Abstract
Objective:We aimed at assessing the molecular adaptation of the renin-angiotensin system (RAS) after successful kidney transplantation (KTX).Materials and methods:In this prospective, exploratory study we analyzed 12 hemodialysis (HD) patients, who received a KTX and had excellent graft function six to 12 months thereafter. The concentrations of plasma Angiotensin (Ang) peptides (Ang I, Ang II, Ang-(1–7), Ang-(1–5), Ang-(2–8), Ang-(3–8)) were simultaneously quantified with a novel mass spectrometry-based method. Further, renin and aldosterone concentrations were determined by standard immunoassays.Results:Ang values showed a strong inter-individual variability among HD patients. Yet, despite a continued broad dispersion of Ang values after KTX, a substantial improvement of the renin/Ang II correlation was observed in patients without RAS blockade or on angiotensin receptor blocker (HD: renin/Ang II R2 = 0.660, KTX: renin/Ang II R2 = 0.918). Ang-(1–7) representing the alternative RAS axis was only marginally detectable both on HD and after KTX.Conclusions:Following KTX, renin-dependent Ang II formation adapts in non-ACE inhibitor-treated patients. Thus, a largely normal RAS regulation is reconstituted after successful KTX. However, individual Ang concentration variations and a lack of potentially beneficial alternative peptides after KTX call for individualized treatment. The long-term post-transplant RAS regulation remains to be determined.
Highlights
Therapeutic blockade of the renin-angiotensin system (RAS) with either angiotensin-converting enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARB) has proven safety and effectiveness in chronic kidney disease (CKD) patients
Underlying renal diseases were heterogeneous: One patient had diabetic nephropathy, another was affected by vascular nephropathy, one had polycystic kidney disease, two had glomerular disease and seven patients had atrophic kidneys without known causes
Two patients suffered from diabetes mellitus while on hemodialysis; both remained on oral antidiabetic medication after KTX
Summary
Therapeutic blockade of the renin-angiotensin system (RAS) with either angiotensin-converting enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARB) has proven safety and effectiveness in chronic kidney disease (CKD) patients. Despite their widespread prescription, RAS blockers remain controversial in hemodialysis (HD) patients and kidney transplant (KTX) recipients.. Being responsible for the secretion of renin, the rate-limiting enzyme of the RAS, this organ is the central mediator of angiotensin II (Ang II) generation representing the “classical” RAS axis as well as formation of Ang-(1–7) as the central mediator of the “alternative” RAS axis that opposes the biological effects of Ang II..
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