Incidence of primary and second cancers in renal transplant recipients: a multicenter cohort study.

Limited data exist about cancer prognosis and the development of second cancers in renal transplant recipients. In a retrospective cohort study on 3537 patients incidence rates of the first and, if any, of a second cancer, and standardized incidence ratios [SIR (95% CI)] were computed. Two hundred and sixty-three (7.5%) patients developed a NMSC, and 253 (7.2%) another type of cancer after a median follow-up of 6.5 and 9.0 years, respectively. A statistically significant excess risk, if compared to an age- and sex-matched reference general population, was observed for Kaposi sarcoma and NMSC, followed by non-Hodgkin lymphoma and carcinoma of cervix uteri; a small number of unusual cancers such as tumors of the salivary glands, small intestine and thyroid also were detected at a level worthy of additional scrutiny. Ten-year survival rate of all noncutaneous cancers was 71.3%, with lower rates for lung carcinoma and non-Hodgkin lymphoma (0% and 41.7%, respectively). Patients with NMSC had an increased risk of developing a second NMSC [SIR 8.3 (7.0-10.0)], and patients with a primary noncutaneous cancer had increased risk of developing a second noncutaneous cancer [SIR 1.8 (1.2-2.8)], if compared to the whole cohort. Our study underscore that the high risk of primary and second cancer in renal transplant recipients, including unusual cancers.

Impact of 3 Major Maintenance Immunosuppressive Protocols on Long-term Clinical Outcomes: Result of a Large Multicenter Italian Cohort Study Including 5635 Renal Transplant Recipients.

BACKGROUND: Although optimization of immunosuppressive schemes in renal transplantation have minimized acute posttransplant complications, long-term outcomes are still not optimal and most of the chronic graft damage is drug-related. Therefore, to define the best long-term maintenance immunosuppressive regimen is of major importance in renal transplantation. To assess this objective, we undertook a large, multicenter cohort study in Italy. METHODS: We retrospectively analyzed data of 5635 patients (enrolled from 1983 to 2012) and we assessed the impact of 3 major immunosuppressive regimens (calcineurin inhibitors+antimetabolites+corticosteroids [CNI+ANT+CS] vs CNI+mammalian target-of-rapamycin (mTOR) inhibitors+CS [CNI+mTOR-I+CS] vs CNI+CS) on long-term clinical outcomes by employing several statistical algorithms. RESULTS: The overall difference in the incidence of outcome over time was not statistically different within the first 5 years of follow-up (P = .13); however, it became significant at 10 years and 20 years (P < .01), with the CNI+CS group showing the lowest cumulative incidence of outcome. Compared with the CNI+ANT+CS group, the CNI+mTOR-I+CS group patients had a significantly higher risk of outcome (hazard ratio [HR], 1.30; P = .024); the difference remained significant and even increased in magnitude after adjustment for potential confounders (HR, 1.38; P = .006). Similarly, patients in the CNI+CS group had a significantly higher risk of the outcome (HR, 1.64; P < .001). CONCLUSION: Our data confirm that CNI+ANT+CS is the "gold standard" therapy in renal transplantation, but, whenever required, the introduction of mTOR-Is instead of ANT may not dramatically modify major clinical outcomes. The use of mTOR-I could be a valuable pharmacologic tool to minimize CNI complications and insure adequate immunosuppression.

Patient mortality after graft failure reduces kidney transplant patient survival only in the long term: an "intention to treat" analysis.

The benefits of kidney transplantation over dialysis on patient survival have been demonstrated without considering the outcomes of patients with graft loss. To determine whether mortality after graft failure reduced the transplantation advantage in patient survival, we retrospectively reviewed the outcomes of 918 first-deceased renal transplant recipients from May 1979 to August 2005. Patient survivals were 88% and 72% at 10 and 20 years; cancer (26%) and cardiovascular disease (25%) were the major causes of death. Graft survivals were 72% and 50% at 10 and 20 years; chronic rejection was the major cause of graft loss (50%). Patient outcomes after return to dialysis were reviewed in 224 of 240 patients. The survivals were 97%, 83%, and 70% at 1, 5, and 10 years, respectively; cardio-cerebrovascular disease (56%), infections (9%), cachexia (9%), and cancer (8%) were the major causes of death. Mortality correlated with patient age at transplantation (P< .001). Re-listed patients (96 of 224) were younger (32+/-10 vs 43+/-11 years; P< .001), had a shorter dialysis period pretransplant (3.2+/-3.1 vs 4.3+/-3.9 years; P< .03), and a better survival at 10 years (98% vs 56%; P< .001). Ten-year mortality for patients who returned to dialysis was 20% higher than for patients with a functioning graft (P< .001). The reduction in overall patient survival was 2.2% at 10 years (P=NS), 5% at 15 years (P=NS), and 14% at 20 years (P< .05). The same results have been demonstrated for patients >50 years at transplantation. In conclusion, the mortality rate after return to dialysis did not influence the long-term benefits of kidney transplantation.

