In 2018, the orthotopic heart transplant (OHT) allocation policy in the United States (US) changed to prioritize more critically ill candidates including those supported with temporary mechanical circulatory support (tMCS). This study evaluated changes in post-transplant bloodstream infection (BSI) rates following the OHT allocation change. We conducted a retrospective cohort study of OHT recipients at two large US transplant centers from 1/1/2015-12/31/2022. Recipients were followed 90 days post-OHT for BSI. The association between policy era and BSI was evaluated using multivariable Cox regression with mediation analysis to explore the effect of tMCS. There were 895 OHT recipients with a >2.5-fold increase in pre-transplant tMCS after the policy change. 95 recipients developed BSIs (10.6%). OHT in the post-policy era was associated with a 2.3-fold increased hazards of BSI (P=0.002). Mediation analysis showed tMCS explained some, but not all of the increased BSI risk post-change. One-year mortality and graft failure were similar across the two policy eras, although there was a significant decrease in one-year rejection following the change (P<0.001). Overall, post-OHT BSI risk doubled following the allocation change, which is not fully explained by tMCS. Additional studies are needed to further investigate factors contributing to BSI risk.

The prevalence of type 2 diabetes mellitus (T2DM) amongst patients with kidney failure is nearly 40%. The therapeutic paradigm for the management of T2DM in the setting of chronic kidney disease (CKD) has undergone a dramatic evolution in recent years. Progressive CKD decreases the need for exogenous insulin allowing non-insulin treatments to be more effective in controlling serum glucose levels. Although diet, exercise, weight loss, and behavioral therapy are important factors in diabetes management, several non-insulin alternatives have risen to the forefront, including glucagon-like peptide-1 receptor agonists (GLP-1RAs), sodium glucose cotransporter 2 (SGLT2) inhibitors, and dual glucose-dependent insulinotropic polypeptide (GI)/GLP-1RAs, particularly in patients with cardiovascular risk factors. Consequently, many patients with T2DM and stage 4/5 CKD previously on insulin are no longer on insulin at transplant referral and are not considered for simultaneous pancreas-kidney transplantation (SPKT). Given the diabetogenic effects of calcineurin inhibitors and steroids, coupled with the more rapid elimination of endogenous insulin associated with improved renal function post-transplant, many patients are denied access to SPKT even though they predictably will become insulin-requiring following kidney transplantation alone. To be, or not to be, on insulin, should no longer be the key question in the evaluation of patients with CKD and T2DM for SPKT.

The Centers for Medicare & Medicaid Services (CMS) evaluates Organ Procurement Organizations (OPOs) based on donation and transplant rates within their donation service area, but individual hospital-level characteristics may also significantly impact organ recovery. We examined how hospital-level factors influence recovery rates using 2023 data from SRTR, CMS Hospital Provider Data, and Cost Reports. A hierarchical negative binomial model with OPO random intercepts was used to evaluate hospital-level organ recovery (organs recovered/total discharges). In 2023, OPOs recovered organs for transplant at 1,776 hospitals. Compared with private hospitals, recovery rates were higher in government-owned (IRR=1.24; 95%CI=1.08-1.42) and non-profit hospitals (IRR=1.19; 95%CI=1.05-1.35). Hospitals located in the most distressed areas (IRR=1.18; 95%CI=1.03-1.35), transplant centers (IRR=1.19; 95%CI=1.05-1.33), trauma level I (IRR=2.21; 95%CI=1.98-2.47) and II (IRR=1.86; 95%CI=1.69-2.05) centers had higher rates. Higher patient experience/trust scores were associated with lower recovery rates (IRR=0.89; 95%CI=0.85-0.93), while mortality/acuity was positively associated (IRR=1.15; 95%CI=1.10-1.21). Recovery rates were higher for hospitals linked to OPOs with transfer models (IRR=1.37; 95%CI=1.06-1.78) or freestanding donor care units (IRR=1.17; 95%CI=1.02-1.34). Interventions at specific donor hospitals may significantly improve organ recovery rates, and prospective OPO performance measures may need to account for hospital-level factors, recognizing their substantial influence on the organ donation process.

