Kidney Transplantation in United States Native Americans: Breaking Barriers.

Advances in the field of solid-organ transplantation (SOT), namely evolution of surgical techniques, developments in immunosuppressive therapies and efforts to maximize utilization of donor allografts (deceased and living), have resulted in growing numbers of SOT performed annually in the United States (U.S.) (36,529 total organs and 21,167 kidneys transplanted in 2018). However, the Native American/American Indian (NA/AI) people of the U.S. experience enormous socioeconomic barriers such as poverty, lack of adequate healthcare, poor health literacy and geographic isolation which limit access to SOT resulting in low rates of organ donation and transplantation, poor quality of life and shorter life expectancy. The NA/AI population is at increased risk for end-stage renal disease secondary to the high prevalence of diabetes mellitus. We review existing challenges to kidney transplantation in NA/AI patients and discuss potential solutions which could improve equitable delivery of specialized healthcare to this underprivileged population.

High-dose hydroxocobalamin in end-stage liver disease and liver transplantation.

Distributive shock is a serious complication in patients with chronic or end-stage liver disease, and can be exacerbated by vasoplegia in this patient population. Vasoplegic syndrome (VS) is a state of shock refractory to catecholamines and vasopressin that is often multifactorial in liver failure patients, and can occur in any phase of liver transplantation (LT) [i.e., pre-transplantation, intraoperative, and post-transplantation]. Methylene blue (MB) has been a well-established pharmacologic therapy for VS. However, it has been known to cause dose-related toxicity. Hydroxocobalamin (HXC) is not currently FDA approved for the management of VS, but studies have demonstrated its ability to cause an increase in systolic blood pressure by hypothesized mechanisms with only minimal side effects. To date, only three other reports have demonstrated the use of HXC in LT patients, which highlighted its use both intraoperatively and post-transplantation. Our report illustrates the utility of HXC in four LT patients with VS. Two of these cases illustrate the usefulness of HXC in the pre-transplantation period, which has never been previously reported. HXC is a useful pharmaceutical agent in the management of VS, especially if contraindications to MB exist or in cases of MB-resistant vasoplegia. Further studies with large sample sizes are necessary to ascertain the optimal dosage of HXC in LT patients.

Factors associated with chronic hepatitis in patients with hepatitis E virus infection who have received solid organ transplants.

BACKGROUND & AIMS: Hepatitis E virus (HEV) infection can cause chronic hepatitis in recipients of solid organ transplants. However, the factors that contribute to chronic infection and the outcomes of these patients are incompletely understood. We performed a retrospective analysis of data from 17 centers from Europe and the United States that described the progression, outcomes, and factors associated with development of chronic HEV infection in recipients of transplanted solid organs. METHODS: We studied data from 85 recipients of solid organ transplants who were infected with HEV. Chronic HEV infection was defined by the persistent increases in levels of liver enzymes and polymerase chain reaction evidence of HEV in the serum and/or stool for at least 6 months. RESULTS: Fifty-six patients (65.9%) developed chronic hepatitis. Univariate analysis associated liver transplant, shorter times since transplant, lower levels of liver enzymes and serum creatinine, lower platelet counts, and tacrolimus-based immunosuppressive therapy (rather than cyclosporin A) with chronic hepatitis. On multivariate analysis, the independent predictive factors associated with chronic HEV infection were the use of tacrolimus rather than cyclosporin A (odds ratio [OR], 1.87; 95% confidence interval [CI], 1.49-1.97; P = .004) and a low platelet count at the time of diagnosis with HEV infection (OR, 1.02; 95% CI, 1.001-1.1; P = .04). Of patients with chronic hepatitis, 18 (32.1%) achieved viral clearance after the dose of immunosuppressive therapy was reduced. No HEV reactivation was observed after HEV clearance. CONCLUSIONS: HEV infection causes chronic hepatitis in more than 60% of recipients of solid organ transplants. Tacrolimus therapy is the main predictive factor for chronic hepatitis. Dose reductions of immunosuppressive therapy resulted in viral clearance in more than 30% of patients.

Kidney Transplant Outcomes in Indigenous People of the Northern Great Plains of the United States.

