Effect of Calcineurin Inhibitor-Free, Everolimus-Based Immunosuppressive Regimen on Albuminuria and Glomerular Filtration Rate After Heart Transplantation

Transplantation. 2017 Nov;101(11):2793-2800. doi: 10.1097/TP.0000000000001706.

Abstract

Background: Albuminuria in maintenance heart transplantation (HTx) is associated with poor renal response when switching to a calcineurin inhibitor (CNI)-lowered or CNI-free immunosuppressive regimen using everolimus (EVR), but the significance of albuminuria associated with EVR treatment after early CNI withdrawal in de novo HTx is unknown.

Methods: We tested if measured glomerular filtration rate (mGFR, by chrome-ethylenediaminetetraacetic acid clearance) was associated with urine albumin/creatinine ratio (UACR) post-HTx in a subgroup of patients included in the Scandinavian Heart Transplant Everolimus De Novo Study With Early Calcineurin Inhibitor Avoidance trial, where de novo HTx patients (n = 115) were randomized to EVR with complete CNI elimination 7 to 11 weeks post-HTx or standard CNI immunosuppression.

Results: In 66 patients, UACR measures were available at 1 year. In 7 patients in the EVR group, a CNI was reintroduced within 12 months. Median mGFR was significantly higher in the EVR group both 1 and 3 years post-HTx (P = 0.0004 and P = 0.03, respectively). Median UACR at 1 year was significantly higher in the EVR group (P = 0.002). There was no correlation between log(UACR) at 1 year and mGFR at 1 or 3 years (r = -0.01, P = 0.9 and r = 0.15, P = 0.26, respectively) and in the EVR group between log(UACR) at 1 year and change in mGFR (Δ1-3 years) (r = 0.27, P = 0.14). Excluding patients in the EVR group in whom a CNI was reintroduced did not significantly change the results.

Conclusions: The effects of EVR with early CNI withdrawal after HTx on albuminuria and renal function seem dissociated; hence, the clinical significance of albuminuria in this setting is uncertain and should not necessarily rule out EVR-based immunosuppression.

Trial registration: ClinicalTrials.gov NCT01266148.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Albuminuria / chemically induced*
  • Albuminuria / diagnosis
  • Albuminuria / physiopathology
  • Calcineurin Inhibitors / administration & dosage*
  • Calcineurin Inhibitors / adverse effects
  • Drug Administration Schedule
  • Drug Therapy, Combination
  • Everolimus / administration & dosage*
  • Everolimus / adverse effects
  • Female
  • Glomerular Filtration Rate / drug effects*
  • Heart Transplantation* / adverse effects
  • Humans
  • Immunosuppressive Agents / administration & dosage*
  • Immunosuppressive Agents / adverse effects
  • Kidney / drug effects*
  • Kidney / physiopathology
  • Male
  • Middle Aged
  • Prospective Studies
  • Scandinavian and Nordic Countries
  • Time Factors
  • Treatment Outcome

Substances

  • Calcineurin Inhibitors
  • Immunosuppressive Agents
  • Everolimus

Associated data

  • ClinicalTrials.gov/NCT01266148