Elizabeth E. Ashcraft

A Randomized Trial of Alemtuzumab Versus Antithymocyte Globulin Induction in Renal and Pancreas Transplantation

Background. Alemtuzumab and rabbit antithymocyte globulin (rATG) are commonly used for induction of immunsuppression for kidney and pancreas transplantation, but the two agents have not been compared directly. Methods. We conducted a prospective randomized single-center trial comparing alemtuzumab and rATG induction in adult kidney and pancreas transplantation in patients treated with similar maintenance immunosuppression. Results. Between February 1, 2005, and September 1, 2007, 222 patients randomly received either alemtuzumab (n=113) or rATG (n=109) induction; 180 (81%) underwent kidney alone, 38 (17%) simultaneous pancreas-kidney, and 4 (2%) pancreas after kidney transplants. Of 180 kidney-alone transplants, 152 (84%) were from deceased donors, including 61 (34%) from expanded criteria donors. Retransplantation, human leukocyte antigen match, antibody titer, expanded criteria donors, race, cytomegalovirus status, delayed graft function, and immunologic risks were similar between the two induction groups. With a median follow-up of 2 years (minimum 1 year), overall patient, kidney, and pancreas graft survival rates were 96%, 89%, and 90%, respectively. Survival, initial length of stay, and maintenance immunosuppression (including early steroid elimination) were similar between alemtuzumab and rATG groups, but biopsy-proven acute rejection (BPAR) episodes occurred in 16 (14%) alemtuzumab patients compared with 28 (26%) rATG patients (P=0.02). Late BPAR (>12 months after transplant) occurred in 1 (8%) alemtuzumab patient and 3 (11%) rATG patients (P=NS). Infections and malignancy were similar between the two induction arms. Conclusion. Alemtuzumab and rATG induction therapies were equally safe, but alemtuzumab was associated with less BPAR.

Does bioequivalence between modified cyclosporine formulations translate into equal outcomes

Neoral was replaced with a generic cyclosporine formulation on our hospital formulary. We compared outcomes for de novo kidney transplant recipients who either received Gengraf (n=88) or Neoral (n=100) in a single-center, retrospective review. As compared to patients who received Neoral, patients who received Gengraf were significantly more likely to have an acute rejection episode (39% vs. 25%, P=0.04), more likely to have a second rejection episode (13% vs. 4%; P=0.03), or to have received an antibody preparation to treat acute rejection (19% vs. 8%; P=0.02). Patients treated with Gengraf had a higher degree of intrapatient variability for cyclosporine trough concentrations as determined by %CV (P<0.05). The incidence of acute rejection at 6 months posttransplant was significantly higher in patients who received Gengraf compared to Neoral. A larger, prospective analysis is warranted to compare these formulations of cyclosporine in de novo kidney transplant recipients.

Valganciclovir prophylaxis in patients at high risk for the development of cytomegalovirus disease

Abstract: Background. Despite advances in antiviral therapies, cytomegalovirus (CMV) remains the leading opportunistic infection in the transplant population. Valganciclovir (VGC), the l‐valyl ester prodrug of ganciclovir (GCV), provides an excellent oral alternative to GCV for the prevention of CMV in transplant recipients. We investigated the use of VGC for CMV prevention in high‐risk renal and pancreas transplant recipients.

Influence of mild obesity on outcome of simultaneous pancreas and kidney transplantation.

The influence of body mass index (BMI) on outcome of simultaneous pancreas-kidney transplantation (SPK) has not been well described. We retrospectively reviewed 88 consecutive primary SPKs performed at our institution between March 15, 1995 and August 28, 2001. All patients received antibody induction and maintenance immunosuppression with tacrolimus, mycophenolate mofetil, and steroids. Systemicenteric implantation was performed in all patients. Primary end points were patient, pancreas, and kidney survival. Secondary end points were rates of anastomotic leakage, pancreas thrombosis, major infection, rejection, repeat laparotomy, and length of hospital stay. Values are shown as mean ± standard deviation, range, or percentage. Fifty-two patients (59.1%) were nonobese with a BMI ≦24.9 (mean 21.7 ± 2.2, range 15.4 to 24.9). Thirty-six patients were mild to moderately obese with a BMI ≧25 (mean 27.7 ± 2.2, range 25 to 35.1). Distribution of recipient age, sex, and ethnicity was similar between groups. Kidney and pancreas preservation times were similar between nonobese and obese patients. One-, three-, and five-year actuarial patient (nonobese: 95%, 95%, 95% vs. obese: 95%, 95%, 89%), kidney graft (nonobese: 91%, 91%, 87% vs. obese: 97%, 91%, 85%), and pancreas graft (nonobese: 78%, 78%, 73% vs. obese: 70%, 62%, 62%) survival were comparable between nonobese and obese (P = NS). The mean rates of pancreas thrombosis, major infection, pancreas rejection, kidney rejection, relaparotomy, and length of hospital stay were similar in the two groups. The overall duodenojejunal anastomotic leakage rate was 8%. Obese patients had a 17% incidence of leakage (6 of 36) compared to a 2% incidence of leakage in nonobese patients (P = 0.012). Six of seven leaks occurred in obese patients. Mean BMI in the seven patients with a leak (27 ± 1.9) was significantly higher than in patients who did not develop a leak (24 ± 3.7; P = 0.05). Although obesity had no effect on patient or graft survival, it was associated with a significantly higher leakage rate. There should therefore be a higher degree of suspicion for the presence of duodenojejunal anastomotic leaks in obese SPK recipients.