[Treatment of post-transplant glomerulonephritis]. / Il trattamento delle glomerulonefriti de novo e recidivate come causa di disfunzione cronica del rene trapiantato.

The treatment of recurrent glomerulonephritis (GN) is often empirical. Plasmapheresis has received the largest consensus for the treatment of focal glomerular sclerosis (FGS), whether associated with cyclophosphamide and steroids or not. To be effective, such therapy needs to be started as quickly as possible after the onset of proteinuria, and prolonged for months when recovery is delayed. Plasmapheresis and cyclophosphamide have also been used to treat GNs with glomerular crescents. However, there has been no consensus on the efficacy of such therapy. The recently introduced rituximab is the most innovative drug but also the most experimental. So far, it has been used for the treatment of ANCA-associated vasculitis, FGS and membranous GN, with results that are still under debate. Cyclophosphamide has been used in patients with severe recurrent GN, but the anedoctal cases described prevent us from drawing any firm conclusions. Steroids have been used for the treatment of many recurrent GNs, but yet again, without any standard protocol. They have been used both in children with FGS and in adults with aggressive GN or severe proteinuria. Both ACE inhibitors and angiotensinreceptor blockers have been suggested as first-line therapy in recurrent GN with proteinuria. This therapy is safe and can be even more effective than others. Finally, it must be kept in mind that the addition of immunosuppression in transplant patients can dramatically increase the risk of infective complications. Moreover, recurrent GNs are often associated with chronic allograft diseases that can cause graft worsening independently of any therapy.

[Outpatient monitoring after renal transplantation: protocols shared between transplant center and local nephrology units]. / Protocolli condivisi per il follow-up decentrato del paziente trapiantato.

Outpatient monitoring plays a key role in the long-term success of kidney transplantation. Shared management of transplanted patients between transplant centers and local nephrology units is becoming common practice and is a benefit both for the patients, who can be followed in an outpatient office closer to their homes, and for the transplant centers, which are overwhelmed by an increasing number of follow-up patients. The program is also well accepted by the referring nephrology units, which are interested in improving their skills. In this article a model of clinical collaboration is discussed, although it is well known that it is impossible to apply the same rules to all centers. However, to make any collaborative program feasible, two main requirements must be met. First, every local unit should have a referent nephrologist responsible for the clinical follow-up of transplant recipients and for the waiting list; second, every transplant center should organize transplant refresher courses for their referring nephrologists.

Blood cyclosporine level soon after kidney transplantation is a major determinant of rejection: insights from the Mycophenolate Steroid-Sparing Trial.

Target organs express antigens directly recognized by antigen-specific T cells, thereby precipitating rejection. When early T-cell activation is inhibited, there is a low risk of rejection. We sought to determine the predictive values of serial posttransplant blood cyclosporine trough (C(0)) concentrations to minimize the risk for a first rejection episode compared with 2-hour postdose (C(2)) drug concentrations. The final aim of the study was to identify a concentration range for the best predictive pharmacokinetic parameter that should be targeted to reduce the risk of rejection. This possibility was explored in 334 de novo kidney transplant recipients who participated in the prospective, multicenter Mycophenolate Steroid-Sparing Trial. Among measurements performed during the first 6 months postsurgery, cyclosporine C(0) levels measured early after transplantation were the strongest predictor of acute graft rejection. Levels within 300 to 440 ng/mL were associated with the lowest risk of rejection, while patients with levels lower than 300 ng/mL showed a more than double risk. Cyclosporine trough values predicted allograft rejection with an accuracy of 74%, while C(2) levels had no predictive value. These findings underline the need to target cyclosporine therapy early posttransplant to modulate T-cell activation.

