Pegylated Bovine Carboxyhemoglobin (SANGUINATE) in a Jehovah's Witness Undergoing Liver Transplant: A Case Report.

Liver transplantation in practicing Jehovah's Witnesses is challenging because of their religious beliefs preventing them from accepting allogenic blood products. Pegylated bovine carboxyhemoglobin (SANGUINATE) is an oxygen transfer agent, currently under investigation for the treatment of sickle cell disease, which may play a role in these patients by maximizing perioperative oxygen delivery. We report a case involving the use of SANGUINATE in a Jehovah's Witness undergoing liver transplant.

Prevention of the Osmotic Demyelination Syndrome After Liver Transplantation: A Multidisciplinary Perspective.

The osmotic demyelination syndrome (ODS) is a serious neurologic condition that occurs in the setting of rapid correction of hyponatremia. It presents with protean manifestations, from encephalopathy to the "locked-in" syndrome. ODS can complicate liver transplantation (LT), and its incidence may increase with the inclusion of serum sodium as a factor in the Mayo End-Stage Liver Disease score. A comprehensive understanding of risk factors for the development of ODS in the setting of LT, along with recommendations to mitigate the risk of ODS, are necessary. The literature to date on ODS in the setting of LT was reviewed. Major risk factors for the development of ODS include severe pretransplant hyponatremia (serum sodium [SNa] < 125 mEq/L), the magnitude of change in SNa pre- versus posttransplant, higher positive intraoperative fluid balance, and the presence of postoperative hemorrhagic complications. Strategies to reduce the risk of ODS include correcting hyponatremia pretransplant via fluid restriction and/or ensuring an appropriate rate of increase from the preoperative SNa via close attention to fluid and electrolyte management both during and after surgery. Multidisciplinary management involving transplant hepatology, nephrology, neurology, surgery, and anesthesiology/critical care is key to performing LT safely in patients with hyponatremia.

Efficacy and Safety Outcomes of Extended Criteria Donor Kidneys by Subtype: Subgroup Analysis of BENEFIT-EXT at 7 Years After Transplant.

The phase III Belatacept Evaluation of Nephroprotection and Efficacy as First-Line Immunosuppression Trial-Extended Criteria Donors Trial (BENEFIT-EXT) study compared more or less intensive belatacept-based immunosuppression with cyclosporine (CsA)-based immunosuppression in recipients of extended criteria donor kidneys. In this post hoc analysis, patient outcomes were assessed according to donor kidney subtype. In total, 68.9% of patients received an expanded criteria donor kidney (United Network for Organ Sharing definition), 10.1% received a donation after cardiac death kidney, and 21.0% received a kidney with an anticipated cold ischemic time ≥24 h. Over 7 years, time to death or graft loss was similar between belatacept- and CsA-based immunosuppression, regardless of donor kidney subtype. In all three donor kidney cohorts, estimated mean GFR increased over months 1-84 for belatacept-based treatment but declined for CsA-based treatment. The estimated differences in GFR significantly favored each belatacept-based regimen versus the CsA-based regimen in the three subgroups (p < 0.0001 for overall treatment effect). No differences in the safety profile of belatacept were observed by donor kidney subtype.

Belatacept Conversion in an HIV-Positive Kidney Transplant Recipient With Prolonged Delayed Graft Function.

We report an HIV-positive renal transplant recipient with delayed graft function who was converted from tacrolimus to belatacept in an attempt to improve renal function. The patient had kidney biopsies at 4 and 8 weeks posttransplant that revealed acute tubular necrosis and mild fibrosis. After 14 weeks of delayed function, belatacept was initiated and tacrolimus was weaned off. Shortly after discontinuing tacrolimus, renal function began to improve. The patient was able to discontinue dialysis 21 weeks posttransplant. HIV viral load was undetectable at last follow-up. To our knowledge, this is the first report of belatacept use in a patient with HIV.

Long-Term Outcomes in Belatacept- Versus Cyclosporine-Treated Recipients of Extended Criteria Donor Kidneys: Final Results From BENEFIT-EXT, a Phase III Randomized Study.

