3D Printing of Renal Arteries for Endovascular Interventions: Feasibility, Utility, and Correlation With Renal Arteriograms

Background. Three-dimensional (3D) printing technology is increasingly being utilized for preprocedural planning of interventional procedures. However, utility of 3D models of obstructive and clinically relevant renal artery disease has not been evaluated and could potentially assist in preprocedural planning of renal artery endovascular interventions. Methods. Five patients with computed tomography angiography (CTA) of abdomen and pelvis who also subsequently underwent renal artery interventions were 3D printed retrospectively. Standard 3D slicer software was used to segment out descending aorta, renal artery, and renal anatomy to create a computer aided image. The 3D-printed models (3D-PMs) were painted with acrylic paint to highlight anatomic features for comparison with renal arteriograms and 3D-CTA to aid in endovascular interventions. Results. 3D-PMs were successfully produced in diverse renal artery pathology: atherosclerotic disease, fibromuscular dysplasia, in-stent restenosis, and bilateral renal artery stenosis. Renal artery ostium angulation and optimal axial guiding catheter engagement were elucidated. Additionally, reference vessel size and lesion length were measured using digital millimeter calipers. Renal arteriogram along with renal interventional devices utilized during each case were compared for size correlation, reproducibility, and clinical utility. Conclusion. Preprocedural 3D printing of renal artery anatomy requiring endovascular intervention could allow for better appreciation of renal anatomy and could serve as an adjunctive tool to minimize use of contrast, fluoroscopy, and procedure time.

J INVASIVE CARDIOL 2021;33(12):E986-E992.

Key words: 3D-printed models, endovascular interventions, renal artery interventions

Hemodynamically significant renal artery stenosis (RAS) clinically manifests as uncontrolled refractory hypertension, deteriorating renal function from ischemic nephropathy, acute recurrent flash pulmonary edema, and/or acute coronary syndrome. In patients undergoing cardiac catheterization, prevalence of atherosclerotic RAS is between 25%-30%, and is additionally seen in 30%-40% of patients who have peripheral arterial disease or abdominal aortic aneurysm.¹ Non-invasive imaging modalities for diagnosis are not without limitations. Renal artery to aorta peak systolic velocity ratio >3.5, measured on renal duplex ultrasound, has a 92% sensitivity for >60% diameter stenosis, but is limited by technician skills and patient body habitus.^2,3 Abdominal computed tomography angiography (CTA) has a sensitivity and specificity for renal diameter stenosis >50% of 90%-100% and 97%, compared with 92-97% and 73%-93% for magnetic resonance angiography (MRA) respectively.³ An added benefit of MRA or CTA includes superior assessment of accessory vessels, differing renal branching patterns and vessel orientation. 3D reconstructed CTA (3D-CTA) goes a step further by allowing multidimensional complex anatomic visualization, but is still limited to a virtual image. The added value of 3D-printed models (3D-PMs) of renal artery pathology for renal artery interventions allows augmented stimulation of sensory, perceptual and tactile understanding of anatomy not provided by aforementioned imaging modalities.

Five patients with varied renal artery pathophysiology, who subsequently required renal artery interventions and also had CTA performed during their work up, were queried for retrospective comparison. DICOM (Digital Imaging and COmmunications in Medicine) images from abdominal CTA were downloaded into the 3D slicer software (Surgical Planning Laboratory) and the renal artery anatomy was segmented with creation of a computer aided image and 3D printed using Ultimaker 3 software (Create Education Limited) and Ender 3 Pro (Creality 3D) printers. Polylactic filament was utilized using fused deposition modeling, a method which extrudes heated filament layer by layer to create a 3D-PM upon cooling at room temperature. The descending aorta and renal artery were painted with red acrylic paint and the renal organ anatomy with yellow paint. Comparisons of the 3D-PMs were systematically made with renal arteriogram and 3D-CTA.

Clinical history, renal ultrasound and CTA of all 5 patients are described in Table 1. Diverse renal artery pathology including atherosclerotic RAS, fibromuscular dysplasia (FMD), in-stent restenosis (ISR), and bilateral RAS were included. The print time of the 3D-PM, on average, was between 6-7 hours. The 3D-PM and pathologic anatomy of each individual renal intervention case along with renal arteriogram correlation are described below. Clinically valuable information derived from the 3D-PM including renal artery ostium angle, 3D-PM reference vessel size (RVS), and lesion length measured by a digital millimeter (mm) caliper, along with actual stent and post-dilation balloon size used during procedure are listed in Table 2 and described below.

