Single-shot antithymocyte globuline and daclizumab induction in simultaneous pancreas and kidney transplant recipient: three-year results

Since 1996, preoperative single-shot dose antithymocyte globuline (ATG) with prednisolone (PRD), mycophenolate mofetile (MMF), and tacrolimus (TAC) is the favorite induction therapy in our center. In a series of 25 first simultaneous pancreas and kidney transplant (SPK) recipients, 5 doses of daclizumab were administered in addition to standard induction. Here we present our 3-year experience. Immunosuppression was started prior to reperfusion consisting of daclizumab (1 mg/kg body weight [bw]), ATG (4-6 mg/kg bw) and 250 mg PRD. After surgery, PRD was reduced gradually, TAC trough levels were between 8-15 ng/mL, MMF was given twice daily (2-3 g/d) as well as 4 further doses dacilzumab every 14 days. After 3 years, patient, pancreas, and kidney graft survival rates are 100%, 84%, and 92%, respectively. Four pancreas grafts were lost (chronic allograft dysfunction, n = 2; recurrent abdominal infection, n = 1; acute rejection [AR] without treatment, n = 1). Both patients suffering from severe infection and untreated AR lost their kidney graft too. During the first 3 months after SPK, 3 AR episodes were observed in 2 patients (8%). After a 3-year period, 8 AR episodes occurred in 7 recipients (28%). AR was treated using PRD (n = 5) or ATG (n = 1). In 1 case, immunosuppression was switched from TAC to sirolimus successfully. Overall, 8 AR episodes occurred in 7 patients (28%) during the first 3 years after SPK. One severe infection led to graft lost 13 months after SPK. In this series, the combination of ATG and daclizumab prevented AR episodes, successfully providing considerable 3-year survival rates.     

Impact of Portal Venous Pancreas Graft Drainage on Kidney Graft Outcome in Simultaneous Pancreas-Kidney Recipients Reported to UNOS

Clinical data on the potential immunologic impact of portal (PD) vs. systemic (SD) venous pancreas graft drainage on outcome remains controversial. We reviewed the UNOS database to study the effect of PD vs. SD on the incidence of kidney graft rejection and survival in first cadaveric simultaneous pancreas-kidney (SPK) recipients transplanted 1994-2001. We studied three groups: all SPK (n=6629, 13% PD) (group I), SPK on tacrolimus (n=3563, 17% PD) (group II), and SPK on tacrolimus performed at centers with significant PD experience (n=948, 46% PD) (group III). The cumulative kidney graft rejection incidence for PD vs. SD was only significantly different in group I (for PD vs. SD, respectively: at 6 months, 31% vs. 36% [p=0.015]; at 1 year, 37% vs. 43% [p=0.006]). Kidney graft survival was similar in all groups for PD vs. SD. Multivariate analysis of group III showed only transplantation during the earlier era (1994-96), but not SD, to be an independent risk factor for kidney graft rejection. Portal venous pancreas graft drainage does not affect kidney graft rejection and survival in SPK recipients on tacrolimus. Our data suggests that the efficacy of current immunosuppressive protocols and increasing center experience are clinically much more relevant than any potential immunologic advantage of portal venous drainage in SPK recipients.     

Pancreas-after-kidney transplantation: an increasingly attractive alternative to simultaneous pancreas-kidney transplantation

