Agnes Lo

Comparison of sirolimus-based calcineurin inhibitor-sparing and calcineurin inhibitor-free regimens in cadaveric renal transplantation

Introduction. This study examines the efficacy and toxicity of sirolimus used as primary immunosuppression in combination with reduced dose tacrolimus (calcineurin inhibitor [CI]-sparing regimen) or mycophenolate mofetil (CI-free regimen) in high-risk cadaveric renal transplantation. Methods. Seventy subjects were treated in a quadruple sequential protocol in which 41 were treated with a CI-sparing regimen and 29 were treated with a CI-free regimen. The efficacy and toxicity profiles of these regimens were prospectively monitored and compared. Results. The study consisted of African Americans (71%), cadaveric donors (100%), donors aged more than 50 years (30%), and patients with delayed graft function (47%). At 1 year, patient survival, graft survival, and incidence of biopsy-proven acute rejection were 98%, 80%, and 10%, respectively, in the CI-sparing group and 100%, 89%, and 7%, respectively, in the CI-free group. Three-month protocol biopsies were performed in 41% (17/41) and 67% (20/29) of the subjects in the CI-sparing and CI-free groups, respectively. Subclinical rejection was detected in 6% (1/17) and 15% (3/20) of the subjects in the CI-sparing and CI-free groups, respectively. Histologic evidence of chronic allograft nephropathy was more prevalent in the CI-sparing group. At 1 year, the mean estimated creatinine clearance was higher in the CI-free group than in the CI-sparing group (72.4±20.0 mL/min vs. 50.5±20.8 mL/min, P <0.01). The two regimens had similar toxicity profiles (hospital readmission, infection, wound complications, and metabolic complications). Conclusions. Both sirolimus-based CI-sparing and CI-free regimens are safe and effective in a population with high immunologic risk. The CI-free regimen is associated with better renal function at 1 year post-transplant. Long-term follow-up will aid in determining the risk and benefit ratio of these regimens.

Polyomavirus in kidney and kidney-pancreas transplant recipients

Abstract: Purpose. To report the incidence and clinical characteristics of polyomavirus (PV) nephritis in kidney (KTX) and kidney–pancreas transplant (KPTX) recipients.

Two-dose daclizumab regimen in simultaneous kidney-pancreas transplant recipients: Primary endpoint analysis of a multicenter, randomized study

Background. Controversy exists about the optimal immunosuppressive regimen in simultaneous kidney-pancreas transplant (SKPT) recipients. This study determined the safety and efficacy of two dosing regimens of daclizumab compared with no antibody induction in SKPT recipients receiving tacrolimus, mycophenolate mofetil, and steroids. Methods. A total of 297 SKPT patients were enrolled in this prospective, multicenter, randomized, open-label study. The patients were randomized into three groups: daclizumab 1 mg/kg per dose every 14 days for five doses (group I, n=107), daclizumab 2 mg/kg per dose every 14 days for two doses (group II, n=112), and no antibody induction (group III, n=78). All patients received tacrolimus, mycophenolate mofetil, and steroids as maintenance immunosuppression. Results. Demographic and transplant characteristics were similar among the groups. At 6 months, there were no differences in patient, kidney, and pancreas graft survival rates among the three groups. The probability of either kidney or pancreas allograft rejection at 6 months was 21%, 17%, and 32% in groups I, II, and III, respectively (P =0.042). The median time to first acute rejection of either the kidney or pancreas was 23 days in group I, 44 days in group II, and 20 days in group III (group I vs. II, P =0.078; group II vs. III, P =0.016). At 6 months, the actuarial event-free survival (no acute rejection, allograft loss, or death) rates were 66%, 77%, and 56% in groups I, II, and III, respectively (group I vs. III, P =0.119; group II vs. III, P =0.002). There were no differences in the incidence of serious adverse events including infectious complications among the groups. All three groups demonstrate excellent kidney and pancreas function at 6 months. Conclusions. Daclizumab is safe and effective in reducing the incidence of acute rejection in SKPT recipients compared with no antibody induction. Moreover, the two-dose regimen of daclizumab (2 mg/kg on days 0 and 14) compares favorably with the standard five-dose regimen.