BACKGROUND: Indigenous people experience higher rates of end-stage renal disease as well as negative predictive factors that undermine kidney transplantation (KT) success. Despite these inequalities, data suggest that short-term outcomes are comparable to those of other groups, but few studies have examined this effect in the Northern Great Plains (NGP) region. METHODS: We performed a retrospective database review to determine outcomes of KT in Indigenous people of the NGP. White and Indigenous people receiving a KT between 2000 and 2018 at a single center were examined. RESULTS: A total of 622 KT recipients were included (117 Indigenous and 505 White). Indigenous patients were more likely to smoke, have diabetes, have higher immunologic risk, receive fewer living donor kidneys, and have longer waitlist times. In the 5 years after KT there were no significant differences in renal function, rejection events, cancer, graft failure, or patient survival. At 10 years posttransplant, Indigenous patients had twice the all-cause graft failure (odds ratio = 2.06; 95% confidence interval, 1.25-3.39) and half the survival rate (odds ratio = 0.47; 95% confidence interval, 0.29-0.76); however, this effect was not maintained once the effects of race, sex, smoking status, diabetes, preemptive transplant, high panel reactive antibody status, and transplant type were adjusted for. CONCLUSIONS: KT outcomes in Indigenous patients in the NGP region are similar to those of White patients 5 years posttransplant, with differences emerging at 10 years that could be diminished with greater emphasis on correcting modifiable risk factors.

Kidney Transplantation in Native Americans: Time to Explore, Expel Disparity.

Native Americans/American Indians (NA/AI) are perhaps the most disadvantaged population in the United States due to poverty, geographic isolation, and poor health care. The prevalence of diabetes mellitus and end-stage renal disease in NA/AI is higher compared with other racial/ethnic groups. Thus, a higher rate of kidney transplantation (KT) candidacy evaluation, wait-listing, and actual transplantation would be expected among NA/AI. However, KT is an underutilized life-saving therapy in this population. Half of the 20 poorest counties in the U.S. are within NA/AI reservations. Native Americans/American Indians residing on reservations are often isolated hundreds of miles from the nearest transplant center. Additionally, factors such as poor health literacy, distrust, and substance abuse contribute to low KT rates. However, collaboration between transplant centers and Indian Health Services, use of telemedicine, constructing socioculturally-competent educational strategies, and maintaining confidence-building measures to bridge the gap, create trust, and maintain patient autonomy could improve outcomes in this population.

Early Cardiopulmonary Cryptococcus neoformans Infection After Liver Transplant: A Case Report.

Cryptococcal infection (CI) is an uncommon fungal disease that poses a particular fatal risk to liver transplant (LT) recipients because of the potential rapid development and dissemination of the disease. Depending on the pathophysiology, CI may manifest with a wide range of clinical presentations that may delay early diagnosis and timely treatment. Additionally, most anticryptococcal therapies may threaten LT recipients owing to the associated hepatotoxicity of these medications. We report a case of a 25-year-old woman who received an LT for cryptogenic cirrhosis and developed rapidly progressive CI with pulmonary, myocardial, and cerebral involvement within a month of transplantation. She presented with severe pulmonary hypertension refractory to medical management and subsequently died despite our efforts. Herein, we review the etiology of cryptococcosis, the natural history of cryptococcal disease, and standard treatments for CI, and we highlight peculiarities of Cryptococcus neoformans infection in solid organ transplant recipients.

Histoplasma capsulatum presenting as generalized lymphadenopathy after renal transplantation.

Histoplasma capsulatum is typically an indolent disease among immunocompetent patients. However, immunocompromised patients, such as solid organ transplant recipients, are at risk of developing severe histoplasmosis. Yet post-transplant histoplasmosis is a rare pathology, representing less than five percent of invasive fungal infections among transplant recipients. Furthermore, patients tend to present with nonspecific clinical symptoms, complicating timely diagnosis and delaying treatment. Disease features that may be more representative of H. capsulatum infection, such as anemia, leukopenia and pulmonary involvement are often not present until late in the disease course, when the patient is at greater risk of decompensation. Unlike H. capsulatum infections among immunocompetent hosts, extrapulmonary infection among immunocompromised hosts is more the rule than the exception. Treatment with liposomal amphotericin B followed by oral itraconazole is the standard therapy, but special considerations must be made for patients with hepatic and/or renal insufficiency, underlying cardiac abnormalities or malabsorptive pathologies and doses of immunosuppressants will need to be adjusted for drug interactions. Herein we present a case of H. capsulatum infection presenting with generalized lymphadenopathy post-renal transplant.