Case 1. Right ostial atherosclerotic renal artery stenosis. Right ostial RAS in a 75-year-old male is shown in Figure 1A. The ostium was posterior and inferiorly directed and best engaged by turning guiding catheter leftward and inferior from the anteroposterior (AP) axis (Figure 1B). RVS as measured by a digital caliper was 5.8 mm and lesion length was 14.9 mm. The actual stent size used during the procedure was 6.0 x 17 mm with a post-dilation balloon of 6 x 20 mm. Renal arteriogram, 3D-CTA and percutaneous intervention are illustrated in Figures 1D-1F.

Case 2. Right renal artery fibromuscular dysplasia. A right renal artery FMD with cork-screw type appearance in a 43-year-old female is shown in Figure 2A. The renal artery ostium was anterior and inferiorly directed, best engaged by rotating a guiding catheter rightward and downward from the AP axis (Figure 2B). RVS was 5.9 mm and lesion length was 26.5 mm as measured on the 3D-PM (Figure 2C). Renal arteriograms and intervention are illustrated in Figures 2D-2F, but further demonstrate the renal artery dissection prior to distal renal bifurcating branches (Figure 2D).

Case 3. Severe in-stent restenosis. Severe right renal artery ISR, particularly at the distal edge of stent, in a 69-year-old male is shown in Figures 3A and 3D. Based on 3D-PM, the ostium of the stent was likely best engaged by rotation of a guiding catheter leftward from the AP axis (Figure 3B). A 6.0 x 16 mm covered stent was deployed making sure to cover beyond the distal edge of prior stent and post-dilated with a 6.0 x 12 mm FLASH Ostial balloon (Ostial Corporation). Renal arteriogram, intravascular ultrasound, and renal artery intervention are illustrated in Figures 3D-3F.

Case 4. Bilateral atherosclerotic renal artery stenosis. Bilateral RAS in a 44-year-old female is shown in Figure 4A. The ostium of the right renal artery was inferiorly directed and best engaged by rotation of a guiding catheter leftward and downward from the AP axis, while the ostium of the left renal artery was posterior and superiorly directed and best engaged by rotation of the guiding catheter rightward from the AP axis (Figure 4B). RVS of the right renal artery was 5.8 mm with a lesion length of 10.9 mm, and RVS of the left was 6.0 mm with a lesion length of 14.6 mm (Figure 4C). A 6.0 x 12 mm stent was deployed in the right and a 6.0 x 17 mm stent in the left renal artery, both post-dilated with 6.0 x 8 mm balloon. Bilateral renal artery arteriograms and percutaneous interventions are illustrated in Figures 4D and 4E.

Case 5. Right ostial atherosclerotic renal artery stenosis. Right ostial RAS  in a 60-year-old female is shown in Figure 5A. The right renal ostium was inferiorly directed and best engaged by rotating the guiding catheter leftward and downward from the AP axis (Figure 5B). Proximal RVS was 5.9 mm and lesion length was 17.7 mm as measured on 3D-PM (Figure 5C). A 6.0 x 18 mm stent was deployed at ostium of right renal artery and post-dilated with 6.0 x 12 mm balloon. Right renal artery arteriogram and intervention are illustrated in Figures 5D-5F.

Three-dimensional printing in cardiovascular percutaneous interventions. 3D-printing has been successfully integrated in pre-procedural planning for percutaneous structural heart interventions, specifically for aortic and mitral valve, left atrial appendage occlusion (LAAO) and congenital heart disease interventions. The current clinical association has been for LAAO device selection, appreciation of adequate atrial rim tissue for atrial septal defect closure, and replication of aortic and mitral anatomy for predictability of physiology and anatomy during interventions.^4-7 Investigation for the role of 3D-printing for percutaneous coronary interventions (PCI) of anatomically complex coronary artery bypass patients including chronic total occlusions (CTO) has been recently published. Appreciation of patient bypass anatomy, including occluded bypass graft buttons, ambiguous CTO caps and vessel course, has the potential to improve contrast, fluoroscopy, procedure time, efficiency and success rate for CTO PCI.⁸ 3D-printing of aortic arch and carotid anatomy for carotid stenting procedures can also aid with enhanced appreciation of aortic arch and carotid vessel tortuosity, pre-procedural selection of catheters, stents and embolic protective devices allowing procedure efficiency, increased success rates, and recognition of anatomy that may be better served with surgery.⁹