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

In this randomized trial renal transplant recipients were treated with basiliximab, everolimus 3 mg/day, low-dose CsA. At transplantation, patients were randomized to stop steroids at the seventh day (group A) or to continue oral steroids in low doses (group B). Of the 113 patients enrolled, 65 were randomized to group A and 68 to group B. All patients were followed for 2 years. During the study 28 (43%) group A patients required reintroduced corticosteroids. One patient died, in group B. The Graft survival rate was 97% in group A and 90% in group B. There were more biopsy-proven rejections in group A (32% vs 16%; P = .044). The mean creatinine clearance was 54 +/- 21 mL/min in group A vs 56 +/- 22 mL/min in group B. Mean levels of serum cholesterol tended to be lower in group A, but the difference was of borderline significance (191 +/- 91 vs 251 +/- 188 mg/dL; P = .07). Vascular thrombosis (0 vs 5) and pneumonia requiring hospitalization (2 vs 7) tended to be more frequent in group B. Only three cases of CMV infection (1 vs 2) occurred. An immunosuppressive therapy with everolimus and low-dose CsA allows one to obtain excellent renal graft survival and stable graft function at 2 years. Early interruption of steroids in patients treated with this regimen may increase the risk of acute rejection, but neither affects graft survival nor graft function, while possibly reducing the risk of hyperlipemia and vascular thrombosis. About 60% of patients given everolimus and low-dose CsA can definitively stop steroids after 1 week.

[Successful treatment with liposomal doxorubicin and foscarnet in a patient with widespread Kaposi's sarcoma and human herpes virus 8-related, serious hemophagocytic syndrome, after renal transplantation]. / Efficacia del trattamento con doxorubicina liposomiale e foscarnet in un caso di sarcoma di Kaposi disseminato e grave sindrome emofagocitica herpes virus 8 correlate, nel post-trapianto di rene.

BACKGROUND: It is well known that the human herpes virus 8 (HHV8) is linked to several malignancies such as Kaposi's sarcoma (KS). Moreover, pancytopenia due to hemophagocytic syndrome could be associated with HHV8 infection. In renal transplant recipients affected by KS, the tapering of immunosuppression often leads to KS remission, but also results in graft loss in >50% of cases. Chemotherapy and antiviral therapy have also been used, mainly in the presence of visceral involvement. CASE REPORT: We describe a transplant recipient with widespread cutaneous and visceral KS HHV8 associated, complicated by hemophagocytic syndrome. At transplantation the patient's serology for HHV8 was negative, but thereafter it became positive. The first step in treatment (cyclosporine dose reduction until suspension) failed to improve the clinical course. Therefore, therapy combining liposomal doxorubicin and foscarnet was started. Clearance of HHV8 in the blood and complete resolution of the KS lesions were achieved. Immunosuppression with cyclosporine was resumed. No KS relapse has occurred, blood tests for HHV8 are negative, and graft function is good after a 5-yr follow-up. CONCLUSIONS: Therapy combining liposomal doxorubicin and foscarnet was effective in this renal transplant recipient with KS and HHV8 infection and enabled us to resume immunosuppressive therapy; therefore, reducing the risk of acute/chronic rejection.

[Renal transplantation in the North Italy Transplant program (NITp): Organ allocation and results]. / Il trapianto renale nel Nord Italia Transplant program (NITp): assegnazione degli organi e risultati.

Renal transplantation is an effective therapeutic tool for patients with end-stage renal diseases (ESRDs). Data reported in this article summarize the results obtained from 30 years' activity in the North Italy Transplant program (NITp), the first transplant organization in Italy that implemented a donor procurement and organ transplantation network. In the NITp kidney allocation is governed by a computerized algorithm, NITK3, put in place in 1997, aimed at ensuring equity, transparency and traceability during the stages of the allocation decision-making process. The NITp working group has recognized the NITK3 criteria and they are periodically reviewed following the results of the analysis of patients' transplantation odds. The results obtained with the use of the NITK3 algorithm have been very satisfactory: after 6 yrs, a significantly higher percentage of patients at immunological risk (sensitized or waiting for re-transplant), of patients waiting for >3 yrs and of patients with 0-1 HLA A,B,DR mismatches have been transplanted. Moreover, a higher percentage of kidneys were used locally (in a hospital within the procurement area), and this is known to stimulate donor procurement. Finally, we performed a preliminary statistical analysis of transplants carried out from 1998-2002 in 5/16 centers of the NITp area, demonstrating the quality of the NITp program in terms of patient and graft survival, and that donor and recipient age are the variables significantly impacting on transplant results.

