A Five-Year Prospective, Randomized, Open-Label Study of Standard-Dose Versus Low-Dose Prolonged-Release Tacrolimus With or Without Angiotensin-Converting Enzyme Inhibitor or Angiotensin II Receptor Blocker Post Kidney Transplantation.
Campbell, P. M., et al.Clinical Transplantation 2025; 39(1): e70067
Aims
This aim of this study was to report the 5-year results of a randomised controlled trial comparing standard-dose with low-dose prolonged-release tacrolimus (TAC) combined with either angiotensin-converting enzyme inhibitor (ACEi)/ angiotensin II receptor blocker (ARB) or other antihypertensive therapy (OAHT) following kidney transplantation.
Interventions
Participants were randomised to either low-dose or standard-dose prolonged-release TAC combined with either ACEi/ARB or OAHT.
Participants
281 adult (≥18 years) kidney transplant recipients.
Outcomes
The main outcomes of interest were patient survival, graft survival, biopsy-proven acute rejection, de novo donor-specific antibodies (dnDSA), graft function, blood pressure, haemoglobin levels and treatment-emergent adverse events.
Follow-up
5 years
CET Conclusions
Blockade of the renin-angiotensin system (RAS) with angiotensin converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB) has been shown to have anti-fibrotic and immunomodulation affects. The authors of this study theorised that this effect could be used to reduce the exposure to tacrolimus in patients following kidney transplantation and conducted a randomized trial to compare low dose tacrolimus combined with ACEI/ARB to standard therapy. The initial analysis showed decreased interstitial fibrosis at 24 months. The current study reports patient and graft outcomes at 5 years. 208 of the original 281 enrolled patients remained in the study for the 5-year follow up period. Patient and graft survival was similar between the groups. Rates of rejection and the development of donor specific antibodies were numerically higher in the low-tacrolimus group, but this difference was not statistically significant. The authors argue that these results support the use of ACEI/ARB to facilitate tacrolimus dose reduction. However, tacrolimus reduction was only reliably controlled for the first month of the trail. Thereafter, tacrolimus trough levels between the two groups gradually equalised. Furthermore, ACEI/ARBs were initiated in up to 40% of patients in the standard group, as part of antihypertensive therapy. These protocol violations resulted in test and control groups that received similar treatment regimens for the majority of the study period, rendering the study and its findings largely invalid.
Data analysis
Per protocol analysis
Trial registration
ClinicalTrials.gov - NCT00933231