Comparison of the effects of standard vs low‐dose prolonged‐release tacrolimus with or without ACEi/ARB on the histology and function of renal allografts Academic Article uri icon

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abstract

  • Targeting the renin-angiotensin system and optimizing tacrolimus exposure are both postulated to improve outcomes in renal transplant recipients (RTRs) by preventing interstitial fibrosis/tubular atrophy (IF/TA). In this multicenter, prospective, open-label controlled trial, adult de novo RTRs were randomized in a 2 × 2 design to low- vs standard-dose (LOW vs STD) prolonged-release tacrolimus and to angiotensin-converting enzyme inhibitors/angiotensin II receptor 1 blockers (ACEi/ARBs) vs other antihypertensive therapy (OAHT). There were 2 coprimary endpoints: the prevalence of IF/TA at month 6 and at month 24. IF/TA prevalence was similar for LOW vs STD tacrolimus at month 6 (36.8% vs 39.5%; P = .80) and ACEi/ARBs vs OAHT at month 24 (54.8% vs 58.2%; P = .33). IF/TA progression decreased significantly with LOW vs STD tacrolimus at month 24 (mean [SD] change, +0.42 [1.477] vs +1.10 [1.577]; P = .0039). Across the 4 treatment groups, LOW + ACEi/ARB patients exhibited the lowest mean IF/TA change and, compared with LOW + OAHT patients, experienced significantly delayed time to first T cell-mediated rejection. Renal function was stable from month 1 to month 24 in all treatment groups. No unexpected safety findings were detected. Coupled with LOW tacrolimus dosing, ACEi/ARBs appear to reduce IF/TA progression and delay rejection relative to reduced tacrolimus exposure without renin-angiotensin system blockade. ClinicalTrials.gov identifier: NCT00933231.

authors

  • Cockfield, Sandra M
  • Wilson, Sam
  • Campbell, Patricia M
  • Cantarovich, Marcelo
  • Gangji, Azim
  • Houde, Isabelle
  • Jevnikar, Anthony M
  • Keough‐Ryan, Tammy M
  • Monroy‐Cuadros, Felix‐Mauricio
  • Nickerson, Peter W
  • Pâquet, Michel R
  • Ramesh Prasad, GV
  • Senécal, Lynne
  • Shoker, Ahmed
  • Wolff, Jean‐Luc
  • Howell, John
  • Schwartz, Jason J
  • Rush, David N

publication date

  • June 2019

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