In the Belatacept Evaluation of Nephroprotection and Efficacy as First-Line Immunosuppression Trial-Extended Criteria Donors (BENEFIT-EXT), extended criteria donor kidney recipients were randomized to receive belatacept-based (more intense [MI] or less intense [LI]) or cyclosporine-based immunosuppression. In prior analyses, belatacept was associated with significantly better renal function compared with cyclosporine. In this prospective analysis of the intent-to-treat population, efficacy and safety were compared across regimens at 7 years after transplant. Overall, 128 of 184 belatacept MI-treated, 138 of 175 belatacept LI-treated and 108 of 184 cyclosporine-treated patients contributed data to these analyses. Hazard ratios (HRs) comparing time to death or graft loss were 0.915 (95% confidence interval [CI] 0.625-1.339; p = 0.65) for belatacept MI versus cyclosporine and 0.927 (95% CI 0.634-1.356; p = 0.70) for belatacept LI versus cyclosporine. Mean estimated GFR (eGFR) plus or minus standard error at 7 years was 53.9 ± 1.9, 54.2 ± 1.9, and 35.3 ± 2.0 mL/min per 1.73 m2 for belatacept MI, belatacept LI and cyclosporine, respectively (p < 0.001 for overall treatment effect). HRs comparing freedom from death, graft loss or eGFR <20 mL/min per 1.73 m2 were 0.754 (95% CI 0.536-1.061; p = 0.10) for belatacept MI versus cyclosporine and 0.706 (95% CI 0.499-0.998; p = 0.05) for belatacept LI versus cyclosporine. Acute rejection rates and safety profiles of belatacept- and cyclosporine-based treatment were similar. De novo donor-specific antibody incidence was lower for belatacept (p ≤ 0.0001). Relative to cyclosporine, belatacept was associated with similar death and graft loss and improved renal function at 7 years after transplant and had a safety profile consistent with previous reports.

Early Liver Transplantation for Severe Alcoholic Hepatitis in the United States--A Single-Center Experience.

Early liver transplantation (LT) in European centers reportedly improved survival in patients with severe alcoholic hepatitis (AH) not responding to medical therapy. Our aim was to determine if a strategy of early LT for severe AH could be applied successfully in the United States. We reviewed 111 patients with severe AH at our center from January 2012 to January 2015. The primary end point was mortality at 6 months or early LT, with a secondary end point of alcohol relapse after LT. Survival was compared between those receiving early LT and matched patients who did not. Using a process similar to the European trial, 94 patients with severe AH not responding to medical therapy were evaluated for early LT. Overall, 9 (9.6%) candidates with favorable psychosocial profiles underwent early LT, comprising 3% of all adult LT during the study period. The 6-month survival rate was higher among those receiving early LT compared with matched controls (89% vs 11%, p<0.001). Eight recipients are alive at a median of 735 days with 1 alcohol relapse. Early LT for severe AH can achieve excellent clinical outcomes with low impact on the donor pool and low rates of alcohol relapse in highly selected patients in the United States.

Tailoring the endovascular management of transplant renal artery stenosis.

In this study we analyze the different types of endovascular interventions (EVIs) in de novo transplant renal artery stenosis (TRAS) and its anatomical subtypes to examine any variation in recovery of allograft function, blood pressure control, EVI patency and allograft survival with respect to EVI type (DES: drug-eluting stent, BMS: bare-metal stent, PTA: percutaneous transluminal angioplasty). Forty-five patients underwent a total of 50 primary EVIs (DES: 18, BMS: 26, PTA: 6). Patients were stratified according to medical co-morbidities, graft characteristics, biopsy results, clinical presentation and TRAS anatomic subtypes (anastomotic: 26, postanastomotic: 17, bend-kink: 2). There was significant improvement in allograft function and mean arterial blood pressure (MAP) control across all interventions (pre-EVI-creatinine [CR]: 2.8 ± 1.4, post-EVI-Cr: 2.1 ± 0.7, p < 0.001; pre-EVI-MAP: 117 ± 16, post-EVI-MAP: 112 ± 17, p = 0.03) with no significant difference among EVI types. There was no significant difference in allograft survival with respect to EVI type. Patency was significantly higher in EVIs performed with DES and BMS compared to PTA (p = 0.001). In the postanastomotic TRAS subtype, patency rates were significantly higher in DES compared to BMS (p = 0.012) in vessels of comparable reference diameter (≤5 mm).

Pulmonary embolus originating from renal vein stump thrombus after laparoscopic living donor nephrectomy: case report.

