Early steroid withdrawal in solitary pancreas transplantation results in equivalent graft and patient survival compared with maintenance steroid therapy

Although steroid withdrawal in simultaneous kidney pancreas transplantation has been shown to be feasible, the results of early steroid withdrawal in immunologically solitary pancreas transplantation are not well known. This study evaluated an early steroid withdrawal protocol in this group. The results of steroid withdrawal at 21 d post-transplant in solitary pancreas transplant recipients was compared with a control group consisting of solitary pancreas transplant recipients maintained on steroids (MG). Additional immunosuppression consisted of rabbit anti-thymocyte globulin induction followed by tacrolimus and mycophenolate mofetil in both groups. The withdrawal group (WG, n = 22) consisted of 11 pancreas transplant alone (PTA), six pancreas after kidney (PAK), and five simultaneous cadaveric pancreas living kidney (SPLK) recipients. The steroid maintenance group (MG, n = 32) consisted of 8 PTA, 11 PAK, and 13 SPLK recipients. Recipient and donor demographic characteristics were similar. Seventy eight percent of MG patients had infection-related complications in the first year compared with 50% of the WG patients (p = 0.04). The one-yr rejection, pancreas graft, and patient survival rates were 27.3% 95.5%, and 100% in the WG, and 37.5%, 81.3%, and 93.8% in the MG respectively and not significantly different. We conclude that early corticosteroid withdrawal in isolated pancreas transplantation results in fewer infections and can be achieved without an increased risk of rejection or graft loss over the first year.     

Early (fifth day) vs. late (sixth month) steroid withdrawal in renal transplant recipients treated with Neoral® plus Rapamune®: four‐yr results of a randomized monocenter study

Sandrini S, Setti G, Bossini N, Chiappini R, Valerio F, Mazzola G, Maffeis R, Nodari F, Cancarini G. Early (fifth day) vs. late (sixth month) steroid withdrawal in renal transplant recipients treated with Neoral^® plus Rapamune^®: four‐yr results of a randomized monocenter study.
Clin Transplant 2009 DOI: 10.1111/j.1399‐0012.2009.01171.x.
© 2009 John Wiley & Sons A/S. Abstract: The most advisable timing for steroid withdrawal (CSWD) after renal transplantation (Tx) is still an open issue. This randomized study has compared early CSWD (at day 5) with late (at month 6) in patients under Neoral + Sirolimus. The primary end point was the percentage of success in CSWD at month 48. Ninety‐six transplants from deceased donors were randomized to withdraw steroids either early (n = 49) or late (n = 47). At four yr, the two strategies were comparable for: success in CSWD (65% in both), graft survival (95% and 98%), patient survival (92% and 96%) creatininemia (1.7 ± 0.3 and 1.6 ± 0.4 mg/dL), side effects, being still on Sirolimus + Neoral (69% and 74%), reversibility of rejection (AR) (all cases), severity of AR (grade 1A/1B: 81% and 63%). The major differences were incidence of AR: at month twelve (48% vs. 30%, p < 0.04), at 48 (53% and 33%, p < 0.03); timing of AR (72 ± 86 d vs. 202 ± 119 d, p < 0.0001). The timing of CSWD influences neither the rate of successful CSWD nor the long‐term results. However, early suspension causes a higher AR rate, mostly arising within month one, but always responsive to steroids. Yet, the early appearance of AR can make patient management easier and safer.     

