Angiotensin Receptor Blockade and Arterial Compliance in Chronic Kidney Disease: A Pilot Study

Abstract

Background: Almost 20 million people in the US have chronic kidney disease (CKD). Cardiovascular disease and arterial wall abnormalities are common in this population. Because angiotensin II may have adverse effects on the arterial wall, we hypothesized that an angiotensin receptor blocker (ARB) would improve arterial compliance as compared with placebo in subjects with CKD. Methods: We performed a double-blinded, placebo-controlled pilot study in which 25 subjects with stages 2 or 3 CKD and proteinuria <1 g were randomized to either the ARB, eprosartan, or placebo and titrated to achieve a goal blood pressure (BP) <130/85 mm Hg. Arterial compliance was measured at baseline and at 8 weeks. Results: Baseline characteristics were similar between the groups and included mean estimated glomerular filtration rate 63 ± 14 ml/min/1.73 m², heart rate 76 ± 10 beats/min, BP 142 ± 12/81 ± 8 mm Hg, 64% diabetic, 44% male, and 40% white, though subjects in the eprosartan group were younger (60 ± 12 vs. 70 ± 6 years, p = 0.01). There were no significant differences between the groups in large or small artery compliance measurements either at baseline or at 8 weeks, but there was a statistically significant improvement from baseline in small artery compliance in the eprosartan group (from median 2.5 ml/mm Hg × 100 [90% CI (1.1, 4.7)] to 4.0 ml/mm Hg × 100 [90% CI (1.9, 6.7)] (p = 0.01)) not seen in the placebo group. Conclusion: Use of an ARB to achieve recommended BP is associated with improved small artery compliance in people with CKD, though larger studies are needed to confirm these findings.

Mild Chronic Kidney Disease Associated with Greater Risk of Arterial Stiffness in Elderly Adults

“…One study using a long‐term angiotensin‐converting enzyme inhibitor with trandolapril revealed that control of the RAAS system reduced arterial stiffness independent of the effects of a reduction in blood pressure . In a double‐blind, placebo‐controlled pilot study that recruited subjects with Stage 2 or 3 CKD, use of angiotensin 2 receptor blockers was associated with better small artery compliance . Higher levels of CRP and inflammatory markers such as interleukin (IL)‐6, IL‐1, tumor necrosis factor alpha, and AGEs were found in malnourished individuals with CKD, and these play a role in the deterioration of renal function .…”

“…16 In a double-blind, placebo-controlled pilot study that recruited subjects with Stage 2 or 3 CKD, use of angiotensin 2 receptor blockers was associated with better small artery compliance. 17 Higher levels of CRP and inflammatory markers such as interleukin (IL)-6, IL-1, tumor necrosis factor alpha, and AGEs were found in malnourished individuals with CKD, and these play a role in the deterioration of renal function. 18 The inflammation-malnutrition-atherosclerosis paradigm has been proved in end-stage renal disease but is not completely established in mild CKD.…”

Differential effects of cyclosporine and tacrolimus on arterial function

“…In the section, we present cardiac index, which is cardiac output divided by body surface. The method has been used in studies on hemodialysis [16] and transplant patients before [6,12,17]. Three measurements were performed and the mean value was used for statistical evaluation.…”

Vascular compliance is secured under angiotensin inhibition in non-diabetic chronic kidney diseases

“…These findings are consistent with those of Asmar et al 35 that perindopril and indapamide were better than atenolol in normalizing arterial function in hypertensives, and have indicated that independent of blood pressure control, angiotensin inhibition attenuated arterial stiffness of not only elastic, but also muscular artery in non-diabetic CKDs. Garg et al 36 demonstrated that the administration of eprosartan for 8 weeks improved small but not large artery compliance in patients with stage 2-3 nondiabetic CKDs. In harmony, our results indicated that within 1 year angiotensin inhibition group exhibited lower baPWV than control group.…”