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Natural history and management of renal artery aneurysms in a single tertiary referral center
From the Society for Vascular Surgery
Natural history and management of renal artery aneurysms in a single tertiary referral center Adam J. Brownstein, BA,a Young Erben, MD,b Sareh Rajaee, MD,b Yupeng Li, PhD,c John A. Rizzo, PhD,d Hamid Mojibian, MD,e Bulat A. Ziganshin, MD, PhD,a,f and John A. Elefteriades, MD,a New Haven, Conn; Glassboro, NJ; Stony Brook, NY; and Kazan, Russia
ABSTRACT Objective: Although renal artery aneurysms (RAAs) are uncommon, several large reports have been published indicating their benign natural history. The objective of our study was to review our single-center experience managing this disease entity. Methods: A retrospective review of the Yale radiologic database from January 1999 to December 2016 was performed. Only patients with RAA and a computed tomography scan of the abdomen were selected for review. Demographics of the patients, aneurysm characteristics, management, postoperative complications, and follow-up data were collected. Results: There were 241 patients with 259 RAAs identified, with a mean age of 69 years (range, 35-100 years); 147 were female (61%). On computed tomography, aneurysms were solitary and right sided in 224 (86%) and 159 (61%), respectively; 64 (27%) patients had aneurysms elsewhere. The breakdown of RAAs by location was as follows: renal bifurcation in 84 (32%), renal pelvis in 77 (30%), distal renal artery in 58 (22%), mid renal artery in 34 (13%), and proximal renal artery in 6 (2%). Five patients had symptoms that were attributed to the RAA and underwent operative repair; all others were observed without an operation. Symptoms in the operative repair group included flank pain in four and uncontrolled hypertension in one. The mean overall diameter of the RAAs was 1.22 6 0.49 cm. The diameter of operatively repaired and observed RAAs was 1.84 6 0.55 cm and 1.21 6 0.48 cm, respectively (P ¼ .002). Operative repair included four coil embolizations and one open resection. There were no renal function changes in any of these patients after operation and no other complications. Mean follow-up was 41 6 35 months for patients in the group that was observed; 18 of these RAAs were >2 cm, and none ruptured. On multivariable regression analysis, female sex (P ¼ .0001), smoking history (P ¼ .00007), left-sided RAA (P ¼ .03), and main renal artery location (P ¼ .03) were inversely related to growth, whereas a history of hypertension was directly related to growth rate (P ¼ .01). The mean growth rate for RAAs was 0.017 6 0.052 cm/y. Conclusions: RAAs tend to have a benign natural history. Although previous reports have not identified any factors that contribute to RAA growth, we observed that RAA location, sex, smoking history, and hypertension may have an impact on growth rates. No ruptures were observed. Operative repair at our institution was rare, with no morbidity or mortality. Observation of RAAs over time seems feasible in the asymptomatic patient with a small RAA. (J Vasc Surg 2018;68:137-44.)
Renal artery aneurysms (RAAs) are extremely rare, with a reported incidence of 0.01% to 0.09% in autopsy studies.1,2 However, more recent angiographic and cross-sectional imaging studies have reported the incidence of RAA to be closer to 1%.3,4 Although multiple reports recommend surgical intervention at a diameter >2 cm, there is no consensus regarding the treatment of RAAs because few studies have analyzed the natural history of these aneurysms.5-7 The prevention of RAA
rupture, which most likely occurs in <3% of cases,1,5,8 is the chief concern, given that rupture leads to an estimated nongestational mortality rate of 10%.1,5,8-10 However, many authors believe that there is not sufficient evidence to support the contention that larger RAAs rupture at higher rates.1,5,8,11,12 Whereas several series have observed patients with RAAs over time without rupture,3,13-15 only three studies have evaluated RAA growth rates to date.16-18 The
From the Aortic Institute at Yale-New Haven Hospital,a and the Section of
Poster presentation at the 2017 Vascular Annual Meeting of the Society for
Vascular and Endovascular Surgeryb and Department of Radiology and
Vascular Surgery, San Diego, Calif, May 31-June 3, 2017.
