Long-term Impact of Antihypertensive Treatment and Tacrolimus Dose in Renal Allograft Recipients 5 Years Post-Transplantation

D. Rush¹, S. Cockfield², S. Wilson³, J. Schwartz⁴

¹University of Manitoba, Winnipeg, MB, Canada, ²University of Alberta Hopspital, Edmonton, AB, Canada, ³Astellas Pharma Global Development, Northbrook, IL, ⁴Astellas Pharma US, Northbrook, IL

Meeting: 2019 American Transplant Congress

Abstract number: C207

Keywords: Biopsy, Fibrosis, Graft survival

Session Information

Session Name: Poster Session C: Kidney: Cardiovascular and Metabolic

Session Type: Poster Session

Date: Monday, June 3, 2019

Session Time: 6:00pm-7:00pm

Presentation Time: 6:00pm-7:00pm

Location: Hall C & D

*Purpose: Inflammation and fibrosis after renal transplantation may be modulated by optimizing tacrolimus exposure, or by use of angiotensin-converting enzyme inhibitors (ACEi), or angiotensin receptor blocker (ARB)-type antihypertensive treatment (AHT).

*Methods: We present 5-year post-transplantation data from a multicenter, prospective, open-label, controlled trial in 281 adult de novo kidney transplant recipients. Participants were randomized in a 2×2 design to receive either standard (STD; target trough 12±2 ng/mL to 8±2ng/mL until month 6) or low (LOW; target trough 5±1 ng/mL until month 6) dose tacrolimus combined with ACEi/ARB vs other AHT (OAHT). Mean tacrolimus levels converged after 19 months and remained similar thereafter. All patients received basiliximab, mycophenolate mofetil, and steroids. Patients in the LOW+OAHT group had a significantly shorter time to T-cell mediated rejection (TCMR) than those in the LOW+ACEi/ARB group (p=0.014). On protocol biopsy at 24 months, patients in the LOW+ACEi/ARB group had less interstitial fibrosis and tubular atrophy (IFTA) and less IFTA + inflammation than did patients in the LOW+OAHT group (p<0.05).

*Results: At 5 years, 208 patients (74%) remained in the study. Patient survival was 95.7% and was comparable across all treatment groups. Overall graft survival was 94.3%; and was 94.4% with LOW+ACEi/ARB, 89.7% with LOW+OAHT, 95.8% with STD+ACEi/ARB, and 97.1% with STD+OAHT. Serum creatinine, estimated glomerular filtration rate, and urine protein:creatinine ratios were similar across all treatment groups, with a trend towards lower urine protein:creatinine ratios in patients receiving an ACEi/ARB over the 5-year follow-up. Donor-specific antibody development was higher in the LOW+OAHT group (17.6%) than in the LOW+ACEi/ARB (9.9%), STD+OAHT (7.2%), or STD+ACEi/ARB (5.6%) treatment groups. By year 4, about 30-40% of patients randomized to OAHT had been switched to ACEi/ARB by their physician.

*Conclusions: Descriptive analyses at 5 years showed lower rates of graft survival and higher levels of donor-specific antibody in patients treated with low versus standard dose tacrolimus. However, ACEi/ARB treatment appeared to improve renal allograft outcomes in patients receiving low dose tacrolimus.

To cite this abstract in AMA style:

Rush D, Cockfield S, Wilson S, Schwartz J. Long-term Impact of Antihypertensive Treatment and Tacrolimus Dose in Renal Allograft Recipients 5 Years Post-Transplantation [abstract]. Am J Transplant. 2019; 19 (suppl 3). https://atcmeetingabstracts.com/abstract/long-term-impact-of-antihypertensive-treatment-and-tacrolimus-dose-in-renal-allograft-recipients-5-years-post-transplantation/. Accessed November 24, 2024.

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