Prednisone-Free Maintenance Immunosuppression—A 5-Year Experience

Concern persists that prednisone-free maintenance immunosuppression in kidney transplant recipients will be associated with an increase in late allograft dysfunction and graft loss. We herein report 5-year follow-up of a trial of prednisone-free maintenance immunosuppression. From October 1, 1999, through January 31, 2005, at our center, 589 kidney transplant recipients were treated with a protocol incorporating discontinuation of their prednisone on postoperative day 6. At 5 years, actuarial patient survival was 91%; graft survival, 84%; death-censored graft survival, 92%; acute rejection-free graft survival, 84% and chronic rejection-free graft survival, 87%. The mean serum creatinine level (+/-SD) at 1 year was 1.6 +/- 0.6; at 5 years, 1.7 +/- 0.8. In all, 86% of kidney recipients with functioning grafts remain prednisone-free as of April 30, 2005. As compared with historical controls, recipients on prednisone-free maintenance immunosuppression had a significantly lower rate of a number of complications, including cataracts (p < 0.001), posttransplant diabetes mellitus (p < 0.001), avascular necrosis (p = 0.001), and fractures (p = 0.004). We conclude that prednisone-related side effects can be minimized in a protocol incorporating prednisone-free maintenance immunosuppression. Five-year graft outcome remains good.     

Long-term immunosuppression, without maintenance prednisone, after kidney transplantation

BACKGROUND: Concern exists that prednisone-free maintenance immunosuppression in kidney transplant recipients will increase acute and/or chronic rejection. METHODS: From October 1, 1999, through February 29, 2004, at our center, 477 kidney transplant recipients (341 living donor, 136 cadaver) discontinued prednisone on postoperative day 6, per our protocol. Immunosuppression consisted of polyclonal antibody (Thymoglobulin) for 5 days, prednisone intraoperatively and for 5 days, a calcineurin inhibitor, and either sirolimus or mycophenolate mofetil. We compared outcome with that of historical controls who did not discontinue prednisone. RESULTS: The recipients on prednisone-free maintenance immunosuppression had excellent 4-year actuarial patient survival (92%), graft survival (90%), acute rejection-free graft survival (86%), and chronic rejection-free graft survival (95%). The mean serum creatinine level (+/- SD) at 1 year was 1.6 +/- 0.6; at 4 years, 1.6 +/- 0.6. We noted that 8% of recipients had cytomegalovirus (CMV) disease; 4.5%, fractures; 2.8%, cataracts; 1%, posttransplant diabetes; 0.2%, avascular necrosis; 0.2%, posttransplant lymphoproliferative disease; and 0%, polyomavirus. In all, 85% of kidney recipients with functioning grafts remain prednisone-free as of April 1, 2004.As compared with historical controls, the recipients on prednisone-free maintenance immunosuppression had better patient (P = 0.02) and graft survival (P < 0.0001) and lower rates of acute (P = 0.0004) and chronic (P = 0.02) rejection. In addition, they had a significantly lower rate of CMV disease (P < 0.0001), cataracts (P < 0.0001), posttransplant diabetes (P < 0.0001), and avascular necrosis (P = 0.0003). CONCLUSIONS: Prednisone-related side effects can be minimized without maintenance immunosuppression; our prednisone-free recipients do not have increased acute or chronic rejection.     

Outcome at 3 Years with a Prednisone-Free Maintenance Regimen: A Single-Center Experience with 349 Kidney Transplant Recipients