Early steroid withdrawal therapy in renal transplant recipients: a steroid-free sirolimus and CellCept-based calcineurin inhibitor-minimization protocol

BACKGROUND: Maintenance steroid therapy is associated with significant morbidity and mortality in renal transplant recipients. Elimination of the many long-term side effects of corticosteroids, including those that impinge on cardiovascular risk, remains a laudable goal in designing immunosuppressive protocols. However, concern persists that prednisone-free maintenance immunotherapy in kidney transplant recipients will result in an increase incidence of acute rejections, renal dysfunction and ultimate graft loss. METHODS: From 24 March 2003 to 1 December 2004, 84 kidney transplant recipients (61 deceased donor, 23 living donors) discontinued prednisone on post-operative day 6. Immunotherapy consisted of polyclonal antibody induction (thymoglobulin) for five d and prednisone intraoperatively with a rapid taper over the next six d. Maintenance therapy consisted of a sirolimus and CellCept-based calcineurin inhibitor-minimization protocol. Tacrolimus and mycophenolate mofetil (CellCept) were initiated on day 0. Sirolimus immunotherpay was started on post-operative day 6 concomitant with the cessation of steroids. We compared outcomes with that of our historical controls, treated with sirolimus and tacrolimus, who did not discontinue steroids. In addition, we analyzed outcomes independently for recipients of living and deceased donors in the steroid-free protocol. RESULTS: The recipients on prednisone-free maintenance immunosuppression had excellent 2.5-yr actuarial patient survival (97%), graft survival (93%), and acceptable acute rejection-free graft survival (89%). The mean serum creatinine level (+/-SD) at one yr was 1.5 +/- 0.6 mg/dL and at two yr was 1.5 +/- 0.6 mg/dL. We noted that 5% of recipients developed cytomegalovirus (CMV) syndrome; 1%, polyoma nephropathy; 1%, post-transplant lymphoproliferative disorder (PTLD), and 5% developed post-transplant diabetes mellitus (PTDM). In all, 91% of kidney recipients with functioning grafts remain steroid-free as of 31 December 2005. When compared with historical controls, the recipients on the early steroid-withdrawal (ESW) protocol had comparable graft survival, acute rejection-free survival, graft function, but significantly better patient actuarial survival (p = 0.048). In addition, recipients on the steroid-free protocol had decreased prevalence of four risk factors for cardiovascular disease when compared with historical controls: hypertension (p = 0.008), hyperlipidemia (p = 0.003), weight gain (p = 0.024), and incidence of PTDM (p = 0.015). CONCLUSION: Early steroid-withdrawal in renal transplant recipients with a sirolimus and CellCept-based calcineurin inhibitor-minimimization protocol can effectively reduce many of the steroid-related side effects, decrease risk factors for cardiovascular disease, and is associated with improved recipient survival without compromising graft function.     

Successful steroid withdrawal guided by surveillance biopsies—A single‐center experience

Steroid withdrawal following renal transplantation is challenging and widely debated. This retrospective study aimed at investigating the frequency and determinants of successful steroid withdrawal guided by surveillance biopsies. We analyzed 156 pretransplant DSA‐negative renal transplants receiving basiliximab induction and maintenance immunosuppression with tacrolimus‐mycophenolate‐steroids. The absence of rejection in surveillance biopsies at 3 or 6 months post‐transplant initiated steroid withdrawal, which was monitored by subsequent indication and/or surveillance biopsies. The primary outcome was the frequency of successful (i.e., rejection‐free) steroid withdrawal at 1 year post‐transplant. In the whole study population, successful steroid withdrawal was achieved in 73 of 156 patients (47%). Steroid withdrawal was initiated in 98 of 156 patients (63%) and successful in 73 of 98 patients (74%). Subsequent clinical rejection occurred in only one of 98 patients (1%), whereas 24 of 98 patients (24%) experienced subclinical rejection. Steroid withdrawal was not initiated in 58 of 156 patients (37%) mainly due to current or prior severe (Banff TCMR ≥IA) subclinical rejection. Prediction of successful steroid withdrawal by pretransplant or early post‐transplant parameters was poor. In conclusion, (sub)clinical rejection‐free steroid withdrawal can be expected in about half of pretransplant DSA‐negative patients. As successful steroid withdrawal cannot be well predicted by pre‐ and early post‐transplant parameters, guidance by surveillance biopsies is an attractive strategy.     

