Reversibility of the Effects of Aliskiren in the Renal Versus Systemic Circulation

Abstract

SummaryBackground and objectives Renal hemodynamic effects of inhibitors of the renin-angiotensin system can increase the risk of acute kidney injury under certain conditions. The BP-lowering effects of the renin inhibitor aliskiren are sustained 3-4 weeks after withdrawal. In this study, the reversibility of the renal hemodynamic effects of aliskiren was tested. Design, setting, participants, & measurementsIn this open-label study, renal perfusion was measured by 1.5-T magnetic resonance imaging-arterial spin labeling in 34 subjects with arterial hypertension before aliskiren (prealiskiren), after 4 weeks of aliskiren treatment (300 mg), and 4-5 days (;2.5-3.03 plasma half-life) after withdrawal (post-aliskiren).Results Aliskiren reduced systolic BP from 152 6 14 to 139 6 16 mmHg (P,0.0001), which was sustained postaliskiren (136 6 13 mmHg, P=1.00 versus aliskiren). Aliskiren significantly altered renal perfusion (P=0.005), increasing from 272 6 25 pre-aliskiren to 287 6 29 ml/min per 100 g during aliskiren (P=0.03). This increase in renal perfusion was completely reversed post-aliskiren (272 6 26 ml/min per 100 g, P=0.03 versus aliskiren, P=0.63 versus pre-aliskiren). No changes were noted in urinary angiotensinogen levels. Plasma renin activity was reduced by aliskiren, which was sustained post-aliskiren. Angiotensin II and aldosterone were reduced by aliskiren but recovered post-aliskiren to pre-aliskiren levels.Conclusions After withdrawal of aliskiren, the effects on BP were sustained, whereas increase in renal perfusion was reversed, which was associated with recovery of angiotensin II and aldosterone to pretreatment levels. Renal hemodynamic effects are more readily reversible than systemic effects of aliskiren.

Vascular and Renal Hemodynamic Changes after Renal Denervation

“…Therefore, repeated measurements can be obtained without dye-related risks to the patient. Previously, we compared MRI-ASL with para-aminohippuric acid plasma clearance (the gold standard of renal perfusion measurements) and found a close relationship (r=0.58; P,0.001), indicating that this technique can approximate kidney perfusion (3,4).…”

Reproducibility of Kidney Perfusion Measurements With Arterial Spin Labeling at 1.5 Tesla MRI Combined With Semiautomatic Segmentation for Differential Cortical and Medullary Assessment

“… 21 Another study demonstrated a significant increase in renal perfusion quantified with ASL, using the renin inhibitor aliskiren. 39 The same group has shown that renal denervation performed in patients with drug-resistant hypertension does not appear to impact renal perfusion, again assessed with ASL. 40 These data suggest that ASL is a promising method for the assessment of renal hemodynamic changes during therapeutic interventions, without the need for more time-consuming methods, the administration of exogenous contrast agents or the use or ionizing radiation.…”

Non-Invasive Renal Perfusion Imaging Using Arterial Spin Labeling MRI: Challenges and Opportunities

“…The effects of a variety of drugs on renal perfusion have been assessed with ASL. For example, RBF has been shown to increase during aliskiren therapy and return to original levels after withdrawal of the drug [ 36 ]. Others include telmisartan [ 28 ], furosemide [ 37 ], losartan [ 53 ] and captopril [ 54 ].…”