Long-term outcome of early steroid withdrawal after kidney transplantation in African American recipients monitored by surveillance biopsy.

Generally chronic steroid therapy is standard care for African American (AA) kidney recipients because of their higher incidence of rejections and lower long-term graft survival. This prospective study evaluated the long-term safety and efficacy of early steroid withdrawal (ESW) in AA recipients. A total of 206 recipients were studied; 103 AA and 103 non-AA recipients monitored by serial surveillance biopsies from 1 to 60 months posttransplantation to evaluate subclinical acute rejections (SCAR) and chronic allograft injury (CAI). Biopsy-proven clinical acute rejections (BPAR) and SCAR were treated. Primary end point was BPAR and secondary end points were 5-year SCAR, CAI and survival. Incidences of BPAR was 16% versus 14% (p = 1.0), prevalence of CAI due to hypertension was 48% versus 30% (p = 0.05) and interstitial fibrosis/tubular atrophy was 47% versus 32% (p = 0.05) and the mean serum creatinine levels were 2.1 versus 1.8 mg/dL (p = 0.05) at 5-years in AA versus non-AA recipients. The incidence of SCAR was 23% versus 11% at 1 month (p = 0.04), 12% versus 3% at 3 years (p = 0.04) and 10% versus 1% at 5 years (p = 0.04) in AA and non-AA recipients, respectively. Five-year patient survivals were 81% and 88% (p = 0.09) and graft survivals were 71% and 73%(p = 0.19) in AA and non-AA groups, respectively. After early steroid withdrawal AA kidney recipients have significantly lower renal function and higher SCAR and CAI but 5-year graft survival are comparable to non-AA recipients.

Simulect induction facilitates Neoral-based steroid-free immunosuppression in primary kidney transplant recipients.

This study compares outcomes of kidney transplantation with two distinct induction protocols Basiliximab (Simulect) versus Muromonab (OTK 3) in the setting of cyclosporine (Neoral)-based immunosuppression. Postinduction protocols included either total prednisone avoidance or prednisone sparing versus standard prednisone dosing. Two hundred forty five adult patients receiving kidney transplantation between 1995 and 2000 were included in the study. Treatment in group 1 was OKT 3 + Neoral + adjunct + standard prednisone; group 2, Simulect + Neoral + adjunct + steroid sparing; group 3, Simulect + Neoral + adjunct + no prednisone. The demographics between all groups were similar. The mean (+/- SD) trough cyclosporine levels at 1 month were 276 +/- 128 versus 291 +/- 180 versus 398 +/- 365 (P=.020); at 3 months were 261 +/- 120 versus 280 +/- 152 versus 399 +/- 408 (P=.32); at 12 month were 235 +/- 144 versus 245 +/- 154 versus 234 +/- 132 (P=.96). Creatinine clearance at 1 month was 59 +/- 24 versus 58 +/- 18 versus 47 +/- 23 mL/min (P=.004); at 3 months was 66 +/- 28 versus 62 +/- 22 versus 53 +/- 25 mL/min (P=.007); at 12 months was 68 +/- 38 versus 65 +/- 22 versus 64 +/- 29 mL/min (P=.556). Serum creatinine at 1 month was 1.8 +/- 0.9 versus 1.6 +/- 1.2 versus 2.8 +/- 2.21 mg/dL (P=.005); at 3 months was 1.7 +/- 0.6 versus 1.9 +/- 1.0 versus 2.3 +/- 1.3 mg/dL (P=.007); at 12 months was 1.9 +/- 1.3 versus 2.1 +/- 1.0 versus 2.3 +/- 1.7 mg/dL (P=.179). The incidence of acute rejection within 1 year in the respective groups were 28% versus 15% versus 16%. Therefore, we conclude that using Simulect in transplant recipients results in long-term patient and graft survival similar to those achieved with OKT 3. The use of Simulect resulted in significant reduction in clinical rejection incidence within the first year regardless of steroid use. Thus, the use of Simulect allows complete steroid avoidance in Neoral-based immunosuppression regimen.

Site for unpurified islet transplantation is an important parameter for determination of the outcome of graft survival and function.

Transplantation of unpurified islets into the liver, unlike that of purified islets, causes portal hypertension and coagulopathy. The aim of this project was to determine the most suitable alternative site for transplantation of unpurified pancreatic islets in autotransplanted dogs. Twenty-five female mongrel dogs were divided into 5 groups depending on the site of islet transplantation: liver (3), spleen (7), skeletal muscle (5), omental pouch (6), and renal subcapsule (4). Pancreatic digestion of the total pancreatectomized specimen was carried out by distension of the pancreas with 1.5 mg/mL collagenase suspended in 250 mL Hanks' balanced salt solution using a semiautomatic method. The total number of islets equivalent isolated from 25 dogs was 90948 +/- 6053. Only islets > 60 microns in diameter were counted, and the mean islet equivalent transplanted per kg body wt was 6762 +/- 429. Islet function was achieved with transplantation into spleen in 71%, omental pouch in 50%, and muscle in 20%, but none in the renal subcapsule or liver groups. Glucose tolerance test at 30 d showed a mean K Value (decline in glucose, %/min) of 1.94 +/- 0.73, 0.79 +/- 0.15 and 1.02 in the splenic, omental pouch and muscle groups, respectively. All animals in the liver group, 2 from the splenic group, and 2 from the renal subcapsule group died of diffuse bleeding. Four out of 5 dogs in the muscle group developed necrosis at the site of transplantation and the islets never functioned. This study demonstrates that in dogs, spleen and omental pouch appear to be suitable sites for transplantation of unpurified islets.