First Results With a Quadruple Therapy Regimen Including Tacrolimus and Mycophenolate Mofetil in Patients After Combined Pancreas and Kidney Transplantation A. Kahl, W.O. Bechstein, K. Platz, A. Mu ¨ ller, S. Berweck, S. Venz, P. Neuhaus, and U. Frei D UE TO better surgical techniques and immunosup- pression pancreas and kidney transplantation (PTX/ NTX) has become a procedure with continuously improving results. The actual survival for patients, kidney, and pan- creas transplants is 91%, 83%, and 78%, respectively, after 1 year and 79%, 68%, and 65%, respectively, after 5 years. These results were reported from about 4000 PTX/NTX patients and are mainly achieved by cyclosporine (CyA)- based regimens. 1 Sollinger et al. 2 improved the results by introducing mycophenolate mofetil (MMF) instead of aza- thioprine to the therapy. Because of its potential diabeto- genic effect the application of tacrolimus is controversial, yet it has shown to be successful for rescue therapy in small PTX/NTX patient populations. 3 The combination of ta- crolimus- and MMF-based immunosuppressive regimens might promise good results 4 but up to now has not been investigated prospectively in PTX/NTX patients. MATERIALS AND METHODS From March 1996 to September 1997 22 PTX/NTX were per- formed in our unit. Seventeen patients received quadruple therapy with ATG (ATG Fresenius, 3 mg/kg body weight for 7 days), tacrolimus (blood level 15 ng/mL during the first month, 12 ng/mL during the second month, and 10 ng/mL during the third month), MMF (2 3 1 g/d), and prednisolone (500 mg before, 250 after PTX/NTX, 100 mg [day 1], 40 mg for the first week, then tapering down with the aim to withdraw steroids completely after 6 to 12 months). Twelve (5 male/7 female) out of these 17 patients have reached a follow-up period of more than 3 months and are considered in this report. The other 5 patients are presently less than 3 months after PTX/NTX. Eleven of the 12 patients were dialysis dependent with an average dialysis time of 17 (0 to 48) months (median, min-max). All of the following values are given as median (min-max). The median age of the patients was 42 years (25 to 52), and the duration of diabetes was 29 years (14 to 38). The waiting time for transplantation was 103 (8 to 404) days, HLA-A, B; DR mismatches 4 (2 to 5), the mean age of the donors was 35 (19 to 46) years. Cold ischemia time was 8.1 (5.7 to 13.3) hours, and warm ischemia time of the pancreas was 32 (25 to 40) minutes. One patient received her third NTX-kidney during PTX/NTX. The other 11 patients were transplanted for the first time. In 10 patients bladder drainage technique and in 2 patients enteric drainage technique of the pancreas transplant was performed. From the Departments of Nephrology and Surgery, Virchow- Klinikum der Humboldt Universita ¨ t zu Berlin, Berlin, Germany. Address reprint requests to Dr A. Kahl, Department of Ne- phrology, Virchow-Klinikum der Humboldt Universita ¨ t zu Berlin, Augustenburger Platz 1, 13353 Berlin, Germany. Table 1. Parameters of Pancreas and Renal Function and Immunosuppression Given as Median (Min-Max) Preoperative (n 5 12) 1 Month (n 5 12) 3 Months (n 5 12) 6 Months (n 5 7) 12 Months (n 5 3) HbA1c (%) 8.9 6.5 5.8 6.2 6.1 (7.5–12.1) (5.1–7.7) (5.4 – 6.4) (5.3– 6.8) (5.2– 6.3) C-peptide (ng/mL) ,0.3 6.0 4.8 3.6 2.4 (3.1–10.4) (2.3– 6.8) (2.0 – 6.0) (2.1–2.5) Insulin dependent 12 patients 2 patients 0 patients 0 patients 0 patients Creatinine (mg%) 5.7 1.3 1.3 1.3 1.2 (3.7– 8.0) (0.9 –2.0) (1.0 –1.7) (0.9 –1.7) (0.9 –1.4) Dialysis 11 patients 0 patients 0 patients 0 patients 0 patients Tacrolimus level (ng/mL) 12.8 11.3 8.7 6.5 (5.6 –19.5) (7.5–15.8) (6.9 –10.3) (6.1–7.4) MMF dose (g) 1.5 1.0 1.0 1.0 (0.75–2) (0 –2) (0 –2) (0 –2) Leukocyte Count (/nL) 7.4 5.8 4.5 4.1 3.9 (5.9 –9.1) (4.9 –12.1) (3.9 –12.1) (3.7–19.4) (3.8 – 4.4) © 1998 by Elsevier Science Inc. 0041-1345/98/$19.00 655 Avenue of the Americas, New York, NY 10010 PII S0041-1345(97)01377-8 Transplantation Proceedings, 30, 505–506 (1998) 505