A prospective randomized trial on azathioprine addition to cyclosporine versus cyclosporine monotherapy at steroid withdrawal, 6 months after renal transplantation.

BACKGROUND: Many attempts have been made to withdraw steroid therapy in renal transplant patients in order to avoid its many side effects. Results have been, so far, controversial. In this randomized prospective study, we compare the efficacy of azathioprine adjuncts to cyclosporine at the time of steroid withdrawal, 6 months after transplantation, versus Cyclosporine monotherapy, in preventing acute rejection. METHODS: One hundred and sixteen kidney transplant patients with good and stable renal function (creatininemia <2 mg/dl) received, in the first 6 months, cyclosporine + steroid. They were then randomized into two groups (A and B), and steroid therapy was withdrawn over 2 months. Group A (58 patients) continued on cyclosporine monotherapy, whereas group B (58 patients) added azathioprine (1 mg/kg/day) at the beginning of randomization and continued on cyclosporine + azathioprine. In both groups, patients resumed steroid therapy at the first episode of acute rejection. Follow-up after randomization was 5.3+/-1.6 years. RESULTS: After 5 years, the incidence of steroid resumption was 57% in group A and 29% in group B (P<0.02); of those, 68% and 88% of them were within 6 months from randomization. Anti-rejection therapy was always successful. Five-year patient and graft survival rates were 90% and 88% in group A and 100% and 91% in group B. Creatininemia did not differ, at follow-up. Side effects differed only for mild and reversible leukopenia caused by azathioprine in group B. CONCLUSION: Cyclosporine plus azathioprine is more effective than cyclosporine monotherapy in reducing the incidence of acute rejection after steroid withdrawal. Graft loss as a result of chronic rejection, mild in both groups, did not differ. Steroid withdrawal is feasible and advantageous, and the addition of azathioprine allowed 71% of our selected patients to remain steroid-free.

Micro-chromatographic measurement of hemoglobin A1 in uremia.

In an investigation of the reliability of the measurement of HbA1 by microcolumn chromatography for monitoring glucose metabolism in chronic renal failure, measurements were made in 96 uremic patients. Thirty-one patients were undialyzed, 42 patients including 10 with primary diabetes mellitus were on hemodialysis, and 23 patients were on continuous ambulatory peritoneal dialysis (6 with primary diabetes mellitus). Significantly raised HbA1 values were observed in all groups, whether their glucose tolerance was normal or decreased. Azotemia was not statistically correlated either with HbA1 values, or with glucose tolerance. Dialyzed primary diabetic patients showed HbA1 levels which were significantly higher than those in non-diabetics, but some overlap was evident. The results suggest that the increased values of HbA1 in uremic patients depend on the plasma concentration of either glucose which leads to the formation of glycosylated Hb or of urea which leads to the formation of carbamylated Hb. These are indistinguishable by microcolumn chromatography. Therefore this method cannot be recommended for evaluation of glucose metabolism in uremic patients.

Body composition and nutritional status in patients on continuous ambulatory peritoneal dialysis (CAPD).

Total body water (TBW), extracellular water (ECW), exchangeable potassium pool (EKP), and alkali-soluble nitrogen in skeletal muscle tissue (N) were determined in 9 CAPD patients on treatment from 5 to 14 months (mean 8.6 months). The parameters were reevaluated in 6 of these patients 5 to 13 months later (mean 8.6 months). The mean value of TBW was normal and directly correlated to body weight (BW), but TBW was abnormally distributed between extracellular and intracellular space. ECW volume was significantly lower than the predicted value (12.1 +/- 1.4 versus 16.8 +/- 1.9 l) and out of proportion to TBW (34.8 +/- 3.9% versus 47.8 +/- 1.5%). The calculated intracellular water, therefore, appeared clearly hyperexpanded. The mean value of EKP was slightly reduced, but in three patients there was a 25% reduction. N content was low in 5 out of 9 patients. When the parameters were re-evaluated BW and TBW were unchanged in two subjects. A third patient showed a simultaneous increase in both BW (12.7%) and TBW (19%). TBW variations (+19%, -23%, -24%) without changes in BW were seen in three patients. The mean value of EKP was unchanged, but there was a 25% reduction in one patient. N content improved in two and worsened in one of the three patients in whom it was determined. The data suggest that cell overhydration was the distinctive feature in our CAPD patients, and that the evolution of the nutritional status was variable, since the patients could remain stable, gain or loose body fat, and probably change their lean body mass.