Norovirus (NoV) may cause or contribute to chronic diarrhea among immunocompromised hosts. Neither vaccines nor antiviral therapies are available to prevent or treat NoV. We conducted an NIH-sponsored multi-center, prospective, randomized, double-blind study of nitazoxanide for the treatment of NoV infected adult transplant patients between 2018 and 2021. Subjects with a positive stool NoV PCR within 14 days of enrollment and active gastrointestinal symptoms were randomly assigned (1:1) to nitazoxanide or placebo for 56 consecutive doses and followed for 6 months. Primary endpoint was time to symptom resolution. Secondary endpoints included virologic efficacy and frequency of adverse events. 31 subjects (16 nitazoxanide,15 placebo) were enrolled. Most had chronic (≥14 days) symptoms (77%) and were solid organ transplant recipients (30/31). In the intention-to-treat population, the median time to symptom resolution was 19.0 days (95% CI: 1.0, 31.0) versus 11.0 days (95% CI: 2.0, 14.0) for the nitazoxanide and placebo groups respectively (p=0.459). Time to first negative stool NoV PCR was not significantly different between treatment arms (p=0.873). There were no serious adverse events related to nitazoxanide. Nitazoxanide did not shorten time to symptom resolution or viral shedding. Although safe, nitazoxanide likely contributes little to the management of chronic NoV. ClinicalTrials.gov: NCT03395405 (registration date 2018-01-04).

Frailty has emerged as a powerful risk stratification tool in kidney transplantation. Frail kidney transplant candidates are significantly more likely to experience post-transplant complications, including delayed graft function, rehospitalizations, and death. While the transplant community's understanding of the relationship between frailty and clinical variables has exploded over the past several decades, our understanding of patient perspectives regarding frailty lags behind. Lack of knowledge regarding patient perspectives regarding frailty can limit the successful integration of clinical research findings into clinical practice. In this viewpoint, we summarize data regarding patient perspectives regarding frailty and suggest how to better incorporate patients' viewpoints regarding frailty into kidney transplant care and research.

Cytomegalovirus (CMV) remains a major contributor to morbidity after kidney transplant. Although valganciclovir (VGC) prophylaxis is effective, its use is limited by leukopenia. Maribavir's (MAR) role in primary CMV prophylaxis is not established. We conducted a 12-month, single-center, open-label, randomized controlled trial including 70 adult recipients at high CMV risk randomized 1:1 to MAR 400 mg twice daily or VGC 900 mg daily. The incidence of clinically significant leukopenia during prophylaxis did not differ between arms (22.9% vs 5.7%, p=0.084). For the secondary endpoint, VGC recipients did spent a greater proportion of prophylaxis days below WBC thresholds (<3,000/μL: 12.2% vs 2.4%, p<0.001; <2,000/μL: 3.0% vs 0.2%, p<0.001; <1,000/μL: 0.3% vs 0.1%, p=0.027). As an exploratory endpoint, CMV outcomes appeared similar between arms, including any viremia (37% vs 43%, p=0.626), PCR >1,000 IU/mL (23% vs 31%, p=0.420), and refractory infection (15% vs 17%, p=0.743). No cases of CMV breakthrough, disease, or resistance occurred. Hospitalizations, rejection, graft loss, and mortality did not differ. In summary, as compared to valganciclovir, MAR had a similar incidence of clinically significant leukopenia with reduced overall leukopenia burden. These findings should be confirmed in larger multicenter studies.

Liver transplants for acute alcohol-associated hepatitis have risen rapidly over the past decade in concert with higher demand and satisfactory patient and graft survival, yet little is known about this population's long-term renal outcomes. Using the United Network for Organ Sharing (UNOS) registry, we identified patients undergoing isolated orthotopic liver transplant for acute alcohol-associated hepatitis in the safety net kidney after liver transplant era (August 2017 to December 2023). We used entropy balancing to identify a comparative control group using patient demographics and kidney disease risk factors. Recipients with acute alcohol-associated hepatitis had both a higher relative risk of being listed for (RR 2.1 CI 1.7-2.8; 10.2% vs 4.8%) and receiving a safety net kidney after liver transplant (2.0 CI 1.6-2.8; 6.2% vs 3.2%) compared to controls. Among patients who were not listed for a kidney transplant, liver recipients with acute alcohol-associated hepatitis had lower post-transplant mean estimated glomerular filtration rates (69.0 vs 75.6, p<0.001) and were more likely to have stage 3 or 4 chronic kidney disease. It remains unclear whether these inferior renal outcomes are due to underlying pathophysiology of acute alcohol-associated hepatitis, care practices (i.e., delays in transfer to transplant center), or a combination of clinical factors.

