De Novo Kidney Transplant Research Articles

1693: Evaluation of the Incidence of Glucose Metabolism Impairments after De Novo Kidney Transplantation Using an Oral Glucose Tolerance Test

1693: Evaluation of the Incidence of Glucose Metabolism Impairments after De Novo Kidney Transplantation Using an Oral Glucose Tolerance Test

FTY720, a Novel Immunomodulator in de Novo Kidney Transplant Patients: Pharmacokinetics and Exposure‐Response Relationship

The pharmacokinetics, safety, and preliminary efficacy of FTY720, a novel immunomodulator, were examined in de novo renal transplant patients. Both noncompartmental and population methods were used to estimate pharmacokinetic estimates in the patients. The steady-state plasma concentrations of FTY720 increased in accordance with maintenance dose level, indicating linearity in clearance and volume of distribution over the 0.25- to 2.5-mg dose range. The pharmacokinetics of FTY720 in de novo renal transplant patients were characterized by the long terminal phase half-life of approximately 200 hours across doses, high volume of distribution (>3000 L), and low clearance (10.8 L/h). The intersubject variation of clearance was 55%, and the intrasubject variation of FTY720 concentrations was 28%. The population analysis revealed significant positive relationships between baseline alkaline phosphatase and clearance, as well as between baseline body weight on apparent volume of distribution. There was no relationship between FTY720 concentrations within a given FTY720 dose cohort and the rate of allograft rejection.

Early Experience With Enteric-Coated Mycophenolate Sodium in De Novo Kidney Transplant Recipients

Introduction We sought to evaluate the efficacy of enteric-coated mycophenolate sodium (EC-MPS) and the gastrointestinal (GI) adverse events in de novo kidney transplant recipients. Methods This noncontrolled, retrospective review includes 22 de novo kidney transplant recipients. All patients received a standard course of basiliximab and were maintained on triple-drug therapy with EC-MPS, cyclosporine microemulsion (CsA), and prednisolone. The follow-up lasted 7.9 ± 1.2 months. The incidence of GI adverse effects were compared with those of historical mycophenolate mofetil (MMF) studies. Results The serum creatinine was maintained within 1.4 ± 0.7 mg/dL. The 2-hour CsA postdose level was 1080 ± 327 ng/mL initially and gradually tapered to 851 ± 435 ng/mL. The daily EC-MPS dose was 1404 ± 180 mg initially and gradually tapered to 1098 ± 288 mg. The GI adverse effects at the daily dose of EC-MPS 1422 ± 126 mg included dyspepsia 27%, acid regurgitation 18.2%, epigastralgia 9%, nausea 9%, vomiting 4.5%, and poor appetite 4.5%. In comparison those from historical MMF 2 g/d studies included dyspepsia 3.1% to 40%, epigastralgia 10%, nausea 3.7% to 34%, and vomiting 0.6% to 10.7%. Conclusion Immunosuppression with CsA, EC-MPS, and steroids maintains stable graft functions. Minimal dose reduction of EC-MPS decreases GI adverse events but without significance. EC-MPC and MMF have respective GI side effects; they can be used alternatively in patients with individual GI intolerance.

Response to: De Novo Kidney Transplantation Without Use of Calcineurin Inhibitors Preserves Renal Structure and Function at 2 Years

Response to: De Novo Kidney Transplantation Without Use of Calcineurin Inhibitors Preserves Renal Structure and Function at 2 Years

Prospective, Multicenter, Randomized Trial to Compare Incidence of New-Onset Diabetes Mellitus and Glucose Metabolism in Patients Receiving Cyclosporine Microemulsion Versus Tacrolimus After De Novo Kidney Transplantation

New-onset diabetes mellitus (NODM) is associated with increased risk of graft failure and death in renal transplant recipients. Some clinical studies have indicated that NODM risk is higher with tacrolimus than cyclosporine, but no comparative trial has used American Diabetic Association (ADA)/World Health Organization (WHO) criteria for diagnosis of diabetes mellitus. The Diabetes Incidence After Renal Transplantation, Neoral C 2 Monitoring Versus Tacrolimus (DIRECT) study is a 6-month open-label, multicenter trial comparing the impact of tacrolimus and Neoral (cyclosporine microemulsion) on glucose metabolism in 700 de novo kidney transplant recipients, based on ADA/WHO criteria. Patients are randomized to tacrolimus (C 0 monitoring) or Neoral (C 2 monitoring), stratified by baseline diabetic status and ethnicity. All patients receive basiliximab, corticosteroids, and mycophenolate mofetil or enteric-coated mycophenolate acid ( myfortic). Pooled interim 3-month results from a subset of 115 patients receiving either tacrolimus or Neoral showed that the primary efficacy end-point (biopsy-proven acute rejection [BPAR], graft loss or death) occurred in 11 patients (10%). There were four graft losses and only one death, which occurred after graft loss. Eight patients experienced BPAR (7.3%). Among 99 patients who were nondiabetic at baseline, 14 developed NODM by month 3, 17 developed impaired fasting glucose or impaired glucose tolerance, and another 5 patients received hypoglycemic treatment for at least 14 consecutive days or at the month 3 visit, resulting in a 36% incidence of impaired glucose metabolism. At 3 months, median GFR (Nankivell) was 63.7 mL/min; median serum creatinine was 137 μmol/L. Full complete results are expected in December 2005.

