Graft and patient outcomes of zero‐human leucocyte‐antigen‐mismatched deceased and live donor kidney transplant recipients

Greater compatibility of human leucocyte antigen (HLA) alleles between kidney donors and recipients may lead to improved graft outcomes. This study aimed to compare the incidence of acute rejection and graft failure in zero‐HLA‐mismatched recipients of living‐related (LD) and deceased donor (DD) kidney transplants. Using data from the Australia and New Zealand Dialysis and Transplant Registry, we compared the risk of any acute rejection and biopsy‐proven acute rejection (BPAR) and graft failure in recipients of zero‐HLA‐mismatched kidneys between LD and DD using logistic and Cox regression models. Of the 931 zero‐HLA‐mismatched recipients transplanted between 1990 and 2012, 19 (2.0%) received kidneys from monozygotic/dizygotic twins (twin), 500 (53.7%) from nontwin LD and 412 (44.3%) from DD. Twin kidney transplant recipients did not experience rejection. Compared to DD transplant recipients, the risk of any acute rejection (adjusted odds ratio 0.52, 95%CI 0.34–0.79, P = 0.002) and overall graft failure (adjusted hazard ratio 0.55, 95%CI 0.41–0.73, P < 0.001) was significantly lower in LD recipients independent of initial immunosuppression, but not for BPAR (adjusted odds ratio 0.52, 95%CI 0.16–1.64, P = 0.263). Zero‐HLA‐mismatched DD kidney transplant recipients have a significantly higher risk of any acute rejection episodes and graft loss compared to zero‐HLA‐mismatched LD kidney transplant recipients. A cautious and careful approach in reducing immunosuppression appears to be warranted in this group of transplant recipients.     

Clinical Practice of Steroid Avoidance in Pediatric Kidney Transplantation

Steroid‐avoidance protocols have recently gained popularity in pediatric kidney transplantation. We investigated the clinical practice of steroid avoidance among 9494 kidney transplant recipients at 124 transplant centers between 2000 and 2012 in the Organ Procurement and Transplantation Network database. The practice of steroid avoidance increased during the study period and demonstrated significant variability among transplant centers. From 2008 to 2012, 39% of transplant centers used steroid avoidance in <10% of all discharged transplant recipients. Twenty‐one percent of transplant centers practiced steroid avoidance in 10–40% of transplant recipients, and 40% of transplant centers used steroid avoidance in >40% of discharged patients. Children receiving steroid avoidance more frequently received induction with lymphocyte‐depleting agents. Repeat kidney transplants were the least likely to receive steroid avoidance. Children who received a deceased donor kidney, underwent pretransplant dialysis, were highly sensitized, or had glomerular kidney disease or delayed graft function were also less likely to receive steroid avoidance. The variation in practice between centers remained highly significant (p < 0.0001) after adjustment for all patient‐ and center‐level factors in multivariate analysis. We conclude that significant differences in the practice of steroid avoidance among transplant centers remain unexplained and may reflect uncertainty about the safety and efficacy of steroid‐avoidance protocols.     

Pre‐existing diabetes significantly increases the risk of graft failure and mortality following renal transplantation

The aim of this study was to examine the impact of pre‐existing diabetes mellitus (DM) on acute rejection, graft loss, and mortality following kidney transplant and whether glycemic control or cardiovascular disease (CVD) risk control with medications influenced outcomes. This was a cohort study of 1002 renal transplants conducted between 2000 and 2008. Patients were included if they received a kidney transplant within the allotted time and were at least 18 yr of age. Cox regression was used to assess acute rejection, graft failure, or death controlling for relevant sociodemographic, clinical, and post‐transplant variables. Five‐yr patient survival (83% vs. 93%, p < 0.001) and graft survival (74% vs. 79%, p = 0.005) were significantly lower in patients with pre‐existing DM. Sequential Cox regression models demonstrated that pre‐existing DM was consistently associated with a higher risk of death (HR 2.3–3.0, p < 0.01) and graft failure (HR 1.5–1.8, p < 0.04) in all models except after adjusting for CVD medication use (HR 1.9, p = 0.174 and HR 1.5, p = 0.210, respectively). These data suggest pre‐existing DM is a significant risk factor for graft failure and death following renal transplantation and aggressive CVD risk reduction with medications may be an important strategy to reduce mortality and graft failure.     