Racial disparity in kidney transplant survival relates to late rejection and is independent of steroid withdrawal

Black kidney transplant recipients have more acute rejection (AR) and inferior graft survival. We sought to determine whether early steroid withdrawal (ESW) had an impact on AR and death‐censored graft loss (DCGL) in blacks. From 2006 to 2012, AR and graft survival were analyzed in 483 kidney recipients (208 black and 275 non‐black). Rates of ESW were similar between blacks (65%) and non‐blacks (67%). AR was defined as early (≤3 months) or late (>3 months). The impact of black race, early AR, and late AR on death‐censored graft failure was analyzed using univariate and multivariate Cox models. Blacks had greater dialysis vintage, more deceased donor transplants, and less HLA matching, yet rates of early AR were comparable between blacks and non‐blacks. However, black race was a risk factor for late AR (HR: 3.48 (95% CI: 1.87‐6.47)) Blacks had a greater rate of DCGL, partially driven by late AR (HR with late AR: 5.6; 95% CI: 3.3‐9.3). ESW had no significant interaction with black race for risk of early AR, late AR, or DCGL. Independent of ESW, black kidney recipients had a higher rate of late AR after kidney transplantation. Late AR was highly predictive of DCGL and contributed to inferior graft survival in blacks.     

Donor kidney microthrombi and outcomes of kidney transplant: a single‐center experience

The kidney wait list has outgrown the supply of available organs every year. Efforts are being made to minimize discard rate of organs. One such area is the use of kidneys with glomerular microthrombi (MT). We retrospectively examined graft/patient outcomes in 28 cases with MT in pre‐implantation biopsies. All patients had follow‐up of at least 36 months, or until graft loss or death. In total, 17 of the 18 patients who underwent follow‐up biopsy within 90 days of transplantation had cleared all MT. Most patients had excellent long‐term graft function. On a closer review of the biopsies included in our study, we found that even in the organs with the most widespread thrombosis, the median percentage of glomeruli with more than 50 percentage of the capillary loops occluded was 8% (range 0–17%). The current practice of mentioning the % of glomeruli with thrombi cannot adequately capture the extent of donor organ pathology, as the actual % glomerular area involved can vary greatly from case to case. Future studies should attempt to quantify donor thrombi by a more robust method and revisit the issue of using clinico‐pathologic parameters to predict allograft function in the setting of MT.     

CNI withdrawal for post‐transplant lymphoproliferative disorders in kidney transplant is an independent risk factor for graft failure and mortality

Post‐transplantation lymphoproliferative disorders (PTLD) are associated with poor patient and graft survival. The risk of rejection and subsequent graft loss are increased by the reduction of immunosuppression therapy, the cornerstone of PTLD treatment. This multicentre, retrospective, nonrandomized cohort study includes 104 adults who developed PTLD after renal or simultaneous renal/pancreatic transplantation between 1990 and 2007. It examines the effect of calcineurin inhibitor (CNI) withdrawal on long‐term graft and patient survival. At 10 years postonset of PTLD, the Kaplan–Meier graft loss rate was 43.9% and graft loss or death with functioning graft was 64.4%. Cox multivariate analysis determined risk factors of graft loss as PTLD stage greater than I‐II and CNI withdrawal, and for graft loss and mortality, these remained risk factors along with age over 60 years. Type and location of PTLD, year of diagnosis, and chemotherapy regime were not independent risk factors. Multivariate analysis determined CNI withdrawal as the most important risk factor for graft loss (HR = 3.07, CI 95%: 1.04–9.09; P = 0.04) and death (HR: 4.00, CI 95%: 1.77–9.04; P < 0.001). While long‐term stable renal function after definitive CNI withdrawal for PTLD has been reported, this review determined that withdrawal is associated with reduced graft and patient survival.     

