Baseline living-donor kidney volume and function associate with 1-year post-nephrectomy kidney function.

Living donors may develop kidney dysfunction more often than equally healthy populations. The purpose of this study was to determine whether computed tomography-assessed remaining kidney volume indexed to body surface area (RKV/BSA) was associated with 1-year post-nephrectomy renal function independent of baseline renal function. Using multivariable regression, we modeled 1-year estimated glomerular filtration rate (eGFR) and eGFR <60 mL /min/1.73 m2 and considered pre-determined baseline eGFR subgroups in 151 consecutive donors. Mean ± SD baseline age, eGFR, RKV, BSA, and RKV/BSA were 38 ± 11 years, 97 ± 16 mL/min/1.73 m2 , 153 ± 29 mL, 1.9 ± 0.2 m2 , and 80.0 ± 12.8 ml/m2 , respectively; 50% were female and 94% were white. Mean baseline eGFR was greater with increasing RKV/BSA tertiles (92 ± 14, 97 ± 16, 107 ± 16 mL/min/1.73 m2 ; P < 0.001). Post-nephrectomy eGFR remained separated by RKV/BSA tertiles. At baseline, each SD greater RKV/BSA and eGFR was independently associated with higher adjusted 1-year eGFR by 2.4 and 9.2 mL/min/1.73 m2 . Each SD greater age associated with 2.2 mL/min/1.73 m2 lower adjusted 1-year eGFR. Adjusted odds of 1-year eGFR <60 increased significantly for donors with RKV/BSA <80 mL/m2 . With baseline eGFR <90, probability of 1-year eGFR <60 increased to >80% with decreasing RKV/BSA values below 80 mL/m2 . Those with baseline eGFR >100 rarely developed 1-year eGFR <60 if RKV/BSA remained >60 mL/m2 . RKV/BSA independently associated with 1-year eGFR <60, especially with lower baseline eGFRs. Additional studies should evaluate the predictive utility of this measure and its potential role in donor evaluations and informed consent.

A randomized, phase 2 study of ASP0113, a DNA-based vaccine, for the prevention of CMV in CMV-seronegative kidney transplant recipients receiving a kidney from a CMV-seropositive donor.

Cytomegalovirus (CMV) is a latent infection in most infected individuals, but can be pathogenic in immunocompromised kidney transplant recipients. ASP0113 is a DNA-based vaccine for the prevention of CMV-related mortality and end-organ disease in transplant recipients. The efficacy, safety, and immunogenicity of ASP0113 was assessed in a phase 2, double-blind, placebo-controlled study in CMV-seronegative kidney transplant recipients receiving a kidney from a CMV-seropositive donor. Transplant recipients were randomized (1:1) to receive 5 doses of ASP0113 (5 mg; n = 75) or placebo (n = 74) on Days 30/60/90/120/180 posttransplant, and they received prophylactic valganciclovir/ganciclovir 10-100 days posttransplant. The primary endpoint was the proportion of transplant recipients with CMV viremia ≥1000 IU/mL from Day 100 through to 1 year after the first study vaccine injection. There was no statistically significant difference in the primary endpoint between the ASP0113 and placebo groups (odds ratio 0.79, 95% confidence interval 0.43-1.47; P = .307). There were similar numbers of transplant recipients with treatment-emergent adverse events between groups; however, more transplant recipients reported injection site pain in the ASP0113 group compared with placebo. ASP0113 did not demonstrate efficacy in the prevention of CMV viremia in this CMV-seronegative kidney transplant population, but demonstrated a safety profile similar to placebo. ClinicalTrials.gov registration number: NCT01974206.

Tacrolimus exposure in the real world: an analysis from the Mycophenolic acid Observational REnal transplant study.