The Success of Continued Steroid Avoidance After Kidney Transplantation in the US

There has been a significant increase in the use of steroid avoidance regimens as initial treatment for kidney transplant recipients. Early results of the effectiveness of this strategy has been mixed with certain prospective trials indicating increased acute rejection but population‐based studies indicating similar or better graft survival as compared to steroid maintenance. We conducted a retrospective study of national registry data to evaluate risk factors for discontinuation of steroid avoidance protocols based on patient characteristics and concomitant immunosuppression. We evaluated 84 647 solitary kidney transplant recipients in the US with at least 6 months graft survival including 24 218 initially discharged without maintenance steroids. We utilized logistic models to assess risk factors for new initiation of steroids after initial steroid‐avoidance and survival models to describe graft survival for patients after return to steroids. The most prominent risk factors for new initiation of steroids after deceased donor kidney transplantation included African‐American race (AOR = 1.32, p < 0.01), retransplants (AOR = 1.81, p < 0.01), highly sensitized recipients (AOR = 1.29, p < 0.01), recipients with Medicaid (AOR = 1.85, p < 0.01), elevated HLA‐MM (AOR = 1.26, p < 0.01) and older donor age (AOR = 1.19, p < 0.01). Concomitant medications were also significantly associated with the propensity to newly initiate steroids. Cumulatively the study suggests that both patient characteristics and concomitant medications are strongly associated with the success of steroid avoidance immunosuppressive regimens.     

Comparison of alemtuzumab vs. antithymocyte globulin induction therapy in primary non‐sensitized renal transplant patients treated with rapid steroid withdrawal

Alemtuzumab and rabbit antithymocyte globulin (rATG) are commonly used for induction therapy in renal transplantation. This retrospective, single‐center, cohort study evaluated cumulative incidence of one‐yr biopsy‐proven acute rejection (BPAR) among 200 consecutive primary non‐sensitized kidney transplant recipients who received either alemtuzumab (n = 100) or rATG (n = 100) induction followed by rapid steroid taper, tacrolimus, and mycophenolate mofetil. Protocol biopsies, plasma and urine BK virus PCR, serum creatinine and iothalamate glomerular filtration rate (iGFR), were obtained at 1, 4, and 12 months from transplantation. The one‐yr BPAR rates were similar between the alemtuzumab and rATG groups; however, rejection Banff IA and higher was more common in the alemtuzumab arm (18% vs. 5%, p = 0.047). After adjusting for confounding variables, alemtuzumab was still associated with Banff IA and higher rejection (adjusted OR: 3.7, CI: 1.2–10.5, p = 0.02). Despite similar rates of BK viremia, more patients in the alemtuzumab arm developed BK nephropathy (16% vs. 3%, p = 0.046). One‐year iGFR (53.4 ± 20.2 vs. 71.9 ± 27.2 mL/min/1.73 m², p = 0.002) and three‐yr graft survival (89.5% vs. 95%, p = 0.05) were lower in the alemtuzumab group. In low immunological risk kidney transplant recipients on steroid‐free immunosuppression, alemtuzumab was associated with more severe rejection and BK nephropathy compared to rATG.     

Incidence,risk factors,and outcomes of stroke post‐transplantation in patients receiving a steroid sparing immunosuppression protocol

Corticosteroid use after transplantation is associated with an increased incidence of cardiovascular events and death. Cerebrovascular disease is a common cause of morbidity and mortality post‐renal transplantation; however, a dedicated analysis of cerebrovascular disease in recipients of a steroid sparing protocol has not been reported. The aim of this study was to examine the incidence, risk factors, and outcomes of CVA in transplant recipients receiving a steroid sparing protocol. We retrospectively analyzed 1237 patients who received a kidney alone or a simultaneous pancreas and kidney (SPK) transplant. Fifty‐six of 1237 (4.53%) patients had a CVA post‐transplant. All‐cause mortality was significantly higher in the CVA group compared with the non‐CVA group, OR: 3.4 (1.7–7.0), p < 0.001. Factors found to be associated with increased risk of CVA by multivariate analysis were older age, HR: 1.07 (1.04–1.09), p < 0.001; diabetes at the time of transplantation, HR: 2.83 (1.42–5.64), p = 0.003; corticosteroid use pre‐transplant, HR: 3.27 (1.29–8.27), p = 0.013 and recipients of a SPK, HR: 4.03 (1.85–8.79), p < 0.001. This study has identified subgroups of patients who are at increased risk of CVA post‐transplant in patients otherwise receiving a steroid sparing immunosuppression protocol.     

