Aim:Progression of chronic kidney disease (CKD) may be accelerated by tissue hypoxia due to impaired blood supply. This could be induced by small artery narrowing resulting in abnormally high intrarenal vascular resistance (RVR). We investigated whether a reduction in RVR achieved by adding vasodilating medical therapy (AVT) is superior to adding nonvasodilating medical therapy (AnonVT) regarding tissue oxygenation and preservation of kidney function.Methods:Eighty-three grade 3 and 4 CKD patients [estimated glomerular filtration rate (GFR) 34.6ml/min per 1.73m 2] were randomized to either AVT with amlodipine and/or renin angiotensin blockade or AnonVT with the nonvasodilating beta-blocker metoprolol. Investigations were performed at baseline and after 18 months of therapy. Systemic vasodilation was documented in the forearm vasculature using resting venous occlusion plethysmography. GFR was measured as 51Chrome-EDTA plasma clearance. Using MRI, renal artery blood flow was measured for calculation of RVR and for estimating renal oxygenation (R 2∗).Results:AVT and AnonVT achieved as planned similar blood pressure levels throughout the study. At follow-up, resistance had decreased by 7% (P<0.05) and RVR by 12% (P<0.05) in the AVT group, whereas in the AnonVT group, resistance increased by 39% (P<0.01), whereas RVR remained unchanged. At follow-up, no significant differences in cortical or medullary R 2∗ values between AVT and AnonVT were observed, and the GFR decline was similar in the two groups (3.0 vs. 3.3ml/min per 1.73m 2).Conclusion:Long-term intensified vasodilation treatment reduced peripheral and RVR, but this was not associated with improvement of R 2∗ or protection against loss of kidney function in CKD patients.