Observations regarding the use of sirolimus and tacrolimus in high‐risk cadaveric renal transplantation

Abstract:  Background:  Balancing the risk of acute rejection (AR) with drug‐induced toxicities complicates the selection of the optimal immunosuppressive regimen, especially in the high‐risk renal transplant recipient. This study was designed to determine the optimal dosage combinations of tacrolimus and sirolimus in a high‐risk cadaveric renal transplant population.

Patterns of cytomegalovirus infection in simultaneous kidney-pancreas transplant recipients receiving tacrolimus, mycophenolate mofetil, and prednisone with ganciclovir prophylaxis.

Abstract: Background: The impact of tacrolimus (TAC), mycophenolate mofetil (MMF) and steroid immunosuppression on cytomegalovirus (CMV) infection in combination with ganciclovir prophylaxis in simultaneous kidney–pancreas transplantation (SKPT) has not been well studied. Methods: A retrospective analysis was made of 75 SKPTs performed between 1 January 1996 and 7 January 1999. All patients received ganciclovir for 3 months, but CMV donor (D)+/ recipient (R)− patients received ganciclovir for 6 months. Results: 16/74 (22%) were CMV D+/R−, 25 (33%) D+/R+, 16 (22%) D−/R+, and 17 (23%) D−/R− (1 patient with unknown donor serology was excluded). The mean time to CMV infection was 198 days post‐transplant. The incidence of either CMV infection or tissue invasive CMV disease was 16/74 (22%), including 9 (12%) with CMV infection and 7 (10%) CMV disease. The one‐year patient, kidney, and pancreas graft survival rates were 91%, 89%, and 83%, respectively. The mean follow‐up was 29 months (minimum of 12 months). CMV infection was not associated with an increased incidence of graft failure or mortality. The D+/R− group had the highest incidence of CMV infection (44%) compared with the other serologic groups (17%, P=0.02). Concurrent CMV and rejection occurred more frequently in the D+/R− than the other serologic groups (25% vs. 7%, P=0.03). The D−/R− group had the best outcomes, with no CMV infection, improved kidney graft survival at the end of follow‐up (82% vs. 72%, P=0.04) and the highest event‐free survival (no CMV infection, rejection, or graft loss) when compared to the other groups (76% vs. 33%, P<0.01). Conclusions: Compared to previous studies, ganciclovir prophylaxis delayed the onset and reduced the severity of CMV infection in patients receiving TAC, MMF, and steroids. Despite ganciclovir prophylaxis, CMV seronegative patients receiving CMV D+ organs had worse outcomes than seronegative recipients receiving CMV D− organs.

Long-term experience with simultaneous kidney-pancreas transplantation with portal-enteric drainage and tacrolimus/mycophenolate mofetil-based immunosuppression.

Abstract: Background/Aims:  Refinements in surgical techniques and advances in clinical immunosuppression have led to steadily improving results in pancreas transplantation (PTX). Although there is renewed interest in enteric exocrine drainage, most PTXs are performed with systemic venous delivery of insulin. To improve the physiology of PTX, we developed a novel technique of portal venous delivery of insulin and enteric drainage of the exocrine secretions (portal‐enteric [P‐E]). The purpose of the study was to analyse outcomes in patients undergoing PTX with P‐E drainage and contemporary immunosuppression.

