Use of organs from donors testing positive for hepatitis B virus (HBV) may safely expand the donor pool. The American Society of Transplantation convened a multidisciplinary expert panel that reviewed the existing literature and developed consensus recommendations for recipient management following the use of organs from HBV positive donors. Transmission risk is highest with liver donors and significantly lower with non‐liver (kidney and thoracic) donors. Antiviral prophylaxis significantly reduces the rate of transmission to liver recipients from isolated HBV core antibody positive (anti‐HBc+) donors. Organs from anti‐HBc+ donors should be considered for all adult transplant candidates after an individualized assessment of the risks and benefits and appropriate patient consent. Indefinite antiviral prophylaxis is recommended in liver recipients with no immunity or vaccine immunity but not in liver recipients with natural immunity. Antiviral prophylaxis may be considered for up to 1 year in susceptible non‐liver recipients but is not recommended in immune non‐liver recipients. Although no longer the treatment of choice in patients with chronic HBV, lamivudine remains the most cost‐effective choice for prophylaxis in this setting. Hepatitis B immunoglobulin is not recommended.
Advances in maintenance immunosuppression over the past three decades have improved solid organ transplantation outcomes dramatically. Uninterrupted access to immunosuppression is paramount to minimize rejection and maintain allograft and patient survival. There is no standardized approach to maintenance immunosuppression management. Agents used vary based on transplanted organ, center‐specific protocol, provider expertise, insurance formularies, ability to cover co‐pays, recipient characteristics and tolerability. Published data reflects this heterogeneity. Despite this limitation, maintenance immunosuppression usage cross pollinates between organ groups with standard of care agents often being used off‐label, making medication access a challenge for many transplant recipients. A multidisciplinary panel of American transplant clinicians was formed to review published literature on maintenance immunosuppression with the goal to formulate consensus recommendations for their use in specific organ groups. These consensus recommendations are intended to provide transplant clinicians with a summary of literature on maintenance immunosuppression in the modern era and to support transplant team members working to secure medication access for patients.
Background
The outcome of HIV-infected kidney transplant recipients managed with an early corticosteroid withdrawal protocol is not known.
Methods
Eleven consecutive HIV-infected patients with undetectable plasma HIV RNA and >200/mm3 CD4+ T-cells underwent deceased (n=8) or living donor (n=3) kidney transplantation at our center. All were managed with an early corticosteroid withdrawal protocol; 9 of 11 received anti-thymocyte globulin and 2 received basiliximab induction. We analyzed patient and graft outcomes, acute rejection (AR) rate, HIV progression, BKV replication, infections and urinary cell mRNA profiles.
Results
The median follow-up was 44.5 months (range: 26-73). The incidence of AR was 9% at one year and patient and allograft survival rates were 100% and 91%, respectively. Estimated glomerular filtration rate at one year (mean ± SD) was 78±39 ml/min/1.73m2. Plasma HIV RNA was undetectable at 24 months and none had BKV replication. Six of the 11 kidney recipients developed eight infections requiring hospitalization. Urinary cell levels of mRNA for complement components and complement regulatory proteins, cell lineage specific proteins CD3, CD4, CD8, CTLA4, Foxp3, chemokine IP-10, cytotoxic perforin and granzyme B and BKV–VP1 mRNA were not different (P>0.05) between HIV-infected patients and HIV-negative recipients (n=22) with stable graft function and normal biopsy results.
Conclusion
An early steroid withdrawal regimen with anti-thymocyte globulin induction was associated with excellent graft and patient outcomes in HIV-infected recipients of kidney allografts. Their urinary cell mRNA profiles are indistinguishable from those of HIV negative patients with stable graft function and normal biopsy results.
