Everolimus as primary immunosuppression in kidney transplantation: experience in conversion from calcineurin inhibitors

Transplantation. 2012 Feb 27;93(4):398-405. doi: 10.1097/TP.0b013e31823ffd0e.

Abstract

Background: We analyzed our clinical experience with everolimus (EVL) and identified prognostic factors for a successful conversion.

Methods: Retrospective study of 220 kidney recipients consecutively converted to EVL with calcineurin inhibitor elimination. We studied risk factors for proteinuria at 1 year after conversion, decline in renal function, and graft survival.

Results: Baseline creatinine clearance was 52.4±17.8 mL/min vs. 53.4±20.1 mL/min 1 year after conversion (P=0.150). Median proteinuria increased from 304 mg/day (interquartile range 160-507) to 458 mg/day (interquartile range 238-892; P<0.001). Risk factors for development of proteinuria ≥900 mg/day (P75) at 1-year postconversion were creatinine clearance less than 60 mL/min (odds ratio [OR] 3.37; 95% confidence interval [CI]: 1.15-9.89), serum triglycerides ≥150 mg/day (OR 4.35; 95% CI: 1.70-11.17), no treatment with prednisone (OR 3.04; 95% CI: 1.22-7.59), baseline proteinuria ≥550 mg/day (OR 10.37; 95% CI: 3.99-26.99), and conversion ≥3 years after transplant (OR 5.77; 95% CI: 1.89-17.59). An interaction was observed between baseline proteinuria and time to conversion: in patients with baseline proteinuria ≥550 mg/day, the risk of developing proteinuria ≥900 mg/day was 77.1% if they were converted after ≥3 years posttransplant. However, this risk was 29.8% in the subgroup converted before (P=0.02). Actuarial graft survival at 1 and 4 years postconversion was 98.2% and 86.5%, respectively. Baseline proteinuria ≥550 mg/day was a risk factor for graft loss in patients converted after the third year but not in patients converted before this time. EVL discontinuation rate was 24% in the first year postconversion.

Conclusions: Conversion to EVL and elimination of calcineurin inhibitors is safe. Success depends on not making late conversions and not converting patients with high baseline proteinuria.

MeSH terms

  • Adult
  • Aged
  • Calcineurin Inhibitors*
  • Cohort Studies
  • Enzyme Inhibitors / adverse effects
  • Enzyme Inhibitors / therapeutic use*
  • Everolimus
  • Female
  • Follow-Up Studies
  • Graft Rejection / epidemiology
  • Humans
  • Immunosuppressive Agents / adverse effects
  • Immunosuppressive Agents / therapeutic use*
  • Kidney Transplantation / immunology*
  • Kidney Transplantation / physiology*
  • Male
  • Middle Aged
  • Prognosis
  • Proteinuria / epidemiology
  • Renal Insufficiency / epidemiology
  • Retrospective Studies
  • Risk Factors
  • Sirolimus / adverse effects
  • Sirolimus / analogs & derivatives*
  • Sirolimus / therapeutic use
  • Treatment Outcome

Substances

  • Calcineurin Inhibitors
  • Enzyme Inhibitors
  • Immunosuppressive Agents
  • Everolimus
  • Sirolimus