BACKGROUND: Historically, the clinical acceptability of pancreas-after-kidney (PAK) transplantation has been hampered by relatively high acute rejection rates and lower pancreas graft survival rates when compared with the more commonly performed simultaneous pancreas-kidney (SPK) transplantation. The purpose of this study was to compare PAK transplantation to SPK transplantation in the Thymoglobulin induction era. METHODS: The authors reviewed all bladder-drained PAK (n=47) transplants receiving rabbit antithymocyte globulin induction from June 1998 to June 2002 and compared them with SPK (n=25) transplants during the same time period at their institution. The authors retrospectively studied data on demographics, patient survival, graft (pancreas and kidney) survival, complications, and biopsy-proven rejection episodes. RESULTS: The actuarial 1-year patient survival was 93% for the PAK group versus 100% for the SPK group (P =not significant [NS]). The actuarial 1-year pancreas graft survival was 87% for the PAK group versus 92% for the SPK group (P =NS). Waiting time for PAK was significantly shorter than for SPK (6.3 +/- 5.2 vs. 16.2 + -13.7 months, P <0.05). Clinical acute rejection rates were similar in the two groups (4.3% for PAK vs. 4.0% for SPK). PAK recipients demonstrated a greater decline in renal function after transplantation compared with SPK. A multivariate analysis failed to elucidate the cause. CONCLUSIONS: Newer immunosuppressive regimens allow PAK transplant patients to achieve immunologic outcomes similar to SPK transplant patients. Although the shorter waiting time and the ability to use living-donor kidneys make PAK an increasingly attractive alternative to SPK transplantation, its effect on renal allograft function deserves further attention.     

Alemtuzumab induction in deceased donor kidney transplantation

BACKGROUND: The use of alemtuzumab for induction therapy in kidney transplantation has been increasing. Herein is a report of graft outcomes associated with alemtuzumab induction from the Organ Procurement and Transplantation Network/United Network for Organ Sharing database. METHODS: A total of 14,362 deceased donor kidney transplants from 2003 to 2004 received no induction (n=4,364), antithymocyte globulin (ATG; n=4,930), interleukin-2 receptor antagonists (IL-2RA; n=4,378), or alemtuzumab (n=690). Acute rejection within the initial hospitalization, 6 months, and 1 year; graft survival; and rejection-free survival were examined. Graft and rejection-free survival of alemtuzumab recipients maintained with tacrolimus (FK) or cyclosporine (CSA), mycophenolate mofetil (MMF), and steroids versus no calcineurin inhibitors (CNI), MMF, and steroids were compared. RESULTS: Alemtuzumab recipients had less acute rejection during the initial hospitalization (2.3%) than no induction, ATG, and IL-2RA (7.6%, 3.4%, and 4.8%, respectively; P<0.001). There was increased acute rejection at 6 months and 1 year with alemtuzumab (14.5% and 19.2%) compared to no induction (12.7% and 14.8%, P<0.001), ATG (8.2% and 10.2%, P<0.001), and IL-2RA (11.1% and 13.0%, P<0.001) with no difference in adjusted relative risk for graft loss. Alemtuzumab recipients receiving FK or CSA, MMF, and steroids had increased graft (FK/MMF/steroids, P<0.001, CSA/MMF/steroids, P=0.007) and rejection-free survival (FK/MMF/steroids, P<0.001, CSA/MMF/steroids, P=0.006) over 24 months compared to no CNI, MMF, and steroids. CONCLUSIONS: Despite reduced early rejection, acute rejection rates at 6 months and 1 year with alemtuzumab induction exceeded other forms of induction therapy. Maintenance with CNI-based immunosuppression may improve graft and rejection-free survival compared to CNI-free regimens among alemtuzumab recipients.     

