutilized Source of Allograft.

Despite increased numbers of donation after circulatory death (DCD) donors, pediatric DCD livers are underused. To investigate possible reasons for this discrepancy, we conducted a retrospective cohort study using 2 data sets from the Organ Procurement and Transplantation Network for all deceased liver donors and for all recipients of DCD liver transplants from March 8, 1993, to June 30, 2018. Pediatric (0-12 years) and adolescent (13-17 years) DCD donors were compared with those aged 18-40 years. We found that pediatric DCD allografts are recovered at a significantly lower rate than from 18-to-40-year-old donors (27.3% versus 56.3%; P < 0.001). However, once recovered, these organs are transplanted at a similar rate to those from the 18-to-40-year-old donor cohort (74.7% versus 74.2%). Significantly more pediatric DCD livers (odds ratio [OR], 3.75; confidence interval [CI], 3.14-4.47) were not recovered compared with adult organs, which were most commonly not recovered due to organ quality (10.2% versus 7.1%; P < 0.001). The 10-year relative risks (RRs) for graft failure and patient death were similar between pediatric and adult DCD donors, with adolescent DCD livers demonstrating improved outcomes. DCD livers transplanted into pediatric donors were protective against graft failure (RR, 0.46; 95% confidence interval [CI], 0.21-0.99) and patient death (RR, 0.16; 95% CI, 0.04-0.69). In conclusion, despite lower rates of recovery, pediatric DCD livers represent a viable organ source for certain adults and children.

Adults transplanted as children as retransplant candidates: Analysis of outcomes support optimism in a population mislabeled as high risk.

Adult liver transplant programs have heretofore been hesitant to perform liver retransplantation in adult patients who underwent primary liver transplantation as a child (P_A). Areas of concern include: (a) potential disruption in care when transferring from a pediatric to an adult transplant center; (b) generally inferior outcomes of retransplantation; (c) reputation of young adults for non-adherence to post-transplant regimen; and (d) potential higher work effort for equivalent outcomes. To examine these concerns, we reviewed data on all US liver adult retransplants from 10/01/1987 to 9/30/2017. We propensity matched the P_A patients to patients who received both primary and retransplantation as adults (A_A), with ≥550 days between transplants. A mixed Cox proportional hazards model with program size and time period of transplantation as random variables revealed that retransplantation of P_A patients produced no significantly different graft survival or patient survival rates than retransplantation of the matched A_A patients. Therefore, inferior rates of liver retransplantation in these patients and concerns about continuity of care in changing transplant programs are not as believed in the wider liver transplant community. In conclusion, liver transplant centers should be optimistic about retransplanting adults who received their primary transplants as children.

Living vs deceased donor liver transplantation in cholestatic liver disease: An analysis of the OPTN database.

BACKGROUND: Living donor liver transplantation (LDLT) and donation after circulatory death (DCD) can expand the donor pool for cholestatic liver disease (CLD) patients. We sought to compare the outcomes of deceased donor liver transplant (DDLT) vs LDLT in CLD patients. METHODS: Retrospective cohort analysis of adult CLD recipients registered in the OPTN database who received primary LT between 2002 and 2018. Cox proportional hazards regression models with mixed effects were used to determine the impact of graft type on patient and graft survival. RESULTS: Five thousand, nine hundred ninety-nine DDLT (5730 donation after brain death [DBD], 269 DCD) and 912 LDLT recipients were identified. Ten-year patient/graft survival rates were DBD: 73.8%/67.9%, DCD: 74.7%/60.7%, and LDLT: 82.5%/73.9%. Higher rates of biliary complications as a cause of graft failure were seen in DCD (56.8%) than LDLT (30.5%) or DBD (18.7%) recipients. On multivariable analysis, graft type was not associated with patient mortality, while DCD was independently associated with graft failure (P = .046). CONCLUSION: DBD, DCD, and LDLT were associated with comparable overall patient survival. No difference in the risk of graft failure could be observed between LDLT and DBD. DCD can be an acceptable alternative to DBD with equivalent patient survival, but inferior graft survival likely related to the high rate of biliary complications.

The impact of public health service increased risk donors in pediatric liver transplantation.

