Division of Renal Diseases and Hypertension, University of Colorado Anschutz Medical Campus.
De novo donor-specific antibodies (dnDSA) have been associated with reduced graft survival. Tacrolimus (TAC)-based regimens are the most common immunosuppression used in in clinical practice today, yet an optimal therapeutic dose to prevent dnDSA has not been established. We evaluated mean TAC C0 and TAC time in therapeutic range for the risk of dnDSA in a cohort of 538 patients in the first year of kidney transplant. Read More
We developed a kidney offer acceptance decision tool to predict the probability of graft survival and patient survival for first-time kidney-alone candidates after an offer is accepted or declined, and we characterized the effect of restricting the donor pool with a maximum acceptable kidney donor profile index (KDPI). For accepted offers, Cox proportional hazards models estimated these probabilities using transplanted kidneys. For declined offers, these probabilities were estimated by considering the experience of similar candidates who declined offers and the probability that declining would lead to these outcomes. Read More
Tufts University School of Medicine, Department of Integrative Physiology Boston, MA, 02111, USA.
Calcineurin inhibitors induce nephrotoxicity through poorly understood mechanisms thereby limiting their use in transplantation and other diseases. Here we define a microRNA (miRNA)-messenger RNA (mRNA) interaction map that facilitates exploration into the role of miRNAs in cyclosporine-induced nephrotoxicity (CIN) and the gene pathways they regulate. Using photoactivatable ribonucleoside-enhanced crosslinking and immunoprecipitation (PAR-CLIP), we isolated RNAs associated with Argonaute 2 in the RNA-Induced Silencing Complex (RISC) of cyclosporine A (CsA) treated and control human proximal tubule cells and identified mRNAs undergoing active targeting by miRNAs. Read More
Cancer remains one of the most serious long-term complications after liver transplantation (LT). Data for all adult LT patients between 1982 and 2013 was extracted from the Nordic Liver Transplant Registry. Through linkage with respective national cancer-registry data, we calculated standardized incidence ratios (SIRs) based on country, sex, calendar time, and age-specific incidence rates. Read More
University of Louisville, Cardiovasular and Thoracic Surgery 201 Abraham Flexner Way Suite 1200, Louisville, KY.
While many aspects of medical care are learning how to cope with the sudden proliferation of publicly reported quality metrics, the transplant community has been interpreting this type of data for over thirty years. Under the National Organ Transplantation Act of 1984, transplant centers are required to report their candidate and recipient information to the Organ Procurement and Transplantation Network (OPTN), and that data is then analyzed by the Scientific Registry of Transplant Recipients (SRTR), with outcomes reported on a twice yearly basis on a public website (www.srtr. Read More
Healthcare reimbursement is increasingly tied to value instead of volume, with special attention paid to resource-intensive populations such as patients with renal disease. To this end, Medicare has sponsored pilot projects to encourage providers to develop care coordination and population health management strategies to provide quality care while reducing resource utilization. In this Personal Viewpoint essay, we argue in favor of expanding one such pilot project-the Comprehensive ESRD Care (CEC) initiative-to include patients with advanced chronic kidney disease and kidney transplant recipients. Read More
HCV infection is associated with reduced patient survival following combined liver-kidney transplantation (LKT). The aim of this study was to assess the efficacy and safety of second generation direct active antiviral (DAAs) in this difficult-to-treat population. The ANRS CO23 CUPILT study is a prospective cohort including transplant recipients with recurrent HCV treated with DAAs. Read More
While trimethoprim-sulfamethoxazole is considered first-line therapy for Pneumocystis pneumonia prevention in renal transplant recipients, reported adverse drug reactions may limit use and increase reliance on costly and less effective alternatives, often aerosolized pentamidine. We report our experience implementing a protocolized approach to trimethoprim-sulfamethoxazole adverse drug reaction assessment and rechallenge to optimize prophylaxis in this patient cohort. We retrospectively reviewed 119 patients receiving Pneumocystis pneumonia prophylaxis prior to and after protocol implementation. Read More
This study was performed to determine if organ selection practices for heart utilization by Region 9 transplant programs were optimal, and to identify opportunities to increase local organ recovery. A retrospective review of de-identified region-wide donor data 1/1/10-12/31/13 was performed. Over the study period 537 heart donors were identified, of which 321 (60%) were transplanted. Read More
Division of Developmental and Translational Diabetes and Endocrinology Research, Department of Diabetes and Metabolic Research, Beckman Research Institute of City of Hope, 1500 E. Duarte Rd, Duarte, CA, 91010, USA.