Historically, late steroid withdrawal after kidney transplants has been associated with an increased rejection rate. Recently, low rejection rates have been reported for recipients treated with complete avoidance or rapid elimination of steroids. However, follow-up has been short. We herein report on 3-year outcome in recipients whose prednisone was rapidly eliminated and who were maintained on a steroid-free regimen. From 10/1/1999 through 5/1/2003, 349 recipients (254 LD, 95 CAD; 319 in first 30 s) were immunosuppressed with polyclonal antibody (Thymoglobulin), a calcineurin inhibitor, either mycophenolate mofetil or sirolimus, and rapid discontinuation of prednisone. Actuarial 3-year patient survival was 95%; graft survival, 93%. Acute rejection-free graft survival at 1 year was 94%; at 3 years, 92%. There was no difference between LD and CAD. At 2 years, the mean (+/- SE) serum creatinine level for LDs was 1.6 +/- 0.5 mg/dL; for CAD, 1.6 +/- 0.4 mg/dL. We have no new cases of PTLD or avascular necrosis; 22 recipients (6%) developed CMV. Currently, 84% of recipients remain prednisone-free. We conclude that excellent 3-year patient and graft survival can be achieved without maintenance prednisone. With such a protocol, steroid-related side-effects are minimal.     

Calcineurin inhibitor avoidance versus steroid avoidance following kidney transplantation: Postoperative complications

This study compared early postoperative complications in kidney transplant recipients treated with either a sirolimus-based calcineurin inhibitor (CNI)-free regimen or a tacrolimus-based steroid-free regimen. We used a single-center, prospective, sequential but nonrandomized study design. Consecutive recipients of primary cadaveric or non-HLA identical kidney transplant recipients received either a CNI-free regimen, consisting of sirolimus 5 mg daily beginning postoperative day 3, mycophenolate mofetil 1 gm twice a day, and methylprednisolone 500 mg intraoperatively, then prednisone 30 mg daily tapered to 10 mg daily at 3 months, or a prednisone-free regimen, consisting of methylprednisolone 500 mg, 250 mg, and 125 mg from days 0 to 2, then no further steroids, tacrolimus 0.075 mg/kg twice a day, and mycophenolate mofetil 1 g twice a day. All patients received thymoglobulin induction 6 mg/kg total dose. Outcome measures were patient and graft survival, BPAR, surgical and wound complications, viral infections and posttransplant diabetes mellitus (PTDM). Both groups had excellent early outcomes with no significant difference in patient or graft survival, early renal function, BPAR, surgical or wound complications, or viral infections between the two groups. Patients in the sirolimus-based CNI-free group had a significantly higher incidence of PTDM and a trend toward more discontinuation due to drug toxicity. Whether either regimen improves long-term outcomes awaits longer follow-up.     

Excellent clinical outcomes in primary kidney transplant recipients treated with steroid-free maintenance immunosuppression

Steroid-free maintenance immunosuppression is desirable to eliminate the side effects of chronic corticosteroid use. Complete steroid avoidance or rapid post-transplant steroid withdrawal has recently been used in renal transplant recipients with encouraging results. The present study evaluated the outcome of a steroid-free maintenance immunosuppressive protocol in kidney transplant recipients with at least one-yr follow up. Between April 2002 and October 2004, a total of 301 primary kidney transplant recipients received steroid-free maintenance immunosuppression. The regimen consisted of induction with thymogobulin and prednisone for the first five d. Patients were maintained on Sirolimus and Neoral. Neoral dose was adjusted to target C2 levels and the Sirolimus dose was adjusted to a target rapamycin trough level. All primary kidney transplants (n = 502) performed in the two yr (starting January 2000) prior to institution of the steroid-free regimen and thus maintained on a steroid-based immunosuppressive protocol were used for comparison. One-year patient and death censored graft survival were 93.1% and 98.1% for the steroid-free group vs. 95.2% and 95.2% for the comparator groups (p = ns). The incidence of biopsy-proven acute rejection was 4.9% in the steroid-free group vs. 9.4% in the comparator group (p < 0.01). Two (0.7%) of 301 patients in the steroid-free group lost their grafts because of acute rejection compared with nine (1.8%) patients in the comparator group (p < 0.05). At one-yr post-transplant the mean serum creatinine level was not different between the two groups. There were no significant differences in mean serum cholesterol and triglycerides levels as well as the percentage of patients on lipid lowering agents between the groups. White blood cell counts, daily doses of Neoral and weight gain were significantly lower in the steroid-free group vs. the comparator group. However, more patients in the steroid-free group required erythropoietin and iron therapy for anemia (p < 0.001). We conclude that excellent graft survival with a significantly lower incidence of acute rejection can be achieved using a steroid-free maintenance immunosuppressive protocol consisting of Neoral and Sirolimus.     