Many transplant programs are reluctant to use organs from deceased donors designated as "PHS increased risk" due to misconceptions regarding the quality of those organs. This study evaluated the impact of PHS increased risk donors on patient and allograft survival in pediatric patients undergoing liver transplantation. Retrospective analysis of the UNOS database from January 2005 through September 2017 revealed 5615 pediatric patients who underwent isolated liver transplantation; of these, 5057 patients received primary isolated liver transplants and 558 patients received isolated liver retransplants. PHS increased risk organs were used in 6.7% and 5.4% of the children receiving primary isolated and retransplant livers, respectively. Cox proportional hazards models adjusted for donor and recipient characteristics determined the relative risk of PHS status on allograft and patient survival. Sicker children (those in ICU [P < .001] and on life support [P = .04]) were more likely to receive PHS increased risk donor organs. There were no differences in overall patient (P = .61) or allograft (P = .68) survival between pediatric patients receiving PHS positive vs PHS negative deceased donor organs; adjusted models also demonstrated no statistically significant differences in patient or allograft survival. Excellent patient and allograft survival can be accomplished with PHS increased risk organs.

Living Donation Versus Donation After Circulatory Death Liver Transplantation for Low Model for End-Stage Liver Disease Recipients.

In this era of organ scarcity, living donor liver transplantation (LDLT) is an alternative to using deceased donors, and in Western countries, it is more often used for recipients with low Model for End-Stage Liver Disease (MELD) scores. We sought to compare the patient survival and graft survival between recipients of liver transplantation from living donors and donation after circulatory death (DCD) donors in patients with low MELD scores. This is a retrospective cohort analysis of adult liver transplant recipients with a laboratory MELD of ≤20 who underwent transplantation between January 1, 2003 and March 31, 2016. Recipients were categorized by donor graft type (DCD or LDLT), and recipient and donor characteristics were compared. Ten-year patient and graft survival curves were calculated using Kaplan-Meier analyses, and a mixed-effects model was performed to determine the contributions of recipient, donor, and center variables on patient and graft survival. There were 36,705 liver transplants performed: 32,255 (87.9%) from DBD donors, 2166 (5.9%) from DCD donors, and 2284 (6.2%) from living donors. In the mixed-effects model, DCD status was associated with a higher risk of graft failure (relative risk [RR], 1.27; 95% confidence interval [CI], 1.16-1.38) but not worse patient survival (RR, 1.27; 95% CI, 0.96-1.67). Lower DCD center experience was associated with a 1.21 higher risk of patient death (95% CI, 1.17-1.25) and a 1.13 higher risk of graft failure (95% CI, 1.12-1.15). LDLT center experience was also predictive of patient survival (RR, 1.03; 95% CI, 1.02-1.03) and graft failure (RR, 1.05; 95% CI, 1.05-1.06). In conclusion, for liver transplant recipients with low laboratory MELD, LDLT offers better graft survival and a tendency to better patient survival than DCD donors.

Advancing the high throughput identification of liver fibrosis protein signatures using multiplexed ion mobility spectrometry.

Rapid diagnosis of disease states using less invasive, safer, and more clinically acceptable approaches than presently employed is a crucial direction for the field of medicine. While MS-based proteomics approaches have attempted to meet these objectives, challenges such as the enormous dynamic range of protein concentrations in clinically relevant biofluid samples coupled with the need to address human biodiversity have slowed their employment. Herein, we report on the use of a new instrumental platform that addresses these challenges by coupling technical advances in rapid gas phase multiplexed ion mobility spectrometry separations with liquid chromatography and MS to dramatically increase measurement sensitivity and throughput, further enabling future high throughput MS-based clinical applications. An initial application of the liquid chromatography--ion mobility spectrometry-MS platform analyzing blood serum samples from 60 postliver transplant patients with recurrent fibrosis progression and 60 nontransplant patients illustrates its potential utility for disease characterization.

Outcomes after combined liver-kidney transplant vs. kidney transplant followed by liver transplant.

