Rituximab is a chimaeric monoclonal antibody directed against the CD20 antigen. It has been successfully used in B-cell malignancy and its efficacy in the treatment of in autoimmune hemolytic anemia and other autoimmune diseases is being investigated. There are also few case reports of its success in thrombotic thrombocytopenic purpura, but no reports of its use in hemolytic-uremic syndrome (HUS). We report a 36-year-old patient who had lost the function of her native kidneys secondary to HUS. After more than 1 year in clinical remission, she received a living unrelated kidney transplant. This immediately precipitated a severe relapse of HUS. The process was abrogated but not completely inactivated, despite over 40 plasma exchange treatments. Consequently, she was given Rituximab in courses of two to three doses, each dose 375 mg/m(2), at weekly intervals with remarkable stabilization of her disease for approximately 6 months.

Background/Aim Multi‐drug resistance (MDR‐1) expression during immunosuppressive therapy (IT) may influence individual drug response in renal transplant patients (RTR). However, no data exist that quantitate MDR‐1 in peripheral mononuclear cells (PBMCs) over IT interval. This was a pilot study in stable RTR to assess MDR‐1 expression in PBMCs before and after IT. Methods An observational study was done in 30 male RTR (ages 24–68 yrs) from a transplant clinic who were stable, > 6 months post‐transplant and receiving cyclosporine (trough: 50 ‐ 300 ng /ml), mycophenolate mofetil and prednisone. At time 0 (prior to IT) & 4 hours after IT, PBMCs were collected for analysis of MDR‐1 by quantitative real time‐polymerase chain reaction (QRT‐PCR). The target MDR‐1 PCR product was cloned, and verified by sequencing. The cloned MDR‐1 was used to establish standard curves (linearr2=0.996)and PCR efficiencies. QRT‐PCR data were normalized using the mean of 3 housekeeping genes: B‐actin, cyclophilin, GAPDH. Results In RTR (15 African American; 15 Caucasian), MDR‐1 expression ranged at time 0 from 11 to 613×10 6 copies (2 orders of magnitude difference) and at 4 hours from 6.6 to 1700×106 copies (3 orders of magnitude difference). MDR‐1 expression differed between time (0 hr= 129.8±132.97×106 vs. 4 hr= 188.7±424.0×10 6 copies; p<0.0001) with no racial difference. Conclusion Notable interpatient variability exists for MDR‐1 expression on PBMCs in RTR with differential expression prior to and following IT. Clinical Pharmacology & Therapeutics (2005) 77, P62–P62; doi:

BACKGROUND/AIMS Cyclosporine (CYA) pharmacokinetics (PK) and its relationship to T regulatory lymphocytes (Tregs) pharmacodynamics (PD) are unknown. Our objective was to examine CYA PK and PD of Tregs in renal transplant recipients (RTR) during immunosuppressive therapy (IT). METHODS 30 male RTR {15 African American (AA); 15 Caucasians (C)} on CYA, mycophenolate mofetil (MMF) and prednisone completed a 12 hour PK‐PD study. LC/MSMS analyzed CYA and WINNONLIN generated CYA PK. Lymphocyte sub‐populations (LSP) including Tregs (CD47+CD25+, CD8+CD25+) were collected at 0‐hr[prior to IT] and 4‐hrs after IT and were analyzed by flow cytometry. General Linear Modeling was used to examine variables {CYA Clearance, CYA AUC, prednisone, MMF dose, race, baseline Tregs {0Tregs}) on LSP change. RESULTS Decline in all LSP was observed with: CD4+CD25+ {0 hrs: 359 ± 148 to 4 hrs: 242 ± 122 cells/uL; p<0.05) and CD8+CD25+ (0 hrs: 26 ± 23 to 4 hrs: 15 ± 11cell/uL; p<0.05). Decline in absolute cells and percent change for LSP (p<0.05) PD was found with no racial influence. A racial difference in CYA clearance (CL) was noted (CL AA = 7.6 1.9 ml/min/kg vs. CL C = 9.3 4.3 ml/min/kg; p = 0.027). CYA CL and 0Tregs were main effects on decline of CD4+CD25+ (CL:p=0.006; 0Tregs:p=0.0001) and CD8+CD25+ (CL:p=0.002; 0Tregs:p=0.0001). An interactive effect between race and prednisone (p<0.05) was noted. CONCLUSION This PK‐PD study indicates that an important relationship between CYA exposure and LSP PD exists which may advance IT monitoring. Clinical Pharmacology & Therapeutics (2005) 79, P21–P21; doi: