Impact of acute rejection on kidney allograft outcomes in recipients on rapid steroid withdrawal.

Background. Our aim was to study the impact of clinical acute rejection (CR) and subclinical rejection (SR) on outcomes in kidney transplant recipients treated with rapid steroid withdrawal (RSW). Methods. All patients who received a living or deceased donor kidney transplant and were treated with RSW were included. The primary outcome was death-censored graft survival. Biopsies with Banff borderline changes were included with the rejection groups. Results. 457 kidney transplant recipients treated with RSW were included; 46 (10%) experienced SR, and 36 (7.8%) had CR. Mean HLA mismatch was significantly higher in the CR group. The Banff grade of rejection was higher in the CR group. There was a larger proportion of patients in both rejection groups with the combination of IFTA and persistent inflammation on the follow-up protocol biopsy done at 1 year. The estimated 5-year death-censored graft survival was 81% in SR, 78% in CR, and 97% in the control group (P < .0001). Significant differences were observed in allograft survival between the CR and control group (HR 9.06, 95% CI 3.39-24.2) and between the SR and control group (HR 4.22, 95% CI 1.30-13.7). Conclusion. Both SR and CR are associated with an inferior graft survival in recipients on RSW.

Alemtuzumab with rapid steroid taper in simultaneous kidney and pancreas transplantation: comparison to induction with antithymocyte globulin.

We compared our experience with alemtuzumab induction and rapid steroid taper (RST) in simultaneous kidney and pancreas transplantation (SKPT) with a historic control group who received rabbit antithymocyte globulin (r-ATG) induction with RST. 74 SKPTs performed at our center between January 2005 to November 2008 who underwent immunosuppression with RST in combination with r-ATG induction (n = 33; 1.5 mg/kg x 4 for a total dose of 6 mg/kg) or alemtuzumab induction (n = 41; 30 mg single dose). Maintenance immunosuppression consisted of tacrolimus and mycophenolate mofetil. Steroids were discontinued after postoperative day 4. Recipient and transplant characteristics were similar between the 2 groups, with 82% of the r-ATG and 80% of the alemtuzumab group steroid free at 1 year. The rate of clinical acute rejection episodes was 12% in the r-ATG group and 15% in the alemtuzumab group. The rates of cytomegalovirus (CMV) infection, BK nephropathy, and graft survival were similar between the 2 groups. There was no difference in mean serum creatinine, calculated GFR, or fasting blood sugar at 1 year between the 2 groups, whereas glycosylated hemoglobin (HbA1c) was lower at 1 year in the alemtuzumab (5.3 +/- 0.4) versus the r-ATG group (5.6 +/- 0.4; P = .0021). Induction with r-ATG or alemtuzumab with RST was safe and effective in SKPT. The incidences of acute rejection episodes, CMV infection, and BK nephropathy were similar. Mean HbA1C at 1 year was lower among the alemtuzumab group. Further long-term follow-up is needed to confirm these results.

Impact of subclinical inflammation on the development of interstitial fibrosis and tubular atrophy in kidney transplant recipients.

Our aim was to study the impact of subclinical inflammation on the development of interstitial fibrosis and tubular atrophy (IF/TA) on a 1-year protocol biopsy in patients on rapid steroid withdrawal (RSW). A total of 256 patients were classified based on protocol biopsy findings at months 1 or 4. Group 1 is 172 patients with no inflammation, group 2 is 50 patients with subclinical inflammation (SCI), group 3 is 19 patients with subclinical acute rejection (SAR) and group 4 is 15 patients with clinical acute rejection (CAR). On the 1-year biopsy, more patients in group 2 (SCI) (34%, p = 0.004) and group 3 (SAR) (53%, p = 0.0002), had an IF/TA score > 2 compared to group 1 (control) (15%). IF/TA was not increased in group 4 (CAR) (20%). The percent with IF/TA score > 2 and interstitial inflammation (Banff i score > 0) was higher in group 2 (16%, p = 0.004) and group 3 (37%, p < 0.0001) compared to group 1 (3%). In a multivariate analysis, patients in groups 2 or 3 had a higher risk of IF/TA score > 2 on the 1-year biopsy (OR 6.62, 95% CI 2.68-16.3). We conclude that SCI and SAR increase the risk of developing IF/TA in patient on RSW.