Steroid withdrawal in pancreas transplant recipients

BACKGROUND: Numerous studies of steroid withdrawal have been carried out in kidney and liver transplant recipients, but only a few in pancreas transplant recipients. Yet, pancreas transplant recipients could have significant long-term benefits from steroid withdrawal. METHODS: We performed a retrospective analysis to determine the feasibility of steroid withdrawal in pancreas transplant recipients. RESULTS: Of 360 recipients who underwent a pancreas transplant between January 1, 1994 and June 30, 1998, 14 attempted steroid withdrawal (12 simultaneous pancreas-kidney [SPK]; 2 pancreas transplant alone [PTA]). Reasons for steroid withdrawal were bone fractures (n = 3), psychiatric disorders (n = 2), severe acne (n = 1), recurrent infections (n = 4), and problems with hypercholesterolemia or hypertension (n = 4). All 14 were maintained on tacrolimus and mycophenolate mofetil (MMF) immunosuppression, except for 1 who was on tacrolimus and azathioprine (AZA). Of the 14 recipients, 11 had no episodes of acute rejection before steroid withdrawal. The remaining 3 had one or more acute rejection episodes. Of the 14 recipients, 10 (72%) currently remain off steroids (mean follow-up 18 months, range 5-51 months). However, 4 recipients have resumed steroids: 2 after an acute rejection episode (at 2 and 21 months post-withdrawal) and 2 because of leukopenia (WBC < 3000) and an inability to tolerate full-dose MMF. Steroid withdrawal was unsuccessful in both PTA recipients and in 2 of the 12 SPK recipients. All 14 recipients currently have a functioning pancreas graft. However, 1 of the SPK recipients, in whom steroid withdrawal failed, has developed chronic kidney rejection and is now back on hemodialysis awaiting a retransplant. CONCLUSION: Steroid withdrawal is possible in up to 70% of pancreas transplant recipients. Further studies are necessary to define ideal candidates for steroid withdrawal. Based on the results of this analysis, we have launched a prospective, randomized trial of steroid withdrawal in pancreas transplant recipients.     

Neoquadruple induction with antithymocyte globulin/azathioprine/cyclosporine/prednisolone in simultaneous pancreas and kidney transplant recipients: 8.5-year results

Ten years ago therapy with antithymocyte globulin or OKT3, azathioprine, cyclosporine, and prednisolone was the most common induction treatment for simultaneous pancreas/ kidney (SPK) recipients. Although immunosuppression was started after surgery, there was a high incidence of acute rejection episodes. In 1995, we modified the application of antithymocyte globulin and prednisolone by starting prior to reperfusion. Between 1995 and 1996, 30 patients underwent a first SPK. Prior to reperfusion, antithymocyte globulin (4-6 mg/kg body weight) and 250 mg prednisolone were administered. Intraoperatively, another 250 mg prednisolone were administered as well as intravenous azathroprine 3 mg/kg. After surgery up to 10 doses of antithymocyte globulin were administered and cyclosporine trough levels targeted to 200 to 250 ng/mL. Prednisolone was reduced gradually. After a median period of 8.5 years (range: 7.8-9.5 years) patient, pancreas, and kidney graft survival were 93.3%, 70%, and 76.7%, respectively. Sixteen acute rejection episodes were diagnosed in 11 patients (36.7%), who were treated with prednisolone bolus (n = 4), prednisolone with OKT3 (n = 8), prednisolone with antithymocyte globulin (n = 1), cyclosporine to tacrolimus conversion (n = 2), or plasmapheresis (n = 1). Two recipients died after SPK due to severe infection or carcinoma with functioning grafts. Seven further pancreas grafts were lost. Five kidney losses were observed besides the two recipients who died with functioning grafts. While previous protocols yielded a rejection incidence after SPK between 50% and 80%, we observed 60% of patients with no rejection episode during an 8.5-year median follow-up.     

Historical controlled trial of OKT3 versus basiliximab induction therapy in simultaneous pancreas-renal transplantation

SUMMARY:   Simultaneous pancreas–kidney (SPK) transplant recipients are at high immunological risk of rejection. Antibody induction is beneficial but lymphocyte-depleting therapy is associated with a high incidence of side-effects. We performed a historical controlled trial to compare OKT3 versus anti-CD25 antibody (basiliximab) induction therapy with regard to patient, kidney and pancreas survival, as well as to examine for any differences in acute rejection, graft function, and infective complications. Twenty-eight consecutive SPK transplants were performed at the Monash Medical Centre between December 1997 and November 2001. Anti CD3 monoclonal antibody (OKT3) was used prior to March 2000 ( n  = 12) and basiliximab was used after ( n  = 16), both in combination with cyclosporin, mycophenolate, and prednisolone. A retrospective comparison of outcomes was performed. At 6 months, patient (100 vs 100%), kidney (91.7 vs 91.7%) and pancreas (75 vs 83.3%) survival were similar in the OKT3 and basiliximab groups, respectively. A minority of subjects in each group remained free from rejection (42% basiliximab vs 25% on OKT3, P  = NS). Renal function was superior in the basiliximab group (mean calculated creatinine clearance 79.4 ± 11.9 vs 54.5 ± 15.9 mL/min for  basiliximab vs OKT3, P  < 0.001). The incidence of major opportunistic infection was lower in basiliximab-treated patients (9 vs 50% in the OKT3 group, P  = 0.033). Basiliximab was associated with similar 6-month patient, kidney and pancreas survival, superior renal function and less opportunistic infection as compared with OKT3 induction therapy in SPK transplants. Basiliximab is at least as effective and is safer than OKT3 for induction therapy in SPK transplantation.     

