Identification of glomerular and podocyte-specific genes and pathways activated by sera of patients with focal segmental glomerulosclerosis.

Focal segmental glomerulosclerosis (FSGS) accounts for about 40% of all nephrotic syndrome cases in adults. The presence of several potential circulating factors has been suggested in patients with primary FSGS and particularly in patients with recurrent disease after transplant. Irrespectively of the nature of the circulating factors, this study was aimed at identifying early glomerular/podocyte-specific pathways that are activated by the sera of patients affected by FSGS.

Antibody-mediated rejection implies a poor prognosis in kidney transplantation: Results from a single center.

Two major barriers to achieving long-term graft survival include patient nonadherence in taking the prescribed immunosuppression and antibody-mediated rejection(AMR). We were therefore interested in determining the prognostic impact of developing an AMR component to rejection in a prospective randomized trial of 200 kidney transplant recipients who received dual induction therapy (rATG combined with either daclizumab or alemtuzumab) and planned early corticosteroid withdrawal. With a median follow-up of 96 months post-transplant, 40/200 developed a first BPAR; 9/200 developed a second BPAR.

Randomized trial of rATg/Daclizumab vs. rATg/Alemtuzumab as dual induction therapy in renal transplantation: Results at 8years of follow-up.

Our goal in using dual induction therapy is to bring the kidney transplant recipient closer (through more effectively timed lymphodepletion) to an optimally immunosuppressed state. Here, we report long-term results of a prospective randomized trial comparing (Group I,N=100) rATG/Dac (3 rATG, 2 Dac doses) vs. (Group II,N=100) rATG/Alemtuzumab(C1H) (1 dose each), using reduced tacrolimus dosing, EC-MPS, and early corticosteroid withdrawal.

Pilot Randomized Trial of Tacrolimus/Everolimus vs Tacrolimus/Enteric-Coated Mycophenolate Sodium in Adult, Primary Kidney Transplant Recipients at a Single Center.

Background: Recent studies suggest that the combination of tacrolimus (TAC) and everolimus (EVL) could become a viable option for use as standard maintenance immunosuppression in non-highly sensitized kidney transplant recipients.

Methods: We conducted a single-center, open-label, randomized pilot trial comparing two maintenance immunosuppression regimens in non-highly sensitized, adult, primary kidney transplant recipients: (TAC/EVL, Group A) vs our standard maintenance regimen of TAC plus enteric-coated mycophenolate mofetil (TAC/EC-MPS, Group B). In both treatment arms, dual induction therapy consisting of anti-thymocyte globulin (Thymoglobulin) and basiliximab was given.

Lower tacrolimus trough levels are associated with subsequently higher acute rejection risk during the first 12 months after kidney transplantation.

The premise that lower TAC trough levels are associated with subsequently higher first BPAR risk during the first 12 mo post-transplant was recently questioned. Using our prospectively followed cohort of 528 adult, primary kidney transplant recipients (pooled across four randomized trials) who received reduced TAC dosing plus an IMPDH inhibitor, TAC trough levels measured at seven time points, 7, 14 days, 1, 2, 3, 6 and 9 months post-transplant, were utilized along with Cox's model to determine the multivariable significance of TAC level(t) (a continuous time-dependent covariate equaling the most recently measured TAC level prior to time t) on the hazard rate of developing first BPAR during the first 12 months post-transplant. The percentage developing BPAR during the first 12 months post-transplant was 10.

Multivariable risk of developing new onset diabetes after transplant-results from a single-center study of 481 adult, primary kidney transplant recipients.

Background: Understanding the relative contributions of baseline demographics and immunosuppressive therapy on NODAT risk may help in developing preventive strategies.

Methods: Using our prospectively followed cohort of 481 adult, primary kidney transplant recipients without pre-transplant diabetes, we determined the significant baseline predictors for the hazard rate of developing NODAT via Cox stepwise regression. The multivariable influence of first BPAR (defined as a time-dependent covariate) was also tested.

Single-centre study of 628 adult, primary kidney transplant recipients showing no unfavourable effect of new-onset diabetes after transplant.

Aims/hypothesis: To better understand the implications of new-onset diabetes after transplant (NODAT), we used our prospectively followed cohort of 628 adult primary kidney transplant recipients to determine the prognostic impact of pretransplant diabetes and NODAT.

