Excellent renal allograft survival in donor-specific antibody positive transplant patients-role of intravenous immunoglobulin and rabbit antithymocyte globulin

Martin Mai, Nasimul Ahsan, Hani M. Wadei, Petrina V. Genco, Xochiquetzal J. Geiger, Darrin L. Willingham, C. Burcin Taner, Winston R. Hewitt, Hani P. Grewal, Justin H Nguyen, Christopher B. Hughes, Thomas A. Gonwa

Research output: Contribution to journalArticle

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Abstract

BACKGROUND.: Timely transplantation of sensitized kidney recipients remains a challenge. Patients with a complement-dependent cytotoxicity negative and flow cytometry (FC) positive crossmatch carry increased risk of antibody-mediated rejection and thus graft loss. Solid phase assays are available to confirm donor specificity for antibody identified by FC crossmatch. Treatment using induction therapy with rabbit antithymocyte globulin (RATG) and intravenous immunoglobulin (IVIG) may allow successful transplant of these high-risk patients. METHODS.: A retrospective study of 264 consecutive patients after exclusions yielded 94 complement-dependent cytotoxicity anti-human globulin crossmatch-negative patients, including group 1: 58 primary transplants with panel-reactive antibody (PRA) less than 20%, group 2: 16 retransplants and PRA more than 20% who were FC crossmatch-negative, and group 3: 20 retransplants and PRA more than 20% who were FC crossmatch-positive. All were treated with RATG induction and maintenance therapy with tacrolimus, mycophenolate mofetil, and corticosteroids. Only group 3 received IVIG at 500 mg/kg daily in three doses. RESULTS.: Eighteen of 20 patients in group 3 had donor-specific antibody identified by solid phase assay. Cellular- and antibody-mediated rejections were statistically higher in group 3. Two-year serum creatinine and glomerular filtration rate along with 3-year patient and graft survival were comparable between the groups. CONCLUSIONS.: Sensitized patients with positive FC crossmatch and donor-specific antibody identified by solid phase assays can be successfully transplanted using standard RATG induction, IVIG, and maintenance immunosuppression with equal renal function and graft survival to immunologically lower risk recipients. Given these results, this patient group should not be excluded from transplantation based on antibody specificities determined by virtual crossmatch techniques.

Original languageEnglish (US)
Pages (from-to)227-232
Number of pages6
JournalTransplantation
Volume87
Issue number2
DOIs
StatePublished - Jan 27 2009

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Antilymphocyte Serum
Intravenous Immunoglobulins
Allografts
Tissue Donors
Rabbits
Transplants
Kidney
Antibodies
Flow Cytometry
Antibody Specificity
Graft Survival
Mycophenolic Acid
Globulins
Graft Rejection
Tacrolimus
Glomerular Filtration Rate
Kidney Transplantation
Immunosuppression
Creatinine
Adrenal Cortex Hormones

Keywords

  • Flow cytometry crossmatch-positive
  • Intravenous immunoglobulin
  • Kidney transplantation

ASJC Scopus subject areas

  • Transplantation

Cite this

Excellent renal allograft survival in donor-specific antibody positive transplant patients-role of intravenous immunoglobulin and rabbit antithymocyte globulin. / Mai, Martin; Ahsan, Nasimul; Wadei, Hani M.; Genco, Petrina V.; Geiger, Xochiquetzal J.; Willingham, Darrin L.; Taner, C. Burcin; Hewitt, Winston R.; Grewal, Hani P.; Nguyen, Justin H; Hughes, Christopher B.; Gonwa, Thomas A.

In: Transplantation, Vol. 87, No. 2, 27.01.2009, p. 227-232.

Research output: Contribution to journalArticle

Mai, M, Ahsan, N, Wadei, HM, Genco, PV, Geiger, XJ, Willingham, DL, Taner, CB, Hewitt, WR, Grewal, HP, Nguyen, JH, Hughes, CB & Gonwa, TA 2009, 'Excellent renal allograft survival in donor-specific antibody positive transplant patients-role of intravenous immunoglobulin and rabbit antithymocyte globulin', Transplantation, vol. 87, no. 2, pp. 227-232. https://doi.org/10.1097/TP.0b013e31818c962b
Mai, Martin ; Ahsan, Nasimul ; Wadei, Hani M. ; Genco, Petrina V. ; Geiger, Xochiquetzal J. ; Willingham, Darrin L. ; Taner, C. Burcin ; Hewitt, Winston R. ; Grewal, Hani P. ; Nguyen, Justin H ; Hughes, Christopher B. ; Gonwa, Thomas A. / Excellent renal allograft survival in donor-specific antibody positive transplant patients-role of intravenous immunoglobulin and rabbit antithymocyte globulin. In: Transplantation. 2009 ; Vol. 87, No. 2. pp. 227-232.
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abstract = "BACKGROUND.: Timely transplantation of sensitized kidney recipients remains a challenge. Patients with a complement-dependent cytotoxicity negative and flow cytometry (FC) positive crossmatch carry increased risk of antibody-mediated rejection and thus graft loss. Solid phase assays are available to confirm donor specificity for antibody identified by FC crossmatch. Treatment using induction therapy with rabbit antithymocyte globulin (RATG) and intravenous immunoglobulin (IVIG) may allow successful transplant of these high-risk patients. METHODS.: A retrospective study of 264 consecutive patients after exclusions yielded 94 complement-dependent cytotoxicity anti-human globulin crossmatch-negative patients, including group 1: 58 primary transplants with panel-reactive antibody (PRA) less than 20{\%}, group 2: 16 retransplants and PRA more than 20{\%} who were FC crossmatch-negative, and group 3: 20 retransplants and PRA more than 20{\%} who were FC crossmatch-positive. All were treated with RATG induction and maintenance therapy with tacrolimus, mycophenolate mofetil, and corticosteroids. Only group 3 received IVIG at 500 mg/kg daily in three doses. RESULTS.: Eighteen of 20 patients in group 3 had donor-specific antibody identified by solid phase assay. Cellular- and antibody-mediated rejections were statistically higher in group 3. Two-year serum creatinine and glomerular filtration rate along with 3-year patient and graft survival were comparable between the groups. CONCLUSIONS.: Sensitized patients with positive FC crossmatch and donor-specific antibody identified by solid phase assays can be successfully transplanted using standard RATG induction, IVIG, and maintenance immunosuppression with equal renal function and graft survival to immunologically lower risk recipients. Given these results, this patient group should not be excluded from transplantation based on antibody specificities determined by virtual crossmatch techniques.",
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T1 - Excellent renal allograft survival in donor-specific antibody positive transplant patients-role of intravenous immunoglobulin and rabbit antithymocyte globulin