Effect of Obesity on Clinical Outcomes of Kidney Transplant Patients

PurposeCorrelating with the obesity epidemic, the number of obese transplant candidates is increasing. This study was designed to evaluate the effect of obesity on the survival of our kidney transplant recipients.MethodsAmong 1033 kidney transplants performed during the last 7.5 years in our center, 750 adult recipients were transplanted from living donors and were evaluated, and 561 of them were included in the study. Demographic and clinical data were collected. Body mass index (BMI) values at the time of transplant and post-transplant during the first year, the presence of delayed graft function, hospitalization duration, number of readmissions within the first year post-transplant, presence of post-transplant diabetes mellitus (PTDM) and cardiovascular disease, and graft and patient survival rates at 1, 3, and 5 years were investigated.ResultsObesity (BMI >30) was observed in 148 (19.7%) at the time of the transplant (initial obesity) and in 174 (23.2%) recipients at post-transplant first year. Initial obesity was not only found to be correlated with delayed wound healing (P = .03), increased hospitalization duration (P = .03), number of readmissions within the first year (P = .04), presence of PTDM (P = .02), and cardiovascular disease (P = .03) but also with lower graft survival rate (P = .04) at the first year. On the other hand, obesity at post-transplant the first year was associated with lower 3- and 5-year grafts (P = .04 and P = .03, respectively) and 5-year patient (P = .03) survival rates.ConclusionObesity should not be considered as a contraindication for kidney transplantation; however, to achieve better results, certain precautions should be taken pre- and postoperatively.     

A prospective study of rapid corticosteroid elimination in simultaneous pancreas-kidney transplantation: comparison of two maintenance immunosuppression protocols: tacrolimus/mycophenolate mofetil versus tacrolimus/sirolimus

BACKGROUND: We examined the feasibility of rapid corticosteroid elimination in simultaneous pancreas kidney transplantation. METHODS: Forty consecutive simultaneous pancreas-kidney (SPK) transplant recipients were enrolled in a prospective study in which antithymocyte globulin induction and 6 days of corticosteroids were administered along with tacrolimus and MMF (n=20) or tacrolimus and sirolimus (n=20). Mean+/-SD follow-up for recipients receiving tacrolimus/MMF and tacrolimus/sirolimus were 12.7+/-3.9 and 13.4+/-2.9 months, respectively. Patient and graft survival, and rejection rates were compared to an historical control group (n=86; mean follow-up 41.5+/-15.4 months) of SPK recipients that received induction and tacrolimus, MMF, and corticosteroids. RESULTS: Demographic characteristics of recipient and donor variables were similar among all groups. The 1-year actuarial patient, kidney, and pancreas survival rates in the 40 SPK transplant recipients with rapid corticosteroid elimination were 100, 100, and 100%, respectively. In the historical control group the 1-year actual patient, kidney, and pancreas survival rates were 96.5, 93.0, and 91.9%, respectively. The 1-year rejection-free survival rate recipients in the rapid steroid elimination group collectively was 97.5 vs 80.2% in the historical control group (P=0.034). At 6 and 12 months posttransplant the serum creatinine values remained stable in all groups. CONCLUSIONS: We conclude that chronic corticosteroid exposure is not required in SPK transplant recipients receiving antithymocyte globulin induction and maintenance immuno-suppression consisting of either tacrolimus and mycophenolate mofetil or tacrolimus and sirolimus.     

