Scholars@Duke
Allan Douglas Kirk

Allan Douglas Kirk

David C. Sabiston, Jr. Distinguished Professor of Surgery
Surgery, Abdominal Transplant Surgery

Featured Works

Anti-Leukocyte Function-Associated Antigen 1 Therapy in a Nonhuman Primate Renal Transplant Model of Costimulation Blockade-Resistant Rejection.

Journal article Am J Transplant · May 2016 Featured Publication Costimulation blockade with the fusion protein belatacept provides a desirable side effect profile and improvement in renal function compared with calcineurin inhibition in renal transplantation. This comes at the cost of increased rates of early acute rej ... Full text Link to item Cite

CD57(+) CD4 T Cells Underlie Belatacept-Resistant Allograft Rejection.

Journal article Am J Transplant · April 2016 Featured Publication Belatacept is a B7-specific fusion protein used to prevent allograft rejection by blocking T cell costimulation. Generally efficacious, it fails to prevent acute rejection in a sizable minority of patients. In experimental models, memory T cells mediate co ... Full text Link to item Cite

Postdepletion Lymphocyte Reconstitution During Belatacept and Rapamycin Treatment in Kidney Transplant Recipients.

Journal article Am J Transplant · February 2016 Featured Publication Belatacept is used to prevent allograft rejection but fails to do so in a sizable minority of patients due to inadequate control of costimulation-resistant T cells. In this study, we report control of costimulation-resistant rejection when belatacept was c ... Full text Link to item Cite

APOL1 Genotype and Kidney Transplantation Outcomes From Deceased African American Donors.

Journal article Transplantation · January 2016 Featured Publication BACKGROUND: Two apolipoprotein L1 gene (APOL1) renal-risk variants in donors and African American (AA) recipient race are associated with worse allograft survival in deceased-donor kidney transplantation (DDKT) from AA donors. To detect other factors impac ... Full text Link to item Cite

First update of the International Xenotransplantation Association consensus statement on conditions for undertaking clinical trials of porcine islet products in type 1 diabetes--Chapter 4: pre-clinical efficacy and complication data required to justify a clinical trial.

Journal article Xenotransplantation · 2016 Featured Publication In 2009, the International Xenotransplantation Association (IXA) published a consensus document that provided guidelines and "recommendations" (not regulations) for those contemplating clinical trials of porcine islet transplantation. These guidelines incl ... Full text Link to item Cite

Immunologic Aging in Adults with Congenital Heart Disease: Does Infant Sternotomy Matter?

Journal article Pediatr Cardiol · October 2015 Featured Publication Thymectomy is performed routinely in infants undergoing cardiothoracic surgery. Children post-sternotomy have decreased numbers of T lymphocytes, although the mechanisms involved and long-term consequences of this have not been defined. We hypothesized tha ... Full text Link to item Cite

Tacrolimus to Belatacept Conversion Following Hand Transplantation: A Case Report.

Journal article Am J Transplant · August 2015 Featured Publication Vascularized composite allotransplantation (VCA) has emerged as a viable limb replacement strategy for selected patients with upper limb amputation. However, allograft rejection has been seen in essentially all reported VCA recipients indicating a requirem ... Full text Link to item Cite

Studies Introducing Costimulation Blockade for Vascularized Composite Allografts in Nonhuman Primates.

Journal article Am J Transplant · August 2015 Featured Publication Vascularized composite allografts (VCAs) are technically feasible. Similar to other organ transplants, VCAs are hampered by the toxicity and incomplete efficacy associated with conventional immunosuppression. Complications attributable to calcineurin inhib ... Full text Link to item Cite

Viral-induced CD28 loss evokes costimulation independent alloimmunity.

Journal article J Surg Res · June 15, 2015 Featured Publication BACKGROUND: Belatacept, a B7-specific fusion protein, blocks CD28-B7 costimulation and prevents kidney allograft rejection. However, it is ineffective in a sizable minority of patients. Although T-cell receptor and CD28 engagement are known to initiate T-c ... Full text Link to item Cite

A pilot trial targeting the ICOS-ICOS-L pathway in nonhuman primate kidney transplantation.

Journal article Am J Transplant · April 2015 Featured Publication Costimulation blockade with the B7-CD28 pathway-specific agent belatacept is now used in clinical kidney transplantation, but its efficacy remains imperfect. Numerous alternate costimulatory pathways have been proposed as targets to synergize with belatace ... Full text Link to item Cite

Mitigation of autophagy ameliorates hepatocellular damage following ischemia-reperfusion injury in murine steatotic liver.