Subclinical Inflammation and Chronic Renal Allograft Injury in a Randomized Trial on Steroid Avoidance in Pediatric Kidney Transplantation

Steroid avoidance is safe and effective in children receiving kidney transplants in terms of graft function and survival, but the effects on allograft histology are unknown. In this multicenter trial, 130 pediatric renal transplant recipients were randomized to steroid‐free (SF; n = 60) or steroid‐based (SB; n = 70) immunosuppression, and underwent renal allograft biopsies at the time of graft dysfunction and per protocol at implantation and 6, 12 and 24 months after transplantation. Clinical follow‐up was 3 years posttransplant. Subclinical acute rejection was present in 10.6% SF versus 11.3% SB biopsies at 6 months (p = 0.91), 0% SF versus 4.3% SB biopsies at 1 year (p = 0.21) and 0% versus 4.8% at 2 years (p = 0.20). Clinical acute rejection was present in 13.3% SF and 11.4% SB patients by 1 year (p = 0.74) and in 16.7% SF and 17.1% SB patients by 3 years (p = 0.94) after transplantation. The cumulative incidence of antibody‐mediated rejection was 6.7% in SF and 2.9% in SB by 3 years after transplantation (p = 0.30). There was a significant increase in chronic histological damage over time (p < 0.001), without difference between SF and SB patients. Smaller recipient size and higher donor age were the main risk factors for chronic histological injury in posttransplant biopsies.     

Complete Steroid Avoidance Is Effective and Safe in Children With Renal Transplants: A Multicenter Randomized Trial With Three‐Year Follow‐Up

To determine whether steroid avoidance in pediatric kidney transplantation is safe and efficacious, a randomized, multicenter trial was performed in 12 pediatric kidney transplant centers. One hundred thirty children receiving primary kidney transplants were randomized to steroid‐free (SF) or steroid‐based (SB) immunosuppression, with concomitant tacrolimus, mycophenolate and standard dose daclizumab (SB group) or extended dose daclizumab (SF group). Follow‐up was 3 years posttransplant. Standardized height Z‐score change after 3 years follow‐up was –0.99 ± 2.20 in SF versus –0.93 ± 1.11 in SB; p = 0.825. In subgroup analysis, recipients under 5 years of age showed improved linear growth with SF compared to SB treatment (change in standardized height Z‐score at 3 years –0.43 ± 1.15 vs. –1.07 ± 1.14; p = 0.019). There were no differences in the rates of biopsy‐proven acute rejection at 3 years after transplantation (16.7% in SF vs. 17.1% in SB; p = 0.94). Patient survival was 100% in both arms; graft survival was 95% in the SF and 90% in the SB arms (p = 0.30) at 3 years follow‐up. Over the 3 year follow‐up period, the SF group showed lower systolic BP (p = 0.017) and lower cholesterol levels (p = 0.034). In conclusion, complete steroid avoidance is safe and effective in unsensitized children receiving primary kidney transplants.     

Organ allocation in pediatric renal transplants: is there an optimal donor?