Very early steroid withdrawal in simultaneous pancreas-kidney transplants.

BACKGROUND: Simultaneous pancreas-kidney (SPK) transplantation is an effective treatment for patients suffering from type 1 diabetes mellitus. Conventional immunosuppressive treatments include steroids that may induce insulin resistance and are responsible for many side effects. In de novo SPK, early withdrawal of corticosteroids may be an important issue. METHODS: A total of 24 consecutive patients with type 1 diabetes mellitus had been treated by SPK transplantation. All of them had a short induction therapy with anti-thymoglobulin (ATG) and steroids for only 4 days, association with CellCept and tacrolimus. The rate of acute rejection, graft and patient survival and side effects have been analysed. RESULTS: Patient and kidney survival was 100% and the pancreas survival was 95.6% at 1 year. The rate of acute rejection of kidney and pancreas was 4.2% and 8.3% at 6 months, respectively. The mean serum creatinine was 98.9+/-19.6 micromol/l and the mean HbA1c concentration was 5.1%+/-0.5% at 6 months. Only four patients developed a cytomegalovirus primo-infection, associated in one case with pneumonia, whereas 75% of patients developed a bacterial infection. Because of the occurrence of leucopenia and/or diarrhoea, CellCept has been dramatically decreased in 33% of cases and required the re-introduction of steroids. CONCLUSION: A short induction with ATG and steroids associated with a chronic therapy with CellCept and tacrolimus is safe and efficient in preventing acute renal rejection in SPK.     

Infectious complications following 72 consecutive enteric-drained pancreas transplants

New immunosuppressive protocols and advanced surgical technique resulted in an improved outcome of pancreatic transplantation (PTx) with infection remaining the most common complication. Seventy-two enteric-drained whole PTxs performed at the Innsbruck University Hospital between September 2002 and October 2004 were retrospectively analyzed. Prophylactic immunosuppression consisted of either the standard protocol consisting of single bolus antithymocyteglobulin (ATG) (Thymoglobulin, Sangstat or ATG Fresenius) induction (9 mg/kg), tacrolimus (TAC), mycophenylate mofetil (MMF) and steroids (38 patients) or a 4-day course of ATG (4 mg/kg) tacrolimus and steroids with MMF (n = 19), or Sirolimus (n = 15). Perioperative antimicrobial prophylaxis consisted of Piperacillin/Tazobactam (4.5 g q 8 h) in combination with ciprofloxacin (200 mg q 12 h) and fluconazole (400 mg daily). Ganciclovir was used for cytomegalovirus (CMV) prophylaxis if donor was positive and recipient-negative. Patient, pancreas, and kidney graft survival at 1 year were 97.2%, 88.8%, and 93%, respectively, with no difference between the groups. All retransplants (n = 8) and single transplants (n = 8) as well as all type II diabetics and nine of 11 patients older 55 years received standard immunosuppression (IS). The rejection rate was 14% and infection rate 46% with no difference in terms of incidence or type according to the three groups. Severe infectious complications included intra-abdominal infection (n = 12), wound infection (n = 7), sepsis (n = 13), respiratory tract infection (n = 4), urinary tract infection (n = 12), herpes simplex/human herpes virus 6 infection (n = 5), CMV infection/disease (n = 7), post-transplant lymphoproliferative disorder (PTLD, n = 3), invasive filamentous fungal infection (n = 4), Clostridial/Rotavirus colitis (n = 1), and endocarditis (n = 1). All four patients in this series died of infectious complications (invasive aspergillosis n = 2) (one with Candida glabrata superinfection), invasive zygomycosis (n = 1), PTLD (n = 1). Five grafts were lost (vascular thrombosis n = 3, pancreatitis n = 1, noncompliance n = 1). Infection represented the most frequent complication in this series and all four deaths were of infectious origin. Better prophylaxis and management of infections now should be the primary target to be addressed in the field of pancreas transplantation.     