The feared five fungal infections in kidney transplant recipients: A single‐center 20‐year experience

Invasive fungal infections are a feared complication in kidney transplant recipients (KTRs). Here we present the University of Wisconsin experience with 5 invasive fungal infections—aspergillosis, cryptococcosis, histoplasmosis, blastomycosis, and coccidioidomycosis—in KTRs transplanted between 01/01/1994 and 06/30/2014. During this period, there were 128 cases of fungal infections; aspergillosis was the most common (72), followed by cryptococcosis (29), histoplasmosis (14), blastomycosis (10), and coccidioidomycosis (3). The mean interval from transplant to fungal infection was 3.19 ± 3.58 years (range 5 days‐15.8 years). By 6 months postinfection, there were 53 (41%) graft failures and 24 (19%) deaths. Graft failure occurred in 46%, 38%, 21%, 40%, and 67% of patients with aspergillosis, cryptococcosis, histoplasmosis, blastomycosis, and coccidioidomycosis, respectively. Anti‐thymocyte globulin (ATG) induction (HR, 1.49; 95% CI, 1.03‐2.16; P = .04), diabetes (HR, 1.53; 95% CI, 1.05‐2.21; P = .03), and age (HR, 1.47; 95% CI, 1.27‐1.70; P ≤ .001) were associated with an increased risk for infection in univariate analysis. Multivariate adjustment retained ATG induction and older age. A large proportion of kidney transplant recipients with invasive fungal infections suffer graft failure within 3 years. Preventive, therapeutic, and monitoring strategies are needed to improve graft and patient outcomes.     

Inferior graft survival of hepatitis B core positive grafts is not influenced by post‐transplant hepatitis B infection in liver recipients—A 35‐year single‐center experience

Nonoptimal liver grafts, and among them organs from anti‐HBc+ donors, are increasingly used for liver transplantation. In this retrospective study including 1065 adult liver transplantations performed between 1977 and 2012, we analyzed long‐term patient and graft survival and occurrence of HBV infection. A total of 52 (5.1%) patients received an anti‐HBc+ graft. The 10‐year graft and patient survival of these recipients were 50.9% and 59.0% compared to 72.0% and 76.5% (P = 0.001; P = 0.004) of patients receiving anti‐HBc‐ grafts, respectively. Cox regression model showed that high urgency allocation (P = 0.003), recipient age (P = 0.027), anti‐HCV+ recipients (P = 0.005), and anti‐HBc+ organs (P = 0.048) are associated with decreased graft survival. Thirteen of 52 (25.0%) patients receiving anti‐HBc+ grafts developed post‐transplant HBV infection within a mean of 2.8 years. In this study, antiviral prophylaxis did not have significant impact on HBV infection, but long‐term survival (P = 0.008). Development of post‐transplant HBV infection did not affect adjusted 10‐year graft survival (100% vs. 100%; P = 1). Anti‐HBc+ liver grafts can be transplanted with reasonable but inferior long‐term patient and graft survival. The inferior graft survival is not, however, related with post‐transplant HBV infection as long as early diagnosis and treatment take place.     

Obstetric and long‐term kidney outcomes in renal transplant recipients: a 40‐yr single‐center study

Female renal transplant recipients of childbearing age may ask what the outcomes are for pregnancy and whether pregnancy will affect graft function. We analyzed obstetric and transplant outcomes among renal transplant recipients in our center who have been pregnant between 1973 and 2013. A case?cohort study was performed identifying 83 pairs of pregnant and non‐pregnant controls matched for sex, age, transplant vintage, and creatinine. There were 138 pregnancies reported from 89 renal transplant recipients. There were live births in 74% of pregnancies with high prevalence of prematurity (61%), low birth weight (52%), and pre‐eclampsia (14%). Lower eGFR (OR 0.98; p = 0.05) and higher uPCR (OR 1.86; p = 0.02) at conception were independent predictors for poor composite obstetric outcome. Lower eGFR (OR 0.98; p = 0.04), higher uPCR (OR 1.50; p = 0.04), and live organ donation (OR 0.35; p = 0.02) were predictors of ≥20% loss of eGFR between immediately pre‐pregnancy and one yr after delivery. There was no difference in eGFR at one, five, and 10 yr in pregnant women compared with non‐pregnant controls and a pregnancy was not associated with poorer 10‐yr transplant or 20‐yr patient survival. Despite high rates of obstetric complications, most women had successful pregnancies with good long‐term transplant function.     

