Evolution of Pancreas Transplantation At A Single Institution-50+ Years and 2,500 Transplants.

OBJECTIVE: To describe the evolution of pancreas transplantation, including improved outcomes and factors associated with improved outcomes over the past five decades. BACKGROUND: The world's first successful pancreas transplant was performed in December 1966 at the University of Minnesota. As new modalities for diabetes treatment mature, we must carefully assess the current state of pancreas transplantation to determine its ongoing role in patient care. METHODS: A single-center retrospective review of 2,500 pancreas transplants performed over >50 years in bivariate and multivariable models. Transplants were divided into six eras; outcomes are presented for the entire cohort and by era. RESULTS: All measures of patient and graft survival improved progressively through the six transplant eras. The overall death censored (DC) pancreas graft half-lives were >35 years for simultaneous pancreas and kidney (SPK), 7.1 years for pancreas after kidney (PAK), and 3.3 years for pancreas transplants alone (PTA). The 10-year DC pancreas graft survival rate in the most recent era was 86.9% for SPK recipients, 58.2% for PAK recipients, and 47.6% for PTA. Overall graft loss was most influenced by patient survival in SPK transplants, whereas graft loss in PAK and PTA recipients was more often due to graft failures. Predictors of improved pancreas graft survival were primary transplants, bladder drainage of exocrine secretions, younger donor age, and shorter preservation time. CONCLUSIONS: Pancreas outcomes have significantly improved over time via sequential, but overlapping, advances in surgical technique, immunosuppressive protocols, reduced preservation time, and the more recent reduction of immune-mediated graft loss.

The landscape of liver transplantation for patients with alcohol-associated liver disease in the United States.

Indications for liver transplants have expanded to include patients with alcohol-associated liver disease (ALD) over the last decade. Concurrently, the liver allocation policy was updated in February 2020 replacing the Donor Service Area with Acuity Circles (ACs). The aim is to compare the transplantation rate, waitlist outcomes, and posttransplant survival of candidates with ALD to non-ALD and assess differences in that effect after the implementation of the AC policy. Scientific Registry for Transplant Recipients data for adult candidates for liver transplant were reviewed from the post-AC era (February 4, 2020-March 1, 2022) and compared with an equivalent length of time before ACs were implemented. The adjusted transplant rates were significantly higher for those with ALD before AC, and this difference increased after AC implementation (transplant rate ratio comparing ALD to non-ALD = 1.20, 1.13, 1.61, and 1.32 for the Model for End-Stage Liver Disease categories 37-40, 33-36, 29-32, and 25-28, respectively, in the post-AC era, p < 0.05 for all). The adjusted likelihood of death/removal from the waitlist was lower for patients with ALD across all lower Model for End-Stage Liver Disease categories (adjusted subdistribution hazard ratio = 0.70, 0.81, 0.84, and 0.70 for the Model for End-Stage Liver Disease categories 25-28, 20-24, 15-19, 6-14, respectively, p < 0.05). Adjusted posttransplant survival was better for those with ALD (adjusted hazard ratio = 0.81, p < 0.05). Waiting list and posttransplant mortality tended to improve more for those with ALD since the implementation of AC but not significantly. ALD is a growing indication for liver transplantation. Although patients with ALD continue to have excellent posttransplant outcomes and lower waitlist mortality, candidates with ALD have higher adjusted transplant rates, and these differences have increased after AC implementation.

Outcomes of Primary Simultaneous Pancreas-kidney Transplants by Induction Agent in the United States.

