Use of high-dose human immune globulin in highly sensitized patients on the kidney transplant waiting list: one center's experience.
BACKGROUND
Transplant rates are low among highly sensitized patients with preformed anti-HLA antibodies, because of the additional immunologic barrier, the increased risk of rejection, and the greater chance of early graft loss. Intravenous infusion of pooled human immune globulin (IVIG) is immunomodulatory, neutralizing circulating antibodies and reducing rejection rates, two factors that may improve long-term transplantation outcomes.


METHODS
We selected for high-dose IVIG treatment (1 g/kg monthly for 4 months) 10 adult, stage V, highly HLA-sensitized (PRA, historical >80% and current 56%-100%) chronic kidney disease patients listed for kidney transplantation with a mean waiting time of 7.5 years. They spanned age of 29-52 years. Anti-HLA titers were monitored monthly before each treatment and 1 month after the last IVIG dose; afterwards, patients were placed on an urgent list and followed for their transplant renal function and rejection episodes.


RESULTS
Although 1 subject was transplanted after the first dose of IVIG, 9 patients completed the study, but their PRA decreased only insubstantially, namely, 14.4% (range, 8%-28%). During 6-12 months follow-up, 6 patients were considered for transplantation (negative crossmatch); 5 received kidneys and 1 was disqualified due to infection. The recipients were treated with antithymocyte globulin (n = 3) or basiliximab (n = 2) as well as tacrolimus/mycophenolate/steroids for baseline immunosuppression. Protocol biopsies (months 1, 3, and 6) in 4 patients (1 denied consent) revealed subclinical acute rejection and C4d positivity in most cases, either repeatedly or in the final biopsy. However at 6-12 months the mean serum creatinine concentration averaged 1.5 +/- 0.4 mg/dL.


CONCLUSIONS
High-dose human IVIG reduced PRA poorly, but short-term transplantation outcomes were encouraging. Surveillance biopsies are advised for sensitized kidney recipients due to the frequent appearance of rejection, particularly of the antibody mediated type.
Department of Transplantation Medicine and Nephrology, The Infant Jesus Teaching Hospital, Medical University of Warsaw, 02-005, Lindley Str. No 4, Poland. jola-md@prokonto.pl
J
J
Gozdowska
A
A
Urbanowicz
A
A
Perkowska-Ptasinska
K
K
Michalska
A
A
Chmura
J
J
Szmidt
M
M
Durlik
D000328:Adult; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D000961:Antilymphocyte Serum / Q000627:therapeutic use; D000077552:Basiliximab; D002908:Chronic Disease; D003404:Creatinine / Q000097:blood; D004359:Drug Therapy, Combination; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000517:prevention & control; D006680:HLA Antigens / Q000276:immunology; D006801:Humans; D007136:Immunoglobulins / Q000627:therapeutic use*; D016756:Immunoglobulins, Intravenous / Q000627:therapeutic use*; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007674:Kidney Diseases / Q000601:surgery; D016030:Kidney Transplantation / Q000276:immunology*; D008875:Middle Aged; D018579:Patient Selection; D011993:Recombinant Fusion Proteins / Q000627:therapeutic use; D014850:Waiting Lists
D000911:Antibodies, Monoclonal; D000961:Antilymphocyte Serum; D006680:HLA Antigens; D007136:Immunoglobulins; D016756:Immunoglobulins, Intravenous; D007166:Immunosuppressive Agents; D011993:Recombinant Fusion Proteins; D000077552:Basiliximab; D003404:Creatinine