INTRODUCTION: The decision for isolated kidney transplant (KT) vs. combined liver-kidney transplant (CLKT) in patients with end-stage renal disease (ESRD) with compensated cirrhosis remains controversial. We sought to determine outcomes of patients requiring listing for a liver transplant (LT) following either a cadaveric or living donor KT and compare these outcomes to similar patients receiving a CLKT. METHODS: Our dataset included the United Network for Organ Sharing (UNOS)/Standard Transplant and Analysis and Research (STAR) kidney files from 1987 to 2012 after being joined with the liver files from 2002 to 2012. Outcomes of patients who received a CLKT with an international normalized ratio (INR) ≤1 and total bilirubin ≤1 were compared to patients who received a primary KT and subsequently required listing for LT between zero and five yr or after five yr. RESULTS: For the three groups, 244 patients had a CLKT, 216 were wait-listed for LT between zero and five yr after KT (0-5 WL), and 320 were wait-listed five yr after KT (+5 WL). From the time of KT, the 0-5 WL group had significantly worse survival than the CLKT group and the +5 WL group. The +5 WL had the best survival of all groups. For the 0-5 WL group, 45% underwent LT and 40% died while waiting compared to the +5 WL group with 53% having LT and 26% died while waiting. At the time of LT, the 0-5 WL group had a higher model for end-stage liver disease (MELD) score, higher incidence of being in the ICU at the time of transplant, and higher incidence of requiring life support. From the time of LT, the CLKT trended toward better survival (p = 0.0549) than both the 0-5 WL and +5 WL groups, which had equivalent survival. CONCLUSION: The 0-5 WL group is a higher risk group with poorer survival due to a higher incidence of dying on the waitlist. Better identification of patients with a high risk for hepatic decompensation following KT and agreement for regional exception for LT in the event of decompensation may improve utilization of organs and better survival for those patients.

Evaluating the Correlation Between Anteroposterior Diameter, Body Surface Area, and Height for Liver Transplant Donors and Recipients.

Background: Small stature and female sex correlate to decreased deceased donor liver transplant (DDLT) access and higher waitlist mortality. However, efforts are being made to improve access and equity of allocation under the new continuous distribution (CD) system. Liver anteroposterior diameter (APD) is a method used by many centers to determine size compatibility for DDLT but is not recorded systematically, so it cannot be used for allocation algorithms. We therefore seek to correlate body surface area (BSA) and height to APD in donors and recipients and compare waitlist outcomes by these factors to support their use in the CD system. Methods: APD was measured from single-center DDLT recipients and donors with cross-sectional imaging. Linear, Pearson, and PhiK correlation coefficient were used to correlate BSA and height to APD. Competing risk analysis of waitlist outcomes was performed using United Network for Organ Sharing data. Results: For 143 pairs, donor BSA correlated better with APD than height (PhiK = 0.63 versus 0.20). For recipient all comers, neither BSA nor height were good correlates of APD, except in recipients without ascites, where BSA correlated well (PhiK = 0.63) but height did not. However, among female recipients, BSA, but not height, strongly correlated to APD regardless of ascites status (PhiK = 0.80 without, PhiK = 0.70 with). Among male recipients, BSA correlated to APD only in those without ascites (PhiK = 0.74). In multivariable models, both BSA and height were predictive of waitlist outcomes, with higher values being associated with increased access, decreased delisting for death/clinical deterioration, and decreased living donor transplant (model concordance 0.748 and 0.747, respectively). Conclusions: Taken together, BSA is a good surrogate for APD and can therefore be used in allocation decision making in the upcoming CD era to offset size and gender-based disparities among certain candidate populations.

Impact of Obesity on Kidney Transplant Outcomes in Older Adults.

BACKGROUND: The prevalence of obesity in older patients undergoing kidney transplantation is increasing. Older age and obesity are associated with higher risks of complications and mortality post-transplantation. The optimal management of this group of patients remains undefined. METHODS: We retrospectively analyzed the United Network for Organ Sharing database of adults ≥70 years of age undergoing primary kidney transplant from January 1, 2014, to December 31, 2022. We examined patient and graft survival stratified by body mass index (BMI) in 3 categories, <30 kg/m2, 30 to 35 kg/m2, and >35 kg/m2. We also analyzed other risk factors that impacted survival. RESULTS: A total of 14,786 patients ≥70 years underwent kidney transplantation. Of those, 9,731 patients had a BMI <30 kg/m2, 3,726 patients with a BMI of 30 to 35 kg/m2, and 1,036 patients with a BMI >35 kg/m2. During the study period, there was a significant increase in kidney transplants in patients ≥70 years old across all BMI groups. Overall, patient survival, death-censored graft survival, and all-cause graft survival were lower in obese patients compared with nonobese patients. Multivariable analysis showed worse patient survival and graft survival in patients with a BMI of 30 to 35 kg/m2, a BMI >35 kg/m2, a longer duration of dialysis, diabetes mellitus, and poor functional status. CONCLUSION: Adults ≥70 years should be considered for kidney transplantation. Obesity with a BMI of 30 to 35 kg/m2 or >35 kg/m2, longer duration of dialysis, diabetes, and functional status are associated with worse outcomes. Optimization of these risk factors is essential when considering these patients for transplantation.