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Angiotensin-converting Enzyme Inhibitor Radionuclide Renogram � ANon-invasive Tool to Suspect Renovascular Hypertension
  JOHTN
REVIEW ARTICLE
Angiotensin-converting Enzyme Inhibitor Radionuclide Renogram - A
Non-invasive Tool to Suspect Renovascular Hypertension
Sampath Santhosh, Prabhu Ethiraj, J. Jonathan Solomon, Rajalakshmi Rajasekar
Department of Nuclear Imaging and Molecular Medicine, Institute of Nuclear Imaging and Molecular Medicine, Tamil Nadu Government Multi Super SpecialityHospital, Chennai, Tamil Nadu, India
Address for correspondence: Dr. Sampath Santhosh, Institute of Nuclear Imaging and Molecular Medicine, Tamil Nadu Government Multi Super Speciality Hospital,Omandurar Government Estate, Anna Salai, Chennai - 600 002, Tamil Nadu, India.
Tel: +91-9444624467.
E-mail: santhosh610@yahoo.com
Received: 21-05-2018; Accepted: 12-12-2018
doi: 10.15713/ins.johtn.0144
 
ABSTRACT
Renal hypoperfusion due to renal artery stenosis (RAS) activates the renin-angiotensin-aldosterone system, leading to an elevatedblood pressure (BP) that constitutes renovascular hypertension (RVH). Differentiation between RVH and RAS is essentialbecause RAS is quiet in many non-hypertensive elderly persons. Furthermore, RAS is an associated but non-causative finding in anumber of hypertensive patients. Angiotensin-converting enzyme inhibitors (ACEIs) renogram helps to detect RAS as the causeof hypertension and predicts curability or improvement in hypertension after intervention. ACEI renogram is most cost effective ifused primarily in patients with moderate-to-high risk of RVH that includes abrupt or severe hypertension, hypertension resistant tothree-drug therapy, bruits in the abdomen or flank, unexplained azotemia or recurrent pulmonary edema in an elderly hypertensivepatient, or worsening renal function during therapy with ACEIs. In this report, we describe how ACEI renogram helped in themanagement of a patient with refractory hypertension due to RAS.
Keywords: ACE inhibitor, renogram, DTPA, renal artery stenosis, renovascular hypertension
How to cite this article: Santhosh S, Ethiraj P, Solomon JJ,Rajasekar R. Angiotensin-converting Enzyme InhibitorRadionuclide Renogram - A Non-invasive Tool to SuspectRenovascular Hypertension. Hypertens 2019;5(1): 17-20.
Source of support: Nil
Conflict of interest: None
 
 

Introduction

A 42-year-old male who is a known smoker and alcoholicpresented to the vascular surgery department with complaintsof gripping pain in both lower limbs over the past 6 months.He is undergoing treatment for refractory hypertension (BP200/130 mmHg) despite optimum medication comprisingcalcium channel blocker, beta-blocker, and diuretics over6 years. His serum creatinine was 1.6 mg/dl while the bloodsugar, electrolytes, cholesterol, and liver function tests werewithin normal limits. He is also being treated for chronic kidneydisease (CKD) (estimated glomerular filtration rate [eGFR] =27 ml/min/1.73m2 at diagnosis) and possible bilateral renal arterystenosis (RAS) was considered. Contrast-enhanced computedtomography showed complete occlusion of the right renal arterywith contracted right kidney and 70-80% occlusion at the originof the left renal artery [Figure 1a and b]. Pan angiogram showeda significant peripheral vascular disease of both iliac arteries whilethe subclavian, carotid, and upper limb vessels were normal. Hewas treated for one episode of flash pulmonary edema 9 monthsago. At that time, his echocardiography showed concentric LVHand global LVEF of 58%. There was no regional wall motionabnormality. ECG showed ST depression in II, III, and aVF, andtherefore, he was started on statins also, along with aspirin. At thetime of referral to our institution, his global LVEF was 43%.