Methods: The study cohort consisted of all participants in four randomised immunosuppression trials performed at our centre since May 2000. For each cause-specific hazard analysed, Cox stepwise regression was used to determine a multivariable model of significant baseline predictors; the multivariable influence of having pretransplant diabetes and NODAT (t) (the latter defined as a zero-one, time-dependent covariate) was subsequently tested.

Randomized trial of three induction antibodies in kidney transplantation: long-term results.

Background: In searching for an optimal induction regimen, we conducted two separate randomized trials of 38 living donor and 90 deceased donor adult, primary kidney transplant recipients comparing antithymocyte globulin (Thymoglobulin) (group A, N=43) versus alemtuzumab (group B, N=43) versus daclizumab (group C, N=42), using exactly the same three treatment arms in each trial.

Methods: For the purpose of maximizing statistical power, results from the two randomized trials were combined. Groups A and C received standard maintenance dosing with tacrolimus (TAC), mycophenolate mofetil (MMF), and corticosteroids.

Graft failure due to noncompliance among 628 kidney transplant recipients with long-term follow-up: a single-center observational study.

Background: In adult kidney transplantation, there is no clear consensus on the incidence of graft failure-due-to noncompliance (GFNC), with some reporting it as relatively uncommon and others as a major cause of late graft failure. We suspected that GFNC was a major cause of late graft loss at our center but did not know the extent of this problem.

Methods: In our prospectively followed cohort of 628 adult, primary kidney-alone transplant recipients with long-term follow-up, GFNC and other graft loss causes were determined from our ongoing clinical evaluations.

A randomized pilot study of donor stem cell infusion in living-related kidney transplant recipients receiving alemtuzumab.

Background: Transplant tolerance would remove the need for maintenance immunosuppression while improving survival and quality of life.

Methods: A prospective, randomized pilot study was undertaken to assess the safety and efficacy of donor stem cell infusion (DSCI) in living-related kidney transplant recipients treated with alemtuzumab (C1H) induction and tacrolimus and mycophenolate maintenance with switch to sirolimus and weaning over 2 years.

Results: Four patients received DSCI; five patients were controls.

Advantage of rapamycin over mycophenolate mofetil when used with tacrolimus for simultaneous pancreas kidney transplants: randomized, single-center trial at 10 years.

Simultaneous pancreas kidney transplantation (SPKT) is the treatment of choice for patients with type 1 diabetes and end-stage renal disease. Rapamycin and mycophenolate mofetil (MMF) have been used for maintenance immunosuppression with tacrolimus in SPKT; however, long-term outcomes are lacking. From September 2000 through December 2009, 170 SPKT recipients were enrolled in a randomized, prospective trial receiving Rapamycin (n = 84) or MMF (n = 86).

Randomized trial of dual antibody induction therapy with steroid avoidance in renal transplantation.

Background: Given our previous experience using dual-induction therapy with antithymocyte globulin (ATG)/daclizumab (Dac) (each with fewer doses than if used alone), we chose to compare two distinct dual-induction strategies.

Methods: Single-center, open-label randomized trial of 200 primary kidney transplant recipients was performed: (group I, n=100) ATG/Dac (3 ATG, 2 Dac doses) versus (group II, n=100) ATG/alemtuzumab (1 dose each), with maintenance consisting of reduced tacrolimus dosing (rTd), enteric-coated mycophenolate sodium (EC-MPS), and early corticosteroid withdrawal. One half of standard EC-MPS dosing was targeted in group II to avoid severe leukopenia previously seen with alemtuzumab.

Machine perfusion following static cold storage preservation in kidney transplantation: donor-matched pair analysis of the prognostic impact of longer pump time.

The impact of machine perfusion (MP) time on kidney transplant outcome is mixed in previous studies using multivariable analyses. In an analysis of 66 pairs of donor-matched adult, first transplant recipients (N = 132) with identical donor characteristics except for pump time, tests of association of shorter versus longer pump time (first versus second kidney removed) by delayed graft function(DGF), slow graft function(SGF), and biopsy proven acute rejection(BPAR) were performed using McNemar's test. Freedom-from-BPAR, graft and patient survival, and renal function were also compared.

Randomized trial of immunosuppressive regimens in renal transplantation.

The optimal long-term regimen for immunosuppression for kidney transplant recipients is unknown. We conducted a randomized trial involving 150 kidney transplant recipients to compare tacrolimus/sirolimus, tacrolimus/mycophenolate mofetil (MMF), and cyclosporine/sirolimus. All patients received daclizumab induction and maintenance corticosteroids.

