Renal oxygen content is increased in healthy subjects after angiotensin-converting enzyme inhibition

Abstract

OBJECTIVE:The association between renal hypoxia and the development of renal injury is well established. However, no adequate method currently exists to non-invasively measure functional changes in renal oxygenation in normal and injured patients.METHOD:R2* quantification was performed using renal blood oxygen level-dependent properties. Five healthy normotensive women (50±5.3 years) underwent magnetic resonance imaging in a 1.5T Signa Excite HDx scanner (GE Healthcare, Waukesha, WI). A multiple fast gradient-echo sequence was used to acquire R2*/T2* images (sixteen echoes from 2.1 ms/slice to 49.6 ms/slice in a single breath hold per location). The images were post-processed to generate R2* maps for quantification. Data were recorded before and at 30 minutes after the oral administration of an angiotensin II-converting enzyme inhibitor (captopril, 25 mg). The results were compared using an ANOVA for repeated measurements (mean ± standard deviation) followed by the Tukey test. ClinicalTrials.gov: NCT01545479.RESULTS:A significant difference (p<0.001) in renal oxygenation (R2*) was observed in the cortex and medulla before and after captopril administration: right kidney, cortex = 11.08±0.56ms, medulla = 17.21±1.47ms and cortex = 10.30±0.44ms, medulla = 16.06±1.74ms, respectively; and left kidney, cortex = 11.79±1.85ms, medulla = 17.03±0.88ms and cortex = 10.89±0.91ms, medulla = 16.43±1.49ms, respectively.CONCLUSIONS:This result suggests that the technique efficiently measured alterations in renal blood oxygenation after angiotensin II-converting enzyme inhibition and that it may provide a new strategy for identifying the early stages of renal disease and perhaps new therapeutic targets.

Inhibition of the Renin‐Angiotensin System Affects Kidney Tissue Oxygenation Evaluated by Magnetic Resonance Imaging in Patients With Chronic Kidney Disease

“…This study confirms the existing experimental evidence of the contribution of Ang II to kidney oxygenation. However, the study by Stein and colleagues measured an alteration in renal blood oxygenation in healthy volunteers after oral administration of RAS inhibitors.…”

Magnetic Resonance Imaging–Derived Renal Oxygenation and Perfusion During Continuous, Steady‐State Angiotensin‐II Infusion in Healthy Humans

“…This effect was predominantly present in the renal medulla . In a similar study in healthy subjects, angiotensin‐converting enzyme inhibition increased oxygenation in both cortex and medulla . However, none of these studies were able to relate BOLD measures of kidney oxygenation among CKD patients to kidney function .…”

“…7,8 In a similar study in healthy subjects, angiotensinconverting enzyme inhibition increased oxygenation in both cortex and medulla. 9 However, none of these studies were able to relate BOLD measures of kidney oxygenation among CKD patients to kidney function. 10,11 This implies that either the hypothesis on the role of hypoxia in the progression of CKD in humans is not correct, or the interpretation of the kidney BOLD signal should be revised.…”

Renal Function and Fluid Homeostasis

“…It is well established that early in course of renal disease, many areas of the kidney become hypoxic and the main defense mechanisms against hypoxia become impaired [ 206 , 207 ]. A recent fi nding that ACE inhibition improves renal cortical and medullary oxygen content in health humans [ 208 ] needs to be tested formally in those with renal disease at high altitude, many of whom particularly with proteinuria may already be on these drugs. These considerations would suggest that patients with chronic kidney injury might have more rapid decline in renal function living at higher altitudes [ 206 , 209 ] simply as a result of a reduction in blood oxygen content or driving gradient for O 2 diffusion.…”