 
We received him in our department to study the functionalsignificance of RAS with 99mTechnetium-DTPA renogramwith angiotensin-converting enzyme inhibitors (ACEIs). Thepatient was prepared as per the Society of Nuclear Medicine andMolecular Imaging guidelines for baseline and ACEI renogram(2 days protocol).[1] He was allowed to continue his medicationduring the study period. On day 1, baseline renogram wasperformed by giving intravenous injection of 100 MBq of99mTc-DTPA in 1.0 ml saline through an intravenous cannula.Sequential dynamic and periodic static images of the abdomenwere acquired in posterior view (patient in supine position)using a dual-headed gamma camera (GE-Discovery NM 670,USA). Similar study was repeated the next day 1 h after oraladministration of 10 mg Enalapril. Blood pressure (BP) inthe right upper limb was continuously monitored with thepatient in supine position and was found to maintain around200/130 mmHg. There was no change in BP 1 h after enalapriladministration.

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Santhosh, et al. ACE inhibitor renogram for RVH

Angiotensin-converting Enzyme Inhibitor Radionuclide Renogram � ANon-invasive Tool to Suspect Renovascular Hypertension
Figure 1: Coronal section of contrast-enhanced computedtomography KUB showing smaller right kidney (a). Digitalsubtraction angiogram showing narrowing at the origin of the leftrenal artery with post-stenotic dilatation and complete occlusionwith non-visualization of the right renal artery (b)

 
The left kidney showed adequate cortical function with timelytracer transit into pelvis and unobstructed subrenal drainageat baseline study. During ACE inhibition (ACEI), it showedmarked parenchymal retention and prolonged intraparenchymaltracer transit, suggesting a high probability of renovascularhypertension (RVH) [Figure 2a and b]. The right kidney didnot show any tracer uptake, suggesting non-functional status.The left kidney renogram showed an upsloping pattern of timeactivity curve during ACEI [Figure 3a and b]. Six differentpatterns of renogram curves have been described in literature,based on the renal excretory function.[1] They are as follows: 0normal; 1 minor abnormalities, but with Tmax >5 min and a20-min/max cortical ratio >0.3; 2 a marked delay in excretion ratewith preserved washout phase; 3 delayed excretion rate withoutwashout phase (accumulation curve); 4 renal failure pattern withmeasurable kidney uptake; and 5 renal failure pattern withoutmeasurable kidney uptake.[1] Our patient's baseline renogramshowed Type 1 curve which changed to Type 3 during ACEIwhich represents a high probability for RVH.[1] Quantitativeestimates also confirmed the impairment in renal function andprolongation of tracer transit time after ACEI by demonstrating>10% reduction in GFR and >0.15 increase in the 30-min/peakratio and 3 min increase in the Tmax from the baseline study,respectively [Table 1].


Angiotensin-converting Enzyme Inhibitor Radionuclide Renogram � ANon-invasive Tool to Suspect Renovascular Hypertension
Figure 2: 2 min/frame images of renogram at baseline (a) and during angiotensin-converting enzyme inhibitors (ACEIs) (b). The left kidneyshows adequate tracer uptake followed by timely transit into pelvis and excretion into the bladder by 8th min (a). After ACEI, there is acontinuous accumulation of tracer in the left kidney with delayed transit into the pelvis and delayed excretion into the bladder by 16th min.An increase in background activity is also seen suggesting impaired tracer clearance by the left kidney. After ACEI, significant tracer retentioncan be noted in the left kidney at the end of dynamic study (the last frame corresponding to 30th min) compared to baseline study

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ACE inhibitor renogram for RVH Santhosh, et al.

Angiotensin-converting Enzyme Inhibitor Radionuclide Renogram � ANon-invasive Tool to Suspect Renovascular Hypertension
Figure 3: Renogram curve-time activity curve of counts in the kidneys (Y-axis) versus time (X-axis) after i.v administration of 99mTc-DTPAat baseline (a) and during angiotensin-converting enzyme inhibitors (ACEIs) (b). An upsloping of the curve during ACEI suggests delayedtime to peak activity, prolonged renal tracer transit, and excretion as given the corresponding quantitative parameters in the right panel


Table 1: Renogram parameters of the left kidney at baseline andduring ACEI study
Angiotensin-converting Enzyme Inhibitor Radionuclide Renogram � ANon-invasive Tool to Suspect Renovascular Hypertension
ACEI: Angiotensin-converting enzyme inhibitors, GFR: Glomerularfiltration rate