Renal artery pathology requiring endovascular intervention

Atherosclerotic stenosis. RAS is predominantly caused by atherosclerosis, seen in 90% of cases, most commonly involving the adjacent aorta, ostium and/or extension into proximal one-third of the artery.¹⁰ Traditional cardiovascular risk factors of advancing age, hypertension, diabetes mellitus, and dyslipidemia increase the prevalence of RAS and result in progressive loss of renal mass and function over time. Data suggest that 27% of patients with RAS will progress to chronic renal failure within 6 years and 14% will succumb to end-stage renal disease with initiation of dialysis.^11,12 Alongside traditional medical therapy, renal artery stenting is superior to percutaneous transluminal angioplasty (PTA) alone due to the common phenomenon of ‘elastic recoil’ and acute vessel closure. A recent meta-analysis of 1,322 patients showed renal artery stenting to have significantly higher technical success rate and lower restenosis rate than PTA alone ((98% vs 77% and 17% vs 26%, respectively, P<.001). Additionally, renal artery stenting had higher cure rates for hypertension than PTA alone (20% vs 10%, P<.001).¹³

Fibromuscular dysplasia. FMD is a non-atherosclerotic cause of RAS related to cellular proliferation from both genetic and environmental factors with a female predominance. Arterio-pathologic manifestation of FMD can be seen as focal or multi-focal lesions in small- to medium-sized arteries in the mid to distal segment, commonly renal, extracranial carotid, and vertebral artery, although almost any arterial bed can be involved in a multivessel pattern. Imaging modalities may show the classic ‘beaded’ or ‘corkscrew’ appearance of the affected arteries, but the characteristics have expanded to include arterial dissection, aneurysm and tortuosity. In addition to anti-platelet and anti-hypertensive medical therapy, renal angioplasty is the traditional treatment of choice with renal artery stenting as bail-out strategy or in select cases of renal artery dissections or aneurysms.¹⁴

In-stent restenosis. ISR has been reported to occur in greater than 50% of renal artery stenting cases in a period of less than or equal to 3 years.^15-17 Clinical predictors of ISR after renal artery stenting as shown in multiple studies include smoking,¹⁸ body weight and body mass index,¹⁹ decreased with pre-operative statin use while increased with preoperative diastolic blood pressure.¹⁶ A retrospective study evaluating clinical and procedural factors of patients who underwent renal artery stenting for RAS found that risk of ISR decreased significantly with stent diameter of  ≥ 6 mm and stent length between 15 and 20 mm.²⁰ Repeat stenting appears to be superior clinically than PTA alone for ISR treatment. In a consecutive series of 43 patients, repeat renal artery stenting incurred a 58% reduction in recurrent ISR than PTA alone (29.4% vs. 71.4%, P=.02) and a greater secondary patency (defined as a ≤50% diameter stenosis after two catheter‐based interventions), P=.05.²¹ Treatment of re-occurrence of restenosis (second ISR), as studied in 31 consecutive patients by Zeller et al, indicated a 71% restenosis rate with PTA alone, 43% with bare metal stent, 18% with covered stent, 100% with use of cutting balloon, and 0% in the drug-eluting stent (DES) group, overwhelmingly favoring DES technology. Nonetheless, caution is advised with use of DES for renal artery stenting as renal artery commonly encompasses bulky atherosclerotic disease and the thin struts of DES can lead to stent compression or deformation.²²

Bilateral renal artery stenosis. Bilateral RAS or unilateral stenosis in a solitary functioning kidney predominantly presents with acute, severe or refractory hypertension with unexplained renal insufficiency or with acute renal insufficiency following initiation of angiotensin converting enzyme inhibitor or angiotensin II receptor blocker.²³ Approximately 24% of patients over 50 years of age with advanced renal failure have bilateral RAS. Aside from presence of concomitant traditional cardiovascular risk factors, coronary artery disease is also highly prevalent, as high as 86% in one study with bilateral RAS requiring bilateral renal artery stenting.²⁵ Treatment is indicated both to improve blood pressure, and, in some cases, to preserve renal function.