BACKGROUND: Pulmonary embolism (PE) is an uncommon, life-threatening complication after living donor nephrectomy (LDN), and is considered among the most common causes for donor mortality. Most cases of postoperative PEs are thought to originate in deep venous thrombosis (DVT) of the lower extremities. CASE REPORT: A 56-year-old, healthy woman underwent laparoscopic left LDN. Her postoperative course was complicated by PE, presenting at postoperative day 7. Doppler ultrasonography of her lower extremities did not demonstrate DVT. Both transthoracic echocardiogram and contrast-enhanced computed tomography demonstrated a floating thrombus within the inferior vena cava (IVC) originating from a thrombus in the left renal vein stump. Symptoms resolved with systemic anticoagulation. Repeat transesophageal echocardiography demonstrated resolution of the IVC thrombus. CONCLUSIONS: Thrombus originating in left renal vein stump should be considered in patients who develop PE after LDN, especially when lower extremity DVT is not demonstrated.

Long-term exposure to belatacept in recipients of extended criteria donor kidneys.

Patients in the BENEFIT-EXT study received extended criteria donor kidneys and a more intensive (MI) or less intensive (LI) belatacept immunosuppression regimen, or cyclosporine A (CsA). Patients who remained on assigned therapy through year 3 were eligible to enter a long-term extension (LTE) study. Three hundred four patients entered the LTE (n = 104 MI; n = 113 LI; n = 87 CsA), and 260 continued treatment through year 5 (n = 91 MI; n = 100 LI; n = 69 CsA). Twenty patients died during the LTE (n = 5 MI; n = 9 LI; n = 6 CsA), and eight experienced graft loss (n = 2 MI; n = 1 LI; n = 5 CsA). Three patients experienced an acute rejection episode (n = 2 MI; n = 1 LI). The incidence rate of serious adverse events, viral infections and fungal infections was similar across groups during the LTE. There were four cases of posttransplant lymphoproliferative disorder (PTLD) from the beginning of the LTE to year 5 (n = 3 LI; n = 1 CsA); two of three PTLD cases in the LI group were in patients who were seronegative for Epstein-Barr virus (EBV(-)) at transplantation. Mean ± SD calculated GFR at year 5 was 55.9 ± 17.5 (MI), 59.0 ± 29.1 (LI) and 44.6 ± 16.4 (CsA) mL/min/1.73 m(2) . Continued treatment with belatacept was associated with a consistent safety profile and sustained improvement in renal function versus CsA over time.

Donor and recipient factors predicting time to graft failure following orthotopic liver transplantation: a transplant risk index.

INTRODUCTION: Much of the success of a transplant depends on appropriate matching of donor to recipient. METHODS: We validated the Donor Risk Index formula (DRI) using Mount Sinai Medical Center's 10-year cohort of over 1000 transplants. RESULTS: The DRI was significantly associated to graft failure with a relative risk (RR) of 1.32. Our cohort had an average DRI of 2.6 with survival of 83% at 3 months, 79% at 1 year, and 70% at 3 years. The low rate of graft failure at a high DRI implies that there are other factors important in transplant pairing that are not considered in the DRI model. To determine these variables and quantify their importance, we constructed a Transplant Risk Index by identifying recipient and donor variables not captured in United Network for Organ Sharing (UNOS) that significantly correlated to graft failure. The most significant independent predictors of time to graft failure were donor age, weight, and peak serum sodium; ischemia time; and recipient creatinine, international normalized ratio, and hepatitis C infection. The coefficients for each of these factors were compiled into a Transplant Risk Index formula. A cutoff of 5 resulted in a graft survival rate of 86% at 3 months, 76% at 1 year, and 62% at 3 years using Kaplan-Meier analysis. The predictive ability of the Transplant Risk Index was greater than the DRI or DMELD (the product of donor age and preoperative MELD) as assessed by the area under the receiver operating curve and the positive and negative predictive values. CONCLUSION: The Transplant Risk Index captures recipient factors and donor factors not captured in UNOS. Including these factors may improve the ability to predict good donor-recipient pairing.

Association of intraoperative blood pressure instability with adverse outcomes after liver transplantation.

