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Background: Predicting long-term mortality postkidney transplantation (KT) using baseline clinical data presents significant challenges. This study aims to evaluate the predictive power of artificial intelligence (AI)-enabled analysis of preoperative electrocardiograms (ECGs) in forecasting long-term mortality following KT., Methods: We analyzed preoperative ECGs from KT recipients at three Mayo Clinic sites (Minnesota, Florida, and Arizona) between January 1, 2006, and July 30, 2021. The study involved 6 validated AI algorithms, each trained to predict future development of atrial fibrillation, aortic stenosis, low ejection fraction, hypertrophic cardiomyopathy, amyloid heart disease, and biological age. These algorithms' outputs based on a single preoperative ECG were correlated with patient mortality data., Results: Among 6504 KT recipients included in the study, 1764 (27.1%) died within a median follow-up of 5.7 y (interquartile range: 3.00-9.29 y). All AI-ECG algorithms were independently associated with long-term all-cause mortality ( P < 0.001). Notably, few patients had a clinical cardiac diagnosis at the time of transplant, indicating that AI-ECG scores were predictive even in asymptomatic patients. When adjusted for multiple clinical factors such as recipient age, diabetes, and pretransplant dialysis, AI algorithms for atrial fibrillation and aortic stenosis remained independently associated with long-term mortality. These algorithms also improved the C-statistic for predicting overall (C = 0.74) and cardiac-related deaths (C = 0.751)., Conclusions: The findings suggest that AI-enabled preoperative ECG analysis can be a valuable tool in predicting long-term mortality following KT and could aid in identifying patients who may benefit from enhanced cardiac monitoring because of increased risk., Competing Interests: The authors declare no funding or conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: Determine if timing of transplantation affects patient mortality., Background: Neoadjuvant therapy and liver transplantation has emerged as an excellent treatment option for select patients with perihilar cholangiocarcinoma (pCCA). However, the optimal timing of transplantation is not known., Methods: We reviewed all patients registered for a standardized pCCA protocol between 1996 - 2020 at our center. After adjusting for confounders, we examined the association of waiting time with patient mortality in an intention-to-treat cohort (n=392) and those who received a liver transplant (n=256)., Results: The median (interquartile range) time from registration to transplant or drop out was 5.74 (3.25-7.06) months. Compared to a short wait time (0-3 months), longer waiting times did not affect all-cause mortality: (3-6 months) hazard ratio (HR) 0.98; 95% CI 0.52-1.84; (6-9 months) HR 0.80; 95% CI 0.39-1.65; (9-12 months) HR 0.56; 95% CI 0.26-1.22. Subgroups with a shorter waiting time had similar survival to those with long waiting times: living donor available HR 0.97; 95% CI 0.67-1.42; AB or B blood group HR 0.93; 95% CI 0.62-1.39. Longer waiting times were associated with decreased all-cause mortality after transplantation (HR 0.92; 95% CI 0.87-0.97). This benefit began after a 6 month waiting time minimum (HR 0.53; 95% CI 0.26-1.10) and increased further after 9 months (HR; 0.43 95% CI 0.20-0.93). Waiting time was not associated with residual adenocarcinoma in the explant (odds ratio 0.99; 95% CI 0.98-1.00)., Conclusions: A waiting time of at least 6 months will optimize results with transplantation without affecting overall (intention-to-treat) patient survival., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Chronic systemic inflammation is associated with mortality in patients with chronic kidney disease, cardiovascular disease, and diabetes. The goal of this study was to examine the relationship between pretransplant inflammatory biomarkers (growth differentiation factor-15 [GDF-15], interleukin-6 [IL-6], soluble tumor necrosis factor receptor-1, monokine induced by gamma interferon/chemokine [C-X-C motif] ligand 9 [MIG/CXCL9], monocyte chemoattractant protein-1, soluble FAS, tumor necrosis factor-α, interleukin-15, and interleukin-1β) and death with function (DWF) after kidney transplantation (KT)., Methods: We retrospectively measured inflammatory biomarker levels in serum collected up to 1 y before KT (time from blood draw to KT was 130 ± 110 d) in recipients transplanted between January 2006 and December 2018. Kaplan-Meier estimation, Cox regression, and Gradient Boosting Machine modeling were used to examine the relationship between inflammatory biomarkers and DWF., Results: Our cohort consisted of 1595 KT recipients, of whom 62.9% were male and 83.2% were non-Hispanic White. Over a mean follow-up of 7.4 ± 3.9 y, 21.2% of patients (n = 338) experienced DWF. Patients with the highest quartile levels of GDF-15 (>4766 pg/mL), IL-6 (>6.11 pg/mL), and MIG/CXCL9 (> 5835 pg/mL) had increased rates of DWF, and each predicted mortality independently of the others. When adjusted for clinical factors (age, diabetes, etc), the highest quartile levels of GDF-15 and IL-6 remained independently associated with DWF. Adding inflammatory markers to a clinical Cox model improved the C-statistic for DWF from 0.727 to 0.762 using a Gradient Boosting Machine modeling approach., Conclusions: These findings suggest that pre-KT serum concentrations of GDF-15, IL-6, and MIG/CXCL9 may help to risk stratify and manage patients undergoing KT and suggests that chronic inflammation may play a role in mortality in KT recipients., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

