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.

Misplaced emphasis, misunderstood risk: a cultural history of Public Health Service infectious disease guidelines.

PURPOSE OF REVIEW: To review and summarize the evolution of the Public Health Service (PHS) guidelines and Organ Procurement and Transplantation Network (OPTN) regulations for the prevention of blood borne virus transmission in solid organ transplant through the lens of popular culture, scientific evolution, patient and practitioner bias and outcomes research. RECENT FINDINGS: The most recent set of guidelines and regulations were released in 2020 and represent a culmination of decades of opinion, research and debate within the scientific and lay communities. SUMMARY: The guidelines were created to address public concern, and the risk of undiagnosed disease transmission in the context of the novel public health crisis of AIDS. We reviewed milestone publications from the scientific and lay press from the first description of AIDS in 1981 to the present to help illustrate the context in which the guidelines were created, the way they changed with subsequent editions, and offer critical consideration of issues with the current set of guidelines and a potential way forward. Further consideration should be given to the way in which the current guidelines identify donors with risk criteria for infectious disease transmission and mandate explanation of donor-specific risk factors to potential recipients, in our era of universal donor screening and recipient surveillance.

Solid organ donation after death in the United States: Data-driven messaging to encourage potential donors.

US deceased donor solid organ transplantation (dd-SOT) depends upon an individual's/family's altruistic willingness to donate organs after death; however, there is a shortage of deceased organ donors in the United States. Informing individuals of their own lifetime risk of needing dd-SOT could reframe the decision-making around organ donation after death. Using United Network for Organ Sharing (UNOS) data (2007-2016), this cross-sectional study identified (1) deceased organ donors, (2) individuals waitlisted for dd-SOT (liver, kidney, pancreas, heart, lung, intestine), and (3) dd-SOT recipients. Using US population projections, life tables, and mortality estimates, we quantified probabilities (Pr) of (1) becoming deceased organ donors, (2) needing dd-SOT, and (3) receiving dd-SOT. Lifetime Pr (per 100 000 US population) for males and females of becoming deceased organ donors were 212 and 146, respectively, and of needing dd-SOT were 1323 and 803, respectively. Lifetime Pr of receiving dd-SOT was 50% for males, 48% for females. Over a lifetime, males were 6.2 and females 5.5 times more likely to need dd-SOT than to become deceased organ donors. Organ donation is traditionally contextualized in terms of charity toward others. Our analyses yield a new tool, in the form of quantifying an individual's own likelihood of needing dd-SOT, which may assist with reframing motivations toward deceased donor organ donation.

Hyperammonemia syndrome due to Ureaplasma infection after liver-kidney transplant.

Hyperammonemia syndrome, with high levels of ammonia and neurologic dysfunction, is a syndrome with historically high mortality that may occur after solid organ transplantation. Recently, this has been associated with infection due to Ureaplasma, mostly following lung transplantation. We describe the first case of hyperammonemia syndrome due to Ureaplasma infection after liver-kidney transplantation. Our patient rapidly recovered after specific antibiotic treatment. It is important to consider these infections in the differential diagnosis for encephalopathy post-transplant, as these organisms often do not grow using routine culture methods and polymerase chain reaction testing is typically required for their detection. This is particularly critical after liver transplantation, where a number of other etiologies may be considered as a cause of hyperammonemia syndrome.

Transplant tourism complicated by life-threatening New Delhi metallo-ß-lactamase-1 infection.

Transplant tourism, which is the practice of traveling to other countries for transplant, continues to be a major problem worldwide. We describe a patient who traveled to Pakistan and underwent commercial kidney transplant. He developed life-threatening infections from New Delhi metallo-ß-lactamase-1-producing Enterobacter cloacae and Rhizopus oryzae, resulting in a necrotizing kidney allograft infection and subsequent external iliac artery rupture. He survived after a prolonged course of nonstandardized antimicrobial therapy, including a combination of aztreonam and ceftazidime-avibactam, and aggressive surgical debridement with allograft nephrectomy. The early timing of infection with these unusual organisms localized to the allograft suggests contamination and substandard care at the time of transplant. This case highlights the challenges of caring for these infections and serves as a cautionary tale for the potential complications of commercial transplant tourism.