Patient survival after renal transplantation: IV. Impact of post-transplant diabetes

BACKGROUND: The development of de novo diabetes mellitus is a serious complication of kidney transplantation. This study examined the cardiovascular risk profile of patients with post-transplant diabetes (PTDM) and assessed the impact of PTDM on patient survival. METHODS: This analysis included 1811 adult, renal allograft recipients, transplanted in a single institution between 1983 and 1998. Patient survival was analyzed by univariable and multivariable Cox regression considering PTDM as a time dependent variable. RESULTS: After a follow-up period of 8.3 +/- 4.5 years, 293 patients (20%) developed PTDM, 14% lost their graft, and 20% died. Compared to patients without DM (NoDM, N = 1186) patients with PTDM were significantly older (40 +/- 14 vs. 48 +/- 12 years, P < 0.001), heavier (76 +/- 23 vs. 86 +/- 25 kg, P < 0.001), and included more African Americans (18 vs. 28%, P = 0.001). In addition, the incidence of PTDM was significantly higher in patients who were transplanted after 1995 than prior to that year. In contrast, there were no significant differences between PTDM and patients who had DM before the transplant (DM; N = 332). Compared to NoDM, patients with PTDM had significantly higher total serum cholesterol and triglycerides (TG), higher systolic blood pressure and higher pulse pressure throughout the post-transplant period. Of interest, all of these abnormalities preceded the development of PTDM. Hypertriglyceridemia was particularly pronounced in PTDM and elevated TG levels correlated with the subsequent development of PTDM, independent of other risk factors (P = 0.001 by multivariate Cox). Compared to NoDM (16% mortality) a significantly higher percent of DM (31%, P < 0.001) and PTDM (22%, P = 0.005) patients died. By Cox regression, PTDM correlated with reduced patient survival (hazard ratio = 1.80, CI 1.35 to 2.41, P = 0.001), and that relationship was independent of other correlates of reduced survival that included: increasing age; transplant year; reduced serum albumin; and male sex. CONCLUSION: s: PTDM is associated with an unfavorable cardiovascular risk profile that precedes the development of hyperglycemia. PTDM is an independent predictor of reduced survival in renal allograft recipients.     

Steroid-Free Immunosuppression Since 1999: 129 Pediatric Renal Transplants with Sustained Graft and Patient Benefits

Despite early promising patient and graft outcomes with steroid-free (SF) immunosuppression in pediatric kidney transplant recipients, data on long-term safety and efficacy results are lacking. We present our single-center experience with 129 consecutive pediatric kidney transplant recipients on SF immunosuppression, with a mean follow-up of 5 years. Outcomes are compared against a matched cohort of 57 concurrent recipients treated with steroid-based (SB) immunosuppression. In the SF group, 87% of kidney recipients with functioning grafts remain corticosteroid - free. Actual intent-to-treat SF (ITT-SF) and still-on-protocol SF patient survivals are 96% and 96%, respectively, actual graft survivals for both groups are 93% and 96%, respectively and actual death-censored graft survivals for both groups are 97% and 99%, respectively. Unprecedented catch-up growth is observed in SF recipients below 12 years of age. Continued low rates of acute rejection, posttransplant diabetes mellitus (PTDM), hypertension and hyperlipidemia are seen in SF patients, with sustained benefits for graft function. In conclusion, extended enrollment and longer experience with SF immunosuppression for renal transplantation in low-risk children confirms protocol safety, continued benefits for growth and graft function, low acute rejection rates and reduced cardiovascular morbidity.     

Rapid Discontinuation of Steroids in Living Donor Kidney Transplantation: A Pilot Study

