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

Abstract

Imaging of the kidney using blood oxygen level dependent (BOLD) magnetic resonance imaging (MRI) presents a major opportunity to examine differences in tissue oxygenation within the cortex and medulla applicable to human disease. The aim of this study was to evaluate BOLD signals before and after treatment with RAS inhibitors in hypertensive chronic kidney disease (CKD) patients. Ten patients with stable CKD and 5 healthy volunteers were included. Five CKD patients were subjected to BOLD MRI scan before and after chronic treatment with 300 mg/day aliskiren for at least 6 weeks. Five other CKD patients received BOLD MRI before and 1 hour after acute treatment with 50 mg captopril. A group of healthy volunteers (n=5) was scanned before and 1 hour after acute treatment with 50 mg captopril. The 10 patients had a mean age of 61±17 years; eGFR of 30±11 mL/min per 1.73 m2. Office systolic and diastolic blood pressures when on a RAS inhibito, were 130±10 and 86±5 mmHg in CKD patients. Control subjects had normal kidney function and were not on any medication. In untreated condition, systolic and diastolic arterial blood pressure elevated, 145±6 and 95±4 mmHg, respectively. After chronic treatment with aliskiren, arterial blood pressure decreased in all patients in this group, 127±3 mmHg and 77±3 mmHg. After acute treatment with captopril arterial blood pressure reduced to 125±4 and 71±8 mmHg. Tissue intensity signal (T2*) was increased in medulla after chronic treatment from 29±6 to 34±6 and after acute treatment with captopril from 34±9 to 38±11 in CKD patients. In addition, T2* ratio between cortex and medulla decreased in CKD patients after chronic treatment and acute treatment. This ratio remained stable in healthy volunteers before and after treatment with captopril 1.62±0.1 and 1.65±0.1, respectively. This study shows for the first time that RAS inhibitors change BOLD signal in CKD patients. Importantly, in healthy volunteers, a RAS inhibitor had no such effect. Further investigation is required.

Comparative Effect of a Renin Inhibitor and a Thiazide Diuretic on Renal Tissue Oxygenation in Hypertensive Patients

“…In hypertensive patients with renal impairment, acute administration of olmesartan has been reported to increase tissue oxygenation, an effect which was not found in healthy controls [25]. Similar acute changes in renal oxygenation were reported on small group of patients receiving captopril or losartan [26,27]. The consumption of oxygen by the kidney is linked predominantly to the reabsorption of sodium [28,29].…”

“…Indeed, contrasting results have been published so far regarding the effect of RAS blockers on renal tissue oxygen utilization. In humans, an acute administration of captopril has been reported to significantly change cortical/medullary T2* ratio in 5 patients with renal diseases but not in 5 healthy volunteers [26]. In another small group of 9 healthy subjects, Djamali et al found an increase in cortical oxygenation after an acute administration of losartan [27].…”

Blood oxygenation level-dependent MRI for assessment of renal oxygenation

“…37 In diuretic-treated subjects with CKD (n=5), no significant change in oxygenation of the renal cortex or medulla was observed after chronic treatment with a direct renin inhibitor or after acute administration of an angiotensin-converting enzyme inhibitor. 38 The authors underscored the observation that the T2* cortex to medulla ratio fell in the CKD subjects, but not in healthy volunteers; however, the significance of this observation may be questioned. 5 Perhaps these inconsistent results reflect different responses to acute versus chronic interruption of the renin/ angiotensin system.…”

“…37 In another group of healthy subjects (n=5), no change in oxygenation of the renal cortex or medulla was observed after chronic treatment with a direct renin inhibitor or after acute administration of an angiotensin-converting enzyme inhibitor. 38 Similarly, no change in cortical oxygenation was observed after acute administration of an angiotensin receptor antagonist in healthy subjects. 39 Pruijm et al 26 found no change in renal tissue oxygenation by BOLD MRI after chronic administration of an angiotensin-converting enzyme inhibitor or an angiotensin receptor blockade in type 2 diabetics (n=12) with proteinuria and mild-moderate renal functional impairment.…”

“…In contrast, Djamali et al 37 utilized BOLD MRI to demonstrate increased oxygenation in the renal medulla and cortex of subjects with CKD due to chronic allograft nephropathy. To add to this confusion, both Siddiqi et al 38 and Khatir et al 17 found no difference in renal cortical or medullary oxygenation in subjects with CKD (n=10 and n=11, respectively) versus healthy controls.…”