The 2005 revised allocation scheme for pediatric renal transplantation made the decision of whether to transplant an available living‐donor (LD) kidney or use a deceased‐donor (DD) kidney controversial. The aim of this study was to examine kidney allograft utilization, sensitization, and outcomes of pediatric transplant recipients. Between January 2000 and December 2009, 91 consecutive pediatric kidney recipients (<20 yr) were transplanted. The LD (n = 38) and DD (n = 53) groups were similar in age, gender, dialysis status at transplant, warm ischemia time, and overall patient survival. LD recipients were more likely to be Caucasian (92 vs. 69%), receive older allografts (39 ± 10 vs. 23 ± 9 yr), and have fewer human leukocyte antigen (HLA) mismatches (3.3 ± 1.6 vs. 4.4 ± 1.5, p < 0.01 for all). Graft survival at one, three, and five yr post‐transplant was longer for LD recipients (97%, 91%, 87% vs. DD 89%, 79%, 58%, respectively, p < 0.05). At the time of transplant, 17 (33%) DD recipients had an available LD (mean age 40 yr). A greater proportion of all patients were moderately (PRA 21–79%) sensitized post‐transplant (p < 0.05). A multivariable analysis of graft survival indicated that the advantage in LD organs was likely due to fewer HLA mismatched in this group. Nonetheless, LD organs appear to provide optimal outcomes in pediatric renal transplants when considering the risk of becoming sensitized post‐transplant complicating later use of the LD kidney.     

Corticosteroid elimination in simultaneous liver–kidney transplantation recipients

Abstract: Background: Simultaneous liver–kidney transplantation (SLK) has more than doubled since 2002. While less common in kidney transplant alone recipients (KTA), corticosteroid discontinuation is performed routinely in liver transplantation, raising the question of optimal immunosuppression for SLK recipients. Methods: A retrospective case series of 16 SLK recipients under a steroid withdrawal protocol was performed to compare short‐term outcomes to a contemporaneous cohort of 32 KTA recipients. Results: In 69% of SLK recipients, corticosteroids were eliminated compared to 3% of KTA recipients, p < 0.0001. When comparing SLK and KTA recipients one yr post‐transplant, there were no significant differences in renal graft rejection (23.1% vs. 6.3%), death‐censored renal graft survival (100% vs. 97%), estimated glomerular filtration rate (74.4 vs. 62.6 mL/min), serum creatinine (1.10 vs. 1.39 mg/dL), or maintenance immunosuppression, respectively. Conclusions: Corticosteroids may be withdrawn safely in SLK recipients with one‐yr renal outcomes comparable to a KTA cohort.     

Outcomes of Pediatric Kidney Transplantation in Recipients of a Previous Non‐Renal Solid Organ Transplant

Children who receive a non‐renal solid organ transplant may develop secondary renal failure requiring kidney transplantation. We investigated outcomes of 165 pediatric kidney transplant recipients who previously received a heart, lung, or liver transplant using data from 1988 to 2012 reported to the United Network for Organ Sharing. Patient and allograft survival were compared with 330 matched primary kidney transplant (PKT) recipients. Kidney transplantation after solid organ transplant (KASOT) recipients experienced similar allograft survival: 5‐ and 10‐year graft survival was 78% and 60% in KASOT recipients, compared to 80% and 61% in PKT recipients (p = 0.69). However, KASOT recipients demonstrated worse 10‐year patient survival (75% KASOT vs. 97% PKT, p < 0.001). Competing risks analysis indicated that KASOT recipients more often experienced graft loss due to patient death (p < 0.001), whereas allograft failure per se was more common in PKT recipients (p = 0.01). To study more recent outcomes, kidney transplants performed from 2006 to 2012 were separately investigated. Since 2006, KASOT and PKT recipients had similar 5‐year graft survival (82% KASOT vs. 83% PKT, p = 0.48), although 5‐year patient survival of KASOT recipients remained inferior (90% KASOT vs. 98% PKT, p < 0.001). We conclude that despite decreased patient survival, kidney allograft outcomes in pediatric KASOT recipients are comparable to those of PKT recipients.     

Long‐term dosing patterns of enteric‐coated mycophenolate sodium or mycophenolate mofetil with tacrolimus after renal transplantation