BACKGROUND: Blood pressure derangements are common in orthotopic liver transplantation (OLT), and are potentially associated with adverse outcomes if they are sustained. While this concept is often believed to be true, few have rigorously demonstrated the validity of this claim, especially in likely vulnerable OLT patients. METHODS: We retrospectively investigated 827 patients who underwent OLT to determine the magnitude of these hemodynamic associations with adverse outcomes. The median value of the mean arterial pressure (MAP) and the fractional change in the median MAP between subsequent epochs (FCM) were calculated for every 5-minute epoch intraoperatively. Epochs were classified according to prespecified ranges of MAP and fractional changes in MAP (lability) between epochs. Multivariate stepwise logistic regression was used to model associations of risk factors and epochs of intraoperative blood pressure (BP) instability with primary (30-day mortality and/or graft failure) and secondary adverse outcomes. RESULTS: Primary adverse outcomes occurred in 10.9% and 12.2% of patients for 30-day mortality and 30-day graft failure, respectively. Independent hemodynamic predictors for 30-day mortality and graft failure included sustained periods of MAP <50 mmHg and BP lability where the MAP changed >25%. All of these values were statistically significant. CONCLUSION: Although severe intraoperative hypotension and BP lability during OLT are often observed in current practice as consequences of major surgical manipulations and patient vulnerability, these are likely not benign conditions based on this retrospective analysis. Prospective trials are warranted to investigate the possibility that interventions tailored to avoidance of hypotension and BP lability may improve outcomes.

Human monoclonal antibody MBL-HCV1 delays HCV viral rebound following liver transplantation: a randomized controlled study.

Rapid allograft infection complicates liver transplantation (LT) in patients with hepatitis C virus (HCV). Pegylated interferon-α and ribavirin therapy after LT has significant toxicity and limited efficacy. The effect of a human monoclonal antibody targeting the HCV E2 glycoprotein (MBL-HCV1) on viral clearance was examined in a randomized, double-blind, placebo-controlled pilot study in patients infected with HCV genotype 1a undergoing LT. Subjects received 11 infusions of 50 mg/kg MBL-HCV1 (n=6) or placebo (n=5) intravenously with three infusions on day of transplant, a single infusion on days 1 through 7 and one infusion on day 14 after LT. MBL-HCV1 was well-tolerated and reduced viral load for a period ranging from 7 to 28 days. Median change in viral load (log10 IU/mL) from baseline was significantly greater (p=0.02) for the antibody-treated group (range -3.07 to -3.34) compared to placebo group (range -0.331 to -1.01) on days 3 through 6 posttransplant. MBL-HCV1 treatment significantly delayed median time to viral rebound compared to placebo treatment (18.7 days vs. 2.4 days, p<0.001). As with other HCV monotherapies, antibody-treated subjects had resistance-associated variants at the time of viral rebound. A combination study of MBL-HCV1 with a direct-acting antiviral is underway.

Three-year outcomes from BENEFIT-EXT: a phase III study of belatacept versus cyclosporine in recipients of extended criteria donor kidneys.

Recipients of extended-criteria donor (ECD) kidneys have poorer long-term outcomes compared to standard-criteria donor kidney recipients. We report 3-year outcomes from a randomized, phase III study in recipients of de novo ECD kidneys (n = 543) assigned (1:1:1) to either a more intensive (MI) or less intensive (LI) belatacept regimen, or cyclosporine. Three hundred twenty-three patients completed treatment by year 3. Patient survival with a functioning graft was comparable between groups (80% in MI, 82% in LI, 80% in cyclosporine). Mean calculated GFR (cGFR) was 11 mL/min higher in belatacept-treated versus cyclosporine-treated patients (42.7 in MI, 42.2 in LI, 31.5 mL/min in cyclosporine). More cyclosporine-treated patients (44%) progressed to GFR <30 mL/min (chronic kidney disease [CKD] stage 4/5) than belatacept-treated patients (27-30%). Acute rejection rates were similar between groups. Posttransplant lymphoproliferative disorder (PTLD) occurrence was higher in belatacept-treated patients (two in MI, three in LI), most of which occurred during the first 18 months; four additional cases (3 in LI, 1 in cyclosporine) occurred after 3 years. Tuberculosis was reported in two MI, four LI and no cyclosporine patients. In conclusion, at 3 years after transplantation, immunosuppression with belatacept resulted in similar patient survival, graft survival and acute rejection, with better renal function compared with cyclosporine. As previously reported, PTLD and tuberculosis were the principal safety findings associated with belatacept in this study population.

Anti-lymphocyte therapy successfully controls late "cholestatic" rejection in pediatric liver transplant recipients.