Ischemia-reperfusion injury drives primary graft dysfunction (PGD) in lung transplantation, yet the metabolic landscape of this process remains unclear. We performed longitudinal untargeted metabolomic studies on lung grafts collected before and after reperfusion, from 39 patients with PGD grade 3 (PGD3) and 40 patients without. The expression levels and pathways of identified metabolites were analyzed and correlated with donor/recipient conditions and early clinical outcomes. Totally 443 metabolites were detected, and metabolites significantly changed following reperfusion were mapped to relevant biological pathways. Reperfusion significantly reduced lysophospholipids in the lung tissue. Metabolomic alterations in carbohydrates, fatty acids and amino acids collectively indicate mitochondrial stress. PGD3 cases showed significantly lower antioxidant levels after cold ischemia time (CIT) and elevated taurine-conjugated bile acids upon reperfusion. Enrichment analysis revealed that in CIT samples, glutathione metabolism was associated with PGD, and dipeptide pathway was associated with ventilation days. During reperfusion, bile acid metabolism demonstrated an inverse correlation with lung oxygenation function and oxidative phosphorylation was associated with ICU stay. This study establishes a metabolomic atlas in human lung transplant, linking primary graft dysfunction to mitochondrial stress. The mitochondrial and redox pathways emerged as potential therapeutic targets to protect lung grafts from reperfusion injury.

Between 2009 and 2019, drug overdose deaths were linked to ∼42% of growth in deceased organ donors in the US. Recent national data indicate a ∼27% decline in overdose mortality from 2023 to 2024, the most substantial reduction in decades. It is unclear whether this public health achievement was accompanied by unintended consequences on transplantation. Using data from the Organ Procurement and Transplantation Network, we analyzed trends in deceased donor kidney transplant (DD-KT) and deceased donor liver transplant (DD-LT) rates, as well as the active waitlist size, from January 2015 to December 2024. Overdose decedent donor (ODD) transplant rates rose until mid-2023, when they comprised nearly 1 in 5 DD-KTs and DD-LTs nationally. Thereafter, rates declined by 45.1% for DD-KTs and 37.3% for DD-LTs. We observed concurrent disruption in two long-standing national trends - the overall DD-KT rate, rising since 2015, plateaued and the active kidney transplant waitlist size, declining since 2015, expanded. These data indicate that the national overdose mortality decline coincided with a significant deceleration in kidney transplantation activity. As overdose prevention efforts continue, concerted efforts are warranted to prevent long-term impact on waitlist candidates.

Kidney retransplantation-the reuse of a previously transplanted allograft-is rare, though limited reports suggest clinical feasibility and an underrecognized opportunity within the existing donor pool. We present a novel case involving a living individual donating a previously transplanted deceased-donor kidney after early graft failure from recurrent focal segmental glomerulosclerosis (FSGS). Five days later, that kidney was transplanted into a second recipient, where it has continued to function for over eight years. This case also exposes structural barriers that limit broader adoption. The current system lacks standardized mechanisms to identify appropriate allografts for regifting. Even when identified, accurate characterization requires attributing the graft to the original donor's profile rather than the interim recipient's, while also accounting for cumulative calcineurin inhibitor exposure and the interim recipient's clinical course. Most consequentially, the interim donor in this case report met criteria for neither living nor deceased donation, leaving him unclassifiable under either existing donor framework. These findings underscore gaps in donor classification, data capture and organ allocation that constrain wider implementation of allograft reuse. Addressing these gaps represents a unique opportunity to expand the donor pool without requiring a single additional donor.

This study aimed to assess whether various pathomic features in automatically segmented glomeruli and tubules associated with death-censored graft loss in kidney transplant recipients. We studied 906 patients who were transplanted between 2000 and 2013, returned to Mayo Clinic for a 5-year surveillance biopsy, and had available subsequent follow-up. Banff scores were obtained from the pathology reports and clinical characteristics from the patients' charts. A multi-compartment segmentation model segmented non-sclerotic glomeruli and tubules and within these compartments, morphometric and textural (pathomic) features were computed. There were 70 death-censored graft losses that occurred during the 5 years of follow-up and Cox models were used to assess the risk of death-censored graft failure with all Banff scores, with two composite pathomic features (glomeruli and tubules), and with Banff scores and pathomic features combined. The composite pathomic score model had similar performance to the Banff score model (c-statistics 0.845 vs 0.823, p = 0.47). A model combining the Banff scores and pathomic scores showed the best performance (c-statistic 0.897). We conclude that multi-compartment segmentation models can identify pathomic features which can complement Banff scoring and are associated with future graft loss.