title: Renal recovery after conversion to an everolimus-based immunosuppression in early and late heart transplant recipients: a 12-month analysis.
abstract: OBJECTIVE
  Calcineurin inhibitor-induced nephrotoxicity reduces long-term patient survival after heart transplant. Proliferation signal inhibitors, in combination with or replacing calcineurin inhibitors, may preserve or improve renal function. We evaluated the effect of calcineurin inhibitor-reduction and withdrawal in everolimus-based immunosuppression on renal function after a heart transplant.
  
  
  METHODS
  Twenty-four patients with creatinine clearance < 1 mL/s (60 mL/min) were switched from tacrolimus and mycophenolate mofetil to low-dose tacrolimus/everolimus if their heart transplant was ≤ 1 year ago (group 1, n=13) and to everolimus/mycophenolate mofetil if their heart transplant was > 1 year ago (group 2, n=11). Serum creatinine levels and calculated creatinine clearance were analyzed up to 12 months after conversion.
  
  
  RESULTS
  The switch in immunosuppression was associated with a significant decrease/increase of serum creatinine/creatinine clearance in both groups between baseline and month 12 (group 1, creatinine, 221.0 ± 70.7 to 159.1 ± 44.2 μmol/L (2.5 ± 0.8 to 1.8 ± 0.5 mg/dL); creatinine clearance, 0.75 ± 0.45 to 1.01 ± 0.50 mL/s (45.1 ± 26.7 to 60.5 ± 29.7 mL/min) (P < .01 each); group 2, creatinine, 247.5 ± 79.6 to 159.1 ± 44.2 μmol/L (2.8 ± 0.9 to 1.8 ± 0.5 mg/dL), creatinine clearance, 0.57 ± 0.23 to 0.93 ± 0.33 mL/s (34.1 ± 13.8 to 55.7 ± 19.6 mL/min) [P < .05 each]) with no significant group difference in the creatinine and the creatinine clearance levels after switching. No acute rejections or deaths occurred during the 12-month follow-up. Four patients (36.4%) from group 2 and 1 patient (7.7%) from group 1 discontinued everolimus because of adverse events.
  
  
  CONCLUSIONS
  Everolimus allows calcineurin inhibitor-reduction and withdrawal after a heart transplant, resulting in improved renal function. However, adverse effects are common and lead to a high reconversion rate.
authors.affiliation: Department of Cardiac Surgery, Klinikum Grosshadern, Ludwig Maximilians University, D-81377 Munich, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Michel
authors.forename: Amir Khosrow
authors.initials: AK
authors.lastname: Bigdeli
authors.forename: Christian
authors.initials: C
authors.lastname: Hagl
authors.forename: Bruno
authors.initials: B
authors.lastname: Meiser
authors.forename: Ingo
authors.initials: I
authors.lastname: Kaczmarek
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D003404:Creatinine / Q000097:blood; D057915:Drug Substitution; D004359:Drug Therapy, Combination; D000068338:Everolimus; D005260:Female; D006084:Graft Rejection / Q000276:immunology / Q000517:prevention & control; D006085:Graft Survival / Q000187:drug effects; D016027:Heart Transplantation / Q000009:adverse effects; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D007674:Kidney Diseases / Q000097:blood / Q000139:chemically induced* / Q000175:diagnosis / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D020127:Recovery of Function; D020123:Sirolimus / Q000031:analogs & derivatives* / Q000627:therapeutic use; D016559:Tacrolimus / Q000009:adverse effects / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D007166:Immunosuppressive Agents; D000068338:Everolimus; D003404:Creatinine; D009173:Mycophenolic Acid; D020123:Sirolimus; D016559:Tacrolimus