Biomedical Imaging, Division of Interventional Radiology,e Yale School of
Correspondence: John A. Elefteriades, MD, Aortic Institute at Yale-New Haven
Medicine, New Haven; the Department of Political Science and Economics,
Hospital, Yale University School of Medicine, 789 Howard Ave, Clinic Bldg
Rowan University, Glassboroc; the Department of Economics and Depart-
CB317, New Haven, CT 06519 (e-mail: [email protected]).
ment of Family, Population and Preventive Medicine, Stony Brook University,
The editors and reviewers of this article have no relevant financial rela-
Stony Brookd; and the Department of Surgical Diseases #2, Kazan State Med-
tionships to disclose per the JVS policy that requires reviewers to
ical University, Kazan.f A.J.B. was supported by the Richard K. Gershon, MD, Student Research Fellowship and the Yale University School of Medicine Medical Student Research Fellowship. Author conflict of interest: none.
decline review of any manuscript for which they may have a conflict of interest. 0741-5214 Copyright Ó 2018 by the Society for Vascular Surgery. Published by Elsevier Inc. https://doi.org/10.1016/j.jvs.2017.10.086
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largest of these studies reported a mean growth rate of 0.086 6 0.08 cm/y for 454 RAAs observed during a mean period of 49 months.16 Given the limited knowledge of the natural history of RAAs in the literature, the objectives of our study were to evaluate outcomes of treated RAAs (open and endovascular) and to delineate the growth and rupture rates of those RAAs managed nonoperatively at Yale-New Haven Hospital.
ARTICLE HIGHLIGHTS d
d
METHODS Patient cohort. RAAs were defined as focal dilations >50% of the normal diameter of the renal artery.19 The Yale radiology database was searched with specific search terms, including “renal artery aneurysm” and “renal aneurysm,” from January 1, 1999, through December 31, 2016, for patients who received a computed tomography (CT) diagnosis of RAA by a radiologist at Yale-New Haven Hospital. Patients were also identified by International Classification of Diseases, Ninth Revision disease codes 442.1 (aneurysm of renal artery) and 442.89 (aneurysm of other specified artery). Data collection included details of each patient’s clinical presentation, comorbidities, management, and followup data as identified through retrospective chart review (Table I). Consistent with prior reports, symptomatic patients were defined as those with flank pain, abdominal pain, hematuria, or difficult-to-control hypertension1,18 without other evident causes. Our primary outcomes included morbidity and mortality of operatively repaired RAAs and aneurysm growth rate and risk of rupture in those patients managed nonoperatively. Consent of individual patients for study inclusion was not obtained or required, and this study received approval from the Yale Institutional Review Board (HIC No. 1411014866) as a retrospective chart review. Imaging data and growth rate calculation. All CT scans were reanalyzed to collect data about aneurysm characteristics, including aneurysm laterality, RAA location (proximal renal artery, mid renal artery, distal renal artery, renal artery bifurcation, or within the renal pelvis), aneurysm calcification, and aneurysm diameter, as well as to identify the presence of other arterial aneurysms. Aneurysm diameter was determined by directly measuring aneurysm size from outer wall to outer wall. Observed growth rates were calculated for all patients with two or more CT scans, as follows: (diameter at last CT scanediameter at initial CT scan)/time interval between CT scans. In addition, estimated growth rates for RAAs were calculated with an instrumental variables approach. This method uses a variable (the time interval between imaging studies) that is measured accurately and correlates with changes in aneurysm size because patients with longer time intervals between CT scans should demonstrate greater true aneurysm growth.20 The estimates were obtained by means of regression
d
Type of Research: Single-center retrospective cohort study Take Home Message: In 241 patients with 259 renal artery aneurysms who were observed for a mean of 41 months, five required intervention for symptoms of flank pain (4) or uncontrolled hypertension (1); others remained asymptomatic with mean rate of growth of 0.017 cm/y. Recommendation: This study suggests that renal artery aneurysms are very slow growing and rarely require repair.