Tacrolimus exposure and renal function data to 36 months post-transplant were analyzed from the prospective, observational Mycophenolic acid Observational REnal transplant (MORE) registry in which de novo kidney transplant patients were managed according to local practice. Tacrolimus trough (C0 ) concentration at month 12 was stratified as low (<6 ng/mL), moderate (6-8 ng/mL), or high (>8 ng/mL) in 724 patients. Estimated glomerular filtration rate (eGFR) was stratified as low (<60 mL/min/1.73 m(2) ) or high (≥60 mL/min/1.73 m(2) ). High tacrolimus C0 (>8 ng/mL) was observed in 47.7%, 34.1%, 26.8%, and 26.7% of patients at baseline and months 12, 24, and 36, respectively. Biopsy-proven acute rejection was similar to month 36 regardless of tacrolimus C0 category at month 12. Tacrolimus C0 >8 ng/mL vs. <6 ng/mL at month 12 was predictive of low eGFR at month 24 (p = 0.023) with a nonsignificant trend at month 36 (p = 0.085). Infections (p < 0.013) and BK virus infection (p < 0.001) were most frequent in the low tacrolimus C0 cohort. Neutropenia was most frequent in the high tacrolimus C0 category (p = 0.010). In conclusion, over a quarter of patients were exposed to high tacrolimus C0 to 36 months post-transplant. Tacrolimus exposure did not affect rejection risk, but tacrolimus C0 >8 ng/mL at month 12 was predictive of subsequent low eGFR compared to C0 <6 ng/mL.

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.

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.

Use of LCP-Tacrolimus (LCPT) in Kidney Transplantation: A Delphi Consensus Survey of Expert Clinicians.

BACKGROUND LCPT (Envarsus XR®) is a common once-daily, extended-release oral tacrolimus formulation used in kidney transplantation. However, there are minimal evidence-based recommendations regarding optimal dosing and treatment in the de novo and conversion settings. MATERIAL AND METHODS Using Delphi methodology, 12 kidney transplantation experts with LCPT experience reviewed available data to determine potential consensus topics. Key statements regarding LCPT use were generated and disseminated to the panel in an online Delphi survey. Statements were either accepted, revised, or rejected based on the level of consensus, perceived strength of evidence, and alignment with clinical practice. Consensus was defined a priori as ≥75% agreement. RESULTS Twenty-three statements were generated: 14 focused on de novo LCPT use and 9 on general administration or LCPT conversion use. After 2 rounds, consensus was achieved for 11/14 of the former and 7/9 of the latter statements. In a de novo setting, LCPT was recognized as a first-line option based on its safety and efficacy compared to immediate-release tacrolimus. In particular, African Americans and rapid metabolizer populations were identified as preferred for first-line LCPT therapy. In a conversion setting, full consensus was achieved for converting to LCPT to address neurological adverse effects related to immediate-release tacrolimus and for the time required (approximately 7 days) for steady-state LCPT trough levels to be reached. CONCLUSIONS When randomized clinical trials do not replicate current utilization patterns, the Delphi process can successfully generate consensus statements by expert clinicians to inform clinical decision-making for the use of LCPT in kidney transplant recipients.

Does reduction in mycophenolic acid dose compromise efficacy regardless of tacrolimus exposure level? An analysis of prospective data from the Mycophenolic Renal Transplant (MORE) Registry.

Prospective data are lacking concerning the effect of reduced mycophenolic acid (MPA) dosing on efficacy and the influence of concomitant tacrolimus exposure. The Mycophenolic Renal Transplant (MORE) Registry is a prospective, observational study of de novo kidney transplant patients receiving MPA therapy under routine management. The effect of MPA dose reduction, interruption, or discontinuation (dose changes) was assessed in 870 tacrolimus-treated patients: 375 (43.1%) reduced tacrolimus (≤ 7 ng/mL at baseline) and 495 (56.9%) standard tacrolimus (>7 ng/mL); enteric-coated mycophenolate sodium 589 (67.7%) and mycophenolate mofetil 281 (32.3%). During baseline to month 1, months 1-3, months 3-6, and months 6-12, 9.3% (78/838), 16.6% (132/794), 20.7% (145/701), and 13.1% (70/535) patients, respectively, required MPA dose changes. These patients experienced an increased risk of biopsy-proven acute rejection at one yr with tacrolimus exposure either included in the model (hazard ratio [HR] 2.60, 95% CI 1.28-5.29, p = 0.008) or excluded (HR 2.58, 95% CI 1.28-5.23, p = 0.008). MPA dose changes were significantly associated with one yr graft failure when tacrolimus exposure was included (HR 2.23; 95% CI 1.01-4.89, p = 0.047) but not when tacrolimus exposure was excluded (HR 2.16; 95% CI 0.99-4.79; p = 0.054). These results suggest that reducing or discontinuing MPA can adversely affect graft outcomes regardless of tacrolimus trough levels.