Journal article Am J Physiol Gastrointest Liver Physiol · December 1, 2014 Featured Publication Ischemia-reperfusion injury (IRI) is a common clinical consequence of hepatic surgery, cardiogenic shock, and liver transplantation. A steatotic liver is particularly vulnerable to IRI, responding with extensive hepatocellular injury. Autophagy, a lysosoma ... Full text Link to item Cite

CD28 negative T cells: is their loss our gain?

Journal article Am J Transplant · November 2014 Featured Publication CD28 is a primary costimulation molecule for T cell activation. However, during the course of activation some T cells lose this molecule and assume a CD28-independent existence. These CD28- T cells are generally antigen-experienced and highly differentiate ... Full text Link to item Cite

Renal transplantation using belatacept without maintenance steroids or calcineurin inhibitors.

Journal article Am J Transplant · May 2014 Featured Publication Kidney transplantation remains limited by toxicities of calcineurin inhibitors (CNIs) and steroids. Belatacept is a less toxic CNI alternative, but existing regimens rely on steroids and have higher rejection rates. Experimentally, donor bone marrow and si ... Full text Link to item Cite

Biomarkers for kidney transplant rejection.

Journal article Nat Rev Nephrol · April 2014 Featured Publication The immune management of organ transplant recipients is imperfect. Beyond general dosing guidelines for immunosuppressive agents and clinical diagnostic tests for rejection or infection, there are few objective tools to determine the aggregate status of a ... Full text Link to item Cite

The allo- and viral-specific immunosuppressive effect of belatacept, but not tacrolimus, attenuates with progressive T cell maturation.

Journal article Am J Transplant · February 2014 Featured Publication Tacrolimus impairs allo- and viral-specific T cell responses. Belatacept, a costimulation-based alternative to tacrolimus, has emerged with a paradoxical picture of less complete control of alloimmunity with concomitant impaired viral immunity limited to v ... Full text Link to item Cite

Islet cell xenotransplantation: a serious look toward the clinic.

Journal article Xenotransplantation · 2014 Featured Publication Type I diabetes remains a significant clinical problem in need of a reliable, generally applicable solution. Both whole organ pancreas and islet allotransplantation have been shown to grant patients insulin independence, but organ availability has restrict ... Full text Link to item Cite

Belatacept and sirolimus prolong nonhuman primate islet allograft survival: adverse consequences of concomitant alefacept therapy.

Journal article Am J Transplant · February 2013 Featured Publication Calcineurin inhibitors (CNI) and steroids are known to promote insulin resistance, and their avoidance after islet transplantation is preferred from a metabolic standpoint. Belatacept, a B7-specific mediator of costimulation blockade (CoB), is clinically i ... Full text Link to item Cite

Belatacept and sirolimus prolong nonhuman primate renal allograft survival without a requirement for memory T cell depletion.

Journal article Am J Transplant · February 2013 Featured Publication Belatacept is an inhibitor of CD28/B7 costimulation that is clinically indicated as a calcineurin inhibitor (CNI) alternative in combination with mycophenolate mofetil and steroids after renal transplantation. We sought to develop a clinically translatable ... Full text Link to item Cite

Platelet-derived CD154: ultrastructural localization and clinical correlation in organ transplantation.

Journal article Am J Transplant · November 2012 Featured Publication CD154 is an immunostimulatory ligand for CD40 that markedly influences alloimmunity. Its presence in platelets suggests that its release and subsequent immune effects are driven by trauma and thus could be relevant following organ transplantation. However, ... Full text Link to item Cite

Alternative immunomodulatory strategies for xenotransplantation: CD40/154 pathway-sparing regimens promote xenograft survival.

Journal article Am J Transplant · July 2012 Featured Publication Immunosuppressive therapies that block the CD40/CD154 costimulatory pathway have proven to be uniquely effective in preclinical xenotransplant models. Given the challenges facing clinical translation of CD40/CD154 pathway blockade, we examined the efficacy ... Full text Link to item Cite

Selective targeting of human alloresponsive CD8+ effector memory T cells based on CD2 expression.

Journal article Am J Transplant · January 2011 Featured Publication Costimulation blockade (CoB), specifically CD28/B7 inhibition with belatacept, is an emerging clinical replacement for calcineurin inhibitor-based immunosuppression in allotransplantation. However, there is accumulating evidence that belatacept incompletel ... Full text Link to item Cite

Identification of a B cell signature associated with renal transplant tolerance in humans.

Journal article J Clin Invest · June 2010 Featured Publication Establishing long-term allograft acceptance without the requirement for continuous immunosuppression, a condition known as allograft tolerance, is a highly desirable therapeutic goal in solid organ transplantation. Determining which recipients would benefi ... Full text Link to item Cite