Impact of pancreas transplantation alone on kidney function: A multicenter clinical cohort study.

Pancreas transplantation alone (PTA) is a ß cell replacement option for selected patients with type 1 diabetes mellitus; concerns have been raised regarding deterioration in kidney function (KF) after PTA. This retrospective multicenter study assessed actual impact of transplantation and immunosuppression on KF in PTA recipients at three Transplant Centers. The primary composite endpoint 10 years after PTA was >50% eGFR decline, eGFR < 30 mL/min/1.73 m2 , and/or receiving a kidney transplant (KT). Overall, 822 PTA recipients met eligibility. Median baseline and 10-year eGFR (mL/min/1.73 m2 ) were 76.3 (58.1-100.8) and 51.3 (35.3-65.9), respectively. Primary composite endpoint occurred in 98 patients (53.5%) with 45 experiencing a >50% decrease in eGFR by 10 years post-transplant, 38 eGFR < 30 mL/min/1.73 m2 and 49 requiring KT. KF declined most significantly within 6 months post-PTA, more often in females and patients with better preserved GFR up to 5 years with 11.6% kidney failure at 10 years. Patient survival and death-censored graft survival were both 68% at 10 years with overall graft thrombosis rate 8%. KF declined initially after PTA but stabilized with further slow progression. In conclusion, prospective intervention studies are needed to test renal sparing interventions while gathering more granular data.

Bone marrow derived long-lived plasma cell phenotypes are heterogeneous and can change in culture.

Bone marrow-derived long-lived plasma cells (LLPCs) are thought to be a major source of alloantibody in sensitized transplant patients. However, studies of LLPCs have been hampered not only by the fact that they are rare and difficult to isolate and culture but also due to the lack of consensus regarding a definitive cell-surface phenotype. The goal of the current study was to determine if LLPCs have a specific, stable cell-surface phenotype. PCs were isolated from high-volume (120cc) bone marrow aspirates that were enriched first by negative selection then positive selection using anti-CD38 antibody-coated beads and purified by cell sorting. A typical isolation resulted in >100,000 PCs that were sorted into 4 populations with variable numbers of PCs: CD19+/CD138+/CD38Hi (64.1% of the PCs), CD19-/CD138+/CD38Hi (20.9%), CD19+/CD138-/CD38Hi (10.7%), and CD19-/CD138-/CD38Hi (4.3%). The purity of each subset was 96-99%. Each subset contained PCs secreting IgG and IgA. Measles- and tetanus-specific PCs (i.e. putative IgG secreting, antigen-specific LLPCs). LLPCs were identified in both the CD19+/CD138+/CD38Hi and CD19-/CD138+/CD38Hi subsets and in the smaller CD138- subsets (when pooled). Thus, all CD38Hi subsets contained LLPCs. Cultured PCs maintained viability (>50%) and function and could be retrieved for analyses. During 7 days of culture, cell surface expression changed from baseline in many PCs. For example, approximately 20% of CD19 + CD138+/CD38Hi cells (the largest PC subset) became CD19-. CFSE assays showed no division and only a small percentage of LLPCs were Ki-67 positive suggesting that the cells did not divide in culture and that the antibody detected was not from plasmablasts. We conclude that human bone marrow LLPCs have a heterogeneous expression of CD19 and CD138, which can change during cell culture. The fact that LLPCs were found in all four subsets raises the possibility that a large percentage of PCs in the bone marrow may be LLPCs.

Complications After Hand-Assisted Laparoscopic Living Donor Nephrectomy.