Evidence for renal artery endovascular interventions. Confirmation of hemodynamic significance along with clinical manifestation (refractory hypertension, recurrent flash pulmonary edema, ischemic nephropathy) is the general consensus for treatment of RAS. The Society for Cardiovascular Angiography and Interventions (SCAI) expert consensus determines hemodynamic significant RAS to be either > 70% stenosis or moderate stenosis (50%-70%) to undergo hemodynamic significance with a resting translesional mean pressure gradient of >10 mmHg, hyperemic peak systolic pressure gradient of >20mmHg or renal pressure_distal/pressure_aortic (fractional flow reserve, FFR) to be ≤ 0.8.²⁶

Randomized controlled trials of renal artery stenting have failed to show a difference in outcomes between guideline directed medical therapy and renal artery stenting. However, the trials have, arguably, been flawed by variability in inclusion/exclusion criteria, inconsistent definitions of effectiveness, and differing renal and hypertension endpoints. The STAR (STent placement in patients with Atherosclerotic Renal artery stenosis and impaired renal function: a randomized trial) randomized patients with >50% and creatinine clearance <80 ml/min/1.73 m² to guideline directed medical therapy versus medical therapy with renal artery stenting and showed no difference in progression of chronic kidney disease between the two arms. However, 30% of patients randomized to the intervention arm had <50% stenosis and were not candidates for renal artery stenting.²⁷ The ASTRAL (Angioplasty and Stenting for Renal Artery Lesions) trial concluded no difference in outcomes between revascularization and medical therapy arms in relation to blood pressure, renal function, cardiovascular events, or mortality; albeit, the intervention arm was on fewer antihypertensives than the medical arm (2.77 vs. 2.97; P=.03). Additionally, only 60% of patients had >70% RAS, and renal ultrasound was the only imaging modality to diagnose severity of RAS, and as such, many enrolled in the trial may not have been revascularization candidates.^28,29 The CORAL (Cardiovascular Outcomes in Renal Atherosclerotic Lesions) trial inclusion criteria included systolic blood pressure ≥155 mm Hg despite being on ≥ 2 antihypertensive medications which is a lenient definition of refractory hypertension considering that the current consensus uses a definition of blood pressure that is difficult to control despite use of ≥ 5 different classes of antihypertensive agents including a diuretic and a mineralocorticoid. The study showed no difference in primary cardiovascular or renal outcomes, and additionally, hemodynamic severity of the lesion was not confirmed and moderate or nonobstructive diameter stenosis of 50%-70% were likely included in the trial arm.³⁰ Due to the significant variability in the randomized renal artery stenting trial designs, significant controversy and variability exists in treatment of RAS and further randomized trials are needed to better adjudicate the optimal threshold for treatment of RAS.

Utility of 3D-printing for renal artery interventions. Patient specific 3D-printing for renal artery endovascular interventions has not been previously investigated. 3D-PM of renal artery anatomy can be beneficial for pre-procedural planning by allowing superior appreciation of 3D-anatomy not provided by CTA or virtual 3D reconstructed CTA. As illustrated case by case, knowledge of ostium angulation and take off can allow pre-procedural planning of guide catheter manipulation for efficient renal artery engagement. Additionally, measurement of RVS and lesion length can also be determined pre-procedurally allowing optimal stent and balloon sizes chosen accordingly. Given that 24%-27% of patients with uni- or bilateral RAS have chronic or acute kidney disease, 3D printing can be an added tool for superior understanding of 3D anatomy pre-procedurally and complementary to intravascular ultrasound for assistance with renal artery interventions. Clinically this could translate to decreased use of contrast, fluoroscopy and procedure time and thereby decrease the risk of contrast-induced nephropathy.

3D printing of renal artery anatomy for renal artery interventions allows better appreciation of 3D anatomy not provided by two-dimensional imaging or virtual 3D reconstructed imaging. The enhanced conceptual, perceptual and tactile feedback allows superior understanding of renal ostial angulation and takeoff for guidance with guide catheter engagement and renal artery stent and balloon sizing pre-procedurally. A decrease in contrast load, fluoroscopy and procedure time can all be the end clinical result and may be especially important in those with concomitant renal insufficiency. A prospective analysis of utility of 3D printing in renal artery interventions to confirm the above theory requires further investigation.

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