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Sökning: WFRF:(Halloran Philip F.)

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1.
  • Claes, Kathleen, et al. (författare)
  • Effect of different immunosuppressive regimens on the evolution of distinct metabolic parameters: evidence from the Symphony study
  • 2012
  • Ingår i: Nephrology Dialysis Transplantation. - : Oxford University Press (OUP). - 1460-2385 .- 0931-0509. ; 27:2, s. 850-857
  • Tidskriftsartikel (refereegranskat)abstract
    • The metabolic syndrome (MS) is an important risk factor for graft dysfunction and patient death after renal transplantation. The aim of this sub-analysis of the Symphony study was to assess the progression of the laboratory parameters associated with MS in the first year after transplantation. Data collected from the Symphony study were used; 1645 patients were randomized to receive standard-dose cyclosporine (Stand-CsA), low-dose cyclosporine (Low-CsA), tacrolimus (Low-Tac) or sirolimus (Low-SRL), in addition to mycophenolate mofetil (MMF) and corticosteroids. Data were collected for levels and progression over the first year post-transplantation of systolic and diastolic blood pressure, uric acid, triglycerides, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol and fasting glucose levels by treatment arm. The low-SRL group had significantly higher levels of triglycerides and LDL. The two CsA arms were associated with the highest uric acid levels at each time point. There were no significant differences in overall levels or changes in glucose or HDL. Patients in the standard-CsA arm had significantly higher diastolic blood pressure than those in the Low-SRL and Low-Tac arms. Systolic blood pressure was higher in the Low-CsA arm than in the Low-Tac arm. The use of antihypertensive and antidiabetic agents was similar between the treatment arms. In the Low-SRL arm, more patients were treated with lipid-lowering therapy. Mean daily steroid doses were the highest in the Low-SRL arm. This sub-analysis demonstrates that there is a difference in metabolic parameters between immunosuppressive groups. CsA therapy was associated with the highest values of uric acid and systolic and diastolic blood pressure. Patients on SRL therapy had the worst lipaemic control. A possible effect of Tac on new-onset diabetes could not be excluded.
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2.
  • Ekberg, Henrik, et al. (författare)
  • Reduced exposure to calcineurin inhibitors in renal transplantation.
  • 2007
  • Ingår i: New England Journal of Medicine. - 0028-4793. ; 357:25, s. 2562-2575
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Immunosuppressive regimens with the fewest possible toxic effects are desirable for transplant recipients. This study evaluated the efficacy and relative toxic effects of four immunosuppressive regimens. METHODS: We randomly assigned 1645 renal-transplant recipients to receive standard-dose cyclosporine, mycophenolate mofetil, and corticosteroids, or daclizumab induction, mycophenolate mofetil, and corticosteroids in combination with low-dose cyclosporine, low-dose tacrolimus, or low-dose sirolimus. The primary end point was the estimated glomerular filtration rate (GFR), as calculated by the Cockcroft-Gault formula, 12 months after transplantation. Secondary end points included acute rejection and allograft survival. RESULTS: The mean calculated GFR was higher in patients receiving low-dose tacrolimus (65.4 ml per minute) than in the other three groups (range, 56.7 to 59.4 ml per minute). The rate of biopsy-proven acute rejection was lower in patients receiving low-dose tacrolimus (12.3%) than in those receiving standard-dose cyclosporine (25.8%), low-dose cyclosporine (24.0%), or low-dose sirolimus (37.2%). Allograft survival differed significantly among the four groups (P=0.02) and was highest in the low-dose tacrolimus group (94.2%), followed by the low-dose cyclosporine group (93.1%), the standard-dose cyclosporine group (89.3%), and the low-dose sirolimus group (89.3%). Serious adverse events were more common in the low-dose sirolimus group than in the other groups (53.2% vs. a range of 43.4 to 44.3%), although a similar proportion of patients in each group had at least one adverse event during treatment (86.3 to 90.5%). CONCLUSIONS: A regimen of daclizumab, mycophenolate mofetil, and corticosteroids in combination with low-dose tacrolimus may be advantageous for renal function, allograft survival, and acute rejection rates, as compared with regimens containing daclizumab induction plus either low-dose cyclosporine or low-dose sirolimus or with standard-dose cyclosporine without induction. (ClinicalTrials.gov number, NCT00231764 [ClinicalTrials.gov].).
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4.
  • Meier-Kriesche, Herwig-Ulf, et al. (författare)
  • Uric Acid Levels Have No Significant Effect on Renal Function in Adult Renal Transplant Recipients: Evidence from the Symphony Study.
  • 2009
  • Ingår i: Clinical Journal of the American Society of Nephrology. - 1555-905X. ; 4, s. 1655-1660
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND AND OBJECTIVES: Uric acid (UA) has been linked to renal damage in experimental models of kidney failure. In humans, no definitive link between UA and renal function has been established, but several epidemiologic studies have suggested that higher UA levels are associated with accelerated loss of renal function, higher incidence of dialysis, and death. Many of the associations have been limited by the colinearity between UA levels and renal function. Renal transplantation is no exception, and limited information is available concerning the independent role of UA on progression of renal function in transplant recipients. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We investigated the association between UA and renal function progression during the first 3 yr after transplantation, adjusted for baseline renal function, in 1645 patients who were enrolled in the Symphony study. RESULTS: When corrected for baseline renal function, UA levels 1 mo after transplantation were not associated with 3-yr renal function (P = 0.62). There was a strong colinearity between calculated renal function and UA levels 1 mo after transplantation. In fact, when not corrected for baseline renal function, there was a significant association between UA and renal function at 3 yr (P = 0.005). CONCLUSIONS: Low renal function is associated with higher UA levels, but higher UA levels are not independently associated with progression of renal dysfunction after kidney transplantation.
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