Renal hypoperfusion due to RAS activates the renin-angiotensin-aldosterone system (RAAS), leading to an elevatedBP that constitutes RVH. Differentiation between RVH andRAS is essential because RAS is quiet in many non-hypertensiveelderly persons. Furthermore, RAS is an associated but noncausativefinding in a number of hypertensive patients. ACEIrenogram helps to detect RAS as the cause of hypertensionand predicts curability or improvement in hypertension afterintervention. The principle of this study is that ACEI decreasesglomerular filtration by inhibiting the compensatory increase invascular tone at the postglomerular arteriole, mediated by highintrarenal activity of the RAAS in the setting of RAS (perfusionpressure, and hence, the filtration across the glomerulusdecreases following ACEI administration). ACEI renogram ismost cost effective if used primarily in patients with moderateto-high risk of RVH that includes abrupt or severe hypertension,hypertension resistant to 3-drug therapy, bruits in the abdomenor flank, unexplained azotemia or recurrent pulmonary edemain an elderly hypertensive patient, or worsening renal functionduring therapy with ACEIs.[1-4] In patients with normal orminimally reduced renal function (creatinine < 1.7 mg/dL),ACEI renography has a sensitivity and specificity of about 90%for diagnosis of RVH,[1] as seen in this case.

 
The Society for Cardiovascular Angiography and Interventionshas issued Expert Consensus Statement on the appropriatenesscriteria for Renal Artery Stenting.[5] Our patient's clinicalpresentation of flash pulmonary edema, resistant hypertension,and CKD with eGFR < 45 cc/min with bilateral significant RASmeets the appropriateness criteria for revascularization of hisleft RAS.[5] Demonstration of the hemodynamic significance inmoderate RAS (50%-70%) by invasive angiography (IA) withmeasures such as fractional flow reserve and translesional gradientis required before planning stenting. IA has its own potentialcomplications like contrast-induced nephropathy in patients withischemic nephropathy and procedure-related complications suchas pseudoaneurysm and hematoma. ACEI renogram could beconsidered as a safe non-invasive procedure that can demonstratethe contribution of RAAS to hypertension and the potentialcomplications with IA can be avoided. IA could be averted withnegative ACEI renogram, while a therapeutic IA can be plannedfollowing a positive ACEI renogram.

Conclusion

a) In our patient with CKD due to bilateral RAS, ACEI renogramdiagnosed RVH due to the left RAS and confers a highprobability of recovery following successful revascularization.
b) In young patients with refractory hypertension, ACEIrenogram could be considered as one of the first-lineinvestigations to identify a potentially curable cause ofsecondary hypertension, i.e., RAS.
c) ACEI renogram can be safely performed in CKDpatients since it uses only micromolar quantity ofradiopharmaceutical (i.e., 99mTc-DTPA) that causes nofunctional overload to the kidneys unlike angiogram, whichcarries a risk of contrast-induced nephropathy/nephrogenicsystemic fibrosis.
d) DTPA renogram can be used to assess the differential renalfunction in patients with bilateral significant RAS to guideoptimal therapeutic strategy.


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References
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  2. Okura T, Irita J, Enomoto D, Manabe S, Kurata M, Miyoshi KI,et al. A case of hyperreninemic hypertension with bilateralpositive captopril renography but without renovascular stenosis.Hypertens Res 2008;31:383-6.

 
  1. Krijnen P, van Jaarsveld BC, Deinum J, Steyerberg EW,Habbema JD. Which patients with hypertension andatherosclerotic renal artery stenosis benefit from immediateintervention? J Hum Hypertens 2004;18:91-6.
  2. Kumar R, Padhy AK, Machineni S, Pandey AK, Malhotra A.Individual kidney glomerular filtration rate in the interpretationof non-diagnostic curves on captopril renography. Nucl MedCommun 2000;21:637-43.
  3. Parikh SA, Shishehbor MH, Gray BH, White CJ, Jaff MR. SCAIexpert consensus statement for renal artery stenting appropriateuse. Catheter Cardiovasc Interv 2014;84:1163-71.

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