Utility of fiber-optic bronchoscopy in pulmonary infections among abdominal solid-organ transplant patients: A comprehensive review.

Pulmonary infections are frequent complications in abdominal solid-organ transplantation (aSOT) which may threaten patient and allograft survival. Accurate diagnosis and treatment of pulmonary infections in this population can be challenging. Immunosuppressive therapy not only increases the risk of acquiring opportunistic and non-opportunistic infections, but it also impairs the inflammatory responses associated with microbial invasion which in an otherwise normal host produce clinical and radiologic responses that allow for early identification of the offending pathogen. Serologic testing is not a reliable diagnostic modality. Direct microbiological sampling is often necessary to make a definitive diagnosis early in the clinical course to optimize timely, targeted therapy while reducing the risk of developing antimicrobial resistance, and minimize adverse effects of therapy, if any. Fiber-optic bronchoscopy (FOB) with bronchoalveolar lavage (BAL) or transbronchial lung biopsy (TBB) offers such diagnostic advantage and possesses a potential therapeutic value too. This comprehensive review discusses the potential benefits of FOB alongside its risks and complications, indications and contraindications, and techniques. Additionally, the essay highlights FOB's utility and yield specifically with regard to type and timing of infections in aSOT patients.

Transplant Critical Care: Is there a Need for Sub-specialized Units? - A Perspective.

The critical care involved in solid-organ transplantation (SOT) is complex. Pre-, intra- and post-transplant care can significantly impact both - patients' ability to undergo SOT and their peri-operative morbidity and mortality. Much of the care necessary for medical optimization of end-stage organ failure (ESOF) patients to qualify and then successfully undergo SOT, and the management of peri-operative and/or long-term complications thereafter occurs in an intensive care unit (ICU) setting. The current literature specific to critical care in abdominal SOT patients was reviewed. This paper provides a contemporary perspective on the potential multifactorial advantages of sub-specialized transplant critical care units in providing efficient, comprehensive, and collaborative multidisciplinary care.

Pancreas transplantation.

Over the last 15 years whole organ pancreas transplantation has emerged as the treatment of choice for selected patients with uremia and Type I Diabetes Mellitus. Improvements in surgical technique, better understanding of transplant related complications and advances in immunosuppressive therapy have encouraged the application of this procedure to an increasing number of patients. Pancreas transplantation occurs under three primary scenarios: simultaneous kidney pancreas transplantation, pancreas transplantation after kidney transplantation, and pancreas transplant alone. Overall results are excellent with 90%-95% one-year patient survival, and 85%-90% of patients achieving normal glycemic control. There also exists a significant long-term survival advantage among the simultaneous kidney pancreas transplant group.

Prevention of obesity-linked renal disease: age-dependent effects of dietary food restriction.

BACKGROUND: Hyperphagic obese Zucker rats develop glomerular injury and die of renal disease, an outcome prevented by food restriction at an early age. We examined the effects of food restriction imposed at different ages on systemic, renal hemodynamic, and hormonal changes to gain insight into the mechanisms of obesity-linked glomerular injury. METHODS: At 6 weeks of age obese Zucker rats were either fed ad libitum or were restricted in food intake at various ages (6, 12, 26, or 50 weeks) to that consumed by lean Zucker rats (14 g/day). Every four weeks 24-hour urine collections, blood pressure, and venous blood samples were obtained until the end of study (60 weeks). RESULTS: Food restriction at 6 or 12 weeks of age prevented glomerular injury and hypertrophy and delayed the development of hypertension, hypercholesterolemia, and hyperinsulinemia. Food restriction at 26 weeks of age reduced proteinuria, while restriction at 50 weeks prevented further increases in proteinuria without altering pre-existing hypercholesterolemia, hypertension, or hyperinsulinemia. Hypertriglyceridemia and glomerular hyperfiltration in the obese animals were reversed at any age by food restriction. Plasma leptin levels were elevated in all obese groups. CONCLUSIONS: (1) Early food restriction provided the greatest metabolic and renal benefits; (2) glomerular injury correlated with hyperphagia-induced hyperfiltration and hypertriglyceridemia and both were prevented by food restriction; (3) hypercholesterolemia was due to an increase in LDL and/or VLDL cholesterol; and (4) leptin does not directly contribute to glomerular injury in the obese Zucker rat.