Expanding access to transplantation with hepatitis C-positive donors: A new perspective on an old issue.

With the need for organs far exceeding supply, donors previously exposed to hepatitis B (HBV) and hepatitis C (HCV) viral infections should be considered for transplantation. Although many centers have protocols for transplanting organs from HBV core antibody-positive (HBcAb+) donors into select recipients, in the era of direct-acting antivirals (DAAs), a new focus should be placed on HCV-positive donors. The transmission rate from HCV antibody-positive (HCVAb+) nucleic acid testing negative (HCV NAT-) donors is expected to be very low, and we encourage use of such organs in HCV recipients provided a normal biopsy, appropriate counseling, and careful post-transplant monitoring. While transmission of HCV from HCV NAT+ donors is universal, the success of DAA in obtaining a sustained viral response in post-transplant recipients should make the use of these organs more appealing. We herein provide information to help guide the use of organs from HCV donors.

Changing the paradigm of organ utilization from PHS increased-risk donors: an opportunity whose time has come?

Approximately 8-11% of all organ donors are classified by Public Health Service (PHS) as increased-risk. The proportion of PHS increased-risk donors is on the rise. At the University of Washington Medical Center, in 2014, the proportion of transplants from PHS increased-risk donors was 28% of liver transplants and 23% of kidney transplants. Nationally, transplant providers have been reluctant to use organs from PHS increased-risk donors because of concern for transmission of HIV, HCV, or HBV. There is also patient apprehension when these organs are being offered, and thus the discard rate of these otherwise good quality organs is high. Because of the organ shortage, preventing underutilization of such organs is essential. We provide data and considerations that should be used to guide the use of organs from PHS increased-risk donors.

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.

Intention-to-treat Analysis of Patients Aged 70 Years and Older Awaiting Kidney Transplantation in Post-Kidney Allocation System Era.

BACKGROUND: The US population is aging, and so the number of patients treated for end-stage renal disease is on the rise. In the United States, 38% of people over 65 y old have chronic kidney disease. There continues to be a reluctance of clinicians to consider older candidates for transplant, including early referrals. METHODS: We conducted a retrospective analysis of the Organ Procurement and Transplantation Network database of all adults ≥70 y old undergoing kidney transplants from December 1, 2014, to June 30, 2021. We compared patient and graft survival in candidates who were transplanted while on hemodialysis versus preemptive with a living versus deceased donor kidney transplant. RESULTS: In 2021, only 43% of the candidates listed for transplant were preemptive. In an intention-to-treat analysis from the time of listing, candidate survival was significantly improved for those transplanted preemptively versus being on dialysis (hazard ratio 0.59; confidence interval, 0.56-0.63). All donor types, donor after circulatory death, donor after brain death, and living donor, had a significant decrease in death over remaining on the waiting list. Patients who were on dialysis or transplanted preemptively with a living donor kidney had significantly better survival than those receiving a deceased donor kidney. However, receiving a deceased donor kidney significantly decreased the chance of death over remaining on the waiting list. CONCLUSIONS: Patients ≥70 y old who are transplanted preemptively, whether with a deceased donor or a living donor kidney, have a significantly better survival than those who are transplanted after initiating dialysis. Emphasis on timely referral for a kidney transplant should be placed in this population.

Anti-GSTT1 antibodies and Null genotype correlate with histological changes of antibody mediated rejection in kidney transplantation.