A multicenter, open-label, comparative trial of two daclizumab dosing strategies vs. no antibody induction in combination with tacrolimus, mycophenolate mofetil, and steroids for the prevention of acute rejection in simultaneous kidney–pancreas transplant recipients: interim analysis

Introduction: The safety and efficacy of daclizumab (1 mg/kg/dose every 14 d for five doses) has been established in kidney and heart transplant recipients. Alternative dosing regimens based on pharmacokinetic simulation and limited clinical trials are being investigated. The purpose of this ongoing multicenter study is to determine the safety and efficacy of two dosing regimens of daclizumab as an adjunctive immunosuppressive agent compared with no antibody induction in simultaneous kidney–pancreas transplant (SKPT) recipients receiving tacrolimus (TAC), mycophenolate mofetil (MMF) and steroids as primary immunosuppression.

Insulin independence achieved using the transmesenteric approach to the portal vein for islet transplantation

Clinical human islet transplantation has been performed successfully using a percutaneous transhepatic approach to access the portal vein. The risks from percutaneous delivery of islets, such as bleeding and puncturing neighboring structures, can be avoided by a transmesenteric approach to the portal vein, which we have used to stent completely or near-completely occluded portal veins in both cirrhotic and noncirrhotic patients with minimum morbidity. After minilaparotomy, a second-order tributary branch of the mesenteric vein is cannulated to provide endovascular access to the portal vein. The islet preparation is infused through a catheter directed under fluoroscopy from the mesenteric vein to the portal vein. Pre- and postinfusion portograms are obtained to confirm the absence of any interval changes in portal venous flow. We have performed this procedure successfully in three islet-transplant recipients each receiving two infusions on separate occasions, with some of these procedures performed under local anesthesia without complications. The transmesenteric approach promises to be a safe alternative to percutaneous islet delivery.

Relationship between patient age and duration of physician visit in ambulatory setting : Does one size fit all?

Objectives: To determine whether patient age, the presence of comorbid illness, and the number of prescribed medications influence the duration of a physician visit in an ambulatory care setting.

Multicenter survey of daclizumab induction in simultaneous kidney-pancreas transplant recipients

We report an experience with 71 simultaneous kidney-pancreas transplant (SKPT) recipients receiving daclizumab induction in combination with tacrolimus (TAC), mycophenolate mofetil (MMF), and steroids. The mean follow-up time was 5.9+/-2.5 (SD) months (range 0.5-11 months). The study population included 47 males (65%) and 24 females (35%) with a mean age of 40+/-8 years. The mean pretransplant duration of diabetes and dialysis were 25+/-8 and 1.5+/-0.9 years (34 hemodialysis, 16 peritoneal dialysis), respectively. Mean HLA match was 1.2+/-1.5, with one patient receiving a second transplant. The mean cold ischemic times for the kidney and the pancreas were 15+/-5 and 16+/-4 hr, respectively. Six-month patient, kidney, and pancreas graft survival and rejection rates were 97, 96, 93, and 35%, respectively. There were two deaths, one due to fungal infection and the other due to a cardiac event. There were three kidney graft losses, two immunological, and one death with function. Of the five pancreas graft losses, two were due to infection, one immunological, one thrombosis, and one death with function. The patient population was then stratified according to the number of daclizumab doses: 4-5 doses (n=45) or 1-3 doses (n=26). There were no differences in patient and kidney graft survival rates, 98 vs. 96%, and 92 vs. 92%, respectively. However, there was a trend toward improved pancreas graft survival in the group receiving 4-5 doses (96%) compared with 1-3 doses (85%), P=0.07. Although more patients receiving 1-3 doses had rejection (54%) than patients receiving 4-5 doses (24%), there was no dose response relationship between the total number of doses or the adjusted total mg/kg dose and time to rejection. All patients with functioning grafts have good renal and pancreas allograft function at 6 and 12 months. The overall incidence of major infection was 27% and there were no differences in the incidence of infection between the two groups. No major adverse events were attributed to daclizumab use. In conclusion, excellent short-term outcomes were noted in this retrospective, multicenter survey of initial experience with daclizumab induction in combination with TAC, MMF, and steroids in SKPT recipients. Optimal dosing strategies for SKPT recipients remain to be determined.