Allan Kirk

Overview:

I am a surgeon with interest in immune management of transplant recipients. I am particularly interested in therapies that influence T cell costimulation pathways and adjuvant therapies that facilitate costimulation blockade to prevent the rejection of transplanted organs without undue suppression of protective immunity. I am also interested in understanding how injury, such as that occurring during trauma or in elective surgery, influences immune responses and subsequent healing following injury.

Positions:

David C. Sabiston, Jr. Distinguished Professor of Surgery

Surgery, Abdominal Transplant Surgery
School of Medicine

Professor of Surgery

Surgery, Abdominal Transplant Surgery
School of Medicine

Chair of Surgery

Surgery
School of Medicine

Professor in Pediatrics

Pediatrics
School of Medicine

Professor in the Department of Immunology

Immunology
School of Medicine

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

B.S. 1983

Old Dominion University

M.D. 1987

Duke University School of Medicine

Ph.D. 1992

Duke University

Intern & Junior Resident, Surgery

Duke University

Research Fellow, Surgery

Duke University

Senior Resident, Surgery

Duke University

Chief Resident, Surgery

Duke University

Fellow, Multi Organ Transplantation

University of Wisconsin - Madison

Grants:

Neonatal Porcine Islet Xenografts for the Treatment of Type 1 Diabetes

Administered By
Surgery
Awarded By
National Institutes of Health
Role
Principal Investigator
Start Date
End Date

Immune Tolerance Network - Flow Cytometry

Awarded By
Benaroya Research Institute at Virginia Mason
Role
Principal Investigator
Start Date
End Date

American Journal of Transplantation

Awarded By
American Society of Transplantation
Role
Principal Investigator
Start Date
End Date

Phase 2 Study of Belatacept, Alemtuzumab, and Sirolimus in Renal Transplantation

Administered By
Surgery
Awarded By
Food and Drug Administration
Role
Principal Investigator
Start Date
End Date

T cell Receptor Diversity as a Determinant of Co-stimulation Blockade Resistance

Awarded By
American Society of Transplant Surgeons
Role
Principal Investigator
Start Date
End Date

Publications:

ASSOCIATION OF A CYTOKINE RESPONSE NETWORK WITH FUNCTIONAL RECOVERY FROM SNAKEBITE ENVENOMING

Authors
Gerardo, CJ; Silvius, E; Schobel, S; Eppensteiner, J; McGowan, L; Limkakeng, AT; Kirk, AD; Elster, EA
MLA Citation
Gerardo, C. J., et al. “ASSOCIATION OF A CYTOKINE RESPONSE NETWORK WITH FUNCTIONAL RECOVERY FROM SNAKEBITE ENVENOMING.” Toxicon, vol. 182, 2020, pp. S15–16.
URI
https://scholars.duke.edu/individual/pub1450888
Source
wos-lite
Published In
Toxicon
Volume
182
Published Date
Start Page
S15
End Page
S16

Clinical risk factors and inflammatory biomarkers of post-traumatic acute kidney injury in combat patients.

BACKGROUND:Post-traumatic acute kidney injury has occurred in every major military conflict since its initial description during World War II. To ensure the proper treatment of combat casualties, early detection is critical. This study therefore aimed to investigate combat-related post-traumatic acute kidney injury in recent military conflicts, used machine learning algorithms to identify clinical and biomarker variables associated with the development of post-traumatic acute kidney injury, and evaluated the effects of post-traumatic acute kidney injury on wound healing and nosocomial infection. METHODS:We conducted a retrospective clinical cohort review of 73 critically injured US military service members who sustained major combat-related extremity wounds and had collected injury characteristics, assayed serum and tissue biopsy samples for the expression of protein and messenger ribonucleic acid biomarkers. Bivariate analyses and random forest recursive feature elimination classification algorithms were used to identify associated injury characteristics and biomarker variables. RESULTS:The incidence of post-traumatic acute kidney injury was 20.5%. Of that, 86% recovered baseline renal function and only 2 (15%) of the acute kidney injury group required renal replacement therapy. Random forest recursive feature elimination algorithms were able to estimate post-traumatic acute kidney injury with the area under the curve of 0.93, sensitivity of 0.91, and specificity of 0.91. Post-traumatic acute kidney injury was associated with injury severity score, serum epidermal growth factor, and tissue activin A type receptor 1, matrix metallopeptidase 10, and X-C motif chemokine ligand 1 expression. Patients with post-traumatic acute kidney injury exhibited poor wound healing and increased incidence of nosocomial infections. CONCLUSION:The occurrence of acute kidney injury in combat casualties may be estimated using injury characteristics and serum and tissue biomarkers. External validations of these models are necessary to generalize for all trauma patients.
Authors
Muñoz, B; Schobel, SA; Lisboa, FA; Khatri, V; Grey, SF; Dente, CJ; Kirk, AD; Buchman, T; Elster, EA
MLA Citation
Muñoz, Beau, et al. “Clinical risk factors and inflammatory biomarkers of post-traumatic acute kidney injury in combat patients.Surgery, June 2020. Epmc, doi:10.1016/j.surg.2020.04.064.
URI
https://scholars.duke.edu/individual/pub1451319
PMID
32600883
Source
epmc
Published In
Surgery
Published Date
DOI
10.1016/j.surg.2020.04.064

Kidney transplantation using alemtuzumab, belatacept, and sirolimus: Five-year follow-up.