Thymoglobulin induction decreases rejection in solitary pancreas transplantation.

BACKGROUND: Solitary pancreas transplants, both pancreas transplant alone (PTA) and pancreas after kidney (PAK), have higher rejection rates and lower graft survivals than simultaneous pancreas-kidney transplants (SPK). The aim of this study is to compare three different antibody induction regimens in solitary pancreas transplant recipients and to assess the role of surveillance pancreas biopsies in the management of these patients. METHODS: Solitary pancreas transplant recipients between 01/98 to 02/00 (n=29) received induction with either daclizumab (1 mg/kg on day 0, 7, 14), OKT 3 (5 mg/day x0-7), or thymoglobulin (1.5 mg/kg/day x0-10). Maintenance immunosuppression was similar for the three groups. All rejections were biopsy-proven either by surveillance/protocol or when clinically indicated. RESULTS: The 1-year graft survival was 89.3% overall and 91.7% in the thymoglobulin group. Thymoglobulin significantly decreased rejection in the first 6 months when compared with OKT3 or daclizumab (7.7 vs. 60 vs. 50%). Acute rejections were seen on surveillance biopsies in the absence of biochemical abnormalities in 40% of patients. CONCLUSIONS: Thymoglobulin induction regimen led to a low incidence of acute rejection and a high rate of graft survival in solitary pancreas transplants. In addition, surveillance biopsies were useful in the detection of early acute rejection in the absence of biochemical abnormalities.     

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.     

Influence of pancreas and kidney transplant function on recipient survival

The aim of this study was to evaluate long-term survival after simultaneous pancreas and kidney (SPK) transplantation in relation to function of both grafts. Among 67 recipients who received SPK transplants between 1988 and 2004, 35 had follow-up longer than 18 months, and were divided into: group I (n = 20), recipients with good function of both grafts; group II (n = 7), patients who had lost transplanted pancreas but had still good kidney graft function; group III (n = 8), patients who had lost both grafts. Comparison of survival rates and analysis of the reason of mortality among groups was performed. The cumulative survival rate was significantly higher in group I than in group III (after 3, 5, 10 years: 100%, 100%, 80% vs 75%, 50%, 37%, respectively). Cumulative survival rate for group II after 3, 5, 10 years was 100%, 100%, 33%, respectively. There were no significant differences in survival rates between groups I and II and between groups II and III. In group I deaths for cardiovascular event and for leukemia were noted. In group II deaths due to cardiovascular event and sepsis were observed. In group III all patients died due to cardiovascular events and the mean time from loss of pancreas and kidney graft function to death was: 75 +/- 51 months (range from 19 to 142), and 49 +/- 26 months (range 19 to 99), respectively. Good pancreas and kidney graft functions prevent death due to cardiovascular event.     

The use of intravenous tacrolimus and mycophenolate mofetil as induction and maintenance immunosuppression in simultaneous pancreas--kidney recipients with previous transplants