analysis in which aneurysm growth followed an exponential path. In particular, the natural logarithm of the last measured size to the first measured size was related to the time interval between the two tests and the disturbance term. Because the dependent variable has been transformed to the natural log form, we use Duan’s smearing estimator to calculate the expected value of the untransformed dependent variable. This method, which has been previously described,21 has been shown to be more accurate for both measuring aneurysm growth rates and estimating risk factors for aneurysm growth than simply calculating mean growth rate.21 This method was employed to minimize the impact of measurement errors on RAA growth rate calculations and to guard against disproportionately overweighting data of patients with stable aneurysms, who may have many repeated aneurysm measurements. Statistical analysis. Our primary outcomes were morbidity and mortality of all operatively repaired RAAs and aneurysm growth rate and risk of rupture in those patients managed nonoperatively. Data are reported using means and standard deviations for continuous variables or frequencies for categorical variables. Student t-tests were used to analyze the difference in aneurysm size between operatively repaired and nonoperatively managed groups. Fisher exact tests were used to compare comorbidity rates between nonoperatively managed and operatively repaired groups. Multivariable regression analysis was used to evaluate the impact of comorbidities and aneurysm characteristics on growth rate. Statistical analyses were performed using R (R Foundation for Statistical Computing, Vienna, Austria) and Social Science Statistics (www.socscistatistics.com).
RESULTS Patients. Between January 1999 and December 2016, we identified 241 patients with 259 RAAs who underwent a CT scan of the abdomen at the Yale-New Haven Hospital. The mean age at presentation was 68.6 6 13.7 (range, 35-100) years. The majority of patients were
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Table I. Comorbidities and clinical presentation of the patients Characteristic
Total patients (N ¼ 241)
Operative repair
Observed without operation
P
Demographics Age at initial presentation, years, mean 6 SD
68.6 6 13.7 (range, 35-100)
44.9 6 7.2
69.1 6 13.4
<.0001
White race
183 (76)
3 (60)
180 (76)
.596
Female
147 (61)
4 (80)
143 (61)
.651
227 (94)
0 (0)
Presentation 227 (96)
<.0001
Flank or abdominal pain
8 (3)
d
d
d
Difficult-to-control hypertension
1 (0.4)
d
d
d
Hematuria
7 (3)
d
d
d
Asymptomatic
Comorbidities Hypertension
173 (75)
3 (60)
170 (76)
NS
Hyperlipidemia
117 (51)
2 (50)
115 (50)
NS
Smoking history
110 (50)
1 (33)
109 (50)
NS
63 (28)
NS
Diabetes mellitus
64 (28)
Coronary artery disease
50 (22)
0 (0)
1 (25)
50 (22)
NS
Chronic kidney disease
39 (17)
0 (0)
39 (17)
NS
Chronic obstructive pulmonary disease
33 (14)
0 (0)
33 (14)
NS
Atrial fibrillation
28 (12)
0 (0)
28 (12)
NS
Congestive heart failure
25 (11)
0 (0)
25 (11)
NS
History of stroke or transient ischemic attack
23 (10)
0 (0)
23 (10)
NS
History of myocardial infarction
19 (8)
0 (0)
19 (8)
NS
Peripheral arterial disease
3 (1)
0 (0)
3 (1)
NS
Connective tissue disorder (Ehlers-Danlos syndrome)
1 (0.4)
0 (0)
1 (0.4)
NS
NS, Nonsignificant; SD, standard deviation. Values are reported as number (%) unless otherwise indicated. Boldface values indicate statistical significance (P < .05).