Association of clinical events with everolimus exposure in kidney transplant patients receiving reduced cyclosporine.

BACKGROUND: The association between clinical events and everolimus exposure in patients receiving reduced-exposure calcineurin inhibitor therapy is poorly explored. METHODS: In a pre-planned, descriptive analysis of data from a randomized controlled trial, events were correlated with everolimus trough concentrations in 556 newly transplanted kidney transplant patients receiving everolimus with reduced-exposure cyclosporine (CsA) and steroids. Influence of everolimus exposure on clinical events was stratified according to predefined time-normalized concentrations. RESULTS: The incidence of treated biopsy-proven acute rejection and graft loss at month 12 was highest in patients with everolimus <3 ng/mL (36.4% and 28.6%, respectively, vs. 9.1-15.3% and 0.9-5.0% with higher concentration ranges). A higher mortality rate was observed in patients with an everolimus trough concentration ≥ 12 ng/mL (10.0% vs. 1.7-5.6% with lower concentration ranges). The lowest rates of renal dysfunction (defined as poor renal function [estimated GFR, serum creatinine] or proteinuria), wound healing events, peripheral edema, new-onset diabetes mellitus, hypercholesterolemia and hypertriglyceridemia were generally observed with everolimus trough concentration in the range 3-8 ng/mL and CsA <100 ng/mL. Proteinuria occurred most frequently in patients with very low or very high everolimus trough concentrations. CONCLUSIONS: These results support an exposure-response relationship between clinical events and everolimus trough concentrations in kidney transplant patients receiving reduced-exposure CsA.

Low-dose fluconazole prophylaxis in kidney transplant recipients receiving tacrolimus.

BACKGROUND: The use of prophylactic antifungal therapy is suggested after kidney transplantation. However, efficacy of low-dose (50 mg) oral fluconazole and its effect on tacrolimus trough levels in patients maintained on tacrolimus and mycophenolic acid, with or without corticosteroids, is unknown. METHODS: A retrospective analysis to evaluate efficacy was performed in 305 kidney transplant recipients. An additional analysis to evaluate the fluconazole-tacrolimus drug interaction was performed in 103 patients. Complete tacrolimus area under the curve measurements were also performed in seven patients to further evaluate this drug interaction. RESULTS: The incidence of fungal infections was very low (0.6%, n = 2). The average tacrolimus trough level at the time of discontinuation and one wk after stopping fluconazole was unchanged (11.69 ± 3.18 and 11.15 ± 3.69 ng/mL, p = 0.145, n = 103). Tacrolimus trough levels on and off of fluconazole in a subgroup of patients continued on corticosteroids, was not significantly different (p = 0.952) but was significantly lower after fluconazole discontinuation if corticosteroids were withdrawn (p = 0.037). However, data from complete tacrolimus pharmacokinetics in the corticosteroid withdrawal group demonstrated no clinically significant differences. CONCLUSION: Low-dose, once daily oral fluconazole is effective antifungal prophylaxis after kidney transplantation without significant effects on tacrolimus trough levels or overall exposure.

Effect of education on racial disparities in access to kidney transplantation.

Higher education level might result in reduced disparities in access to renal transplantation. We analyzed two outcomes: (i) being placed on the waiting list or transplanted without listing and (ii) transplantation in patients who were placed on the waiting list. We identified 3224 adult patients with end-stage renal disease (ESRD) in United States Renal Data System with education information available (mean age of ESRD onset of 57.1 ± 16.2 yr old, 54.3% men, 64.2% white, and 50.4% diabetics). Compared to whites, fewer African Americans graduated from college (10% vs. 16.7%) and a higher percentage never graduated from the high school (38.6% vs. 30.8%). African American race was associated with reduced access to transplantation (hazard ratio [HR] 0.70, p < 0.001 for wait-listing/transplantation without listing; HR 0.58, p < 0.001 for transplantation after listing). African American patients were less likely to be wait-listed/transplanted in the three less-educated groups: HR 0.67 (p = 0.005) for those never completed high school, HR 0.76 (p = 0.02) for high school graduates, and HR 0.65 (p = 0.003) for those with partial college education. However, the difference lost statistical significance in those who completed college education (HR 0.75, p = 0.1). In conclusion, in comparing white and African American candidates, racial disparities in access to kidney transplantation do exist. However, they might be alleviated in highly educated individuals.