Randomized trial of mycophenolate mofetil versus enteric-coated mycophenolate sodium in primary renal transplantation with tacrolimus and steroid avoidance: four-year analysis.

Background: Our single-center, open-labeled randomized trial of 150 adult, primary kidney transplant recipients receiving 2 g mycophenolate mofetil (group A, n=75) versus 1.440 g enteric-coated mycophenolate sodium (group B, n=75), with reduced maintenance tacrolimus dosing, steroid elimination at 1 week, and combined rabbit antithymocyte globulin/daclizumab induction, previously showed at 1 year posttransplant low biopsy-proven acute rejection (BPAR), acceptably high renal function, and no differences in incidence of symptomatic gastrointestinal (GI) side effects between the two groups. This report includes 3 additional years of follow-up with similar endpoints as in the original study.

Randomized trial of thymoglobulin versus alemtuzumab (with lower dose maintenance immunosuppression) versus daclizumab in living donor renal transplantation.

Background: We performed a randomized trial evaluating alemtuzumab, a humanized anti-CD52 monoclonal antibody, in living donor (LD) kidney transplantation.

Methods: Thirty-eight LD first renal transplant recipients were randomized into three single-agent antibody induction groups: thymoglobulin (group A); alemtuzumab (group B); and daclizumab (group C). In groups A and C, target tacrolimus trough levels were 6 to 8 ng/mL, with 1 gm mycophenolate mofetil (MMF) administered twice daily, and maintenance methylprednisolone.

Favorable outcomes with machine perfusion and longer pump times in kidney transplantation: a single-center, observational study.

Background: Hypothermic machine perfusion (MP) preservation is used for all deceased donor kidney transplants at our center. Kidneys are placed in cold storage at retrieval, then transferred to MP on arrival. Because a lack of consensus regarding optimal use of MP still exists, we evaluated the overall impact of using MP at our center and the prognostic value of MP (Pump) time.

Randomized trial of mycophenolate mofetil versus enteric-coated mycophenolate sodium in primary renal transplant recipients given tacrolimus and daclizumab/thymoglobulin: one year follow-up.

Background: It was of interest to compare enteric-coated mycophenolate sodium (EC-MPS) versus mycophenolate mofetil (MMF) among renal transplant recipients receiving a tacrolimus-based immunosuppressive regimen.

Methods: Between December 2004 and February 2006, a single-center, open-label randomized trial of MMF (group A, n=75) versus EC-MPS (group B, n=75) was performed in primary renal transplant recipients receiving combined thymoglobulin/daclizumab induction along with reduced tacrolimus dosing and elimination of corticosteroids 1 week postoperatively. The primary endpoint was the incidence rate of acute rejection (AR) during the first 12 months posttransplant; secondary aims were to compare graft and patient survival, renal function, drug dosing and monitoring, gastrointestinal side effects, and other adverse events at 12 months of follow-up.

Campath-1H induction therapy in African American and Hispanic first renal transplant recipients: 3-year actuarial follow-up.

Background: In a retrospective study of the first 75 primary renal transplant patients given alemtuzumab induction at our center, 20 were African American (27%), 32 were Hispanic (43%), and 23 were non-African American, non-Hispanic (31%).

Methods: Alemtuzumab was given intraoperatively and 4 days later (0.3 mg/kg), with planned low-dose maintenance mycophenolate mofetil (500 mg twice daily) and tacrolimus (targeted trough levels of 5 to 7 ng/ml) and no corticosteroid therapy after the first week.

A randomized trial of thymoglobulin vs. alemtuzumab (with lower dose maintenance immunosuppression) vs. daclizumab in renal transplantation at 24 months of follow-up.

Introduction: A long-term prospective randomized trial evaluating alemtuzumab, a humanized anti-CD52 monoclonal antibody, in a predominantly non-Caucasian population has yet to be reported.

Methods: Ninety deceased donor (DD) first renal transplant recipients were randomized into three different antibody induction groups: group A, thymoglobulin (Thymo); group B, alemtuzumab; group C, daclizumab (Dac). In groups A and C, the target trough levels of tacrolimus were 8-10 ng/mL, mycophenolate mofetil (MMF) 1 g administered twice daily, and maintenance methylprednisolone.