MORE was a four‐yr, prospective, observational study at 40 transplant centers in the US. Data were analyzed to evaluate changes in mycophenolic acid (MPA) dosing over time in 904 de novo kidney transplant recipients receiving enteric‐coated mycophenolate sodium (EC‐MPS, n = 616) or mycophenolate mofetil (MMF, n = 288) with tacrolimus. Induction therapy and steroid treatment were similar in the two subpopulations. The proportion of patients receiving the maximal recommended MPA dose was 80.5%, 43.9%, 39.2%, 34.6%, and 30.1% at baseline and years 1, 2, 3, and 4, respectively. More patients received the maximal recommended MPA dose with EC‐MPS vs. MMF at month 1 (79.2% vs. 71.7%, p = 0.016), month 3 (68.5% vs. 56.9%, p = 0.001), and month 6 (52.9% vs. 44.0%, p = 0.028). Multivariate analysis showed the risk of biopsy‐proven acute rejection, graft loss or death to be similar for EC‐MPS vs. MMF. Estimated glomerular filtration rate (GFR) was similar with EC‐MPS vs. MMF at all time points. There were no significant differences in any category of adverse event between the EC‐MPS and MMF cohorts during follow‐up, including gastrointestinal events. In conclusion, MPA dose was maintained more effectively in the first six months after kidney transplantation using EC‐MPS vs. MMF, without an increase in adverse events.     

Should living-unrelated renal transplant recipients receive antibody induction? Results of a clinical experience trial

BACKGROUND: Living-donor kidney transplant recipients generally do not receive antibody induction. Induction avoidance may not be appropriate, particularly for living-unrelated renal transplant (LURT) recipients, in whom matching may not be optimal. We compared the incidence of acute rejection and graft outcome of LURT recipients who were administered no induction and cadaveric renal transplant (CRT) recipients who were administered anti-CD25 antibody. These groups both had immediate graft function and similar maintenance immunosuppression. METHODS: This retrospective analysis included patients who received kidney transplants between 1999 and 2000. CRT recipients received basiliximab, corticosteroids, mycophenolate mofetil (MMF), and delayed tacrolimus (serum creatinine <3 mg/dL). LURT recipients received tacrolimus (initiated pretransplantation), MMF, and corticosteroids. RESULTS: The analysis included 136 LURT recipients and 126 CRT recipients. CRT recipients included more African Americans (52.4% vs. 30.9%, P<0.01). LURT recipients included more patients with at least one human leukocyte antigen mismatch (97.8% vs. 85.7%, P<0.01). A higher acute rejection rate was observed in LURT recipients at both 6 months (LURT recipients 19.1% vs. CRT recipients 3.2%, P<0.01) and 1 year (21.3% vs. 4.0%, P<0.0004); a higher rate also was observed in African American LURT recipients compared with African American CRT recipients (35.7% vs. 4.5%, P<0.0015) at 1 year. LURT recipients demonstrated a threefold greater rejection risk than CRT recipients who were administered basiliximab (relative risk: 3.6, P<0.002). Graft survival was similar at 1 year. CONCLUSION: The higher rejection rates in LURT recipients (no induction) compared with CRT recipients (basiliximab induction), despite similar chronic immunosuppression (tacrolimus, MMF, and steroids) and immediate graft function, indicate the potential advantage of anti-CD25 induction in LURT protocols to reduce the risk of acute rejection.     

Outpatient Management of Delayed Graft Function Is Associated With Reduced Length of Stay Without an Increase in Adverse Events

Delayed graft function (DGF) is a common and costly complication of kidney transplantation. In July 2011, we established a multidisciplinary DGF clinic managed by nurse practitioners to facilitate early discharge and intensive management of DGF in the outpatient setting. We compared length of stay, 30‐day readmission, acute rejection, and patient/graft survival in 697 consecutive deceased donor kidney transplantations performed between July 2009 and July 2014. Patients were divided into three groups: no DGF (n = 487), DGF before implementation of the DGF clinic (n = 118), and DGF clinic (n = 92). Baseline characteristics including age, gender, panel reactive antibody, retransplantation rates, HLA mismatches, induction, and maintenance immunosuppression were not significantly different between pre‐ and post‐DGF clinic groups. Length of stay was significantly longer in pre‐DGF clinic (10.9 ± 6.2 vs. 6.1 ± 2.1 days, p < 0.001). Thirty‐day readmission (21% vs. 16%), graft loss (7% vs. 20%), and patient death (2% vs. 11%) did not differ significantly between pre‐ and post‐DGF clinic. Patients in the DGF clinic were less likely to develop acute rejection (21% vs. 40%, p = 0.006). Outpatient management of DGF in a specialized clinic is associated with substantially shorter hospitalization and lower incidence of acute rejection without significant difference in 30‐day readmission or patient and graft survival.     