Factors associated with nonadherence to medication in kidney transplant recipients.

Nonadherence in kidney transplant recipients was evaluated in this report using a questionnaire with five binary questions and one question on a continuous scale. Study participants at the University of Utah Transplant Program (n = 199) were 43.0 ± 14.2 years old; 67% were males, and 81% were White. Two questions that produced heterogeneous outcome were analyzed: 'Do you ever forget to take your medication?' (79% no, 21% yes) and 'Have you ever taken your medications late?' (67% no, 33% yes). Responses to these questions correlated (χ² 65.2, p < 0.001; correlation coefficient 0.57, p < 0.001). We performed a logistic regression analysis to identify factors associated with the combined outcome of forgetting/not taking medications altogether or taking medications off schedule. Higher comorbidity index [odds ratio (OR) 2.19, p < 0.001], living (compared to deceased) donor (OR 2.81, p = 0.005) and full-time employment were associated with forgetting medications or taking them late (OR 3.12, p = 0.01). Recipient age tended to be associated with lower risk of nonadherence, but did not reach statistical significance (OR 0.98 per year of age, p = 0.13). Education level, smoking status, recipient race, dialysis modality, number of medications and the time since first kidney transplantation were not associated with the outcome. In conclusion, renal transplant recipients with greater comorbidity, receiving kidney from a living donor and with full-time employment reported lower levels of medication adherence.

Urine TGF- beta1 assay validation: spinning down urine samples could diminish TGF-beta1 signal.

BACKGROUND: TGF-beta1 is a mediator of immune and anti-inflammatory responses. The present research was dedicated to the validation of the urine Quantikine Human TGF-beta1 ELISA assay. METHODS: A reference interval was developed utilizing 100 urine samples from healthy donors. Samples containing precipitate were centrifuged and supernatants or un-spun specimens were run with TGF-beta1 assay. RESULTS: Supernatant TGF-beta1 concentrations are only a fraction of the un-spun sample values (77% to 29%, even less for the low concentration samples). Validation involving un-centrifuged urine samples demonstrated the following TGF-beta1 assay characteristics: linearity from 23 to 1286 pg/mL, recovery from 95 to 116%; precision: < 17%; analytical specificity 3 pg/mL; reference interval from 0 to 39 pg/mg creatinine; freeze-thaw stability: after first thawing, urine samples could loose from 5 to 40% of TGF-beta1 activity on each following freeze-thaw circle. CONCLUSIONS: For TGF-beta1 assay, urine sample preparation should not include a centrifugation step; repeating freeze-thawing should be avoided.

Role of cellular cholesterol in pharmacologic preconditioning with cyclosporine in experimental kidney transplantation.

BACKGROUND/AIMS: Ischemia reperfusion injury in the early posttransplant period affects immediate graft function and late allograft dysfunction. Recently, we showed that pharmacologic preconditioning with a calcineurin inhibitor improved transplant outcomes in rat syngeneic kidney transplantation. There is also evidence that cellular cholesterol content increases after many types of renal injury. METHODS: In this study, we looked at the effect of cyclosporine (CsA) on the donor kidney free cholesterol (FC) content in this model. Donor rats were pretreated with one dose of CsA 10 mg/kg administered 24 h or 7 days before being subjected to 2 h cold ischemia and then transplanted. RESULTS: Pharmacologic preconditioning with CsA significantly improved renal function and histology and increased donor kidney FC content. On the other hand, fluvastatin co-administration with CsA abrogated that beneficial effect in association with a decrease in donor kidney FC content. CONCLUSION: CsA preconditioning leads to better outcomes in kidney transplantation and is associated with up-regulation of renal FC content. The latter may then contribute to acquired cytoresistance, possibly by stabilizing the plasma membrane. Thus, use of statins around the time of transplantation may need to be evaluated until further studies are conducted to determine the clinical relevance of this observation.