Long-term outcome data by induction type in simultaneous pancreas-kidney (SPK) is limited. Methods: Utilizing the Scientific Registry of Transplant Recipients, we examined all primary SPK transplants between 2000 and 2020, excluding crossmatch-positive recipients. We grouped recipients according to induction regimen into 3 groups: rabbit anti-thymocyte globulin (r-ATG) (n = 5678), alemtuzumab (n = 1199), and interleukin-2 receptor antagonist (IL-2RA; n = 1593). We analyzed the 10-y recipient and composite (kidney and pancreas) graft survival using the Kaplan-Meier survival function. Cox-proportion hazard models were generated to examine the association between induction type, the 10-y recipient, and graft survival. Models were adjusted for recipient age, sex, ethnicity, HLA-mismatch, diabetes type, dialysis dependency, cold-ischemia time, local versus imported organs, panel reactive antibody, steroid maintenance, and Pancreas Donor Risk Index. Results: r-ATG was associated with the lowest 1-y kidney and pancreas rejection rates compared with other agents (P < 0.001). In the univariable analysis, induction type was not associated with recipient (log-rank P = 0.11) or graft survival (log-rank P = 0.36). In the multivariable model for the composite graft survival, alemtuzumab use was associated with 22% increased kidney or pancreas graft loss compared with r-ATG (adjusted hazard ratio, 1.22; 95% confidence interval, 1.05-1.42), whereas IL-2RA use was not a predictor of graft survival. Induction type did not influence recipient survival in the adjusted model. Conclusions: r-ATG use was associated with the lowest SPK rejection rates. Compared with r-ATG, alemtuzumab but not IL-2RA was associated with worse long-term death-censored SPK graft outcome. Our analysis supports the common use of r-ATG for induction in US primary SPK recipients.

Orchialgia After Living Donor Nephrectomy: An Underreported Entity.

Laparoscopic donor nephrectomy (LDN) offers advantages to the donor. The reported incidence of testicular pain after LDN varies in the literature ranging from 3% to 55%. Methods: A survey was sent to 322 male LDN patients who donated from February 5, 2009, to February 5, 2019. The survey assessed if the donor had testicular pain or saw an additional medical professional after donation. Results: Of the 322 surveyed, 147 (46%) responses were received. Of those who had a left nephrectomy, 39% had testicular pain; 23.8% of those patients had testicular swelling in addition. Of those who had pain, laterality of kidney donated did not impact if the patient had pain, pain onset, pain level, or pain duration. Of those who donated their right kidney, 35% had testicular pain, and 16.7% of those patients reported testicular swelling in addition. Twenty-seven symptomatic patients sought additional medical care for the testicular symptoms postdonation. Seven (25%) had hydroceles, 2 (7%) had testicular cysts, 1 had a urinary tract infection, and 16 (59%) had reassurance or no additional procedures provided. Conclusions: Our results suggest that orchialgia is not as uncommon as previously thought and may be one of the most common minor complications experienced by male donors.

Predictors of Survival After Liver Transplantation in Patients With the Highest Acuity (MELD ≥40).

OBJECTIVE: To identify factors that accurately predict 1-year survival for liver transplant recipients with a MELD score ≥40. BACKGROUND: Although transplant is beneficial for patients with the highest acuity (MELD ≥40), mortality in this group is high. Predicting which patients are likely to survive for >1 year would be medically and economically helpful. METHODS: The Scientific Registry of Transplant Recipients database was reviewed to identify adult liver transplant recipients from 2002 through 2016 with MELD score ≥40 at transplant. The relationships between 44 recipient and donor factors and 1-year patient survival were examined using random survival forests methods. Variable importance measures were used to identify the factors with the strongest influence on survival, and partial dependence plots were used to determine the dependence of survival on the target variable while adjusting for all other variables. RESULTS: We identified 5309 liver transplants that met our criteria. The overall 1-year survival of high-acuity patients improved from 69% in 2001 to 87% in 2016. The strongest predictors of death within 1 year of transplant were patient on mechanical ventilator before transplantation, prior liver transplant, older recipient age, older donor age, donation after cardiac death, and longer cold ischemia. CONCLUSIONS: Liver transplant outcomes continue to improve even for patients with high medical acuity. Applying ensemble learning methods to recipient and donor factors available before transplant can predict survival probabilities for future transplant cases. This information can be used to facilitate donor/recipient matching and to improve informed consent.

Risk Factors for Abnormal Cervical Cytology in Women Undergoing Kidney Transplant Evaluation.