Experience with cyclosporine.

Six hundred thirty-eight cadaveric kidney transplant patients between 1983 and 2001 were treated with cyclosporine (CsA) for 87 +/- 58 months. Among 571 patients with follow-up greater than 12 months, the 15-year renal function was investigated to assess the probability of a >30% increase in serum creatinine (sCr) above the month-6 value (baseline) and the impact on graft survival. At 15 years, patient and graft survival rates were 82.7% and 56.1%, respectively, with a 19.5-year half-life (censored for deaths). The main causes of graft loss were chronic rejection (33.0%) and patient death (24%). Cardiovascular disease and neoplasms were the main causes of death. Renal function remained stable in 266 patients (46.6%) with excellent sCr values observed even after a 15-year treatment period. An increased sCr was observed in 305 patients (53.4%) with a 15-year probability of 74%. In 178 patients (59.3%) it was self-limited; their grafts are still functioning well. One hundred three patients (32.8%) lost their graft which was more likely when the sCr had increased >45%. Twenty-four patients (7.9%) died with a functioning graft. Multivariate analysis showed the progression of graft deterioration to be related to proteinuria (P<.0001), a late acute rejection episode (P<.002), or the extent of sCr increase (P<.008). In conclusion, the long-term use of CsA has allowed us to achieve excellent long-term patient and transplant survival rates. Our data indicate a high 15-year probability of an increased sCr, but the rate of progression is slow.

Body fluid spaces in patients on CAPD.

Total body water (TBW) and extracellular water (ECW) were determined in 9 CAPD patients on treatment from 5 to 14 months (mean 8.6 months). The mean value of TBW was normal and directly correlated to body weight, but TBW was abnormally distributed between extracellular and intracellular space. ECW volume was significantly lower than the predicted value (12.1 +/- 1.4 l versus 16.8 +/- 1.9 l) and out of proportion to TBW (34.8 +/- 3.9% versus 47.8 +/- 1.5%). The calculated ICW, therefore, appeared clearly hyperexpanded. The data suggest that cell overhydration was the distinctive feature in our CAPD patients.

Hospitalization: CAPD versus hemodialysis and transplant.

We studied morbidity in 648 patients treated in our center in a ten-year period as indicated by duration of hospitalization: 232 patients were on CAPD, 188 on hemodialysis (HD) and 228 had cadaveric kidney transplants (Tx). Duration of hospitalization was divided into four groups according to its causes. The age of the patients on CAPD was 61 +/- 14 years, 53 +/- 17 on HD and 36 +/- 10 in the Tx group. The total follow-up was 629 patient-year (p-y) on CAPD, 458 p-y on HD and 928 p-y on Tx. The first admission was longer on CAPD (30 +/- 18 days) and on Tx (36 +/- 18 days) than on HD (18 +/- 12). After the first admission, the total days of hospitalization (days/patient-year, d/p-y) were more for CAPD than HD and Tx. Analysis of these data showed that the difference was due to peritonitis and to the different percentage of elderly patients in the CAPD group. With a reduction in the incidence of infectious complications (peritonitis, tunnel or exit-site), hospitalization in CAPD could be reduced to a length of time similar to that currently needed by HD and Tx patients. This can result in important cost-saving.

Intercomparison of sampling and measurement of 7Be in air at four high-altitude locations in Europe.

For several years 7Be measurements have been conducted at high-altitude stations in Austria (Sonnblick, 3106 m), Switzerland (Jungfraujoch, 3580 m), Germany (Zugspitze, 2962 m), and Italy (Mt. Cimone, 2165 m) with the aim to support a study on vertical ozone transport in the Alps (VOTALP project). Aerosol samples, collected on filtering media with high volume samplers, are analysed for 7Be by high-resolution gamma-spectrometry. Prior to evaluation of the 7Be time series of the four stations, both sampling and measurement procedures were checked for comparability. The results of an intercomparison exercise performed within the mentioned project are reported.