Subcutaneous tissue is a promising site for islet transplantation, due to its large area and accessibility, which allows minimally invasive procedures for transplantation, graft monitoring, and removal of malignancies as needed. However, relative to the conventional intrahepatic transplantation site, the subcutaneous site requires a large number of islets to achieve engraftment success and diabetes reversal, due to hypoxia and low vascularity. We report that the efficiency of subcutaneous islet transplantation in a Lewis rat model is significantly improved by treating recipients with inhaled 50% oxygen, in conjunction with prevascularization of the graft bed by agarose-bFGF. Read More
This study evaluated the independent contribution of voriconazole to the development of squamous cell carcinoma (SCC) in lung transplant recipients, by attempting to account for important confounding factors, particularly immunosuppression. This international, multicenter, retrospective, cohort study included adult patients who underwent lung transplant during 2005-2008. Cox regression analysis was used to assess the effects of voriconazole and other azoles, analyzed as time-dependent variables, on the risk of developing biopsy-confirmed SCC. Read More
Department of Emergency Medicine and Transplant Coordination, Hospital de la Santa Creu i Sant Pau. Universitat Autònoma de Barcelona, Avinguda Sant Antoni Mª Claret167, 08025, Barcelona, Spain.
We read with interest the report by Witjes et al regarding the influence of end-of-life care on organ donor potential (1). The report promotes innovation in management of potential organ donors outside the ICU, particularly in patients admitted to the emergency department (ED) with acute devastating brain injury (DBI) and imminent brain death. This article is protected by copyright. Read More
In this week's journal, Axelrod and colleagues examine costs incurred by various US centers undertaking Incompatible Live-Donor Kidney Transplantation (ILDKT) - living donor renal transplantation in the presence of preformed antibody (ies) directed against donor HLA (DSAb) . As expected, cost increased as the immunological barrier intensified (as defined by solid phase and cell based assays). While certain aspects of cost recovery are specific to US health care, effectively managing humoral allo-immunity is important to all transplant clinicians, with little progress despite nearly 2 decades of ILDKT [2, 3]. Read More
The aim of this study was to determine whether kidney transplantations performed after previous non-renal solid organ transplants are associated with worse graft survival when there are repeated HLA mismatches (RMM) with the previous donor(s). We performed a retrospective cohort study using data from the Scientific Registry of Transplant Recipients. Our cohort comprised 6, 624 kidney transplantations performed between January 1(st) 1990 and January 1(st) , 2015. Read More
During the last 3 decades lung transplantation (LTx) has become a proven modality to increase both survival and health-related quality of life (HRQoL) in patients with various end-stage lung diseases. Most previous studies have reported improved HRQoL shortly after LTx. With regard to long-term effects on HRQoL, however, the evidence is less solid. Read More
Biliary atresia (BA) is the most common indication for liver transplantation (LT) in pediatric population. This study analyzed the comprehensive factors that might influence the outcomes of patients with BA who undergo living donor LT by evaluating the largest cohort with the longest follow-up in the world. Between November 1989 and December 2015, 2,085 BA patients underwent LDLT in Japan. Read More
Multi Organ Transplant Program, Department of Surgery, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada.
Normothermic ex vivo kidney perfusion (NEVKP) represents a novel approach for graft preservation and functional improvement in kidney transplantation. We investigated whether NEVKP also allows graft quality assessment prior to transplantation. Kidneys from 30kg pigs were recovered in a model of heart-beating donation (HBD) (group A), following 30min of warm ischemia (WI) (group B), or 60min WI (group C) (n=5/group). Read More
Lung transplantation represents a highly successful therapy for patients with end-stage lung diseases. Nevertheless, compared with other types of solid-organ transplants, the survival rate of lung transplantation is one of the lowest: 50% of patients will lose their graft 5 years after transplantation. A technically challenging mouse model of orthotopic lung transplant has been helpful in unveiling the singularity of the immune response during the course of a lung transplant(1) . Read More
Despite advances in treatment for end stage liver disease (ESLD), death from cirrhosis and chronic liver disease remains a major source of morbidity and mortality, particularly in younger patients. The National Center for Health Statistics estimates that the years of life lost prior to age 75 due to ESLD has increased from 164.1 per 100,000 in 2000 to 190. Read More
University of Pittsburgh School of Medicine, Children's Hospital of Pittsburgh of UPMC Pittsburgh, PA.
