Stephen Jensik

University of Michigan, Ann Arbor, MI, United States

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Publications (9)25.95 Total impact

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    ABSTRACT: Cyclosporine exposure, as estimated by the area under the curve (AUC), predicts outcomes in renal transplantation. Cyclosporine concentration at two h post-dose (C(2)) has been shown to be the most reliable, single-point surrogate marker for AUC. The objective of this study was to measure renal function beyond month 2 post-transplant using two different C(2) maintenance targets in combination with enteric-coated mycophenolate sodium (EC-MPS), corticosteroids, and basiliximab induction. In this open-label, multicenter trial, renal transplant recipients entered one of two randomized groups at day 61 post-transplant: group A (higher-C(2) range) or group B (lower-C(2) range). Patients (164) were recruited, and 141 patients were entered the randomized groups (group A, n = 66; group B, n = 75). At 12 months, the mean calculated creatinine clearance was significantly greater in group B than in group A (79.2 vs. 71.0 mL/min, p < 0.05). Biopsy-proven acute rejection occurred in 14.7% patients in group B and in 24.2% patients in group A (n.s.). During the 12-month trial, 17.7% patients discontinued EC-MPS because of adverse events. Group B (44.0%) had fewer serious adverse events when compared with group A (62.1%; p = 0.04). Overall patient and graft survival were 99.4% and 95.7% respectively. Among 99 high-risk patients (i.e., African-American race, previous transplant, PRA >35% or >4 HLA mismatches), mean creatinine clearance at 12 months was 65.6 mL/min and biopsy-proven rejection occurred in 20.2% patients. Low cyclosporine C(2) levels are associated with improved renal function compared with higher C(2) levels when used in conjunction with EC-MPS, steroids and basiliximab induction. EC-MPS with low cyclosporine C(2) levels, corticosteroids and basiliximab provides excellent renal function with good efficacy even in high-risk patients.
    Clinical Transplantation 01/2007; 21(2):192-201. · 1.63 Impact Factor
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    ABSTRACT: This is the 1-year report of a randomized, multicenter, clinical trial comparing the combination of sirolimus or mycophenolate mofetil (MMF) with tacrolimus-based immunosuppression in kidney transplantation. Prior to transplantation, recipients were randomized to receive tacrolimus plus corticosteroids with either sirolimus (n=185) or MMF (n=176). The incidence of biopsy-confirmed acute rejection at 6 months was the primary endpoint of the study. Patient and graft survival, renal function, study drug dosing and discontinuations were evaluated at 1 year. At 1 year, there was no difference in patient survival (95.7% sirolimus vs. 97.2% MMF; P=0.45) or graft survival (90.8% sirolimus vs. 94.3% MMF; P=0.22). Patients without delayed graft function (DGF) receiving MMF had significantly better graft survival (99% vs. 93%; P=0.01). Patients receiving a transplant from a live donor had a trend towards better graft survival with MMF as compared to sirolimus (98% vs. 91%; P=0.07). Patients receiving sirolimus had a significantly higher incidence of study drug discontinuation (26.5% vs. 14.8% MMF; P=0.006). Patients receiving MMF had significantly better renal function as shown by median serum creatinine levels (1.3 mg/dL vs. 1.5 mg/dL; P=0.03) and a trend towards higher calculated creatinine clearance (CrCl), (58.4 ml/min vs. 54.3 ml/min; P=0.06). More patients in the sirolimus group had a serum creatinine >2.0 mg/dL, (20.4% vs. 11.0%; P=0.02). Tacrolimus is safe and effective in live and deceased donor kidney transplantation when given in combination with sirolimus or MMF. Patient and graft survival were excellent in both arms. Renal function is superior for patients treated with tacrolimus + MMF combination.
    Transplantation 09/2005; 80(3):303-9. · 3.78 Impact Factor