Rejection is independently associated with liver graft loss in children. We report the successful rescue of grafts using ATG+/-OKT3 in late rejection associated with cholestasis. Retrospective chart review was performed after IRB approval. Between 2003 and 2010, 14 pediatric liver transplant recipients received anti-lymphocyte treatment for "cholestatic" rejection. Median age at transplantation was 12.7 yr (range 0.9-23.4), eight were boys, and immunosuppression was tacrolimus based. Median time from transplantation to rejection was five yr (range 1.1-10.5). Median peak total bilirubin was 11.1 mg/dL (range 1.4-18). All showed moderate to severe acute rejection and hepatocellular cholestasis on histology. ATG/OKT3 was started as first-line therapy in six and in the remaining eight as second-line therapy after failure of pulse steroids. Thirteen responded with normalization of aminotransferases and bilirubin, median time 16 wk (range 7-112); one non-adherent recipient has still not achieved normal graft function at last follow-up. Patient survival is 100%, with no re-transplantation and no post-transplant lymphoproliferative disease, median follow-up 2.9 yr (range 1.1-7.2). Cholestasis associated with acute rejection occurring late after liver transplantation may herald steroid resistance. First-line therapy with anti-lymphocyte preparations, prophylactic anti-microbial therapy, and close monitoring allow excellent rates of patient and graft survival.

A phase III study of belatacept versus cyclosporine in kidney transplants from extended criteria donors (BENEFIT-EXT study).

Recipients of extended criteria donor (ECD) kidneys are at increased risk for graft dysfunction/loss, and may benefit from immunosuppression that avoids calcineurin inhibitor (CNI) nephrotoxicity. Belatacept, a selective costimulation blocker, may preserve renal function and improve long-term outcomes versus CNIs. BENEFIT-EXT (Belatacept Evaluation of Nephroprotection and Efficacy as First-line Immunosuppression Trial-EXTended criteria donors) is a 3-year, Phase III study that assessed a more (MI) or less intensive (LI) regimen of belatacept versus cyclosporine in adult ECD kidney transplant recipients. The co-primary endpoints at 12 months were composite patient/graft survival and a composite renal impairment endpoint. Patient/graft survival with belatacept was similar to cyclosporine (86% MI, 89% LI, 85% cyclosporine) at 12 months. Fewer belatacept patients reached the composite renal impairment endpoint versus cyclosporine (71% MI, 77% LI, 85% cyclosporine; p = 0.002 MI vs. cyclosporine; p = 0.06 LI vs. cyclosporine). The mean measured glomerular filtration rate was 4-7 mL/min higher on belatacept versus cyclosporine (p = 0.008 MI vs. cyclosporine; p = 0.1039 LI vs. cyclosporine), and the overall cardiovascular/metabolic profile was better on belatacept versus cyclosporine. The incidence of acute rejection was similar across groups (18% MI; 18% LI; 14% cyclosporine). Overall rates of infection and malignancy were similar between groups; however, more cases of posttransplant lymphoproliferative disorder (PTLD) occurred in the CNS on belatacept. ECD kidney transplant recipients treated with belatacept-based immunosuppression achieved similar patient/graft survival, better renal function, had an increased incidence of PTLD, and exhibited improvement in the cardiovascular/metabolic risk profile versus cyclosporine-treated patients.

Long-term outcome of single pediatric donor kidney transplants between African-American and non-African-American adults.

BACKGROUND: African-American (AA) ethnicity has been considered a risk factor for graft loss after kidney transplant. The long-term graft survival of single pediatric donor kidney transplants in AA adults has not been reported. METHODS: We retrospectively compared the outcome of 43 AA and 32 non-African-American (NAA) adults transplanted with single pediatric kidneys from donors aged 10 years or less in our center. A combination of tacrolimus, mycophenolic acid and steroid was utilized as the maintenance therapy. RESULTS: Similar immunosuppressive dose and targeted level were achieved between the AA and the NAA groups. Median body weight (BW) of donors was 20 kg (8 - 36) in the AA group and 19 kg (8.5 - 35) in NAA group. There was no statistically significant difference in the incidence of rejection between the AA and NAA groups (26 vs. 16%, p = 0.45). The surgical complications, delayed graft function, and development of proteinuria and focal and segmental glomerulosclerosis (FSGS) were similar in both groups. The patient and graft survivals in the AA group were slightly higher compared to the NAA group. The death-censored analysis demonstrated no difference in graft survival between the AA and NAA groups (p = 0.90): 86 vs. 82% at 1 year, 70 vs. 71% at 3 years, and 62 vs. 64% at 5 years. CONCLUSIONS: Single pediatric donor kidney transplant in AA adults can be achieved with acceptable complications and equivalent long-term outcomes as in NAA adults in the era of potent immunosuppressive regimen.

Once-daily tacrolimus extended-release formulation: 1-year post-conversion in stable pediatric liver transplant recipients.