Steroids are associated with significant postoperative complications (hypertension, cosmetic changes, bone loss, hyperlipidemia, diabetes, and cataracts). Most develop early; in addition, late post-transplant steroid withdrawal in kidney transplant recipients has been associated with increased acute rejection (AR). To obviate these problems, we studied outcome of a protocol of rapid discontinuation of prednisone (RDS) (steroids stopped on POD6). Between November 1, 1999 and October 31, 2000, 51 adult living donor (LD) first transplant recipients (2 HLA-id, 28 non-id relative, 21 LURD) were immunosuppressed with thymoglobulin (1.25 mg/kg intraoperatively and then qdx4); prednisone (P) (500 mg methylprednisolone intraoperatively, 1 mg/kg x 1 day, 0.5 mg/kg x 2 days, 0.25 mg/kg x 2 days, then d/c); MMF, 1 g b.i.d.; and CSA, 4 mg/kg b.i.d. adjusted to achieve levels of 150-200 ng/mL (by HPLC). Exclusion criteria were delayed graft function or primary disease requiring P. Minimum follow-up was 5.5 months (range 5.5 to 17.5 months). Outcome was compared vs. previous cohorts of LD recipients immunosuppressed with P/AZA/CSA (n = 171) or P/MMF/CSA (n = 43) (both without antibody induction). RESULTS: For the RDS group, average CSA level (+/- S.E.) at 3 and 6 months was 190 +/- 12 and 180 +/- 9; avg. MMF dose, 1.7 +/- 0.1 g and 1.7 +/- 0.1 g. There was no significant difference in 6- and 12-month actuarial patient survival, graft survival and rejection-free graft survival between recipients on the RDS protocol vs. historical controls. For RDS recipients, actuarial 6- and 12-month rejection-free graft survival was 87%. Of the 51 RDS recipients, five (10%) have had AR (at 20 days, 1 month, 3 months, 3 months, and 3.5 months post-transplant). After treatment, all five were maintained on 5 mg P; there have been no second AR episodes. Two additional recipients were started on 5 mg P due to low white blood count (WBC) and low/no MMF. Of the 51 grafts, one has failed (death with function). Average serum Cr level (+/- S.E.) at 3 and 6 months for RDS recipients was 1.7 +/- 0.5 (NS vs. historical controls). CONCLUSION: For low-risk LD recipients, a kidney transplant with an RDS protocol does not increase risk of AR or graft loss. Future studies will need to be done to assess AR rates with an RDS protocol in cadaver transplant recipients and in recipients with delayed graft function.     

Steroid-free maintenance immunosuppression with rapamune and low-dose neoral in pancreas transplant recipients

BACKGROUND: Steroid-free immunosuppression is an attractive option because it avoids the many side effects of chronic corticosteroid use. It is especially attractive in pancreas recipients because it avoids the diabetogenic effects of steroids. METHODS: We evaluated the outcome of a steroid-free maintenance immunosuppressive protocol in pancreas transplant recipients. Between August 2003 and May 2006, a total of 97 pancreas transplant recipients received steroid-free maintenance immunosuppression, consisting of induction with thymoglobulin and prednisone for the first 5 days. Patients were maintained on sirolimus adjusted to a target rapamycin trough level and reduced-dose cyclosporine adjusted to target C2 levels. All pancreas transplants (n=124) performed in the previous 3 years and maintained on a steroid-based immunosuppressive protocol with cyclosporine and mycophenolate mofetil were used for comparison. RESULTS: One-year patient and death censored pancreas graft survival were 93.8% and 94.8% for the steroid free group versus 95.2% and 87.9% for the comparator group, respectively. The incidence of acute rejection was 9.3% in the steroid-free group versus 28.3% in the comparator group (P<0.01). No pancreas loss in the steroid-free group was caused by acute rejection, whereas seven (5.6%) patients in the comparator group lost their pancreases because of acute rejection (P<0.05). At 1 year after transplant, the mean serum glucose and creatinine levels were not different between the two groups. CONCLUSION: We conclude that excellent graft survival with a significantly lower incidence of acute rejection can be achieved using a steroid-free maintenance immunosuppressive protocol consisting of sirolimus and cyclosporine.     

A Prospective Randomized Trial of Steroid-Free Maintenance Regimens in Kidney Transplant Recipients—An Interim Analysis

We compared three maintenance immunosuppressive regimens in a rapid discontinuation of prednisone protocol. From March 1, 2001, through December 31, 2003, 239 first and second kidney transplant recipients (166 LD; 73 DD) were randomized. All recipients were treated with Thymoglobulin; all received steroids intraoperatively and for 5 days postoperatively. Randomization was to cyclosporine-mycophenolate mofetil (n = 85); high-level tacrolimus (TAC) (8-12 ng/mL)-low-level sirolimus (SRL) (3-7 ng/mL) (n = 72); or low-level TAC (3-7 ng/mL)-high-level SRL (8-12 ng/mL) (n = 82). We found no difference at 24 months between groups in patient, graft, death-censored graft, or acute rejection-free graft survival, or in kidney function. Wound complications were more common in SRL-treated recipients (p = 0.02); we found no other differences between groups in complication rates. Our data suggest that excellent patient and graft survival and low rejection rates can be obtained using a variety of maintenance protocols without prednisone.     