We read with interest the meeting report by Levitsky et al.(1) , detailing the American Society of Transplantation consensus conference on the use of hepatitis C (HCV) viremic donors. We commend the authors of the meeting report for their excellent discussion of HCV risk, and their caution regarding the research frameworks to be used moving forward. Read More
Department of Internal Medicine, section Nephrology and Transplantation, Erasmus MC, University Medical Center, Rotterdam, the Netherlands.
Proinflammatory, cytotoxic CD4(+) CD28(null) T cells can be substantially expanded in patients with end-stage renal disease. These cells have been associated with the risk for rejection, but their alloreactive potential is unknown. CD4(+) CD28(null) T cells were stimulated with HLA-mismatched antigen presenting cells in the absence/presence of exogenous cytokines. Read More
In this edition of AJT, Sawinski et al examine the impact of combined antiretroviral therapy (cART) on kidney transplant outcomes performed in HIV infected recipients using the Scientific Registry of Transplant Recipients (SRTR) linked to IMS pharmacy refills (1). They found that the use of cART regimens based on protease inhibitors (PI) had a marked detrimental impact on patient and graft survival. The etiology of the surprisingly poorer results in HIV positive recipients on PI based regimens could not be ascertained based on their analysis. Read More
The intestinal tract is inhabited by a large and diverse community of bacteria collectively referred to as the gut microbiota. The intestinal microbiota is composed by 500-1000 distinct species, and alterations in its composition are associated with a variety of diseases including obesity, diabetes, and inflammatory bowel disease (IBD). Importantly, microbiota transplantation from diseased patients or mice (IBD, metabolic syndrome, etc. Read More
Annette C. and Harold C. Simmons Transplant Institute, Baylor University Medical Center, Dallas, TX, USA.
Uterus transplantation has proven successful when performed with a living donor. Subsequently, interest in the novel field of reproductive transplantation is growing. The procedure is still considered experimental, with fewer than 25 cases performed worldwide, and the techniques of both uterus procurement and transplantation are still developing. Read More
We read with interest the response by Martini et al to our consensus conference and recommendations on the use of hepatitis C viremic organs in negative recipients (1,2). Their case report is certainly provocative in considering fibrotic viremic donors, given the ability to eradicate HCV early and prevent further damage to a more injured graft. As we mentioned in our report, we should see an increase number of HCV-infected baby boomers within the next decade who have more likelihood of hepatic fibrosis compared to the younger, drug-injecting population (3). Read More
30% of kidney transplant recipients are readmitted in the first month post-transplant. Those with donor-specific antibody requiring desensitization and incompatible live donor kidney transplantation (ILDKT) constitute a unique subpopulation that might be at higher readmission risk. Drawing on a 22-center cohort, 379 ILDKTs with Medicare primary insurance were matched to compatible transplant matched controls and to waitlist-only matched controls on panel reactive antibody, age, blood group, renal replacement time, prior kidney transplantation, race, gender, diabetes, and transplant date/waitlisting date. Read More
Morbid obesity is a barrier to kidney transplantation due to inferior outcomes, including higher rates of new-onset diabetes after transplantation (NODAT), delayed graft function (DGF), and graft failure. Laparoscopic sleeve gastrectomy (LSG) increases transplant eligibility by reducing BMI in kidney transplant candidates, but the effect of surgical weight loss on posttransplantation outcomes is unknown. Reviewing single-center medical records, we identified all patients who underwent LSG before kidney transplantation from 2011-2016 (n = 20). Read More
It has already been shown that neutralization of the activating NK cell receptor NKG2D in combination with co-stimulation blockade prolongs graft survival of vascularized transplants. In order to clarify the underlying cellular mechanisms, we transplanted complete MHC-disparate BALB/c-derived cardiac grafts into C57BL/6 wildtypes or mice deficient for NKG2D (Klrk1(-/-) ). Although median survival was 8 days for both recipient groups, we detected already at day 5 posttransplantation significantly greater intragraft frequencies of NKp46(+) NK cells in Klrk1(-/-) recipients than in wildtypes. Read More