The pharmacokinetics, safety and tolerability of a once-daily formulation of tacrolimus (tacrolimus extended-release formulation; XL formerly referred to as MR or MR4) were assessed in 18 stable pediatric liver transplant recipients who were converted from the twice-a-day formulation of tacrolimus (TAC) to XL. Patients received their twice-a-day dose of TAC on study days 1 through 7. Beginning on the morning of study day 8, patients were converted to XL on a 1:1 (mg:mg) basis for their total daily dose, and were maintained on a once-daily AM dosing regimen using the same therapeutic monitoring and patient care techniques employed with TAC. Based on pharmacokinetic profiles obtained on study days 7 (TAC) and 14 (XL), steady state exposure (AUC(0-24)) was equivalent between XL and TAC; the mean XL/TAC ratio for lnAUC(0-24) was 100.9% (90% CI: 90.8%, 112.1%). AUC(0-24) and C(min) were strongly correlated at steady state (correlation coefficient: XL 0.90, TAC 0.94). During the first year post-conversion, there were no cases of acute rejection, discontinuation of XL, graft loss or death. The safety profile of XL was consistent with that known for TAC. These results support the safe and convenient conversion of pediatric liver transplant recipients from twice-a-day TAC to once-daily XL.

A comparison of long-term survivals of simultaneous pancreas-kidney transplant between African American and Caucasian recipients with basiliximab induction therapy.

African Americans (AA) have traditionally been thought to have higher immunologic risk than Caucasians (CA) for rejection and allograft loss. The impact of ethnicity on the outcome of simultaneous pancreas-kidney (SPK) transplant with basiliximab induction has not been reported. In this study, we retrospectively analyze the long-term results of 36 AA and 55 CA recipients of primary SPK. The actual patient survival rates of AA and CA groups were 91.7% vs. 90.1% at 1 year, 93.3% vs. 88.1% at 3 years, and 94.4% vs. 83.3% at 5 years. The actual kidney survival of AA and CA were 91.7% vs. 89.1% at 1 year, 90% vs. 81% at 3 years, and 83.3% vs. 75% at 5 years. The actual pancreas survival of AA and CA were 88.9% vs. 85.5% at 1 year, 83.3% vs. 78.6% at 3 years and 72.2% vs. 70.8% at 5 years. Death-censored analyses also found no difference in pancreas and kidney graft survival rates over 5 years. Higher rejection rate, but the same low CMV infection, and comparable quality of graft function were noted in AA group. AA may not have worse long-term outcomes than CA recipients of SPK with basiliximab induction and tacrolimus (TAC), mycophenolate acid (MFA) and steroid maintenance immunotherapy.

Conversion of stable liver transplant recipients from a twice-daily Prograf-based regimen to a once-daily modified release tacrolimus-based regimen.

INTRODUCTION: Modified release (MR) tacrolimus is an extended release formulation administered once daily. The purpose of this pharmacokinetic (PK) study was to evaluate tacrolimus exposure in stable liver transplant recipients converted from Prograf twice a day to MR tacrolimus once daily. METHODS: This was an open-label, multicenter study with a single sequence, four-period crossover design. Eligible patients were 18 to 65 years of age, >6 months posttransplant with stable renal and hepatic function and receiving stable doses of Prograf twice a day for >2 weeks prior to enrollment. Patients received Prograf twice a day on days 1 to 14 and 29 to 42. Patients were converted to the same milligram-for-milligram daily dose of MR once daily on days 15 to 28 and 43 to 56. Twenty-four-hour PK profiles were obtained on days 14, 28, 42, and 56. Laboratory and safety parameters were also evaluated. RESULTS: Of 70 patients, 62 completed all four PK profiles. The AUC0-24 of tacrolimus was comparable for Prograf twice a day (days 14 and 42) and MR tacrolimus once daily (days 28 and 56). The 90% confidence intervals for MR tacrolimus versus Prograf at steady state (days 28 and 56 vs days 14 and 42) was 0.85 to 0.92 for AUC0-24. MR tacrolimus was well tolerated with a safety profile comparable to that of Prograf. AUC0-24 was highly correlated to Cmin for Prograf (day 14, r = .93; Day 42, r = .89) and for MR tacrolimus (day 28, r = .93; day 56, r = .92). Renal and liver function remained stable. One patient experienced acute rejection. CONCLUSION: The steady-state tacrolimus exposure of MR tacrolimus once daily is equivalent to Prograf twice a day after a milligram-for-milligram conversion in stable liver transplant recipients.