female (61%) and white (76%). Information on a number of comorbidities (Table I) was collected, including hypertension (75%), history of smoking (50%), chronic renal insufficiency (17%), diabetes mellitus (28%), and presence of connective tissue diseases (one patient had EhlersDanlos syndrome). Additional aneurysms were identified in 61 patients (25%), of which the most common locations were aneurysms of either the same or opposite renal artery (8%), the thoracic aorta (6%), the abdominal aorta (5%), the splenic artery (5%), and the iliac artery (3%). The majority of patients were asymptomatic (Table II) at presentation (94%). Operatively repaired patients presented at a significantly younger age than nonoperatively managed patients (P < .0001). Five patients had symptoms that were attributed to an RAA, including four patients with flank pain and one patient with difficult-to-control hypertension. Nine patients had hematuria or flank pain as described in a clinical note or in the indication for CT scan in the radiology report without another evident cause, so these patients were classified as symptomatic as well. Aneurysm characteristics. The distribution and location of RAAs are depicted in Fig 1, with the mean size
for each location depicted in Table II. CT scans of patients with RAAs in each location are displayed in Fig 2. The most common location of RAA was at the renal bifurcation (32%), followed by the renal pelvis (30%), the distal renal artery (22%), the mid renal artery (13%), and the proximal renal artery (2%). The majority of RAAs were located on the right side (61%; Table II) and were calcified (76%); 15 RAAs (6%) were bilateral. The mean diameter of all RAAs was 1.22 6 0.49 cm. The mean diameter of the 5 RAAs that underwent operative repair was 1.84 6 0.55 cm, whereas the mean diameter of the 254 RAAs that were observed was 1.21 6 0.48 cm (P ¼ .002). Treated RAAs. An overview of the management of those RAAs treated during our study period is shown in Fig 3. The five patients whose symptoms were attributed to the RAA underwent operative repair. One patient underwent open aneurysmorrhaphy of a 2.2-cm distal RAA; four patients underwent endovascular repair by coil embolization for three RAAs located in the renal pelvis and one RAA located at the renal artery bifurcation (Fig 4). One of the endovascular repairs was for a 0.81-cm traumatic pseudoaneurysm of the renal artery, which was the only identified pseudoaneurysm in our cohort. There were no perioperative complications,
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Table II. Renal artery aneurysm (RAA) characteristics
Characteristic
RAAs (N ¼ 259); mean 6 SD and/or No. (%)
Laterality Right sided Bilateral
159 (61) 15 (6)
Calcification Calcified Noncalcified
198 (76) 61 (24)
Location Proximal renal artery
6 (2); 1.62 6 0.77 cm
Mid renal artery
34 (13); 1.19 6 0.43 cm
Distal renal artery
58 (22); 1.22 6 0.42 cm
Renal bifurcation
84 (32); 1.16 6 0.53 cm
Renal pelvis
77 (30); 1.27 6 0.46 cm
Overall average diameter
1.22 6 0.49 cm
SD, Standard deviation.
Fig 1. Distribution of renal artery aneurysms (RAAs) by location.