Kidney transplant outcomes are limited by toxicities associated with calcineurin inhibitors and steroids. This trial was conducted to determine whether a costimulation blockade (CoB)-based regimen could achieve acceptable long-term outcomes and graft survival could be maintained solely with CoB. Forty patients underwent alemtuzumab induction followed by belatacept and sirolimus maintenance therapy. Patients were offered weaning to belatacept monotherapy after 1 year and followed for 5 years. Five-year patient and graft survival rates were 100% and 95%, respectively. Graft function remained stable with a mean estimated glomerular filtration rates of 67 ± 21 and 71 ± 19 at 36 and 60 months, respectively. There was no clinical rejection in the first year; subclinical rejection was detected by protocol biopsy in 4 patients. Twelve patients were successfully weaned to belatacept monotherapy. Cytomegalovirus and Epstein-Barr virus reactivations were well controlled, but 9 patients experienced transient BK viremia during the first year. Alemtuzumab produced profound lymphopenia followed by gradual T cell and more rapid B cell reconstitution to a repertoire deviated toward naïve cells with increased regulatory T cells. This regimen effectively prevents allograft rejection without using steroids or calcineurin inhibitors, enriches for naïve cells susceptible to control with CoB, and permits control of rejection with belatacept monotherapy in selected patients.
Authors
Schmitz, R; Fitch, ZW; Xu, H; Ghali, A; Mehta, AK; Guasch, A; Kirk, AD
MLA Citation
Schmitz, Robin, et al. “Kidney transplantation using alemtuzumab, belatacept, and sirolimus: Five-year follow-up.Am J Transplant, June 2020. Pubmed, doi:10.1111/ajt.16121.
URI
https://scholars.duke.edu/individual/pub1446805
PMID
32515087
Source
pubmed
Published In
Am J Transplant
Published Date
DOI
10.1111/ajt.16121

An age-independent gene signature for monitoring acute rejection in kidney transplantation.

Acute rejection (AR) remains a significant problem that negatively impacts long-term renal allograft survival. Numerous therapies are used to prevent AR that differ by center and recipient age. This variability confounds diagnostic methods. Methods: To develop an age-independent gene signature for AR effective across a broad array of immunosuppressive regimens, we compiled kidney transplant biopsy (n=1091) and peripheral blood (n=392) gene expression profiles from 12 independent public datasets. After removing genes differentially expressed in pediatric and adult patients, we compared gene expression profiles from biopsy and peripheral blood samples of patients with AR to those who were stable (STA), using Mann-Whitney U Tests with validation in independent testing datasets. We confirmed this signature in pediatric and adult patients (42 AR and 47 STA) from our institutional biorepository. Results: We identified a novel age-independent gene network that identified AR from both kidney and blood samples. We developed a 90-probe set signature targeting 76 genes that differentiated AR from STA and found an 8 gene subset (DIP2C, ENOSF1, FBXO21, KCTD6, PDXDC1, REXO2, HLA-E, and RAB31) that was associated with AR. Conclusion: We used publicly available datasets to create a gene signature of AR that identified AR irrespective of immunosuppression regimen or recipient age. This study highlights a novel model to screen and validate biomarkers across multiple treatment regimens.
Authors
Shaw, BI; Cheng, DK; Acharya, CR; Ettenger, RB; Lyerly, HK; Cheng, Q; Kirk, AD; Chambers, ET
MLA Citation
Shaw, Brian I., et al. “An age-independent gene signature for monitoring acute rejection in kidney transplantation.Theranostics, vol. 10, no. 15, 2020, pp. 6977–86. Pubmed, doi:10.7150/thno.42110.
URI
https://scholars.duke.edu/individual/pub1447710
PMID
32550916
Source
pubmed
Published In
Theranostics
Volume
10
Published Date
Start Page
6977
End Page
6986
DOI
10.7150/thno.42110

Cultured thymus tissue implantation promotes donor-specific tolerance to allogeneic heart transplants.

Eighty-six infants born without a thymus have been treated with allogeneic cultured thymus tissue implantation (CTTI). These infants, who lack T cells and are profoundly immunodeficient at birth, after CTTI from an unmatched donor develop T cells similar to those of recipient that are tolerant to both their own major histocompatibility antigens and those of the donor. We tested use of CTTI with the goal of inducing tolerance to unmatched heart transplants in immunocompetent rats. We thymectomized and T cell-depleted Lewis rats. The rats were then given cultured thymus tissue from F1 (Lewis × Dark Agouti ) under the kidney capsule and vascularized Dark Agouti (DA) heart transplants in the abdomen. Cyclosporine was administered for 4 months. The control group did not receive CTTI. Recipients with CTTI showed repopulation of naive and recent thymic emigrant CD4 T cells; controls had none. Recipients of CTTI did not reject DA cardiac allografts. Control animals did not reject DA grafts, due to lack of functional T cells. To confirm donor-specific unresponsiveness, MHC-mismatched Brown Norway (BN) hearts were transplanted 6 months after the initial DA heart transplant. LW rats with LWxDA CTTI rejected the third-party BN hearts (mean survival time 10 days); controls did not. CTTI recipients produced antibody against third-party BN donor but not against the DA thymus donor, demonstrating humoral donor-specific tolerance. Taken together, F1(LWxDA) CTTI given to Lewis rats resulted in specific tolerance to the allogeneic DA MHC expressed in the donor thymus, with resulting long-term survival of DA heart transplants after withdrawal of all immunosuppression.
Authors
Kwun, J; Li, J; Rouse, C; Park, JB; Farris, AB; Kuchibhatla, M; Turek, JW; Knechtle, SJ; Kirk, AD; Markert, ML
MLA Citation
Kwun, Jean, et al. “Cultured thymus tissue implantation promotes donor-specific tolerance to allogeneic heart transplants.Jci Insight, vol. 5, no. 11, June 2020. Pubmed, doi:10.1172/jci.insight.129983.
URI
https://scholars.duke.edu/individual/pub1439765
PMID
32352934
Source
pubmed
Published In
Jci Insight
Volume
5
Published Date
DOI
10.1172/jci.insight.129983