The impact of bariatric surgery (BS) on kidney transplantation (KT) outcomes in patients with obesity remains controversial. We systematically searched MEDLINE, EMBASE, Scopus, Web of Science, and Cochrane Central Register of Controlled Trials for studies reporting outcomes of KT recipients that underwent prior BS. Common/random effects meta-analyses were performed to obtain summary ratios of the postoperative outcomes. Eighteen eligible studies involving 315 patients were identified. Sleeve gastrectomy was the most common BS type (65.7%) followed by Roux-en-Y gastric bypass (27.6%) and gastric banding (4.4%). Across studies that provided the data, the %excess weight loss from BS to KT was 62.79% (95% confidence interval [CI], 52.01-73.56; range, 46.2%-80.3%). The rates of delayed graft function and acute rejection were 16% (95% CI, 7%-28%) and 16% (95% CI, 11%-23%) in 14 and 11 studies that provided this data, respectively. The rates of wound, urinary, and vascular complications following KT were 5% (95% CI, 0%-13%),19% (95% CI, 2%-42%), and 2% (95% CI, 0%-5%), in 12, 9, and 11 studies that provided this data, respectively. Follow-up time after KT was reported in 11 studies (61.1%) and ranged from 16 mo to >5 y. Graft loss was reported in 14 studies with an average of 3% (95% CI, 1%-6%). Four studies that included a comparator group of patients with obesity who did not undergo BS before KT showed comparable outcomes between the groups. We conclude that currently there is a paucity of robust evidence to suggest that pretransplant BS has a major effect on post-KT outcomes. High-quality studies are needed to fully evaluate the impact of BS on KT outcomes., Competing Interests: The authors declare no funding or conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: At 5 and 10 y after kidney transplantation, chronic histologic changes such as arteriolar hyalinosis and mesangial expansion are common; however, determining cause is difficult. We compared surveillance biopsies in living donor kidney transplants (LDKTx) from HLA-matched siblings (termed HLA-identical [HLA-ID]) with HLA non-ID to investigate which histologic changes were likely due to alloimmune injury and which were due to nonalloimmune injury., Methods: We performed a retrospective, cohort study comparing HLA-ID sibling LDKTx (n = 175) with HLA non-ID LDKTx (n = 175; matched for age, sex, and year of transplant ±2 y) performed at a single institution from March 1999 to November 2018., Results: Baseline characteristics and maintenance immunosuppression were similar. Mortality rates were similar, but in the HLA-ID group, 10-y death-censored graft survival was higher (93.8% versus 80.9% HLA non-ID LDKTx; P < 0.001), rejection rates were lower (after 1 y 9.6% versus 27.1%; P < 0.001), and Banff inflammation scores including glomerulitis and peritubular capillaritis were lower on surveillance biopsies at 1, 5, and 10 y. In contrast, chronic Banff scores (interstitial fibrosis, arteriolar hyalinosis, mesangial expansion, etc) were similar in prevalence and severity on surveillance biopsies at 1, 5, and 10 y., Conclusions: HLA-ID LDKTx have less inflammation and less transplant glomerulopathy, but most chronic histologic changes were similar to less well-matched LDKTx. We conclude that these types of chronic changes are not associated with HLA mismatches and may be due to nonimmunologic causes (hypertension, obesity, etc), suggesting that new management approaches to prevent these lesions may be needed., Competing Interests: The authors declare no funding or conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Graft survival after kidney transplant (KTX) is often estimated by the Kaplan-Meier (KM) method censoring for competing endpoints, primarily death. This method overestimates the incidence of graft loss., Methods: In 3157 adult KTX recipients followed for a mean of 79.2 months, we compared kidney and patient survival probabilities by KM versus competing risk analysis (CRA). These methods are extended to comparing different regression methods., Results: Compared with CRA, the probabilities of death and graft loss (censored for the other outcome) were substantially higher by KM. These differences increased with increasing follow-up time. Importantly, differences in graft losses were magnified in subgroups with greater probabilities of death. Among recipients with diabetes, the probabilities of graft loss at 20 years were 57% by KM and 32% by CRA, while for non-diabetes mellitus corresponding values were 44% and 35%. Similar results are noted when comparing older versus younger recipients. Finally, we find that the Fine-Gray method assumptions are violated when using age and gender as covariates and that the alternative method of Aalen-Johansen may be more appropriate., Conclusions: CRA provides more accurate estimates of long-term graft survival and death, particularly in subgroups of recipients with higher rates of the competing event. Overestimation of risk by KM leads to both quantitative and qualitative misinterpretations of long-term KTX outcomes. When using regression analyses, care should be taken to check assumptions to guide the choice of appropriate method., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Background: We previously showed that bortezomib (BTZ) partially depletes plasma cells, yet has limited efficacy for desensitization in kidney transplant candidates when up to 16 doses is given., Methods: This study aimed to determine the safety and efficacy of 32 doses of BTZ (1.3 mg/m of body surface area) in 10 highly sensitized kidney transplant candidates with alloantibodies against their intended living donor., Results: Dose reduction was needed in 2 patients and 2 others completely discontinued therapy for adverse events. Anti-HLA antibodies mean fluorescence intensity (MFI) values were stable prior to BTZ (P = 0.96) but decreased after therapy (mean decrease of 1916 [SE, 425] MFI, P < 0.01). No patient developed a negative crossmatch against their original intended donor, and the calculated panel-reactive antibodies based on MFI of 2000, 4000, and 8000 was unchanged in all patients., Conclusions: These data suggest that 32 doses of BTZ monotherapy was not well tolerated and resulted in only a modest reduction in anti-HLA antibodies.