Clinical trials using quadruple immunosuppression that include the combination of tacrolimus (TAC) and mycophenolate mofetil (MMF) have been shown to reduce the incidence of acute rejection episodes in simultaneous pancreas-kidney (SPK) transplantation. In attempting to obtain a low rejection rate without antibody induction therapy, we proceeded with the combination of TAC intravenous (i.v.), MMF, and steroids as induction therapy and as primary immunosuppression for recipients with previous transplants. In this study, we analyzed 10 patients who received previous transplants, treated with low-dose TAC i.v. as induction therapy. Group A consisted of 6 patients with previous transplants that underwent SPK and group B consisted of four recipients with previous SPK that underwent cadaveric kidney transplants. For group A, the previous transplants were: living related kidney (LRK) followed by islet cell (IC) transplant (n=2), LRK transplant (n=1), cadaver kidney (CAD) and IC transplant (n=1), SPK (n=1), and three previous CAD kidney transplants (n=1). In group A, all six kidneys were lost due to recurrent diabetic nephropathy, IC possibly to rejection, and the pancreas due to thrombosis. In group B with previous SPK transplants, three recipients lost their kidney to chronic rejection and one to long-term use of a nephrotoxic antibiotic. Currently, in all group A and B patients, the kidney and the pancreas are functioning, although 1 patient in group A developed type 2 diabetes (normal fasting C-peptide). Two patients in group A developed three rejection episodes that responded to steroid treatment. The results indicate the TAC i.v. in combination with oral TAC, MMF, and steroids offer effective induction therapy in patients with previous transplants.     

Observations on quadruple immunosuppression maintenance therapy using rapamycin, low-dose cyclosporine, mycophenolate mofetil, and prednisone following ATG induction

INTRODUCTION: We prospectively evaluated an immunosuppressive regimen consisting of rapamycin (Rapa), low-dose cyclosporine (CsA), low-dose mycophenolate mofetil (MMF), and prednisone (group 1) versus a regimen of CsA, MMF, and prednisone (group 2) in mismatched living related donor (LRD) and living unrelated donor (LUD) kidney transplantation. METHODS: Group 1 included 24 transplant recipients of eight mismatched LRD and 16 LUD, treated with Rapa, low-dose MMF, CsA, and prednisone. Group 2 included 53 transplant recipients (25 LRD, 27 LUD, and one cadaveric donor), treated with MMF, CsA, and prednisone. All patients in group 1 received a single bolus of rabbit-anti-human T-lymphocyte immune serum (ATG-Fresenius 4 to 6 mg/kg). In group 2, patients received either a single ATG or an extended ATG course (3 to 5 days postoperatively). RESULTS: Acute rejection occurred in one patient in group 1 (4.2%) and in five patients (9.4%) in group 2, all of which resulted in graft loss. Serum creatinine was not significantly different between the two groups. CONCLUSION: The immunosuppressive protocol of Rapa, CsA, MMF, and prednisone with single-bolus induction ATG achieves excellent immunosuppression and graft survival with no apparent risks in the short and intermediate term.     

Combined pancreas kidney transplantation after isolated kidney transplantation

Simultaneous pancreas kidney transplantation (SPK) is an established therapy for type 1 diabetics with end stage or preterminal renal disease. SPK is superior to isolated kidney transplantation (KTX) in diabetic patients. Even pancreas-re-transplantations are more common in these patients now, mostly after SPK. But Experience with SPK after KTX is rare. Between 1994 and 2003 six Re-SPK 4.5 to 8.5 years after KTX were performed in our department. Average age of the recipients was 40.5 years. They had been suffering from diabetes for an average of 29.3 years. Four recipients were on dialysis again, whereas two had preterminal renal insufficiency. Pancreas transplants were drained through the bladder (n = 1) or into the small intestine (n = 5) with systemic venous anastomosis. After a median observation period of 28 months (8 to 99 months) all six recipients are insulin free. One patient lost his kidney graft due to severe acute rejection. Therefore kidney graft survival is 83 %. Four acute rejections (66 %) were observed in 4 patients. Only one rejection was treated successfully by steroids. Two rejections could be stopped with antibodies. 3 patients had infections in the early postoperative period (sinusitis, urinary tract infection, wound infection). Even after KTX with graft failure, diabetic patients suffering from renal disease can be re-transplanted successfully with SPK.     