OBJECTIVE: To study the complications of hand-assisted laparoscopic living donor nephrectomy (HALLDN) with an emphasis on complications occurring early after hospital discharge up to 120 days after surgery. PATIENTS AND METHODS: We retrospectively categorized complications using the Clavien-Dindo classification in 3002 HALLDNs performed at 1 center from January 1, 2000, through December 31, 2019. In addition to overall summaries, modeling was used to identify correlates of complications before and after living donation. RESULTS: Of these donors, 87% were White, 59% were female, the mean age was 45 years (range, 18-77 years), 30.3% had a body mass index of at least 30, and 36.3% had previous abdominopelvic surgery. There were no deaths related to the surgery. The incidence of major complications (intraoperative complications plus Clavien-Dindo grade ≥III postoperatively) was 2.5% (n=74). The overall complication rate was 12.4% (n=371), including 15 intraoperative, 76 postoperative before discharge, and 280 after discharge to 120 days. Reoperation was required in 1.8% of patients (n=54), and all but 1 of these were incision-related problems. Seventy-six percent of all complications occurred after discharge, including 85% of the reoperations. For major complications, no risk factor was found. Risk factors for any complication included paramedian incision (hazard ratio [HR], 2.54; 95% CI, 1.49 to 4.34; P<.001); a history of abdominopelvic surgery (HR, 1.37; 95% CI, 1.07 to 1.76; P=.01), male sex (HR, 1.37; 95% CI, 1.07 to 1.76; P=.01), non-White race (HR, 1.40; 95% CI, 1.05 to 1.88; P=.02), and early era of the experience. CONCLUSION: Most major complications of HALLDN occur after discharge, suggesting that close follow-up is warranted and that the current literature may underestimate the true incidence.

Mesangial expansion at 5 years predicts death and death-censored graft loss after renal transplantation.

Death with a functioning graft and death-censored renal allograft failure remain major problems for which effective preventative protocols are lacking. The retrospective cohort study aimed to determine whether histologic changes on a 5-year surveillance kidney biopsy predict adverse outcomes after transplantation in recipients who had: both Type 2 diabetes (T2DM) and obesity (BMI ≥ 30 kg/m2 ) at the time of transplantation (T2DM/Obesity, n = 75); neither (No T2DM/No obesity, n = 78); No T2DM/Obesity (n = 41), and T2DM/No obesity (n = 47). On 5-year biopsies, moderate-to-severe mesangial expansion was more common in the T2DM/Obesity group (Banff mm score ≥2 = 49.3%; Tervaert classification MS ≥ 2b = 26.7%) compared to the other groups (p < .001 for both scores). Risk factors included older age, higher BMI, HbA1C, and triglycerides at 1-year post-transplant. Moderate-to-severe mesangial expansion correlated with death with function (HR 1.74 (1.01, 2.98), p = .045 Banff and 1.89 (1.01, 3.51) p = .045 Tervaert) and with death-censored graft loss (HR 3.2 (1.2, 8.8), p = .02 Banff and HR 3.8 (1.3, 11.5), p = .01 Tervaert) over a mean of 11.6 years of recipient follow-up post-transplant. These data suggest that mesangial expansion in recipients with T2DM and obesity may reflect systemic vascular injury and might be a novel biomarker to predict adverse outcomes post renal transplant.

Analysis of Linguistically and Culturally Tailored Initiatives in Websites of Kidney Transplant Programs in the United States Between 2013-2018.

INTRODUCTION: Minority patients constitute the majority of the kidney transplant waiting list, yet they suffer greater difficulties in listing and longer wait times to transplantation. There is a lack of information regarding targeted efforts by transplant centers to improve transplant care for minority populations. RESEARCH QUESTION: Our aim was to analyze all kidney transplant websites in the United States to identify changes over a 5-year period in the number of multilingual websites, reported culturally targeted initiatives, and center and provider diversity. DESIGN: Surveys were developed to analyze center websites of all transplant programs in the United States. Those with incomplete information about their nephrology or surgical teams were excluded, resulting in 174 (73%) sites in 2013 and 185 (76%) in 2018. Results: Few websites were available in a language other than English, 6.3% in 2013 and 9.7% in 2018 (P = 0.24). Only 3 websites (1.3%) in 2013 and 7 (3.7%) in 2018 reported any evidence of a culturally targeted initiative (P = 0.23). In 2018, 35% of centers employed a Hispanic transplant physician, 77% had a transplant physician who spoke a language other than English, and 39% had a transplant physician who spoke Spanish. DISCUSSION: Although minority patients are expected to grow in the United States, decreased access to transplantation continues to vex the transplant community. Very little progress has been made in the development of multilingual websites and culturally targeted initiatives.