A population-based assessment of the familial component of acute kidney allograft rejection.

BACKGROUND: The genetic determinants of acute kidney transplant rejection (AR) are not well studied, and familial aggregation has never been demonstrated. The goal of this retrospective case-control study was to exploit the unique nature of the Utah Population Database (UPDB) to evaluate if AR or rejection-free survival aggregates in families. METHODS: We identified 891 recipients with genealogy data in the UPDB with at least one year of follow-up, of which 145 (16.1%) had AR and 77 recipients had biopsy-proven rejection graded >or=1A. We compared the genealogical index of familiality (GIF) in cases and controls (i.e. recipients with random assignment of rejection status). RESULTS: We did not find evidence for familial clustering of AR in the entire patient population or in the subgroup with early rejection (n = 52). When the subgroup of recipients with rejection grade >or=1A (n = 77) was analysed separately, we observed increased familial clustering (GIF = 3.02) compared to controls (GIF = 1.96), although the p-value did not reach the level of statistical significance (p = 0.17). Furthermore, we observed an increase in familial clustering in recipients who had a rejection-free course (GIF = 2.45) as compared to controls (GIF = 2.08, p = 0.04). When all recipients were compared to non-transplant controls, they demonstrated a much greater degree of familiality (GIF = 2.03 versus GIF 0.63, p < 0.001). CONCLUSIONS: There is a familial component to rejection-free transplant course and trend to familial aggregation in recipients with AR grade 1A or higher. If a genetic association study is performed, there are families in Utah identified in the current study that can be targeted to increase the power of the test.

The role of the economic environment in kidney transplant outcomes.

The relationship between global economic indicators and kidney allograft and patient survival is unknown. To investigate possible relationships between the two, we analyzed kidney transplant recipients receiving transplants between January of 1995 and December of 2002 (n = 105,181) in the USA using Cox regression models. We found that: The Dow Jones Industrial Average had a negative association with outcome at one year post-transplant (HR 1.03 and 1.06, p < 0.001 for graft and recipient survival, respectively) but changed to a protective effect in the late period (HR 0.77, p < 0.001, and HR 0.83, p < 0.001 for graft and recipient survival, respectively, five yr after transplantation). Unemployment rate had a protective effect at the time of transplantation (HR 0.97, p < 0.005) and at one year after transplantation (HR 0.95, p < 0.005) but changed to the opposite in the late period at the fifth post-transplant year (HR 1.35, p < 0.001, and HR 1.20, p < 0.001, for graft and recipient survival respectively). The Consumer Price Index measured at different post-transplant time points seems to have had a protective effect on the graft (HR 0.77, p < 0.001 at five yr) and recipient (HR 0.83, p < 0.001 at five yr) survival. Beyond three yr after transplantation, when some of the recipients lose Medicare benefits, economic downturns might have a negative association with the kidney graft and recipient survival.

RIFLE criteria accurately identifies renal dysfunction and renal failure in elderly patients with upper gastrointestinal hemorrhage: a pilot study.