Surgical stress, corticosteroids, and mycophenolate may contribute to gastrointestinal ulcers/bleeding after kidney transplantation. Prophylactic acid suppression with H2RAs or PPIs is often utilized after transplantation, although unclear if truly indicated after early corticosteroid withdrawal (CSWD). PPIs have been associated with increased risks of Clostridium difficile infection (CDI), pneumonia, and acute rejection. This retrospective cohort study investigated benefits and risks of prolonged PPI use following kidney transplantation and included 286 kidney recipients undergoing CSWD within five d of transplant who were maintained on tacrolimus and mycophenolate mofetil/sodium. Patients on PPI before transplant, H2RA before/after transplant, and/or those with pre-transplant GI complications were excluded. A total of 171 patients received PPI>30 d, mean duration 287 ± 120 d (PPI group); 115 patients were not maintained on acid suppression (No-PPI group). GI ulceration and bleeding events were rare in PPI group (1.2% and 2.3%, respectively) and not observed in No-PPI group (p = NS). The incidence of infectious or hematological complications was not significantly different between groups. The PPI group experienced more biopsy-proven acute rejection (9.4% vs. 2.6%, p = 0.03). No direct benefit was observed with PPI in reducing the incidence of GI ulcers and bleeding events in kidney transplant recipients undergoing early CSWD. Further studies are needed to investigate the association of PPI and acute rejection.
Immunosuppression management after lung transplantation continues to evolve, with an increasing number of agents available for use in various combinations allowing for more choice and individualization of immunosuppressive therapy. Therapeutic developments have led to improved outcomes including lower acute rejection rates and improved survival. However, a one size fits all approach for any immunosuppressive strategy may not be best suited to the individual patient and ultimately patient specific factors must be considered when designing the immunosuppressive regimen. Recipient factors including age, race, co-morbidities, immunologic risk, genetic polymorphisms, concomitant and previous pharmacotherapy, and overall immunosuppression burden should be considered. There are several significant drug-drug interactions with select immunosuppressive agents utilized in lung transplant pharmacotherapy that must be considered when choosing and devising a dosing strategy for an individual immunosuppressive agent. Herein, considerations for immunosuppression management in the individual patient will be reviewed.
Advances in maintenance immunosuppression over the past three decades have improved solid organ transplantation outcomes dramatically. Uninterrupted access to immunosuppression is paramount to minimize rejection and maintain allograft and patient survival. Agents used vary based on transplanted organ, center-specific protocol, provider expertise, insurance formularies, ability to cover co-pays, recipient characteristics and tolerability. Published data reflects this heterogeneity. Despite these obstacles, the information about maintenance immunosuppression use cross pollinates between organ groups with standard of care agents often being used offlabel, making medication access a challenge for many transplant recipients. A multidisciplinary panel of American transplant clinicians was formed to review published literature on maintenance immunosuppression with the goal to formulate consensus
Transplantation provides the best outcomes and quality of life for people with end-stage renal disease and therefore offers the optimum treatment of choice. Preemptive living donor (LD) transplantation is an increasingly preferable alternative to dialysis as transplantation outcomes indicate lower morbidity and mortality rates and greater graft and patient survival rates compared to those who are transplanted after dialysis has commenced. Despite nursing and medical teams giving information to patients regarding transplantation and living donation, the number of people coming forward for preemptive transplant work-up remained limited. Changing the format, environment, and quality of information given to patients and families seemed necessary in order to increase the number of preemptive transplants. Our data show that we have improved the access to the information seminars with attendance rising from 5 to 15 attendees per seminar (3 per year) in 2005 to average 65 attendees per seminar (6 per year) in 2010. By expanding the access to information for patients, their families and friends, living donation has increased with a growth in the proportion of preemptive LD transplants from 28% (23/81) in 2006 to 44% in 2010 (29/66; p = 0.05). We can conclude that expanding the pool accessing information has increased the number of preemptive (LD) transplants in our center.
Left ventricular assist devices (LVADs) are now widely used for the management of end-stage heart failure. Unfortunately, in spite of the indisputable positive impact LVADs have on patients, the frequency and severity of complications are limitations of this therapy. Stroke, pump thrombosis, and gastrointestinal bleeding are among the most serious and frequent complications in these patients. The balance between hemorrhagic and thrombotic complications in patients supported with CF-LVAD is difficult as most patients do not necessarily fit a "bleeder" or a "clotter" profile but rather move from one side to the other of the thrombotic/bleeding spectrum. Further research is necessary to better understand the risk factors and mechanisms involved in the development of these complications.
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