IF/TA may be delayed using ACEi- or ARB-type AHTs, which target the renin-angiotensin system (RAS), as well as by optimizing tacrolimus (TAC) exposure. The effect on IF/TA of combined RAS blockade and reduced-dose Advagraf^® (prolonged-release TAC) is unknown.

Multicenter prospective, open-label, controlled trial in adult de novo renal Tx patients (pts) randomized in a 2×2 design to ACEi/ARBs vs other (O) AHTs (Mo 1–24) and to low TAC (LOW; target trough [C₀] 5±1 ng/mL to Mo 6) vs standard TAC (STD; target C₀ declining from 12±2 to 8±2 ng/mL by Mo 6). All pts received basiliximab, MMF and steroids. TAC target after Mo 6 was by physician choice. Co-primary endpoints were IF/TA score (Banff ci+ct) ≥2 at Mo 6 (LOW vs STD TAC) and at Mo 24 (ACEi/ARB vs OAHT). Follow-up of secondary outcomes is planned at Yr 5 post-Tx.

Previously reported 6-Mo comparisons between STD and LOW pts showed different mean C₀ but no difference in incidence of IF/TA≥2. C₀ levels numerically converged by Mo 13–24 (Mean [SD]; LOW: 5.94 [1.266]; STD: 6.34 [1.093] ng/mL). Median time on ACEi/ARBs was 22.2 Mo vs 0.0 Mo for ACEi/ARB and OAHT pts, respectively. Of 281 ITT pts, 163 provided adequate biopsy samples at baseline and Mo 24.Of these, 55% of ACEi/ARB and 58% of OAHT pts had IF/TA≥2 at Mo 24 (P=NS). Mean [SD] IF/TA change from Mo 6–24 was similar in ACEi/ARB vs OAHT pts (+0.56 [1.431] vs +0.91 [1.675], respectively; P=NS) but lower in LOW vs STD TAC pts (+0.42 [1.477] vs +1.10 [1.577]; P=0.0123). Of the 4 treatment groups, progression was lowest in LOW + ACEi/ARB (Figure 1). There were 3 deaths and 11 cases of graft loss overall. BK viremia was most prevalent in the first 6 Mo and in the STD TAC arm.

Incidence of IF/TA≥2 was similar at Mo 6 for LOW vs STD TAC and at Mo 24 for ACEi/ARB vs OAHT. In pts on LOW TAC, RAS-blocking AHTs appeared to reduce IF/TA progression.

Post-Tx IF/TA Change (6-24 Mo)

CITATION INFORMATION: Cockfield S, Rush D, Wilson S, Howell J, FKC-014 Study Group Impact of Antihypertensive (AHT) Choice and Advagraf^® Dose on Interstitial Fibrosis/Tubular Atrophy (IF/TA) and IF/TA Progression in Renal Allografts 24 Months Post-Transplantation (Tx). Am J Transplant. 2017;17 (suppl 3).

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