BACKGROUND: The incidence of acute kidney injury (AKI) as a complication of acute upper gastrointestinal bleeding (AUGIB) is not known. Recently, RIFLE criteria were used widely in the medical research to identify patients with different degrees of renal insufficiency. OBJECTIVES: Our purpose is to determine the incidence, clinical presentations, endoscopic findings and outcomes of AKI in the elderly presenting with AUGIB using RIFLE criteria. The study was conducted in a community hospital in Washington State. This was a retrospective pilot study of elderly patients (≥60 years old) presenting with AUGIB. Categorical variables were analyzed using the Chi-square test. The Student t-test was used to compare continuous variables. A total of 113 patients were included (52 males and 61 females) in the study. The patients were classified into those with AKI based on RIFLE criteria and those without. The two groups were compared in regard to clinical presentations, laboratory and endoscopic findings, complications, length and cost of hospitalization. RESULTS: Fifty five patients (48.7%) met RIFLE criteria for AKI, while 58 patients did not develop any renal dysfunction. Patients with AUGIB complicated with AKI tend to be residents at nursing homes (38% vs. 14%, P < 0.004), present with weakness (49% vs 29%., P < 0.04) and altered mental status (25% vs. 55%, P < 0.003), have higher serum creatinine at presentation (1.8 mg/dL vs. 1.2 mg/dL, P < 0.002), have less incidence of gastritis/gastric ulcers (67% vs. 42%, P < 0.007), have nondiagnostic upper endoscopic examination (29% vs. 14%, P < 0.05), higher incidences of cardiac complications including myocardial infarction (9% and 0%, P < 0.02), longer lengths of stay (5.0 days vs. 2.37 days, P < 0.005) and higher hospitalization costs ($20,230 vs. $11,779, P < 0.02). CONCLUSION: The incidence of developing AKI as a consequence of AUGIB in the elderly is very common. Those with AKI tend to have a more complicated clinical course in the hospital.

A prospective, randomized, double-blind, placebo-controlled multicenter trial comparing early (7 day) corticosteroid cessation versus long-term, low-dose corticosteroid therapy.

OBJECTIVE: To compare outcomes with early corticosteroid withdrawal (CSWD) and chronic low dose corticosteroid therapy (CCS). SUMMARY BACKGROUND DATA: Final, 5-year results from the first randomized, double-blind, placebo-controlled trial of early CSWD (at 7 days posttransplant) are presented. METHODS: Adult recipients of deceased and living donor kidney transplants without delayed graft function were randomized to receive prednisone (5 mg/d after 6 months posttransplant) or CSWD. Blinding was maintained for 5 years. This clinical trial is registered at www.clinicaltrials.gov (NCT00650468). RESULTS: Results in 386 patients CSWD (n = 191), CCS (n = 195) are presented (CSWD; CCS). No differences were observed at 5 years in the proportion of patients experiencing: primary end point (composite of death, graft loss, or moderate/severe acute rejection) (30/191 (15.7%); 28/195 (14.4%)), patient death (11/191(5.8%);13/195 (6.7%)), death-censored graft loss (11/191 (5.8%); 7/195(3.6%)), biopsy confirmed acute rejection (BCAR) (34/191 (17.8%); 21/195 (10.8%), P = 0.058), moderate/severe acute rejection (15/191 (7.9%); 12/195 (6.2%)). Kaplan Meier analyses of the primary end point and its components also showed no differences; but BCAR was higher with CSWD (P = 0.04). Increased BCAR episodes were primarily corticosteroid-sensitive Banff 1A rejections: the incidence of antibody-treated BCAR was similar between groups (11/191 (5.8%); 13/195 (6.7%)). No differences in renal function were observed at 5 years: mean serum creatinine (1.5 +/- 0.6; 1.5 +/- 0.7 mg/dL), or Cockroft Gault calculated creatinine clearance (58.6 +/- 19.7; 59.8 +/- 20.5 mL/min). CSWD was associated with improved serum triglycerides (evaluated by mean and median change from baseline) at all time points (except at 5 years measured by mean change). Weight change also demonstrated changes favoring CSWD (median change from baseline at 5 years: 5.1 vs. 7.7 kg, P = 0.05). New onset diabetes after transplant (NODAT) was similar with respect to proportions who required treatment (23/107 (21.5%)); 18/86 (20.9%); however, fewer CSWD patients required insulin for NODAT at 5 years (4/107 (3.7%)); 10/86 (11.6%), P = 0.049). Changes in HgA1c values (from baseline) were lower in CSWD patients at all time points except 4 years. CONCLUSIONS: Early CSWD, compared with CCS, is associated with an increase in BCAR primarily because of mild, Banff 1A, steroid-sensitive rejection, yet provides similar long-term renal allograft survival and function. CSWD provides improvements in cardiovascular risk factors (triglycerides, NODAT requiring insulin, weight gain). Tacrolimus/MMF/antibody induction therapy allows early CSWD with results comparable to long-term low dose (5 mg/d) prednisone therapy.