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    ABSTRACT: This pilot study was designed to evaluate the safety and efficacy of converting from a calcineurin inhibitor (CI) to a sirolimus (SRL)-based regimen in established renal transplant recipients with moderate renal insufficiency. Sixty renal transplant recipients on CI-based immuno-suppression with a serum creatinine (SCr) between 159 and 265 microM (1.8 and 3.0 mg/dL) and a glomerular filtration rate (GFR) between 30 and 70 mL/min were enrolled. SRL dosing was dependent upon concomitant immunosuppressive therapy. The mean patient age was 45 yr and the mean time from transplant to study enrollment was 60.8 months (range: 7-198). The median SCr was 168 microM (1.9 mg/dL) and the median GFR was 51 mL/min. Twelve months after conversion the patient and graft survival rates were 96.7% and 95%, respectively. The incidence of biopsy-proven acute rejection was 3.3% (two cases reported, Banff grades IA and IB). The median SCr and median creatinine clearance were 168 microM (1.9 mg/dL) and 53 mL/min, respectively. Hyperlipidemia, diarrhea, peripheral edema, rash, and anemia were the most commonly reported adverse events. Patients with moderate renal insufficiency can be converted from CI to SRL-based therapy and maintain renal function over a 1-yr period.
    Clinical Transplantation 03/2005; 19(1):130-6. · 1.63 Impact Factor
  • Transplantation 01/2004; 78:263-264. · 3.78 Impact Factor
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    ABSTRACT: This is the first report of a randomized, multicenter, clinical trial comparing the combination of sirolimus or mycophenolate mofetil (MMF) with tacrolimus-based immunosuppression in kidney transplantation. Results at 6 months of follow-up are presented. Before transplantation, patients were randomized to receive tacrolimus plus corticosteroids with sirolimus (n=185) or MMF (n=176). The primary endpoint of the study was the incidence of biopsy-confirmed acute rejection. Patient and graft survival, renal function, and composite endpoints also were evaluated. Safety was assessed by monitoring laboratory parameters and adverse events. By 6 months of follow-up, the incidence of biopsy-confirmed acute rejection was similar in both treatment groups (13.0% tacrolimus+sirolimus vs. 11.4% tacrolimus+MMF; P=0.64 log-rank). Patient survival (97.3% tacrolimus+sirolimus vs. 97.7% tacrolimus+MMF) and graft survival (93.0% tacrolimus+sirolimus vs. 95.5% tacrolimus+MMF) were equivalent (P=0.53, overall survival log-rank). There was a significantly higher incidence of study drug discontinuation in patients receiving sirolimus (21.1% vs. 10.8%; P=0.008). Renal function was significantly better in the MMF-treatment group (serum creatinine 1.44+/-0.45 mg/dL vs. 1.77+/-1.42 mg/dL; P=0.018). Hyperlipidemia was significantly more prevalent in the sirolimus-treatment group. Diastolic blood pressure was significantly higher in sirolimus-treated patients. There were significantly more leukopenia and gastrointestinal adverse events in the MMF-treatment group. The incidence of posttransplant diabetes mellitus was 7.6% in the sirolimus group and 7.7% in the MMF group. Tacrolimus is equally effective in renal transplantation when combined with sirolimus or MMF. The tacrolimus-MMF combination may be superior in terms of improved renal function and improved cardiovascular risk factors including hyperlipidemia and hypertension.
    Transplantation 05/2003; 75(8):1213-20. · 3.78 Impact Factor
  • Transplantation Reviews. 01/2003; 17(4):S66–S67.
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    ABSTRACT: The 1-year results of the Phase III U.S. Multicenter Trial comparing tacrolimus (FK506)- and cyclosporine (CsA)-based immunosuppressive therapy in kidney transplantation revealed a significant reduction in the incidence and severity of acute rejection episodes among patients maintained on tacrolimus. The present report at 5 years of follow-up focuses on the long-term impact of tacrolimus treatment on kidney allograft outcome. The study protocol permitted crossover of patients to the alternate treatment arm under stringent conditions. The effect of crossover on graft survival was analyzed. Cardiovascular risk factors and serious adverse events were also monitored over 5 years. Intent-to-treat analysis revealed equivalent patient and graft survival between treatment arms at 5 years of follow-up (79.1% vs. 81.4%; P=0.472 and 64.3% vs. 61.6%; P=0.558 among tacrolimus and CsA-treated patients, respectively). However, the rate of crossover was significantly higher among patients randomized to receive CsA-based therapy (27.5% vs. 9.3%; P<0.001). The incidence of treatment failure (43.8% vs. 56.3%; P=0.008) was significantly lower among tacrolimus-treated patients. Graft survival was significantly improved in the tacrolimus treatment arm when crossover due to rejection was counted as graft failure (63.8% vs. 53.8%; P=0.014). Tacrolimus therapy was also associated with a significantly reduced requirement for medications to control hypertension and hyperlipidemia. There was a substantial rate of reversal of tacrolimus-associated insulin dependence. Tacrolimus-based therapy resulted in significantly reduced risk of graft failure, without an increase in the incidence of adverse events associated with long-term immunosuppression.