Clinical factors associated with graft fibrosis in kidney-transplant recipients on steroid-avoidance immunosuppression

Abstract: Background: Recent studies have documented good patient and graft outcomes and a low risk of acute rejection with steroid‐avoidance immunosuppression in kidney‐transplant recipients, but the risk of progressive graft fibrosis is not well studied. Methods: All adult primary kidney transplant or combined kidney and pancreas transplant recipients on steroid avoidance immunosuppression were eligible for study. All recipients received induction with antithymocyte globulin or basiliximab. Corticosteroids were stopped after day 4 post‐transplantation. Patients were maintained with tacrolimus and mycophenolate mofetil. Protocol biopsies were done at reperfusion and at one, four, and 12 months after transplantation. Results: Eighty one‐yr protocol biopsies with adequate specimens were obtained from 132 kidney or kidney–pancreas transplant recipients. Fifteen (19%) of the biopsies showed moderate to severe graft interstitial fibrosis (GIF) (Banff ci score ≥2). Recipients with GIF were older, had lower body mass index, greater human lymphocyte antigen (HLA) mismatch, older donors, serum creatinine ≥1.6 mg/dL at one month, a Banff ci score >0 on one‐month biopsy, BK nephropathy, and interstitial cellular infiltrates on the one‐yr biopsy. In the unadjusted logistic regression analysis, BK nephropathy, serum creatinine ≥1.6 mg/dL at one month, recipient age, Banff ci score >0 on one‐month biopsy, and donor age were the only variables associated with a higher risk of GIF on the one‐year biopsy. In the multivariate logistic regression model adjusted for these variables, BK nephropathy, serum creatinine ≥1.6 mg/dL at one month after transplantation, and recipient age were independently associated with the risk of GIF on the one‐year biopsy. Conclusion: In this small study of primary kidney or combined kidney–pancreas transplant recipients on steroid‐avoidance immunosuppression, we found that 19% had GIF on a one‐year protocol biopsy. BK nephropathy, serum creatinine ≥1.6 mg/dL one month after transplantation, and recipient age correlated with an increased risk for GIF on the one‐yr biopsy.     

Stable kidney function in the second decade after kidney transplantation while on cyclosporine-based immunosuppression

BACKGROUND: Calcineurin inhibitors (CNIs) have been the mainstay of immunosuppressive protocols in kidney transplantation over the past 20 years. However, in some recipients, the adverse effects of CNIs contribute to chronic allograft nephropathy and death with function--the two leading causes of late graft loss. Other recipients maintain stable graft function. METHODS: We studied the impact of continuing CNI-based immunosuppression in the second decade after kidney transplantation. From 1984 through 1996, a total of 1,263 patients underwent a primary kidney transplant at the University of Minnesota and received cyclosporine-based immunosuppression. Antibody induction was used only in deceased donor recipients. RESULTS: The actuarial 20-year patient survival rate was 38%; graft survival, 30%; and death-censored graft survival, 60%. The annual mean serum creatinine level for recipients whose grafts survived > or =1 year remained stable, although recipients with a history of > or =1 acute rejection episode had a higher serum creatinine level vs. recipients who were rejection-free. The annual mean calculated creatinine clearance was also stable over time. In addition, for recipients who were acute rejection-free, chronic allograft nephropathy/chronic rejection was only responsible for 9% of graft losses. CONCLUSIONS: Our study suggests that some kidney transplant recipients tolerate long-term CNI-based immunosuppression with stable creatinine levels. Identifying certain recipients' predisposition to CNI toxicity and individualizing immunosuppressive therapy may be important in order to improve long-term kidney function, while simultaneously preserving low short-term acute rejection rates.     

