title: Association of a change in immunosuppressive regimen with hemodynamic and inflammatory markers of cardiovascular disease after kidney transplantation.
abstract: BACKGROUND
  Although rejection rates and short-term graft survival have significantly improved in kidney transplantation with the introduction of calcineurin inhibitor (CNI), cardiovascular disease (CVD) and metabolic complications are being increasingly recognized as important causes of morbidity and mortality. We hypothesize that non-CNI proliferation signal inhibitor (PSI)-based immunosuppressive regimen is associated with improved arterial stiffness after kidney transplantation compared with CNI-based immunosuppressive regimens.
  
  
  METHODS
  This is a prospective, single-center study of renal transplant (RT) recipients comparing the metabolic, cardiovascular (pulse wave velocity and aortic augmentation index (AI) adjusted for heart rate (AI × 75)), inflammatory cytokines (interleukins (ILs) 6, 12, and 18) and graft-related outcomes at 3 and 15 months posttransplantation between RT recipients maintained on CNI- (CNI-CNI) or PSI-based (CNI-PSI) regimens including sirolimus and everolimus.
  
  
  RESULTS
  Fifty and 17 RT recipients maintained on CNI-CNI and CNI-PSI, respectively, were included in this study. Median time to PSI conversion from CNI was 5 months. Compared with CNI-CNI recipients, CNI-PSI recipients had significantly lower fasting blood glucose in nondiabetics (coefficient = -16.2; 95% confidence interval (CI) = -14.4 to -18.0; P < 0.01), lower IL-18 levels (coefficient = -229.16; 95% CI = -343.94 to -114.38; P < 0.01), and lower AI × 75 (coefficient = -5.14; 95% CI = -9.99 to -0.28; P = 0.04) at 15 months posttransplant in the multivariable models.
  
  
  CONCLUSIONS
  Our study suggests from the elimination of CNI for PSI may lower AIx75 and IL-18, both surrogate markers of CVD, but adequately powered, randomized, controlled studies are required to establish the causal relationship between immunosuppressive agents and CVD risk.
authors: Department of Renal Medicine, Sir Charles Gairdner Hospital, Perth, Australia.
authors: Kenneth
authors: K
authors: Yong
authors: Hung Do
authors: HD
authors: Nguyen
authors: Lawrence
authors: L
authors: Hii
authors: Doris T
authors: DT
authors: Chan
authors: Neil
authors: N
authors: Boudville
authors: Adriana
authors: A
authors: Messineo
authors: Ee Mun
authors: EM
authors: Lim
authors: Gursharan K
authors: GK
authors: Dogra
authors: Wai H
authors: WH
authors: Lim
mesh_terms: D015415:Biomarkers / Q000097:blood; D002318:Cardiovascular Diseases / Q000097:blood* / Q000209:etiology / Q000503:physiopathology; D016207:Cytokines / Q000097:blood*; D005260:Female; D005500:Follow-Up Studies; D005919:Glomerular Filtration Rate; D006084:Graft Rejection / Q000097:blood / Q000503:physiopathology / Q000517:prevention & control*; D006085:Graft Survival; D006439:Hemodynamics; D006801:Humans; D007165:Immunosuppression Therapy / Q000379:methods*; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D007676:Kidney Failure, Chronic / Q000601:surgery; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D016207:Cytokines; D007166:Immunosuppressive Agents
keywords: blood pressure; calcineurin inhibitor; everolimus; hypertension; interleukins; renal transplant; sirolimus; vascular function.