The cause of death was not identified in eight patients. During the observation period, none of the RAAs ruptured, including in 11 patients with RAAs $2.0 cm who underwent CT imaging separated by a mean period of 53 6 28 months (range, 9-97 months). The overall growth rate, which was calculated using the 171 RAAs that were observed over time, was 0.017 6 0.052 cm/y. The majority of aneurysms (76%) did not grow, so the median and mode growth rates were both 0 cm/y. The frequency distribution of observed growth rates is depicted in Fig 5. RAA estimated growth rate, calculated using the instrumental variables approach described in the Methods section, was 0.022 6 0.008 cm/y. The frequency distribution of these estimated growth rates is depicted in Fig 6. To evaluate the impact of comorbidities and aneurysm characteristics on observed growth rates, a multivariable regression analysis was conducted. As shown in Table III, five variables were found to be statistically significant (P < .05). Hypertension was significantly associated with faster growth (odds ratio [OR], 1.011; 95% confidence interval [CI], 1.003-1.019; P ¼ .01), whereas a history of smoking (OR, 0.987, 95% CI, 0.981-0.993; P < .0001), female sex (OR, 0.987; 95% CI, 0.981-0.993; P < .0001), and aneurysm location on the left side (OR, 0.993; 95% CI, 0.988-0.999; P ¼ .03) were significantly associated with slower growth. Compared with aneurysms located in the renal pelvis, aneurysms located in the mid renal artery (OR, 0.983; 95% CI, 0.973-0.993; P ¼ .001), distal renal artery (OR, 0.990; 95% CI, 0.983-0.996; P ¼ .003), and renal artery bifurcation (OR, 0.992; 95% CI, 0.984-0.999; P ¼ .03) exhibited slower growth. In addition, aneurysm calcification was almost found to be significantly associated with slower growth (OR, 0.991; 95% CI, 0.982-1.000; P ¼ .05). The other nonsignificant variables analyzed included age, presence of chronic obstructive pulmonary disease, coronary artery disease, diabetes mellitus, chronic kidney disease, history of stroke, congestive heart failure, connective tissue disease, and multiple aneurysms.
DISCUSSION including no change in renal function, and no perioperative mortality. All patients who presented with flank pain improved after intervention. However, the patient who presented with hypertension remained hypertensive after intervention. Observed RAAs. There were 236 patients with 254 RAAs who did not undergo operative repair, of whom 159 patients with 171 RAAs had two or more CT scans that were on average 41 6 35 months apart (range, 1-142 months). There were 77 patients with 83 RAAs who were considered lost to follow-up because they had only one CT scan of the abdomen. Of these 77 patients, 22 died before the study data were analyzed, 14 of whom died of a known cause unrelated to the RAA.
Only three studies to date have documented the natural history of RAAs using growth rates (Table IV).16-18 This dearth of knowledge in the literature regarding the natural history of RAAs is consequential because it has traditionally been recommended that RAAs >2.0 cm undergo repair to avert a potentially fatal rupture event.5-7,22-24 However, controversially, some current evidence indicates that a 2.0-cm threshold for intervention may be too aggressive.5,16 Given the increased use of abdominal cross-sectional imaging in recent decades,18 the incidental detection of RAAs most likely will continue to increase, prompting the question of how these patients should optimally be managed. Because of these controversies and uncertainties, our study was undertaken.
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Fig 2. Examples of renal artery aneurysms (RAAs) by location (arrow): (A) proximal renal artery, (B) mid renal artery, (C) distal renal artery, (D) renal artery bifurcation, and (E) within the renal pelvis.
Fig 3. Management of patients with renal artery aneurysms (RAAs).
Our study is consistent with prior reports indicating that RAAs tend to have a benign natural history as we found no cases of RAA rupture. Also, these aneurysms grow at very slow rates. Early studies demonstrated rupture rates considerably higher (4.8% and 14% in two studies24,25) than the accepted contemporary rate of <3%.5,8 In the two largest studies to date of RAAs observed over time, no RAAs ruptured in the observed cohort in each study. Henke et al13 observed 86 RAAs during a mean followup of 72 months, whereas Klausner et al16 observed 454 aneurysms during a mean follow-up of 49 months. Henke et al and Klausner et al each reported three cases of RAA rupture at presentation, leading to overall
rupture rates of 1.2% and 0.3%, respectively. Importantly, Klausner et al observed 88 aneurysms between 2 and 3 cm that did not rupture, whereas the aneurysms that did rupture were all >3.0 cm, leading to a rupture rate of 18% for RAAs >3.0 cm. Wayne et al17 also reported no ruptures in a study of 68 RAAs observed during a median follow-up of 19.4 months, although 6 patients underwent elective repair of RAAs $2.5 cm. Moreover, Tham et al3 and Cinat et al,14 in a pooled analysis, reported no aneurysm ruptures among 69 RAAs during a mean follow-up of 4.3 years and 200 RAAs during a mean follow-up of 17 years, respectively. In our study, no ruptures among 259 RAAs occurred, including 171
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Fig 4. Renal artery aneurysm (RAA) before and after embolization. A, Saccular RAA at the renal artery bifurcation (red circle). B, Status after coil embolization of the RAA (arrow).
