title: Late calcineurin inhibitor withdrawal prevents progressive left ventricular diastolic dysfunction in renal transplant recipients.
abstract: BACKGROUND
  Calcineurin inhibitor (CNI)-based therapy is associated with adverse cardiovascular effects. We examined the effects of late CNI or mycophenolate mofetil (MMF) withdrawal on echocardiographic parameters.
  
  
  METHODS
  This study was conducted as a substudy of a randomized trial in stable renal transplant recipients who were on a triple CNI-based regimen with prednisone and MMF that evaluated late concentration-controlled withdrawal of CNI or MMF on renal function. A total of 108 patients (age, 52.3±11.5 years; 67% male; at a median of 2.0 years post-transplantation, (interquartile range 1.3-3.3 years); estimated glomerular filtration rate, 57±16 mL/min/1.73 m; 66% on cyclosporine and 34% on tacrolimus) entered the cardiovascular substudy examining echocardiographic parameters at baseline and 2 years after randomization. In all patients, traditional cardiovascular risk factors were treated according to predefined targets.
  
  
  RESULTS
  Late CNI withdrawal prevented progressive development of left ventricular (LV) diastolic dysfunction, as assessed by markers of LV diastolic function (mitral deceleration time and mitral annular e' velocity). Conversely, in the MMF-withdrawal group, the left atrial volume index (an indicator of chronic LV diastolic dysfunction) was significantly increased at 2 years (from 24.1±6.7 to 27.0±7.0 mL/m, P<0.05). In addition, CNI withdrawal resulted in a higher proportion of patients achieving the predefined blood pressure targets (<130/85 mm Hg: 41.5% vs. 12.7%, P=0.001) at 2 years while requiring less antihypertensive drugs. Changes in the left atrial volume index were significantly associated with treatment arm (P=0.03) and changes in systolic (P=0.005) and diastolic (P=0.005) blood pressure.
  
  
  CONCLUSIONS
  Late CNI withdrawal, from a triple-drug regimen in stable renal transplant recipients, prevented progressive deterioration of LV diastolic function and facilitated better blood pressure control.
authors.affiliation: Department of Nephrology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Jacqueline S
authors.initials: JS
authors.lastname: Mourer
authors.forename: See Hooi
authors.initials: SH
authors.lastname: Ewe
authors.forename: Marko J K
authors.initials: MJ
authors.lastname: Mallat
authors.forename: Arnold C T
authors.initials: AC
authors.lastname: Ng
authors.forename: Ton J
authors.initials: TJ
authors.lastname: Rabelink
authors.forename: Jeroen J
authors.initials: JJ
authors.lastname: Bax
authors.forename: Victoria
authors.initials: V
authors.lastname: Delgado
authors.forename: Johan W
authors.initials: JW
authors.lastname: de Fijter
mesh_terms: D000328:Adult; D000959:Antihypertensive Agents / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects; D065095:Calcineurin Inhibitors; D016009:Chi-Square Distribution; D016572:Cyclosporine / Q000008:administration & dosage*; D003971:Diastole / Q000187:drug effects*; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D018619:Echocardiography, Doppler, Pulsed; D005260:Female; D006325:Heart Atria / Q000187:drug effects / Q000503:physiopathology; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D016030:Kidney Transplantation / Q000009:adverse effects / Q000276:immunology; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D008943:Mitral Valve / Q000187:drug effects / Q000503:physiopathology; D009173:Mycophenolic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives; D009426:Netherlands; D011237:Predictive Value of Tests; D011241:Prednisone / Q000008:administration & dosage; D011446:Prospective Studies; D016559:Tacrolimus / Q000008:administration & dosage*; D013997:Time Factors; D016896:Treatment Outcome; D018487:Ventricular Dysfunction, Left / Q000000981:diagnostic imaging / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D016277:Ventricular Function, Left / Q000187:drug effects*
chemical_list: D000959:Antihypertensive Agents; D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D009173:Mycophenolic Acid; D011241:Prednisone; D016559:Tacrolimus