New-onset diabetes mellitus after kidney transplantation: the role of immunosuppression

BACKGROUND: Complications related to posttransplantation immunosuppressive therapy remain common. New-onset diabetes mellitus after transplantation (PTDM) is a well-recognized complication associated with reduced graft and patient survival. The type of immunosuppression may be responsible for more than two thirds of PTDM. We retrospectively reviewed our experience in a population of 284 kidney transplant recipients, evaluating the incidence of PTDM with regard to the type of immunosuppression. PATIENTS AND METHODS: From January 2001 to December 2005, 284 kidney transplantations were performed using tacrolimus-based (TAC) immunosuppression in 192 patients and a cyclosporine-based (CyA) regimen in 62 patients, whereas 30 patients received sirolimus-based immunosuppression. RESULTS: The overall incidence of PTDM was 4.9%. Among the immunosuppression protocols, 8 patients (4.1%) received TAC and 6 patients (9.6%) received CyA, whereas no patients treated with sirolimus developed PTDM. Graft and patient survival rates were 93% and 100%, respectively. CONCLUSIONS: The overall risk of PTDM with recent immunosuppressive protocols is low, but it is increased among calcineurin inhibitor (CNI)-treated kidney transplant recipients. Sirolimus did not increase the risk of PTDM, allowing potential clinical application in diabetic recipients and in patients affected by PTDM.     

Increased risk of post-transplant diabetes mellitus despite early steroid discontinuation in Hispanic kidney transplant recipients

Early steroid discontinuation (ESD) has been associated with a lower incidence of post-transplant diabetes mellitus (PTDM). We retrospectively reviewed the incidence of PTDM in relation to racial groups in kidney transplant recipients treated with ESD. Between January 2002 and September 2003, 125 consecutive primary adult kidney transplants were performed. Group A (n = 91) had steroids discontinued on postoperative day 6 and maintenance immunosuppression of Tacrolimus and mycophenolate mofetil. Group B (n = 34), received the same immunosuppression but was maintained on steroids indefinitely. Induction consisted of thymoglobulin in African-Americans; all others received Simulect. At 1 yr, patient/graft survival, serum creatinine and rate of acute rejection were similar in both groups. The incidence of PTDM was significantly lower in group A (7%) compared with group B (26%, p = 0.0209). The incidence of PTDM in group A was limited to Hispanic patients with a family history of diabetes mellitus. African-Americans and Caucasians in group A did not experience PTDM (p = 0.005 compared with African-American in group B). Our steroid free protocol nearly eliminated the incidence of PTDM in African-Americans and Caucasians, but was still associated with significant rate of PTDM in Hispanic recipients. Alternative immunosuppression may benefit this population.     

Alemtuzumab Induction and Prednisone-Free Maintenance Immunotherapy in Kidney Transplantation: Comparison with Basiliximab Induction—Long-Term Results

This study examined alemtuzumab (anti-CD 52, Campath-1H) and basiliximab (anti-CD 25, Simulect) as induction immunosuppression in kidney transplantation. We used a single-center, nonrandomized, retrospective, sequential study design to evaluate outcomes in kidney transplant recipients given either alemtuzumab (n = 123) or basiliximab (n = 155) induction in combination with a prednisone-free maintenance protocol using tacrolimus and mycophenolate mofetil. Kaplan-Meier analyses of long-term patient and graft survivals and rejection rates were determined according to induction agent, donor source and recipient ethnicity. Secondary endpoints included the quality of renal allograft function and the etiology of infectious complications. Overall long-term patient and graft survival rates did not significantly differ between patients treated with alemtuzumab and basiliximab. A lower rate of early (<3 months) rejection was observed in the alemtuzumab (4.1%) versus the basiliximab (11.6%) group, but the rates for both groups were equivalent at 1 year. Patient and kidney survival and rejection rates were nearly identical between Caucasians and African Americans that received alemtuzumab. Quality of renal function and incidence of infectious complications were similar in the two groups. Alemtuzumab induction therapy was similar in efficacy to basiliximab in a prednisone-free maintenance immunosuppressive protocol for an ethnically diverse population of kidney transplant recipients.     