Kidney Allocation System (KAS) was enacted in 2014 to improve graft utility, while facilitating transplantation of highly-sensitized patients and preserving pediatric access to high-quality kidneys. Central to this system is the Kidney Donor Profile Index (KDPI), a metric intended to predict transplant outcomes based on donor characteristics but derived using only adult donors. We posited that KAS had inadvertently altered the profile and quantity of kidneys made available to pediatric recipients. Read More
There is limited information about the role of protocol kidney biopsies for de novo donor specific antibodies (dnDSA) in kidney transplant recipients, especially in those with stable graft function. We initiated a routine post-transplant DSA monitoring and surveillance biopsy program for dnDSA since 2014. We identified 45 kidney transplant recipients with dnDSA detected between January 2014 and February 2017 that underwent kidney biopsy within 60 days of detection of dnDSA. Read More
Primary central nervous system lymphoma (PCNSL) risk is greatly increased in immunosuppressed human immunodeficiency virus-infected people. Using data from the US transplant registry linked with 17 cancer registries (1987-2014), we studied PCNSL and systemic non-Hodgkin lymphoma (NHL) in 288 029 solid organ transplant recipients. Transplant recipients had elevated incidence for PCNSL compared with the general population (standardized incidence ratio = 65. Read More
While donation after circulatory death (DCD) has expanded options for organ donation, many who wish to donate are still unable to do so. We conducted face-to-face interviews with family members (N = 15) who had direct experience with unsuccessful DCD and 5 focus groups with professionals involved in the donation process. We used qualitative content analysis to characterize the harms of nondonation as perceived by participants. Read More
Hemodynamic instability is generally considered as a contraindication to liver splitting, in particular when using an in-situ technique. We describe the cases of two young donors with brain death in whom refractory cardiac arrest and hemodynamic instability were supported by veno-arterial extracorporeal membrane oxygenation (VA-ECMO), allowing uneventful in situ splitting. Two adult and two pediatric liver recipients were successfully transplanted with immediate graft function. Read More
To assess whether biopsy-guided selection of kidneys from very old brain-dead donors enables more successful transplantations, the authors of this multicenter, observational study compared graft survival between 37 recipients of 1 or 2 histologically evaluated kidneys from donors older than 80 years and 198 reference-recipients of non-histologically evaluated single grafts from donors aged 60 years and younger (transplantation period: 2006-2013 at 3 Italian centers). During a median (interquartile range) of 25 (13-42) months, 2 recipients (5.4%) and 10 reference-recipients (5. Read More
Although laparoscopic donor hepatectomy is increasingly common, few centers with substantial experience have reported the results of pure laparoscopic donor right hepatectomy (PLDRH). Here, we report the experiences of 60 consecutive liver donors undergoing pure laparoscopic donor hepatectomy (PLDH), with most undergoing right hepatectomy. None of the 60 donors who underwent PLDH had intraoperative complications and none required transfusions, reoperation, or conversion to open hepatectomy. Read More
A symptom-limited incremental cycle ergometer test was performed in 17 young adult patients treated with hematopoietic cell transplantation and total body irradiation for hematologic malignancies during childhood. These 17 young adult patients were compared with 17 sex- and age-matched healthy control subjects. Assessments of pulmonary function, cardiac function, body composition, and levels of growth hormone were made. Read More
Pulmonary infection is a common complication after lung transplantation, and early detection is crucial for outcome. However, the condition can be clinically difficult to diagnose and to distinguish from rejection. The aim of this prospective study was to evaluate heparin-binding protein (HBP), lysozyme, and the cytokines interleukin (IL)-1β, IL-6, IL-8, IL-10 and tumor necrosis factor (TNF) in bronchoalveolar lavage fluid (BALF) as potential biomarkers for pulmonary infection in lung-transplanted patients. Read More