Gender differences in long‐term survival post‐transplant: A single‐institution analysis in the lung allocation score era

The purpose of this study was to clarify the significance of recipient gender status on lung transplant outcomes in a large single‐institution experience spanning three decades, we analyzed data from all lung transplants performed in our institution since 1986. Kaplan‐Meier curves and Cox proportional hazard models were used to evaluate the effect of recipient characteristics on survival and BOS score ≥1‐free survival. Logistic regression analysis was used to explore the association of gender with short‐term graft function. About 876 lung transplants were performed between 1986 and 2016. Kaplan‐Meier survival estimates at 5 years post‐transplant for females vs males in the LAS era were 71% vs 58%. In the LAS era, females showed greater unadjusted BOS≥1‐free survival than males (35% vs 25%, P=.02) over 5 years. Female gender was the only factor in the LAS era significantly associated with improved adjusted 5‐year survival [HR 0.56 (95% CI 0.33, 0.95) P=.03]. Conversely, in the pre‐LAS era female gender was not associated with improved survival. Female recipients showed significantly improved survival over 5 years compared to males in the LAS era. A prospective analysis of biologic and immunologic differences is warranted.     

Liver retransplantation in children. A 21‐year single‐center experience*

In this study, the epidemiology and outcome of graft loss following primary pediatric liver transplantation (LT) were analysed, with the hypothesis that early retransplantation (reLT) might be associated with lower immunologic risks when compared with late reLT. Between March 1984 and December 2005, 745 liver grafts were transplanted to 638 children at Saint‐Luc University Hospital, Brussels. Among them, a total of 90 children (14%) underwent 107 reLT, and were categorized into two groups (early reLT, n = 58; late reLT, n = 32), according to the interval between either transplant procedures (< or >30 days). Ten‐year patient survival rate was 85% in recipients with a single LT, vs. 61% in recipients requiring reLT (P < 0.001). Ten‐year patient survival rates were 59% and 66% for early and late reLT, respectively (P = 0.423), the corresponding graft survival rates being 51% and 63% (P = 0.231). Along the successive eras, the rate of reLT decreased from 17% to 10%, whereas progressive improvement of outcome post‐reLT was observed. No recurrence of chronic rejection (CR) was observed after reLT for CR (0 of 19). Two children developed a positive cross‐match at reLT (two of 10, 20%), both retransplanted lately for CR secondary to immunosuppression withdrawal following a post‐transplant lymphoproliferative disease. In summary, the results presented could not evidence better results for late reLT when compared with early reLT. The former did not seem to be associated with higher immunologic risk, except for children having withdrawal of immunosuppression following the first graft.     

Early cyclosporine withdrawal from a sirolimus-based regimen results in better renal allograft survival and renal function at 48 months after transplantation

We report the 48-month results of a trial testing whether withdrawal of cyclosporine (CsA) from a sirolimus (SRL)-CsA-steroid (ST) regimen would impact renal allograft survival. Eligible patients receiving SRL-CsA-ST from transplantation were randomly assigned at 3 months to remain on triple therapy (SRL-CsA-ST, n = 215) or to have CsA withdrawn and SRL trough concentrations increased (SRL-ST, n = 215). SRL-ST therapy resulted in significantly better graft survival, either when including death with a functioning graft as an event (84.2% vs. 91.5%, P = 0.024) or when censoring it (90.6% vs. 96.1%, P = 0.026). Calculated glomerular filtration rate (43.8 vs. 58.3 ml/min, P < 0.001) and mean arterial blood pressure (101.3 vs. 97.1 mmHg, P = 0.047) were also improved with SRL-ST. Differences in the incidences of biopsy-proven acute rejection after randomization (6.5% vs. 10.2%, SRL-CsA-ST versus SRL-ST, respectively) and mortality (7.9% vs. 4.7%) were not significant. SRL-CsA-ST-treated patients had significantly higher incidences of adverse events generally associated with CsA, whereas those in the SRL-ST group experienced greater frequencies of events commonly related to higher trough levels of SRL. In conclusion, early withdrawal of CsA from a SRL-CsA-ST regimen rapidly improves renal function and ultimately results in better graft survival.     