OBJECTIVES: Cervical cytology screening has been successful in reducing deaths from cervical cancer. We sought to determine risk factors for abnormal Pap test results in women undergoing kidney transplant evaluation. MATERILAS AND METHODS: We retrospectively examined women undergoing kidney transplant evaluations from 2008 to 2011. Patients were stratified based on normal cytology and atypical/malignant cytology. RESULTS: Of 404 patients, 293 patients (72.5%) had normal cytologic findings, whereas 111 (27.5%) had abnormal findings. On univariate logistic regression analyses, patients who had chronic kidney disease with an autoimmune cause (odds ratio = 2.71 [95% confidence interval, 1.41-5.19]; P = .003), previous renal transplants (odds ratio = 2.64 [95% confidence interval, 1.20-5.82], P = .016), or age ≤ 50 years (odds ratio = 1.68 [95% confidence interval, 1.08-2.61], P = .022) were more likely to have abnormal findings. Patients with normal and abnormal findings had similar rates of dialysis use. On multivariate logistic regression, patients who had chronic kidney disease with autoimmune causes (odds ratio = 2.48 [95% confidence interval, 1.26-4.88]; P = .008) and who had previous renal transplants (odds ratio = 2.67 [95% confidence interval, 1.20-5.95]; P = .017) were more likely to have abnormal findings. CONCLUSIONS: Previous kidney transplant, autoimmune disease, and age ≤ 50 years were associated with abnormalities on cervical cancer screening in our female group of patients. Patients with these characteristics may benefit more from routine cervical cancer screening than other patients evaluated for kidney transplant.

The Utility of Screening Colonoscopy During Kidney Transplant Evaluation.

OBJECTIVES: Transplant centers often recommend, but not necessarily require, screening colonoscopies for people over 50 years of age in accordance with the US Preventative Services Task Force guidelines for the general population. We sought to identify risk factors affecting colonoscopy results in renal failure patients undergoing kidney transplant evaluation. MATERIALS AND METHODS: We retrospectively examined patients undergoing kidney transplant evaluation from 2009 to 2012 (n = 469 patients). Comparisons were made between colonoscopy reports categorized as normal (no finding or hyperplastic polyp) or abnormal (adenomatous polyp or carcinoma). RESULTS: Of 469 patients who met the study criteria, 303 (64.6%) had normal colonoscopies and 166 (35.4%) had abnormal colonoscopies. Logistic regression analysis showed that male sex (odds ratio = 2.09; 95% confidence interval, 1.37-3.20; P = .001) and increasing age (odds ratio = 1.04; 95% confidence interval, 1.01-1.08; P = .019) were more likely to correspond to abnormal findings. Those with dialysis vintage (length of time on dialysis) up to 3 years (odds ratio = 2.10; 95% confidence interval, 1.09-4.06; P = .027) and hypertension as the cause of renal failure (odds ratio = 1.79; 95% confidence interval, 1.05-2.87; P = .002) had more abnormal findings. No differences in length of evaluation, rate of being listed for transplant, and rate of transplant were shown. CONCLUSIONS: The overall rate of adenomatous findings on colonoscopy was higher among patients with pretransplant end-stage renal disease than in the general population, as shown in other studies. Age, sex, dialysis vintage up to 3 years, and hypertensive renal failure were associated with adenomatous polyps of the colon in this study population. Because adenomatous polyp rates are high in patients with chronic kidney disease who are undergoing transplant evaluation and colonoscopic findings do not appear to delay transplant evaluations or listing rates, screening colonoscopies should be encouraged.

Utility of mammography for chronic kidney disease patients undergoing kidney transplant evaluation.

UNLABELLED: Transplant centers typically require screening mammography (MMG) for women ≥40 during evaluation. American Cancer Society recommends starting annual MMG at 40, while USPSTF recommends biennial MMG at 50. We sought to determine the effect of age and other breast malignancy risk factors on screening MMG in the pre-transplant renal failure population undergoing transplant evaluation. METHODS: We retrospectively examined women ≥40 undergoing kidney transplant evaluation from 2006 to 2012 (n = 541). RESULTS: Patients aged 40.0-49.9 and ≥50 had similar rates of breast biopsy and breast malignancy. African Americans underwent a higher rate of biopsies (OR 2.391, 95%CI 1.111-5.019, p = 0.026), with a lower rate of biopsy in those already on dialysis at presentation (OR 0.434, 95%CI 0.212-0.888, p = 0.022). Higher breast density (>50% fibroglandular tissue) increased both rate of biopsy (OR 2.876, 95%CI 1.377-6.010, p = 0.005) and malignancy (OR 5.061, 95%CI 1.012-25.315, p = 0.048). CONCLUSIONS: As we found no independent differences in biopsy or malignancy between age groups, it is reasonable for transplant centers to use the same evaluation MMG screening policy for all women ≥40. However, as malignancy risk increased with higher breast density, a lower threshold for additional workup may be warranted in patients with dense breasts or an indeterminate lesion on MMG.

