Effects of late cyclosporine withdrawal on renal graft function and survival

J Nephrol. 2019 Apr;32(2):315-321. doi: 10.1007/s40620-018-0554-7. Epub 2018 Nov 15.

Abstract

Objective: Attempts to discontinue calcineurin inhibitors (CNIs) early after renal transplantation without conversion to an alternative immunosuppressive have failed due to high rates of acute rejection. Data on "late" CNI withdrawal are lacking so far.

Design and method: We carried out a matched case-control study on the effects of CNI withdrawal on graft loss and mortality in 90 patients (1500 screened) with advanced graft dysfunction (serum creatinine > 3.5 mg/dl) and a cyclosporine-based triple immunosuppressive regimen at the Charité University Hospital, Berlin.

Results: Cyclosporine was withdrawn at a mean of 54.0 ± 32.8 months post-transplant in 45 subjects. Whereas estimated glomerular filtration rate (eGFR) did not significantly differ between the groups at this time (12.4 ± 2.7 vs. 14.7 ± 8.9 in the control group, p = 0.08), it was significantly higher in subjects undergoing withdrawal after 120 months (Δ 4.1 ml/min; p < 0.001). In a Cox regression analysis adjusted for age, gender and eGFR, patients with CNI withdrawal showed better survival rates for the combined endpoint death/graft loss (hazard ratio, HR [95% confidence interval]: 0.19 [0.12-0.33], p = 0.001) compared to matched controls. The survival benefit was significant for the endpoints death (p = 0.01) and graft loss (p = 0.001).

Conclusions: CNI withdrawal was associated with improved survival rates in patients with advanced graft dysfunction in this retrospective analysis.

Keywords: Cyclosporine; Graft loss; Graft survival; Kidney transplantation; Mortality.

MeSH terms

  • Adult
  • Calcineurin Inhibitors / administration & dosage*
  • Calcineurin Inhibitors / adverse effects
  • Cyclosporine / administration & dosage*
  • Cyclosporine / adverse effects
  • Drug Administration Schedule
  • Female
  • Germany
  • Graft Rejection / diagnosis
  • Graft Rejection / immunology
  • Graft Rejection / mortality
  • Graft Rejection / prevention & control*
  • Graft Survival / drug effects*
  • Humans
  • Immunosuppressive Agents / administration & dosage*
  • Immunosuppressive Agents / adverse effects
  • Kidney Transplantation* / adverse effects
  • Kidney Transplantation* / mortality
  • Male
  • Middle Aged
  • Retrospective Studies
  • Risk Assessment
  • Risk Factors
  • Time Factors
  • Treatment Outcome

Substances

  • Calcineurin Inhibitors
  • Immunosuppressive Agents
  • Cyclosporine