Fig 5. Frequency distribution of observed growth rates. RAA, Renal artery aneurysm.
RAAs that were observed for a mean follow-up between CT scans of 41 6 35 months, 11 RAAs $2.0 cm observed during a period of 53 6 28 months, and 2 RAAs of 3.0 cm in diameter. Therefore, our results are consistent with those of Klausner et al, who posited that observation of RAAs between 2.0 and 3.0 cm among asymptomatic, nonpregnant patients may be warranted.16 However, RAAs can rupture at sizes <3.0 cm and even <2.0 cm.1,2628 These findings highlight the unpredictability of behavior in some cases. In addition to simple arithmetic calculation, we employed an instrumental variables method21 to estimate RAA growth rates to reduce measurement error. This method has been demonstrated to be more accurate for calculating aneurysm growth rates than using mean growth rate.21 Table IV depicts our observed mean and estimated RAA growth rates, which were 0.017 6 0.052 cm/y and 0.022 6 0.008 cm/y, respectively, compared with growth rates observed in the three other studies in the literature.
Fig 6. Frequency distribution of estimated growth rates. RAA, Renal artery aneurysm.
Our finding that 76% of RAAs observed did not grow during the follow-up period is consistent with prior reports as the majority of RAAs reported by Wayne et al and Klausner et al remained the same size. Morita et al29 also found that among 30 RAA patients managed conservatively, only two experienced growth during a median follow-up of 65.4 months. However, our observed and estimated growth rates are four and five times slower, respectively, than the growth rate reported by Klausner et al. Because most of our patients were identified by a search of the Yale radiology database, it is more likely that we would identify RAAs incidentally. In fact, 94% of our RAAs were asymptomatic and were detected incidentally, whereas Klausner et al reported that only 75% of their patients were asymptomatic at presentation. As a result, our cohort of RAAs may be predisposed to have a benign natural history. According to the literature, approximately 70% of RAA patients have hypertension,30 which is similar to the 75% of patients we identified with hypertension.
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Table III. Multivariable regression analysis analyzing the impact of comorbidities and aneurysm characteristics on growth rate Direction of impact on renal aneurysm growth
Variable
(OR; 95% CI) P value
Hypertension
Increased
(1.011; 1.003-1.019) .01
Smoking history
Decreased
(0.987; 0.981-0.993) <.001
Female sex
Decreased
(0.987; 0.981-0.993) <.001
Mid renal artery location (relative to renal pelvis aneurysms)
Decreased
(0.983; 0.973-0.993) .001
Distal renal artery location (relative to renal pelvis aneurysms)
Decreased
(0.990; 0.983-0.996) .003
Renal artery bifurcation location (relative to renal pelvis aneurysms)
Decreased
(0.992; 0.984-0.999) .03
Left side
Decreased
(0.993; 0.988-0.999) .03
Aneurysm calcification
Decreased
(0.991; 0.982-1.000) .05
CI, Confidence interval; OR, odds ratio.
Table IV. Studies reporting growth rates of renal artery aneurysms (RAAs) in the literature Study
No. of aneurysms Mean follow-up, Mean aneurysm Method for calculating Rupture observed months size, cm Growth rate, cm/y growth rate rate, %
Klausner et al, 201418
14
36 6 9
Wayne et al, 2014
68
19.4
1.6 6 0.64
49
Klausner et al, 201516 Yale a
454 171
41 6 35
1.4 6 0.1
0.06 6 0.016
Mean
0
0.006
Median
0
1.3 6 0.1
0.086 6 0.08
Mean
0a
1.21 6 0.48
0.017 6 0.052 (0.022 6 0.008)
Mean (estimated)
0
Three patients in this study presented with a ruptured renal artery aneurysm, leading to an overall rupture rate of 0.3%.