Longterm health-related quality of life after living liver donation.

There are little data on longterm outcomes, health-related quality of life (HRQoL), and issues related to living donor right hepatectomy specifically. We studied longterm HRQoL in 127 living liver donors. A donor-specific survey (DSS) was used to evaluate the living liver donor morbidity, and the 36-item short-form health survey (short-form 36 health survey, version 1 [SF-36]) was used to assess generic outcomes. The DSS was completed by 107 (84.3%) donors and the SF-36 by 62 (49%) donors. Median follow-up was 6.9 years. Of the 107 donors, 12 (11.2%) donors reported their health as better, whereas 84 (78.5%) reported their health the same as before donation. Ninety-seven (90.7%) are currently employed. The most common postdonation symptom was incisional discomfort (34%). Twenty-four donors (22.4%) self-reported depression symptoms after donation. Ninety-eight (91.6%) rated their satisfaction with the donation process ≥ 8 (scale of 1-10). Three factors-increased vitality (correlation, 0.44), decreased pain (correlation, 0.34), and a recipient who was living (correlation, 0.44)-were independently related to satisfaction with the donor experience. Vitality showed the strongest association with satisfaction with the donor experience. Mental and physical component summary scale scores for donors were statistically higher compared to the US population norm (P < 0.001). Donors reported a high satisfaction rate with the donation process, and almost all donors (n = 104, 97.2%) would donate again independent of experiencing complications. Our study suggests that over a longterm period, liver donors continue to have above average HRQoL compared to the general population.

Outcome differences between young children and adolescents undergoing kidney transplantation.

BACKGROUND/PURPOSE: Although graft loss remains the biggest challenge for all pediatric kidney transplant (KT) recipients, unique challenges exist within different age groups. We aim to evaluate the different characteristics and graft survival outcomes of young children and adolescents undergoing KT. METHODS: Children who underwent isolated KT between 2000 and 2013 at our institution were included in this retrospective analysis. Patient characteristics and outcomes were compared using student's t-test, chi-square test, Kaplan-Meier curve and Cox proportional hazards model. RESULTS: Of 73 children who underwent KT, 31 were <12 (young children), and 42 were ≥ 12 years old (adolescents). Overall patient survival was 100%. The younger group had superior 5-year (100% vs. 75.5%) and 10-year (94.4% vs. 43.8%) graft survival (p=0.008). Factors predictive of poor graft survival on multivariate analysis were older age at transplantation (HR 1.2, CI 1-1.4, p=0.047), female gender (HR 9.0, CI 1.9-43, p=0.006), and acute rejection episodes (HR 13, CI 2-90, p=0.008). The most common causes of graft loss were acute and chronic rejection episodes and immunosuppression nonadherence. CONCLUSION: Adolescents undergoing KT have inferior graft survival compared to younger children. In adjusted modeling, children with older age, female gender, and acute rejection episodes have inferior graft survival.

SLC24A5, a putative cation exchanger, affects pigmentation in zebrafish and humans.

Lighter variations of pigmentation in humans are associated with diminished number, size, and density of melanosomes, the pigmented organelles of melanocytes. Here we show that zebrafish golden mutants share these melanosomal changes and that golden encodes a putative cation exchanger slc24a5 (nckx5) that localizes to an intracellular membrane, likely the melanosome or its precursor. The human ortholog is highly similar in sequence and functional in zebrafish. The evolutionarily conserved ancestral allele of a human coding polymorphism predominates in African and East Asian populations. In contrast, the variant allele is nearly fixed in European populations, is associated with a substantial reduction in regional heterozygosity, and correlates with lighter skin pigmentation in admixed populations, suggesting a key role for the SLC24A5 gene in human pigmentation.