Osteopenia associated with renal transplantation remains a problem in the cyclosporine era. The loss of vertebral bone in our subjects was due to an imbalance in bone remodeling consistent with a toxic effect of glucocorticoids.

No abstract

Leukocyte function associated antigen-1 (LFA-1) has a multifaceted role in the immune response, including adhesion and trafficking of leukocytes, stabilizing the immune synapse of the MHC-TCR complex and providing costimulation signals. Monoclonal antibodies to the CD11a chain of LFA-1 have been seen to result in effective immunosuppression in experimental models. Efalizumab, a humanized IgG1 antiCD11a, is approved for use in psoriasis and may provide effective immunosuppression in organ transplantation. Thirty-eight patients undergoing their first living donor or deceased renal transplant were randomized to receive efalizumab 0.5 or 2 mg/kg weekly subcutaneously for 12 weeks. Patients were maintained on full dose cyclosporine, mycophenolate mofetil and steroids or half dose cyclosporine, sirolimus and prednisone. At 6 months following transplant patient survival was 97% and graft survival was 95%. Clinical biopsy-proven acute rejection in the first 6 months after transplantation was confirmed in 4 of 38 patients (11%). Three patients (8%) developed post transplant lymphoproliferative disease, all treated with the higher dose efalizumab and full dose cyclosporine. The two doses of efalizumab resulted in comparable saturation and modulation of CD11a. This phase II trial suggests that efalizumab may warrant further investigation in transplantation.

Use of the monoclonal antibody OKT3 to prevent or treat allograft rejection has become commonplace. Its administration is often complicated by serious side effects, usually occurring within one to two hours after OKT3 is given, and is termed first-dose reaction. The mechanism underlying these signs and symptoms is poorly defined, but may be related to cytokine release. Twenty-three kidney or kidney/pancreas transplant recipients received OKT3 as treatment of acute rejection. Signs and symptoms occurring after the first dose were observed and quantitated prospectively, and a reaction score was calculated. Blood was drawn immediately before, and at 2 and 24 hours after the first dose of OKT3 for determination of interleukin-2 (IL2), interferon-gamma (IFN gamma), and tumor necrosis factor-alpha (TNF alpha) levels, and flow cytometric analysis of T cell subsets. Two groups were defined based on severity of first-dose reaction. Group 1 patients (N = 11) had very mild reactions (reaction score less than or equal to 3); Group 2 patients (N = 12) had more severe reactions (score greater than or equal to 5). All patients demonstrated a significant rise in serum TNF alpha from baseline to two hours after OKT3 (9 +/- 3 pg/ml to 378 +/- 54 pg/ml, P less than 0.0001), and there was significant correlation between reaction scores and two-hour TNF alpha levels (P = 0.005). Group 2 patients had higher TNF alpha levels at two hours than did Group 1 patients (484 +/- 75 pg/ml vs. 263 +/- 62 pg/ml, P = 0.04). Levels of IL2 and IFN gamma were not elevated at any sampling time.(ABSTRACT TRUNCATED AT 250 WORDS)