In addition, we observed that 61% of RAA patients were female, which is consistent with prior reports demonstrating that up to 72% of RAA patients are female, most likely attributable to the increased prevalence of fibromuscular dysplasia among women.30 Our multivariable analysis findings, including faster RAA growth among patients with hypertension and slower growth among female patients, indicate that these variables may have very small effects on RAA growth. In our cohort, operative repair was safe with no associated perioperative morbidity or mortality, although our cohort of patients who underwent RAA repair was small. Four of our patients underwent coil embolization for RAAs within the renal pelvis or at the renal bifurcation, whereas one underwent open resection of a distal RAA. As reviewed by Coleman and Stanley,30 endovascular repair and open repair both lead to low rates of morbidity and mortality and have not been shown to be significantly different from each other in terms of outcomes. The patient’s comorbidities, the aneurysm’s location and morphology, and the surgeon’s preference should all be considered in deciding the best mode for operative repair. The main limitations of this study are our small sample size and short follow-up. Our calculated growth rates should be assessed with a degree of skepticism, given these limitations. To obtain as accurate a growth rate as possible, we included only patients with CT scan imaging to minimize measurement error due to differences in
imaging modalities. Furthermore, we also used only two size measurements per patient (even when there were more available) because, in general, patients with less stable aneurysms will tend to have fewer measured sizes, as they are more likely to be eventually selected out for surgical repair. However, this potential source of bias in calculating growth rates did not apply to our study in any event as only one patient in the operatively repaired group had been observed over time and ultimately underwent repair because of the presence of symptoms as opposed to rapid RAA growth. Last, because we did not observe any aneurysm ruptures, we could not identify any risk factors for RAA rupture.
CONCLUSIONS Our single-center study is consistent with recent reports indicating that RAAs tend to have a benign natural history with extremely low rupture rates and slow growth rates. Therefore, as other authors have articulated,5,16 a size threshold of 2.0 cm may be too aggressive for asymptomatic, nonpregnant patients. Our study is the first to report significant associations with RAA growth rates, including several patient characteristics (hypertension, female sex, and smoking history) and aneurysm characteristics (laterality and location within the renal artery). The clinical significance of these findings is unclear, given that we observed no RAA ruptures, and the effects of these variables on RAA growth appear to be quite small.
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AUTHOR CONTRIBUTIONS Conception and design: AB, YE, JE Analysis and interpretation: AB, YE, SR, YL, JR, HM, BZ, JE Data collection: AB, YE, SR, HM Writing the article: AB, YE, BZ, JE Critical revision of the article: AB, YE, SR, YL, JR, HM, BZ, JE Final approval of the article: AB, YE, SR, YL, JR, HM, BZ, JE Statistical analysis: AB, YL, JR Obtained funding: Not applicable Overall responsibility: JE AB and YE contributed equally to this article and share first authorship.