Electrocardiographic alterations associated with heart transplantation. Triggers, mechanisms and meaning / Alteraciones electrocardiográficas en el paciente con trasplante cardíaco. Desencadenantes, mecanismos y su significado

Abstract Introduction: Heart rhythm disorders are associated with increased morbidity and mortality. However, triggers and implications in patients with heart transplantation are not clear. Objectives: The purpose of this research paper is to identify and explain the determinants for the onset of electrical conductivity alterations in patients with a heart transplant, as well as to describe the most common arrhythmias and their pathological implications. Materials and methods: A literature review was made in the PubMed online database for a total of 411 results. In addition, clinical practice guidelines on cardiac transplantation, cardiovascular electrophysiology and infective endocarditis were searched. Sixty articles related to the objectives of this study were chosen. Results: Surgical technique, heart denervation, sinus node trauma, graft rejection, endomyocardial biopsies and infections are the main factors that compromise organ viability and the life of transplanted patients. These factors can be observed as sinus rhythm disturbances. Conclusions: When a cardiac arrhythmia is detected, the medical team must provide a treatment that is not limited to symptomatic and sinus rhythm control. An active search of the etiology must be initiated since it may indicate an underlying pathological process.

Resumen Introducción. Las alteraciones del ritmo cardíaco están asociadas con un aumento en la morbimortalidad; sin embargo, en pacientes con trasplante cardíaco no son claros sus desencadenantes ni implicaciones. Objetivos. Realizar una búsqueda en la literatura para identificar y explicar los determinantes en la generación de alteraciones de la conducción eléctrica en pacientes con trasplante cardíaco, así como describir las principales arritmias que pueden presentarse, explicando sus implicaciones patológicas. Materiales y métodos. Se realizó una búsqueda en la base de datos PubMed que arrojó un total de 411 resultados. Además, se buscaron las guías de práctica clínica sobre trasplante cardíaco, electrofisiología cardiovascular y endocarditis infecciosa. Se eligieron 60 artículos que lograban responder a los objetivos de este estudio. Resultados. La técnica quirúrgica, la denervación cardíaca, las lesiones del nodo sinusal, el rechazo del injerto, las biopsias endomiocárdicas y las infecciones son los principales factores que comprometen la viabilidad del órgano y la vida del paciente trasplantado, manifestándose como alteraciones del ritmo sinusal. Conclusiones. Ante la detección de alguna arritmia cardíaca, el equipo médico debe proporcionar un manejo que no se limite al control sintomático y del ritmo sinusal, sino que se debe iniciar una búsqueda activa de su etiología, ya que esta puede ser la manifestación de un proceso patológico subyacente.

Basic aspects of the pathogenesis and prevention of non-melanoma skin cancer in solid organ transplant recipients: a review.

INTRODUCTION: As numbers of transplant recipients and survival rates increase, the vulnerability of this population to several malignancies also rises. Non-melanoma skin cancer (NMSC) carries the highest rates of morbidity and mortality in this population. To avoid these malignancies, it is necessary to identify particular risk factors in transplant recipients and to follow preventive protocols. METHODS: The MEDLINE and EMBASE databases were reviewed using as keywords the medical subject headings (MeSH) "transplantation", "skin neoplasm" and "prevention". The search was limited to clinical trials, randomized clinical trials and case-control studies conducted during the previous 20 years. RESULTS: The most important risk factors for the development of NMSCs in the transplant recipient population are cumulative ultraviolet radiation exposure, use of immunosuppressive agents (especially azathioprine as a photosensitizing agent) and infections by human papillomaviruses. The use of sun protection and retinoids were identified as possible protective factors. Other potential therapies, such as antioxidants, difluormethylornithine and cyclooxygenase-2 inhibitors, require further study. CONCLUSIONS: Patient risk factors for the development of NMSC should be reviewed during the transplant consultation. Individuals found to be at increased risk should undergo closer follow-up and preventive care counseling. This article proposes an algorithm for the prevention of NMSC.