A single center's clinical experience with quadruple immunosuppression including ATG or IL2 antibodies and mycophenolate mofetil in simultaneous pancreas–kidney transplants

Acute rejection remains a major problem in simultaneous pancreas–kidney (SPK) transplant and occurs in 60–100% of the cases.
With the introduction of mycophenolate mofetil (MMF) replacing azathioprine (AZA) as a basis immunosuppressant, reduced rates of rejection have been reported. This study investigates the frequency and clinical relevance of allograft rejection in SPK patients receiving anti‐thymocyte globulin (ATG) or Basiliximab® induction therapy and cyclosporine Neoral® (CyA), MMF, steroid basis immunosuppression.
Between December 1996 and October 1999, 21 consecutive patients (15 males, 6 females) received a SPK transplant at our institution with a mean±standard deviation (SD) age of 42±6 yr. Of these, 14 patients were treated with anti‐thymocyte globulin (ATG) Fresenius® (rabbit) 3–5 mg/kg for 6±2 d, cyclosporine Neoral (CyA) (trough levels 350–400 ng/mL), MMF 3 g/d and low dose steroid therapy. Seven SPK patients were treated with Basiliximab (Simulect®, Novartis 20 mg on d 0 and d 4 post‐transplant) instead of ATG. The patients had an average human leucocyte antigen (HLA) mismatch of 3.9/6 and a negative cross match. All patients remained on triple drug therapy. Three patients were switched to tacrolimus instead of Neoral for CyA intolerance. The mean±SD cold ischemia time (CIT) of the organs was 10.1±2.4 h for the pancreas and 10.5±2.6 h for the kidney.
Results: Biopsy‐proven rejection occurred in the kidney of 1 ATG patient (8%), which responded to steroid bolus therapy. One of the patients (14%) with Basiliximab induction developed renal allograft rejection, which was resolved after a 6‐d course of anti‐CD3 mAb (OKT3) treatment. All patients (100%) were free from rejection in the pancreas, as measured by urine amylase levels and glycemic control without the need for exogenous insulin with a mean glycosylated hemoglobin (HBA₁C) of 5.1±0.7% and serum creatinine with a mean of 1.24±0.24 mg/dL in a mean follow‐up period of 17±15 months (median 12, range 2–37).
Conclusion: Triple drug immunosuppression including cyclosporine, MMF and low dose steroids with ATG or interleukin 2 (IL2) receptor antibodies induction therapy appears to be a very suitable immunosuppressive regimen for combined pancreas–kidney transplant (PKT) with a marked reduction in the incidence of rejection.     

胰肾联合移植的排斥反应

目的　探讨胰肾联合移植术后的排斥反应。方法　对我院施行的 3例胰肾联合移植的病人 ,采用FK5 0 6 MMF Perid Zenapax四联免疫治疗方案 ,通过床边彩超及Cr、BUN、血糖等来监测移植物的排斥反应。对排斥反应采用激素冲击疗法 ,对激素不敏感者采用OKT3治疗。结果　3例患者中有 2例出现排斥反应 ,其发生率达 6 6 % ;在出现排斥反应时 ,首先表现为低热、全身不适 ,尿量减少 ,血Cr、BUN升高 ,彩超示移植物血流阻抗升高 ,之后才是血糖升高。结论　胰肾联合移植中 ,排斥反应与多种因素有关 ,移植肾对移植胰具有保护作用 ,肾脏可以作为监测胰腺排异的窗口 ,彩超检查可以作为筛选移植物排异反应的手段。     

Tacrolimus plus low-dose mycophenolate mofetil in renal transplant recipients: better 2-year graft and patient survival than with a higher mycophenolate mofetil dose