Retroperitoneoscopic live‐donor nephrectomy: 5‐year single‐center experience in China

Objective: To evaluate the efficacy and the learning‐curve period of our modified retroperitoneoscopic live‐donor nephrectomy. Methods: From December 2003 to May 2009, 138 consecutive retroperitoneoscopic live‐donor nephrectomies were carried out at our institution. Donors were separated into four groups in consecutive sequence in order to determine the learning‐curve period. Groups 1–3 included forty consecutive cases each, whereas group 4 included the last eighteen cases. The renal artery and vein were controlled with two plastic locking clips at proximal ends without any clips on the kidney side. The kidney was manually retrieved through lumbar incision. Results: Mean operative times were 160.5, 116.9, 101.4 and 109.2 min in groups 1–4, respectively (group 1 vs group 2, 3 or 4, P < 0.01). Mean warm ischemic time was 3.5 min. Mean estimated blood loss was 88.8, 73.0, 69.3 and 43.9 mL in groups 1–4, respectively (group 1 vs group 4, P < 0.01). No blood transfusion or open conversion was required. Mean hospital stay was 7.8, 6.9, 6.6 and 5.8 days in groups 1–4, respectively (group 1 vs group 4, P < 0.05). Eight donors and seven grafts suffered from complications. Complication rates were 22.5%, 7.5%, 5.0% and 6.0% in groups 1–4, respectively (group 1 vs group 3, P < 0.05). Conclusion: Our modified retroperitoneoscopic live‐donor nephrectomy can be carried out safely with a learning‐curve period of about 40 cases.     

Long‐term survival in visceral transplant recipients in the new era: A single‐center experience

There is a paucity of data on long‐term outcomes following visceral transplantation in the contemporary era. This is a single‐center retrospective analysis of all visceral allograft recipients who underwent transplant between November 2003 and December 2013 with at least 3‐year follow‐up data. Clinical data from a prospectively maintained database were used to assess outcomes including patient and graft survival. Of 174 recipients, 90 were adults and 84 were pediatric patients. Types of visceral transplants were isolated intestinal transplant (56.3%), combined liver‐intestinal transplant (25.3%), multivisceral transplant (16.1%), and modified multivisceral transplant (2.3%). Three‐, 5‐, and 10‐year overall patient survival was 69.5%, 66%, and 63%, respectively, while 3‐, 5‐, and 10‐year overall graft survival was 67%, 62%, and 61%, respectively. In multivariable analysis, significant predictors of survival included pediatric recipient (P = .001), donor/recipient weight ratio <0.9 (P = .008), no episodes of severe acute rejection (P = .021), cold ischemia time <8 hours (P = .014), and shorter hospital stay (P = .0001). In conclusion, visceral transplantation remains a good option for treatment of end‐stage intestinal failure with parenteral nutritional complications. Proper graft selection, shorter cold ischemia time, and improvement of immunosuppression regimens could significantly improve the long‐term survival.     

