Plasma exchange and tacrolimus-mycophenolate rescue for acute humoral rejection in kidney transplantation.
BACKGROUND
Acute renal allograft rejection associated with the development of donor-specific alloantibody (acute humoral rejection, AHR) typically carries a poor prognosis. The best treatment of this condition remains undefined.


METHODS
During a 14-month period, 73 renal transplants were performed. During the first postoperative month, five recipients (6.8%) with AHR were identified. The diagnosis was based on: (1) evidence of severe rejection, resistant to steroid and antilymphocyte therapy; (2) typical pathologic features; and (3) demonstration of donor-specific alloantibody (DSA) in recipient's serum at the time of rejection. Pretransplant donor-specific T- and B-cell cross-matches were negative.


RESULTS
Plasma exchange (PE, four to seven treatments per patient) significantly decreased circulating DSA to almost pretransplant levels in four of five patients, and improvement in renal function occurred in all patients. One patient had recurrent renal dysfunction in the setting of an increase in circulating DSA. A second series of five PE treatments decreased DSA and reversed the rejection episode. Rescue therapy with tacrolimus (initial mean dose: 0.14+/-0.32 mg/kg/day) and mycophenolate mofetil (2 g/day) was used in five of five and four of five patients, respectively. With a mean follow-up of 19.6+/-5.6 months, patient and allograft survival are 100%. Renal function remains excellent with a mean current serum creatinine of 1.2+/-0.3 mg/dl. (range: 0.9-1.8 mg/dl).


CONCLUSIONS
Our findings suggest that a therapeutic approach combining PE and tacrolimus-mycophenolate mofetil rescue has the potential to improve the outcome of AHR.
Pascual
M
M
Department of Surgery, Massachusetts General Hospital and Harvard Medical School, Boston 02114, USA.
Saidman
S
S
Tolkoff-Rubin
N
N
Williams
W W
WW
Mauiyyedi
S
S
Duan
J M
JM
Farrell
M L
ML
Colvin
R B
RB
Cosimi
A B
AB
Delmonico
F L
FL
D000208:Acute Disease; D000917:Antibody Formation; D001706:Biopsy; D005260:Female; D006084:Graft Rejection / Q000276:immunology / Q000473:pathology / Q000517:prevention & control; D006680:HLA Antigens / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000032:analysis; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007518:Isoantibodies / Q000276:immunology; D007668:Kidney / Q000473:pathology; D016030:Kidney Transplantation / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000031:analogs & derivatives* / Q000627:therapeutic use; D010951:Plasma Exchange; D016559:Tacrolimus / Q000627:therapeutic use*
D006680:HLA Antigens; D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D007518:Isoantibodies; D009173:Mycophenolic Acid; D016559:Tacrolimus