BACKGROUND: The presence of anti-Glutathione S-transferase T1 (GSTT1) antibodies (abs) has been hypothesized as a pathogenic contributor in antibody-mediated rejection (AMR). METHODS: We aimed to evaluate the relationship between genetic variants of GSTT1, anti-GSTT1 abs and AMR in a cohort of 87 kidney transplant (KTx) patients using Immucor's non-HLA Luminex assay. Patients were classified according to biopsy-proven AMR and HLA-DSA status: AMR with positive anti-HLA-DSAs (AMR/DSA+, n = 29), AMR but no detectable anti-HLA-DSAs (AMR/DSA-, n = 28) and control patients with stable allograft function and no evidence of rejection (n = 30). RESULTS: At an MFI cut-off of 3000, the overall prevalence of anti-GSTT1 abs was 18.3%. The proportion of patients with anti-GSTT1 abs was higher in the AMR/DSA- group (25%), compared to the control (13.3%) and AMR/DSA+ group (3.4%) (p = 0.06). Among patients with anti-GSTT1 abs, the MFI was higher in AMR/DSA- and GSTT1-Null patients. Of 81 patients who underwent GSTT1 genotyping, 19.8% were homozygotes for the null allele (GSTT1-Null). GSTT1-Null status in the transplant recipients was associated with the development of anti-GSTT1 abs (OR, 4.49; 95%CI, 1.2-16.7). In addition, GSTT1-Null genotype (OR 26.01; 95%CI, 1.63-404) and anti-GSTT1 ab positivity (OR 14.8; 95%CI, 1.1-190) were associated with AMR. Within AMR/DSA- patients, the presence of anti-GSTT1 abs didn't confer a higher risk of failure within the study observation period. CONCLUSION: The presence of anti-GSTT1 abs and GSTT1-Null genotype is associated with AMR, but do not appear to lead to accelerated graft injury in this cohort of early allograft injury changes, with a limited period of follow-up.

Events in procurement as risk factors for ischemic cholangiopathy in liver transplantation using donation after cardiac death donors.

The use of donation after cardiac death (DCD) liver grafts is controversial because of the overall increased rates of graft loss and morbidity, which are mostly related to the consequences of ischemic cholangiopathy (IC). In this study, we sought to determine the factors leading to graft loss and the development of IC and to compare patient and graft survival rates for recipients of DCD liver grafts and recipients of donation after brain death (DBD) liver grafts in a large series at a single transplant center. Two hundred liver transplants with DCD donors were performed between 1998 and 2010 at Mayo Clinic Florida. Logistic regression models were used in the univariate and multivariate analyses of predictors for the development of IC. Additional analyses using Cox regression models were performed to identify predictors of graft survival and to compare outcomes for DCD and DBD graft recipients. In our series, the patient survival rates for the DCD and DBD groups at 1, 3, and 5 years was 92.6%, 85%, and 80.9% and 89.8%, 83.0%, and 76.6%, respectively (P = not significant). The graft survival rates for the DCD and DBD groups at 1, 3, and 5 years were 80.9%, 72.7%, and 68.9% and 83.3%, 75.1%, and 68.6%, respectively (P = not significant). In the DCD group, 5 patients (2.5%) had primary nonfunction, 7 patients (3.5%) had hepatic artery thrombosis, and 3 patients (1.5%) experienced hepatic necrosis. IC was diagnosed in 24 patients (12%), and 11 of these patients (5.5%) required retransplantation. In the multivariate analysis, the asystole-to-cross clamp duration [odds ratio = 1.161, 95% confidence interval (CI) = 1.021-1.321] and African American recipient race (odds ratio = 5.374, 95% CI = 1.368-21.103) were identified as significant factors for predicting the development of IC (P < 0.05). This study has established a link between the development of IC and the asystole-to-cross clamp duration. Procurement techniques that prolong the nonperfusion period increase the risk for the development of IC in DCD liver grafts.

Asystole to cross-clamp period predicts development of biliary complications in liver transplantation using donation after cardiac death donors.

This study sought to determine the procurement factors that lead to development of intrahepatic bile duct strictures (ITBS) and overall biliary complications in recipients of donation after cardiac death (DCD) liver grafts. Detailed information for different time points during procurement (withdrawal of support; SBP < 50 mmHg; oxygen saturation <30%; mandatory wait period; asystole; incision; aortic cross clamp) and their association with the development of ITBS and overall biliary complications were examined using logistic regression. Two hundred and fifteen liver transplants using DCD donors were performed between 1998 and 2010 at Mayo Clinic Florida. Of all the time periods during procurement, only asystole-cross clamp period was significantly different between patients with ITBS versus no ITBS (P = 0.048) and between the patients who had overall biliary complications versus no biliary complications (P = 0.047). On multivariate analysis, only asystole-cross clamp period was significant predictor for development of ITBS (P = 0.015) and development of overall biliary complications (P = 0.029). Hemodynamic changes in the agonal period did not emerge as risk factors. The results of the study raise the possibility of utilizing asystole-cross-clamp period in place of or in conjunction with donor warm ischemia time in determining viability or quality of liver grafts.