M.F Egidi

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.

Conversion to sirolimus in solid organ transplantation: a Single-Center experience

BACKGROUND Calcineurin inhibitors are associated with adverse events, including nephrotoxicity and diabetes that might reduce the benefits of long-term graft survival. We report our experience in converting kidney (K), kidney-pancreas (KP), pancreas (P), and (L) recipients from a calcineurin inhibitor/mycophenolate mofetil (MMF)/prednisone dose-induced nephrotoxicity (K = 9, KP = 5, P = 1, L = 5), hemolytic uremic syndrome (HUS) (K = 7, KP = 5), chronic allograft nephropathy (K = 12, L = 1), and glucose intolerance (K = 9, KP = 6, P = 2, L = 2). METHODS The conversion protocol consisted of an abrupt discontinuation of the calcineurin inhibitor with sirolimus (8-12 mg, PO loading dose) initiated 24-72 hours after stopping the calcineurin inhibitor. Sirolimus was titrated to target trough levels of 12-16 ng/mL. Daclizumab 2 mg/kg IV was given to all KP and P recipients on days 0 and 14 postconversion. RESULTS Resolution of HUS occurred in 12 of 12 patients (100%) with a drop in serum creatinine from 3.3 +/- 1.5 to 1.8 +/- 0.9 mg/dL (P =.04). Sirolimus conversion due to nephrotoxicity, HUS, and chronic allograft nephropathy improved serum creatinine from 2.9 +/- 1.4 to 2.2 +/- 0.9 mg/dL (P =.01). Eleven of 19 patients (58%) resolved glucose intolerance. Two patients suffered rejection due to noncompliance. Increases in cholesterol (208 +/- 70 to 243 +/- 77 mg/dL, P <.05) and triglycerides (232 +/- 145 to 265 +/- 148 mg/dL, P = NS), and minimal reduction in platelet values (243 +/- 85 to 237 +/- 85, P = NS) occurred. CONCLUSIONS These data suggest that a calcineurin inhibitor-free immunosuppressive regimen with sirolimus, mycophenolate mofetil, and steroids preserves graft function in patients with clinical indications warranting calcineurin inhibitor discontinuation.

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.

Evolving experience of hepatitis B virus prophylaxis in liver transplantation

Abstract: Passive immunoprophylaxis with hepatitis B immunoglobulin (HBIG) is important to prevent recurrence of hepatitis B virus (HBV) after orthotopic liver transplantation (OLT) for chronic HBV cirrhosis. With availability of lamivudine (3TC), the use of combination prophylaxis with long‐term HBIG/3TC has been shown to prevent short‐term HBV recurrence. This report compares HBV recurrence rates between groups receiving no/short‐term HBIG, long‐term HBIG alone, or HBIG/3TC prophylaxis, and describes HBIG requirements during the first 6 and 12 months in the latter two groups. This study involved patients undergoing OLT at the University of Tennessee‐Memphis between May 1990 and July 2001. During this period, 388 liver transplants were performed at our center. All hepatitis B surface antigen (HBsAg)‐positive recipients (n = 27) were included in this retrospective analysis. The groups were similar with regard to pre‐transplant demographic characteristics such as age, gender, weight, and pre‐transplant diagnosis. Owing to the retrospective study design, median follow‐up was longer for the no‐prophylaxis (5.6 years) and the HBIG‐alone (6.0 years) groups compared to the HBIG/3TC group (4.2 years). Patient survival was 50% in the no‐prophylaxis and 71% in the HBIG‐alone groups compared to 100% in the HBIG/3TC group (P = 0.09). When censored for death with a functioning graft, graft survival was 50% in the no‐prophylaxis and 86% in the HBIG‐alone group compared to 100% in the HBIG/3TC group (P = 0.07). The overall incidence of HBV recurrence in the no‐prophylaxis era was 100% and 21% in the HBIG‐alone era compared to 0% in the HBIG/3TC era (P < 0.001), despite similar mean and median HBIG trough titers in the HBIG‐alone and HBIG/3TC groups. The incidence of HBV recurrence in HBV DNA‐positive recipients was 100% in the no‐prophylaxis era, 30% in the HBIG‐alone era, and 0% in the HBIG/3TC era (P < 0.001). Recipients in the HBIG‐alone group had a nearly two‐fold increase in HBIG requirement at 6 and 12 months in order to maintain similar HBIG trough titers post‐transplant compared to recipients in the HBIG/3TC group despite similar pre‐transplant HBV serology. This increased HBIG requirement in the HBIG‐alone group resulted in a marked increase in the mean overall cost of HBV prophylaxis in this group (

Human granulocytic ehrlichiosis in pancreas transplant recipients

47,367 at 6 months;

Observations on the use of sirolimus and tacrolimus in high-risk renal transplant recipients

84,280 at 12 months) compared to the HBIG/3TC group (

Lifestyle behaviors affect cardiovascular risk status in men 1 year after kidney transplantation

25,931 at 6 months;

Long-term outcomes in simultaneous kidney-pancreas transplant recipients with portal-enteric versus systemic-bladder drainage

49,599 at 12 months). These data demonstrate an improvement in patient and graft survival rates in the group receiving combination HBIG/3TC prophylaxis compared to the HBIG‐alone and no‐prophylaxis groups. There was a significant reduction in HBV recurrence in the group receiving combination HBIG/3TC when compared to the groups receiving HBIG alone or no prophylaxis. Furthermore, we demonstrated that the addition of 3TC to the long‐term HBIG regimen led to elimination of the disparity previously described in HBV recurrence rates between HBV DNA‐positive and HBV DNA‐negative recipients. Importantly, our data demonstrates a complete lack of HBV recurrence in the HBIG/3TC group at a median follow‐up of 4.2 years. Additionally, the data show that the addition of 3TC to the post‐operative prophylaxis regimen resulted in a reduction in the requirement of HBIG at 6 and 12 months, which markedly reduced the overall cost of post‐transplant HBV prophylaxis.

Role of surveillance biopsies in monitoring recipients of pancreas alone transplants

Abstract: Human ehrlichioses are tick‐borne infections caused by bacteria in the genus Ehrlichia of the family Rickettsiaceae. To date there have been three cases of ehrlichiosis reported in the transplant population, a human monocytic ehrlichiosis (HME) infection in a liver transplant recipient and two cases of human granulocytic ehrlichiosis (HGE) in kidney transplant recipients. We report three pancreas transplant patients who developed HGE in the last two years at a single southeastern center in the United States. All three patients had clinical, laboratory, and pathophysiologic findings on bone marrow biopsy and peripheral blood smears consistent with HGE, and responded to doxycycline therapy.