Long‐term outcomes in African American kidney transplant recipients under contemporary immunosuppression: a four‐yr analysis of the Mycophenolic acid Observational REnal transplant (MORE) study

Mycophenolic acid Observational REnal transplant (MORE) was a prospective, observational study of de novo kidney transplant patients receiving mycophenolic acid (MPA). Four‐yr data on 904 patients receiving tacrolimus and enteric‐coated mycophenolate sodium (EC‐MPS) or mycophenolate mofetil (MMF) were analyzed to evaluate immunosuppression and graft outcomes in African American (AA, n = 218) vs. non‐AA (n = 686) patients. Mean tacrolimus dose was higher in AA vs. non‐AA patients but mean tacrolimus trough concentration was similar. Use of the recommended MPA dose in AA patients decreased from 78.9% at baseline to 33.1% at year 3. More AA patients received the recommended MPA dose with EC‐MPS than MMF at month 6 (56.2% vs. 35.7%, p = 0.016) and month 36 (46.6% vs. 16.7%, p = 0.029), with no safety penalty. Significantly, more AA patients received corticosteroids than non‐AA patients. Biopsy‐proven acute rejection was higher in AA vs. non‐AA patients (18.9% vs. 10.7%, p = 0.003), as was graft loss (10.9% vs. 4.4%, p = 0.003); differences were confirmed by Cox regression analysis. Patient survival was similar. Estimated GFR was comparable in AA vs. non‐AA patients. Kidney allograft survival remains lower for AA vs. non‐AA recipients even under the current standard of care.     

Daclizumab Versus Rabbit Antithymocyte Globulin in High‐Risk Renal Transplants: Five‐Year Follow‐up of a Randomized Study

We previously reported a randomized controlled trial in which 227 de novo deceased‐donor kidney transplant recipients were randomized to rabbit antithymocyte (rATG, Thymoglobulin) or daclizumab if they were considered to be at high immunological risk, defined as high panel reactive antibodies (PRA), loss of a first kidney graft through rejection within 2 years of transplantation, or third or fourth transplantation. Patients treated with rATG had lower incidences of biopsy‐proven acute rejection (BPAR) and steroid‐resistant rejection at 1 year. Patients were followed to 5 years posttransplant in an observational study; findings are described here. Treatment with rATG was associated with a lower rate of BPAR at 5 years (14.2% vs. 26.0% with daclizumab; p = 0.035). Only one rATG‐treated patient (0.9%) and one daclizumab‐treated patient (1.0%) developed BPAR after 1 year. Five‐year graft and patient survival rates, and renal function, were similar between the two groups. Overall graft survival at 5 years was significantly higher in patients without BPAR (81.0% vs. 54.8%; p < 0.001). In conclusion, rATG is superior to daclizumab for the prevention of BPAR among high‐immunological‐risk renal transplant recipients. Overall graft survival at 5 years was approximately 70% with either induction therapy, which compares favorably to low‐risk cohorts.     

A randomized,controlled trial of everolimus‐based dual immunosuppression versus standard of care in de novo kidney transplant recipients

Kidney transplant recipients receiving calcineurin inhibitor‐based immunosuppression incur increased long‐term risks of cancer and kidney fibrosis. Switch to mammalian target of rapamycin (mTOR) inhibitors may reduce these risks. Steroid or Cyclosporin Removal After Transplant using Everolimus (SOCRATES), a 36‐month, prospective, multinational, open‐label, randomized controlled trial for de novo kidney transplant recipients, assessed whether everolimus switch could enable elimination of mycophenolate plus either steroids or CNI without compromising efficacy. Patients received cyclosporin, mycophenolate and steroids for the first 14 days then everolimus with mycophenolate and CNIwithdrawal (CNI‐WD); everolimus with mycophenolate and steroid withdrawal (steroid‐WD); or cyclosporin, mycophenolate and steroids (control). 126 patients were randomized. The steroid WD arm was terminated prematurely because of excess discontinuations. Mean eGFR at month 12 for CNI‐WD versus control was 65.1 ml/min/1.73 m² vs. 67.1 ml/min/1.73 m² by ITT, which met predefined noninferiority criteria (P = 0.026). The CNI‐WD group experienced a higher rate of BPAR(31% vs. control 13%, P = 0.048) and showed a trend towards higher composite treatment failure (BPAR, graft loss, death, loss to follow‐up). The 12 month results from SOCRATES show noninferiority in eGFR, but a significant excess of acute rejection when everolimus was commenced at week 2 to enable a progressive withdrawal of mycophenolate and cyclosporin in kidney transplant recipients.