Effect of Ethnicity on Outcome of Simultaneous Pancreas and Kidney Transplantation

The influence of ethnicity on outcome of simultaneous pancreas‐kidney transplantation (SPK) is poorly defined. After excluding technical failures, we retrospectively reviewed 96 consecutive SPKs (63 Caucasians [C], 33 African‐Americans [AA]). All patients received antibody induction, tacrolimus, mycophenolate mofetil, and steroids. One‐, 3‐, and 5‐year actuarial patient survival was similar between C (98%, 95%, 87%) and AA (90%, 90%, 81%), p=NS. One‐, 3‐, and 5‐year kidney graft survival was similar between C (98%, 86%, 81%) and AA (85%, 85%, 78%), p =NS. One‐, 3‐, and 5‐year pancreas graft survival was significantly worse in AA (71%, 68%, 46%) than in C (90%, 85%, 81%), p = 0.008. The cumulative incidence of kidney and pancreas acute rejection (AR) was higher in AA compared with C. Distribution of kidney and pancreas rejection grade was similar between C and AA. AA experienced more pancreas graft losses from early death with functioning graft, AR, and late chronic rejection. The higher incidence of AR and resistance to currently employed induction, maintenance, and antirejection immunosuppression therapies in AA may account for their inferior pancreas graft survival. More aggressive immunosuppression strategies may improve pancreas graft survival in AA but may be associated with increased morbidity and mortality. Further study is warranted.

No difference between smokers, former smokers, or nonsmokers in the operative outcomes of laparoscopic donor nephrectomies.

The laparoscopic donor nephrectomy has revolutionized the living donation process for kidney transplantation. Because this surgery is elective and altruistic and smoking has been associated with greater technical difficulty and increased risk for postoperative complications for other types of surgeries, the potential risk of smoking must be addressed with regard to surgical complications. We reviewed 221 laparoscopic kidney donors with known smoking status. Forty-two (19%) were smokers, 39 (18%) were former smokers, and 140 (63%) were nonsmokers. Important donor demographics were similar between groups. There was no difference between the 3 groups for mean operative time (4.5 h vs. 4.6 h vs. 4.4 h), median or mean length of stay (2 days for all groups), estimated blood loss (173±137 mL vs. 209±184 mL vs. 188±198 mL), narcotic use (0.57±0.48 mg/kg vs. 0.49±0.26 mg/kg vs. 0.53±0.36 mg/kg of total 4 morphine equivalents), or postoperative complications. Smoking status does not seem to impact perisurgical patient outcomes in patients undergoing laparoscopic nephrectomies.

Long-term outcome of sirolimus rescue in kidney-pancreas transplantation

Sirolimus (SRL) rescue in kidney-pancreas transplantation has not been well described. We reviewed 112 KPTxs performed at our institution between December 3, 1995 and June 27, 2002. All patients received antibody induction, tacrolimus (TAC), mycophenolate mofetil (MMF), and steroids. In 35 patients, SRL was substituted for MMF for the following reasons: acute rejection (AR) of kidney or pancreas despite adequate TAC levels, MMF intolerance, increasing creatinine levels, and TAC-induced hyperglycemia. Three-year kidney and pancreas graft survivals were 97% and 90%, respectively. Of 10 patients who were switched to SRL because of AR, one kidney failed because of antibody-resistant AR, and one kidney developed borderline AR; the other eight patients remain AR-free. AR developed in seven other patients despite therapeutic SRL levels; six had TAC levels less than 4.5 ng/mL. The mean creatinine levels overall and for the group with increasing creatinine remained stable. All patients who were switched to SRL for TAC-induced hyperglycemia or MMF intolerance improved. Kidney-pancreas transplant recipients can be safely switched to SRL with excellent graft and patient survival.