AU - Mai, Martin

AU - Ahsan, Nasimul

AU - Wadei, Hani M.

AU - Genco, Petrina V.

AU - Geiger, Xochiquetzal J.

AU - Willingham, Darrin L.

AU - Taner, C. Burcin

AU - Hewitt, Winston R.

AU - Grewal, Hani P.

AU - Nguyen, Justin H

AU - Hughes, Christopher B.

AU - Gonwa, Thomas A.

PY - 2009/1/27

Y1 - 2009/1/27

N2 - BACKGROUND.: Timely transplantation of sensitized kidney recipients remains a challenge. Patients with a complement-dependent cytotoxicity negative and flow cytometry (FC) positive crossmatch carry increased risk of antibody-mediated rejection and thus graft loss. Solid phase assays are available to confirm donor specificity for antibody identified by FC crossmatch. Treatment using induction therapy with rabbit antithymocyte globulin (RATG) and intravenous immunoglobulin (IVIG) may allow successful transplant of these high-risk patients. METHODS.: A retrospective study of 264 consecutive patients after exclusions yielded 94 complement-dependent cytotoxicity anti-human globulin crossmatch-negative patients, including group 1: 58 primary transplants with panel-reactive antibody (PRA) less than 20%, group 2: 16 retransplants and PRA more than 20% who were FC crossmatch-negative, and group 3: 20 retransplants and PRA more than 20% who were FC crossmatch-positive. All were treated with RATG induction and maintenance therapy with tacrolimus, mycophenolate mofetil, and corticosteroids. Only group 3 received IVIG at 500 mg/kg daily in three doses. RESULTS.: Eighteen of 20 patients in group 3 had donor-specific antibody identified by solid phase assay. Cellular- and antibody-mediated rejections were statistically higher in group 3. Two-year serum creatinine and glomerular filtration rate along with 3-year patient and graft survival were comparable between the groups. CONCLUSIONS.: Sensitized patients with positive FC crossmatch and donor-specific antibody identified by solid phase assays can be successfully transplanted using standard RATG induction, IVIG, and maintenance immunosuppression with equal renal function and graft survival to immunologically lower risk recipients. Given these results, this patient group should not be excluded from transplantation based on antibody specificities determined by virtual crossmatch techniques.

AB - BACKGROUND.: Timely transplantation of sensitized kidney recipients remains a challenge. Patients with a complement-dependent cytotoxicity negative and flow cytometry (FC) positive crossmatch carry increased risk of antibody-mediated rejection and thus graft loss. Solid phase assays are available to confirm donor specificity for antibody identified by FC crossmatch. Treatment using induction therapy with rabbit antithymocyte globulin (RATG) and intravenous immunoglobulin (IVIG) may allow successful transplant of these high-risk patients. METHODS.: A retrospective study of 264 consecutive patients after exclusions yielded 94 complement-dependent cytotoxicity anti-human globulin crossmatch-negative patients, including group 1: 58 primary transplants with panel-reactive antibody (PRA) less than 20%, group 2: 16 retransplants and PRA more than 20% who were FC crossmatch-negative, and group 3: 20 retransplants and PRA more than 20% who were FC crossmatch-positive. All were treated with RATG induction and maintenance therapy with tacrolimus, mycophenolate mofetil, and corticosteroids. Only group 3 received IVIG at 500 mg/kg daily in three doses. RESULTS.: Eighteen of 20 patients in group 3 had donor-specific antibody identified by solid phase assay. Cellular- and antibody-mediated rejections were statistically higher in group 3. Two-year serum creatinine and glomerular filtration rate along with 3-year patient and graft survival were comparable between the groups. CONCLUSIONS.: Sensitized patients with positive FC crossmatch and donor-specific antibody identified by solid phase assays can be successfully transplanted using standard RATG induction, IVIG, and maintenance immunosuppression with equal renal function and graft survival to immunologically lower risk recipients. Given these results, this patient group should not be excluded from transplantation based on antibody specificities determined by virtual crossmatch techniques.

KW - Flow cytometry crossmatch-positive

KW - Intravenous immunoglobulin

KW - Kidney transplantation

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