Long-term,prolonged-release tacrolimus-based immunosuppression in de novo kidney transplant recipients: 5-year prospective follow-up of the ADHERE study patients

The objectives of this study were to assess long-term graft survival, patient survival, renal function, and acute rejections in de novo kidney transplant recipients, treated with once-daily prolonged-release tacrolimus-based therapy. The study was a 5-year non-interventional prospective follow-up of patients from the ADHERE study, a Phase IV 12-month open-label assessment of patients randomized to receive prolonged-release tacrolimus in combination with mycophenolate mofetil (MMF) (Arm 1) or sirolimus (Arm 2). From 838 patients in the randomized study, 587 were included in the long-term follow-up, of whom 510 completed the study at year 5. At 1 year post-transplant, graft and patient survival rates were 93.0% and 97.8%, respectively, and at 5 years were 84.0% and 90.8%, respectively. Cox proportional hazards analysis showed no association between graft loss, initial randomized treatment arm, donor age, donor type, or sex. The 5-year acute rejection-free survival rate was 77.4%, and biopsy-confirmed acute rejection-free survival rate was 86.0%. Renal function remained stable over the follow-up period: mean ± SD eGFR 4-variable modification diet in renal disease formula (MDRD4) was 52.3 ± 21.6 ml/min/1.73 m² at 6 months and 52.5 ± 23.0 ml/min/1.73 m² at 5 years post-transplant. These findings support the role of long-term once-daily prolonged-release tacrolimus-based immunosuppression, in combination with sirolimus or MMF, for renal transplant recipients in routine clinical practice.     

Reduction of CMV Disease with Steroid-Free Immunosuppresssion in Simultaneous Pancreas–Kidney Transplant Recipients

The impact of a prednisone-free immunosuppressive regimen was evaluated in simultaneous pancreas-kidney (SPK) recipients. Patient and graft survivals, rejection rates and the incidence of CMV disease were determined. Two hundred consecutive SPK transplant recipients received tacrolimus-based immunosuppression with (n = 100) or without (n = 100) chronic prednisone therapy. Patients were induced with lymphocyte depleting antibodies or IL-2 receptor blockers and received prophylactic antiviral therapy. Patient and graft survivals and rejection rates were not statistically significantly different between treatment groups. Two-year cumulative incidence of CMV in recipients in the prednisone-free protocol was reduced (7.2% vs. 16%; p = 0.15). Considering only recipients at highest risk (D+/R- or D+R+), incidence of CMV disease in the prednisone-free group (n = 61) compared to the steroid-treated group (n = 48) was reduced from 36% to 18% (p < 0.05). Multivariate analysis confirmed the independent effect of prednisone treatment on the incidence of CMV (RR 2.3; p = 0.04). In the prednisone-free protocol, incidence of CMV was less frequent in recipients receiving induction with Campath versus rabbit antilymphocyte globulin (2.4% vs. 12.6%; p = 0.14). Eliminating prednisone immunotherapy did not adversely affect outcomes and was associated with a reduced rate of CMV in SPK recipients of organs from sero-positive donors.     