[Clinical anatomical features of chronic dysfunction in the transplanted kidney]. / Aspetti anatomo clinici della disfunzione cronica del rene trapiantato.

Histopathological features of transplanted kidneys which gradually lose graft function have been traditionally reported with the term of chronic rejection (CR). In 1997 Banff's classification indicated the adoption of a new term for all these histological features, namely Chronic allograft nephropathy (CAN), recommending that the presence of morphological aspects suggestive of chronic rejection, such as chronic transplant glomerulopathy (CTG) and proliferative endoarteritis (PE), has to be specified. On the basis of these criteria we reviewed the renal biopsies of 92 patients who underwent kidney transplantation from 1999 to 2002. In all cases the biopsy had been performed 6 months after organ transplantation. In 30 of the 92 patients CTG and/or PE was evident supporting a diagnosis of CR; on the contrary, in 11 of the 92 patients the final diagnosis based on histological evidence was that of CAN. Clinical and laboratory tests revealed that the presence of proteinuria in patients with CR at the time of diagnosis was the single statistically significant difference between these two groups. In 7 of the 32 patients where the diagnosis of CR was based on the presence of early features of CTG, the treatment with ACE-I induced complete remission of the proteinuria. Cyclosporine-induced arteriolopathy (CSA) represents an additional histological finding which has been associated with graft loss in the transplanted kidney. The observation of arteriolopathy, similar to CSA in patients who did not receive calcineurine inhibitors, suggests some caution in the use of this diagnostic criteria.

[Cancer after kidney transplantation]. / La complicanza neoplastica dopo trapianto di rene.

In our experience, cancer is the second cause of death after renal transplantation. In fact, 27% of the deaths we observed at 15-year follow-up were due to neoplasm and 30% to cardiovascular disease. Cancer is a late complication that becomes more common after the fifth year of transplantation. The probability of suffering from cancer is 8.2% and 29.2% at 5 and 15 year, respectively. More specifically, after a 15-year follow-up, the probability rate for skin cancer is 16.4%, solid cancer 12.8%, lymphoproliferative disease (PTLD) 3% and Kaposi's sarcoma 2.2%, respectively. PTLD has the highest mortality rate (44% after 12 months from diagnosis), followed by solid cancer (24%) and Kaposi's sarcoma (8%). According to the literature, patient-age is the main risk factor for neoplasm; double therapy (Cyclosporine + Azathioprine) can increase both the skin cancer and PTLD risk but not the risk of solid cancer. No difference between Cyclosporine and Tacrolimus has been observed in the incidence of neoplasm. Both in vitro and in vivo studies have documented the ability of Rapamycin to inhibit primary and metastatic tumour growth. If these results are also obtained on patients, Rapamycin will be of considerable interest for the future of immunosuppression. In cancer patients, immunosuppression must always be reduced, especially when dealing with PTLD. After standard chemotherapy, patient mortality rate due to infectious complications is very high. Therefore, chemotherapy should be a second-choice therapy and administered in reduced doses. Many studies have documented that lymphocytes B-cells CD20 positive PTLD can be efficiently treated with Retuximab.

A randomized trial of everolimus and low-dose cyclosporine in renal transplantation: with or without steroids?

This multicenter, randomized, prospective, controlled trial (EVIDENCE study) aimed to determine short-term effects of early steroid withdrawal in renal transplant patients initially treated with everolimus, low-dose cyclosporine (CsA), and steroids. Patients were randomized to standard triple therapy with CsA, everolimus twice daily and steroids (group A), steroid-free immunosuppression (group B), or triple therapy once daily (group C). However, since patient enrollment was slower than expected, group C randomization was prematurely discontinued. The primary end point was treatment failure rate (composite end point of death, graft loss, biopsy-proven acute rejection, and loss to follow-up) between randomization and month 12. Patients evaluable for the primary end point included 139 randomized patients. According to intention-to-treat analysis, 2.8% of patients in group A and 14.7% in group B experienced treatment failure (95% upper confidence limit 19.7%). As this was higher than the predefined noninferiority limit of 10%, noninferiority could not be proved. No conclusive statements can be made on noninferiority of the steroid withdrawal regimen vs the standard regimen in these patients. Additional studies with longer follow-up are required to determine the efficacy of steroid-free immunosuppression in renal transplant recipients receiving everolimus.