Steroid‐free and steroid withdrawal protocols in heart transplantation: the review of literature

Corticosteroids (CSs) are still the mainstay of induction, rescue, and maintenance in heart transplantation (HTx). However, their use is associated with significant and well‐documented side effects usually related to the dose administered and the duration of therapy. Moreover, CSs interfere with the recipient's quality of life and with the active process of graft tolerance. Physicians have been exploring ways to avoid or reduce CSs in association with other immunosuppressive drugs, minimizing side effects and costs. The regimens are classified as steroid‐free or steroid withdrawal protocols. The studies analyzed in this review come to similar conclusions as benefits and adverse consequences: steroid‐free protocols should be advisable and mandatory in pediatric patients, insulin‐dependent diabetes mellitus (IDDM), presence of infection, familial metabolic disorders/obesity, severe osteoporosis, and in the elderly. On the other hand, steroid withdrawal can be successfully achieved in 50–80%, with late better than early withdrawal, no increase in rejection‐related mortality, no adverse impact on survival, and probably a better quality of live. Safety and efficacy can certainly be improved by an individualized approach to the transplant recipient.     

Long‐term patient survival and kidney allograft survival in post‐transplant diabetes mellitus: a single‐center retrospective study

A decade ago, observations suggested that post‐transplant diabetes mellitus (PTDM) was linked to allograft loss and shorter patient survival. Increasing awareness, improvements in care, and changes in the immunosuppressive regimen may have modified this association. Single‐center analysis of 1990 (age>18; transplantation date 1996–2012) primary kidney recipients (KTR). Patients with <12 months follow‐up were excluded. Diabetes was diagnosed according to ADA criteria and characterized as follows: No diabetes, PTDM in the first post‐transplant year not treated with glucose‐lowering medications (GLM) at 12 months, PTDM in the first post‐transplant year treated with GLM at 12 months, and pretransplant diabetes. Cox proportional hazards models were used to examine the relationship of PTDM with allograft and patient survival. Mean follow‐up time was 6.8 years for allograft survival and 7.4 years for patient survival. PTDM treated with medication at year one was not associated with allograft survival (HR 1.28, 95% CI 0.97–1.69), but was significantly associated with overall mortality and death with functioning graft (DWFG) (HR overall: 1.81, 95% CI 1.36–2.39; HR DWFG: 1.59 95% CI 1.05–2.38). In this cohort, KTR with PTDM being treated with glucose‐lowering medication at 12 months experienced significantly shorter overall survival and survival with functioning graft.     

A randomized exploratory trial of steroid avoidance in renal transplant patients treated with everolimus and low-dose cyclosporine.

BACKGROUND: Everolimus and cyclosporine exhibit synergistic immunosuppressive activity when given in combination. In this randomized trial, we explored whether the use of everolimus associated with low-dose cyclosporine could allow an early avoidance of steroids in de novo renal transplant recipients. METHODS: In this exploratory multicenter trial, 65 out of 133 patients treated with basiliximab (days 0 and 4), everolimus 3 mg/day and cyclosporine were randomized to stop steroids on the seventh post-transplant day (group A), whereas the remaining 68 continued low-dose steroid treatment (group B). RESULTS: During the follow-up, 30 patients of group A (46%) resumed steroids. According to the intention-to-treat analysis, the 3-year graft survival rate was 95% in group A and 87% in group B (P = ns). There were more biopsy-proven rejections in group A, the difference being of borderline significance (32% vs 18%; P = 0.059). After 3 years, mean creatinine clearance was 52.3 +/- 17.1 ml/min in group A and 52.2 +/- 21.5 ml/min in group B. It was similar in the group A patients who experienced rejection (49.8 +/- 14.7 ml/min) and those who did not (53.6 +/- 18.3 ml/min; P = 0.319). Mean serum cholesterol and triglyceride levels were, respectively, less than 250 mg/dl and less than 200 mg/dl in both groups, without any significant difference. Vascular thrombosis (0 vs 11.7%; P = 0.0043) was more frequent in group B. CONCLUSIONS: Treatment based on everolimus and low-dose cyclosporine allowed excellent renal graft survival and stable graft function at 3 years. An early discontinuation of steroids increased the risk of acute rejection, but was associated with a better graft survival in the long-term. However, it was well tolerated only by 54% of patients.