Development of Diabetes Mellitus Following Kidney Transplantation: A Canadian Experience

The onset of diabetes mellitus following kidney transplantation or post-transplant diabetes mellitus (PTDM) is now recognized as being an increasingly common complication that is associated with poor graft and patient survival. The incidence and clinical correlates of PTDM in a Canadian kidney transplant population has not been examined and may vary based on differences in demographics (i.e. race). Furthermore, little information exists on the association of variables such as cumulative dose of corticosteroids and trough calcineurin inhibitor levels and PTDM. We examined all recipients of a kidney transplant in our center between 1995 and 2001 and found an overall PTDM rate of 9.8%. Five clinical factors were independently associated with PTDM: older recipient age, deceased donor, hepatitis C antibody status, rejection episode and use of tacrolimus (vs. cyclosporine). Furthermore, cumulative corticosteroid dose and calcineurin inhibitor trough level were not associated with PTDM. This study demonstrates that in a Canadian kidney transplant population that there is a significant risk of PTDM following kidney transplantation, and it is therefore advisable to minimize this risk.     

Long-term renal allograft function on a tacrolimus-based, pred-free maintenance immunosuppression comparing sirolimus vs. MMF.

It is not known how different steroid-free immunosuppressive combinations affect renal graft survival and long-term kidney transplant function. Here we sought to compare the impact on graft survival and long-term graft function of two tacrolimus (Tac)-based, prednisone-free maintenance immunosuppressive protocols: Tac/Mycophenolate Mofetil (MMF) vs. Tac/Sirolimus (SRL). Renal transplant patients given induction therapy with IL2-RA and methylprednisolone on days 0, 1 and 2 post-transplant were prospectively randomized to two maintenance immunosuppressive regimens with Tac/MMF (n = 45) or Tac/SRL (n = 37). During the 3-year follow-up the following data were collected: patient survival, renal allograft survival, incidence of acute rejection and glomerular filtration rate (GFR) at different time-points post-transplant. Cumulative graft survival was significantly different in the two groups: one kidney loss in the Tac/MMF vs. six kidney losses in the Tac/SRL (log-rank test p = 0.04). GFR at different time-points post-transplant was consistently and statistically better in the Tac/MMF than in the Tac/SRL group. The slope of GFR decline per month was flatter in the Tac/MMF than in the Tac/SRL group. This study showed that renal graft survival and graft function were significantly lower in the combination of Tac/SRL than Tac/MMF.     

Steroid minimization in liver transplant recipients: impact on hepatitis C recurrence and post-transplant diabetes

BACKGROUND: Steroid minimization regimens have become increasingly popular for kidney transplant recipients. We studied outcomes for liver transplant recipients with a regimen using rapid discontinuation of prednisone (RDP). RESULTS: The study group consisted of 83 recipients transplanted between June 2004 and January 2006. Immunosuppression consisted of tacrolimus, MMF, and two doses of basiliximab with six d of steroids. Patients with underlying autoimmune disorders (PSC, autoimmune hepatitis) were not included as they were maintained on steroids. The control group consisted of 83 recipients transplanted between January 2002 and May 2004. Immunosuppression consisted of tacrolimus, MMF and steroids, with no antibody induction. Mean MELD score at time of transplant was significantly higher in the steroid free group vs. the control group (28 vs. 23, p = 0.02); mean donor age was also higher (42 vs. 37 yr, p = 0.02). Other characteristics including recipient age, cold ischemic time, donor source, and cause of liver disease were similar (p = ns). Mean length of follow-up was 16.1 months in the RDP group and 32 months in the control group; a minimum of six months follow up was present for all patients. Patient and graft survival rates were not statistically different in the two groups (p = ns). Biopsy proven rejection was low in both groups and not significantly different (at one yr post-transplant 11% in the RDP group vs. 12% in control, p = 0.53). Based on protocol biopsy data, histologic recurrence of hepatitis C was demonstrated in 56% of the control group hepatitis C positive recipients vs. 39% in the RDP group (p = 0.05). There was a significantly lower incidence of post-transplant diabetes (PTDM) in the RDP vs. control group (at 6 months post-transplant 12% vs. 32%, p = 0.004). CONCLUSIONS: Rapid discontinuation of prednisone in liver transplant recipients is not associated with an increased risk of rejection, and may be associated with lower morbidity, especially PTDM and hepatitis C recurrence.