    Transplantation 03/2002; 73(5):775-82. · 3.78 Impact Factor
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    ABSTRACT: Background. Tacrolimus (FK506) is a safe and effective treatment for the prevention of rejection of renal allografts. Mycophenolate mofetil (MMF) has been used as adjunct immunosuppressive therapy with cyclosporine and corticosteroids for the same purpose. The objective of this study was to investigate the safety and efficacy of FK506 and MMF in renal transplant recipients. Methods. After cadaveric renal transplant, patients were randomized to receive tacrolimus in combination with either azathioprine (AZA, n=59), MMF 1 g/day (n=59), or MMF 2 g/day group (n=58). Patients were followed for 1 yr posttransplant for the incidence of biopsy-confirmed acute rejection, patient and graft survival, and adverse events. Results. Tacrolimus doses and trough concentrations were similar between treatment groups at all time points; 80% of patients were maintained within a range of 5.0-13.9 ng/ml at 12 months posttransplant. The mean dose of MMF decreased in the 2 g/day group to 1.5 g/day by 6 months posttransplant, primarily due to gastrointestinal GI-related disorders. The incidence of biopsy-confirmed acute rejection at 1 year was 32.2%, 32.2%, and 8.6% in the AZA, MMF 1 g/day, and MMF 2 g/day groups, respectively (P <0.01). The use of antilymphocyte antibodies for the treatment of rejection was comparable across treatment groups. The incidence of most adverse events was similar across treatment groups and comparable with previous reports. The overall incidence of posttransplant diabetes mellitus was 11.9%, with the lowest rate observed in the MMF 2 g/day group (4.7%), and was reversible in 40% of patients. The incidence of malignancies and opportunistic infections was low and not different across treatment groups. Conclusion. Tacrolimus in combination with an initial dose of MMF 2 g/day is a very effective and safe regimen in cadaveric kidney transplant recipients.
    Transplantation 03/2000; 69(5):875-880. · 3.78 Impact Factor
  • Source
    J Miller, R Mendez, J D Pirsch, S C Jensik
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    ABSTRACT: Tacrolimus (FK506) is a safe and effective treatment for the prevention of rejection of renal allografts. Mycophenolate mofetil (MMF) has been used as adjunct immunosuppressive therapy with cyclosporine and corticosteroids for the same purpose. The objective of this study was to investigate the safety and efficacy of FK506 and MMF in renal transplant recipients. After cadaveric renal transplant, patients were randomized to receive tacrolimus in combination with either azathioprine (AZA, n=59), MMF 1 g/day (n=59), or MMF 2 g/day group (n=58). Patients were followed for 1 yr posttransplant for the incidence of biopsy-confirmed acute rejection, patient and graft survival, and adverse events. Tacrolimus doses and trough concentrations were similar between treatment groups at all time points; 80% of patients were maintained within a range of 5.0-13.9 ng/ml at 12 months posttransplant. The mean dose of MMF decreased in the 2 g/day group to 1.5 g/day by 6 months posttransplant, primarily due to gastrointestinal GI-related disorders. The incidence of biopsy-confirmed acute rejection at 1 year was 32.2%, 32.2%, and 8.6% in the AZA, MMF 1 g/day, and MMF 2 g/day groups, respectively (P<0.01). The use of antilymphocyte antibodies for the treatment of rejection was comparable across treatment groups. The incidence of most adverse events was similar across treatment groups and comparable with previous reports. The overall incidence of posttransplant diabetes mellitus was 11.9%, with the lowest rate observed in the MMF 2 g/day group (4.7%), and was reversible in 40% of patients. The incidence of malignancies and opportunistic infections was low and not different across treatment groups. Tacrolimus in combination with an initial dose of MMF 2 g/day is a very effective and safe regimen in cadaveric kidney transplant recipients.
    Transplantation 03/2000; 69(5):875-80. · 3.78 Impact Factor

Publication Stats

544 Citations
25.95 Total Impact Points

Institutions

  • 2007
    • University of Michigan
      • Department of Internal Medicine
      Ann Arbor, MI, United States
    • Aurora St. Luke's Medical Center
      Milwaukee, Wisconsin, United States
  • 2000
    • Jackson Memorial Hospital
      Miami, Florida, United States