De Novo Kidney Transplantation Without Use of Calcineurin Inhibitors Preserves Renal Structure and Function at Two Years

We performed a randomized prospective trial comparing calcineurin inhibitor (CNI)-free to CNI-based immunosuppression to determine the impact on renal function, structure and gene expression. Sixty-one kidney recipients treated with basiliximab mycophenolate mofetil (MMF) and prednisone (P) were randomly assigned to concentration-controlled sirolimus or cyclosporine. Two years post-transplant 55 patients underwent renal function studies, 48 (87%) underwent transplant biopsies; all classified by Banff scoring and 41 by DNA microarrays. Comparing sirolimus/MMF/P to cyclosporine/MMF/P there was a significantly lower serum creatinine (1.35 vs. 1.81 mg/dL; p = 0.008), higher Cockroft-Gault glomerular filtration rate (GFR) (80.4 vs. 63.4 mL/min; p = 0.008), iothalamate GFR (60.6 vs. 49.2 mL/min; p = 0.018) and Banff 0 (normal) biopsies (66.6 vs. 20.8%; p = 0.013). Regression analysis of calculated GFRs from 1 to 36 months yielded a positive slope for sirolimus of 3.36 mL/min/year, and a negative slope for cyclosporine of -1.58 mL/min/year (p = 0.008). Gene expression profiles from kidneys with higher Banff chronic allograft nephropathy (CAN) scores confirmed significant up-regulation of genes responsible for immune/inflammation and fibrosis/tissue remodeling. At 2 years the sirolimus-treated recipients have better renal function, a diminished prevalence of CAN and down-regulated expression of genes responsible for progression of CAN. All may provide for an alternative natural history with improved graft survival.

1949: Six Month Randomized Study Comparing Cyclosporine Microemulsion with C2 Monitoring and Tacrolimus in De Novo Kidney Transplantation

You have accessJournal of UrologyPodium, Wednesday, May 12, 2004, 1:30 - 3:30 pm1 Apr 20041949: Six Month Randomized Study Comparing Cyclosporine Microemulsion with C2 Monitoring and Tacrolimus in De Novo Kidney Transplantation Felipe G. Balbontin, Bryce Kiberd, Philip Belitsky, Dharm Singh, Albert Fraser, and Joseph G. Lawen Felipe G. BalbontinFelipe G. Balbontin More articles by this author , Bryce KiberdBryce Kiberd More articles by this author , Philip BelitskyPhilip Belitsky More articles by this author , Dharm SinghDharm Singh More articles by this author , Albert FraserAlbert Fraser More articles by this author , and Joseph G. LawenJoseph G. Lawen More articles by this author View All Author Informationhttps://doi.org/10.1016/S0022-5347(18)39141-9AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail "1949: Six Month Randomized Study Comparing Cyclosporine Microemulsion with C2 Monitoring and Tacrolimus in De Novo Kidney Transplantation." The Journal of Urology, 171(4S), p. 515 © 2016 by American Urological AssociationFiguresReferencesRelatedDetails Volume 171Issue 4SApril 2004Page: 515 Advertisement Copyright & Permissions© 2016 by American Urological AssociationMetricsAuthor Information Felipe G. Balbontin More articles by this author Bryce Kiberd More articles by this author Philip Belitsky More articles by this author Dharm Singh More articles by this author Albert Fraser More articles by this author Joseph G. Lawen More articles by this author Expand All Advertisement PDF downloadLoading ...

Enteric Coated Mycophenolate Sodium is Therapeutically Equivalent to Mycophenolate Mofetil in de novoRenal Transplant Patients

sThe introduction of mycophenolate mofetil (MMF) represented a major advance in transplant medicine, although optimal use may be limited by gastrointestinal (GI) side effects. An enteric coated formulation of mycophenolate sodium (EC MPS; myfortic®) has been developed with the aim of improving the upper GI tolerability of mycophenolic acid. Therapeutic equivalence of EC MPS (720 mg b.i.d.) and MMF (1000 mg MMF b.i.d.), with concomitant cyclosporine microemulsion (Neoral®) and corticosteroids, was assessed in 423 de novokidney transplant patients recruited to a 12 month, double blind study. Efficacy failure (biopsy proven acute rejection [BPAR], graft loss, death or loss to follow up) at 6 months (EC MPS 25.8% vs. MMF 26.2%; 95% CI: [−8.7, +8.0]) demonstrated therapeutic equivalence. At 12 months, the incidence of BPAR, graft loss or death was 26.3% and 28.1%, and of BPAR alone was 22.5% and 24.3% for EC MPS and MMF, respectively. Among those with BPAR, the incidence of severe acute rejection was 2.1% with EC MPS and 9.8% with MMF (p = ns). The safety profile and incidence of GI adverse events were similar for both groups. Within 12 months, 15.0% of EC MPS patients and 19.5% of MMF patients required dose changes for GI adverse events (p = ns). Enteric coated MPS 720 mg b.i.d. is therapeutically equivalent to MMF 1000 mg b.i.d. with a comparable safety profile.