OBJECTIVES: Mycophenolate mofetil (MMF) has become more widely prescribed in recent years, but its adverse effects on the gastrointestinal system and bone marrow restrict its use in certain settings. The aim of this study was to compare the demographic features and clinical data for 173 renal transplant recipients who received tacrolimus (TAC) plus 1 g/d MMF (group I, n = 112) versus TAC plus 2 g/d MMF (group II, n = 61 patients) over a 2-year period. Each patient received similar TAC doses. METHODS: We compared demographic data and clinical data for each case: acute rejection (AR) episodes, chronic rejection (CR) episodes, death, graft loss, development of posttransplantation diabetes mellitus (PTDM), and posttransplantation hypertension rates. RESULTS: Demographic features were similar. There were also no significant differences between groups I and II with respect to number of AR episodes (17/112 vs 12/61, respectively), number of CR episodes (4/112 vs 1/61, respectively), PTDM, and hypertension rate (P > .05). Kaplan-Meier survival analysis revealed 2-year graft survival rates of 94% in group I versus 83% in group II. The corresponding 2-year patient survival rates were 100% in group I versus 91% in group II. The graft survival and patient survival rates in group I were significantly higher than those in group II (log-rank 0.005 and 0.001, respectively). CONCLUSIONS: The 2-year graft and patient survival rates for the renal transplant recipients in this study suggest that the combination of a full TAC dose with 1 g/d MMF is a better choice than 2 g/d MMF.     

Immunoprophylaxis with Basiliximab Compared with Antithymocyte Globulin in Renal Transplant Patients Receiving MMF-containing Triple Therapy

Acute graft rejection remains a major problem in renal transplant recipients, and there is no consensus on the optimal immunosuppressive strategy. Immunoprophylaxis with Thymoglobulin or basiliximab has significantly reduced the incidence of acute rejection episodes and graft loss following kidney transplantation. This open, randomized, multicenter study investigated the efficacy and tolerability of basiliximab (20mg day 0-day 4) plus early cyclosporine from day 0 (n = 50) compared with Thymoglobulin plus delayed cyclosporine (n = 50) in adult kidney transplant patients. In addition, all patients received steroids and mycophenolate mofetil (MMF) at standard doses from day 0. Patient and graft survival rates at 12 months were 98 and 94% in the basiliximab group, respectively, compared with 100 and 96% in the Thymoglobulin' group. The incidences of biopsy-confirmed acute rejection (8.0% in each group) and treatment failure (14% in the basiliximab group vs. 8% in the Thymoglobulin group) were comparable in the two groups. There was a non-significant tendency to more dialysis (14 vs. 6%), and fewer cytomegalovirus (CMV) infections (p = 0.005) in the basiliximab group, but the percentage of clinical CMV was not different between the two groups (6 vs. 12%). Both strategies give excellent results, despite the differences in patterns, in nonhyperimmunized patients receiving their first cadaveric renal allograft.     

Tacrolimus versus cyclosporine after lung transplantation: a prospective, open, randomized two-center trial comparing two different immunosuppressive protocols.

BACKGROUND: The need for better immunosuppressive protocols after lung transplantation led us to investigate tacrolimus (Tac) in combination with mycophenolate mofetil (MMF) and steroids or cyclosporine (CsA) in combination with MMF and steroids in a prospective, open, randomized trial after lung transplantation. METHODS: Between September 1997 and April 1999, 50 lung transplant recipients were randomized to receive either Tac (n = 26) or CsA (n = 24) in combination with MMF and steroids. All patients underwent induction therapy with rabbit antithymocyte globulin (ATG) for 3 days. Freedom from acute rejection (AR), patient survival, infection episodes, and side effects were monitored. RESULTS: There was no difference in patient demographics between the two groups. Six-month and 1-year survival was similar (84.6% and 73.1% in the Tac group vs 83.3% and 79.2% in the CsA group). Freedom from AR at 6 months and 1 year after lung transplantation was slightly higher in the Tac group (57.7% and 50% vs 45.8% and 33.3%, p = not significant [n.s.]), whereas the number of treated rejection episodes per 100 patient days in the Tac group was significantly lower (0.225 vs 0.426, p < .05). Four patients in the CsA group had to be switched to Tac. Two patients in the CsA group had to be retransplanted. Incidence of infections was similar in both groups with a trend toward more fungal infections in the Tac group (n = 7 vs n = 1, p = n.s.). CONCLUSIONS: The combination of Tac and MMF seems to have slightly higher immunosuppressive potential compared with CsA and MMF. The effectiveness of Tac as a rescue agent is not paralleled with undue signs of overimmunosuppression.