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13. Henke PK, Cardneau JD, Welling TH 3rd, Upchurch GR Jr, Wakefield TW, Jacobs LA, et al. Renal artery aneurysms: a 35-year clinical experience with 252 aneurysms in 168 patients. Ann Surg 2001;234:454-62; discussion: 462-3. 14. Cinat M, Yoon P, Wilson SE. Management of renal artery aneurysms. Semin Vasc Surg 1996;9:236-44. 15. Henriksson C, Lukes P, Nilson AE, Pettersson S. Angiographically discovered, non-operated renal artery aneurysms. Scand J Urol Nephrol 1984;18:59-62. 16. Klausner JQ, Lawrence PF, Harlander-Locke MP, Coleman DM, Stanley JC, Fujimura N, et al. The contemporary management of renal artery aneurysms. J Vasc Surg 2015;61:978-84. 17. Wayne EJ, Edwards MS, Stafford JM, Hansen KJ, Corriere MA. Anatomic characteristics and natural history of renal artery aneurysms during longitudinal imaging surveillance. J Vasc Surg 2014;60:448-52. 18. Klausner JQ, Harlander-Locke MP, Plotnik AN, Lehrman E, DeRubertis BG, Lawrence PF. Current treatment of renal artery aneurysms may be too aggressive. J Vasc Surg 2014;59: 1356-61. 19. Peterson LA, Corriere MA. Treatment of renal artery aneurysms. J Cardiovasc Surg (Torino) 2015;56:559-65. 20. Rizzo JA, Chen J, Fang H, Ziganshin BA, Elefteriades JA. Statistical challenges in identifying risk factors for aortic disease. Aorta (Stamford) 2014;2:45-55. 21. Rizzo JA, Coady MA, Elefteriades JA. Procedures for estimating growth rates in thoracic aortic aneurysms. J Clin Epidemiol 1998;51:747-54. 22. Eskandari MK, Resnick SA. Aneurysms of the renal artery. Semin Vasc Surg 2005;18:202-8. 23. Ippolito JJ, Leveen HH. Treatment of renal artery aneurysms. J Urol 1960;83:10-6. 24. Harrow BR, Sloane JA. Aneurysm of renal artery: report of five cases. J Urol 1959;81:35-41. 25. McCarron JP Jr, Marshall VF, Whitsell JC 2nd. Indications for surgery on renal artery aneurysms. J Urol 1975;114:177-80. 26. Li G, Sun Y, Song H, Wang Y. Embolization of ruptured renal artery aneurysms. Clin Exp Nephrol 2015;19:901-8. 27. Hidai H, Kinoshita Y, Murayama T, Miyai K, Matsumoto A, Ide K, et al. Rupture of renal artery aneurysm. Eur Urol 1985;11:249-53. 28. Reiher L, Grabitz K, Sandmann W. Reconstruction for renal artery aneurysm and its effect on hypertension. Eur J Vasc Endovasc Surg 2000;20:454-6. 29. Morita K, Seki T, Iwami D, Sasaki H, Fukuzawa N, Nonomura K. Long-term outcome of single institutional experience with conservative and surgical management for renal artery aneurysm. Transplant Proc 2012;44:1795-9. 30. Coleman DM, Stanley JC. Renal artery aneurysms. J Vasc Surg 2015;62:779-85.
Submitted Jul 10, 2017; accepted Oct 26, 2017.
Natural history and management of renal artery aneurysms in a single tertiary referral center Adam J. Brownstein, BA,a Young Erben, MD,b Sareh Rajaee, MD,b Yupeng Li, PhD,c John A. Rizzo, PhD,d Hamid Mojibian, MD,e Bulat A. Ziganshin, MD, PhD,a,f and John A. Elefteriades, MD,a New Haven, Conn; Glassboro, NJ; Stony Brook, NY; and Kazan, Russia
ABSTRACT Objective: Although renal artery aneurysms (RAAs) are uncommon, several large reports have been published indicating their benign natural history. The objective of our study was to review our single-center experience managing this disease entity. Methods: A retrospective review of the Yale radiologic database from January 1999 to December 2016 was performed. Only patients with RAA and a computed tomography scan of the abdomen were selected for review. Demographics of the patients, aneurysm characteristics, management, postoperative complications, and follow-up data were collected. Results: There were 241 patients with 259 RAAs identified, with a mean age of 69 years (range, 35-100 years); 147 were female (61%). On computed tomography, aneurysms were solitary and right sided in 224 (86%) and 159 (61%), respectively; 64 (27%) patients had aneurysms elsewhere. The breakdown of RAAs by location was as follows: renal bifurcation in 84 (32%), renal pelvis in 77 (30%), distal renal artery in 58 (22%), mid renal artery in 34 (13%), and proximal renal artery in 6 (2%). Five patients had symptoms that were attributed to the RAA and underwent operative repair; all others were observed without an operation. Symptoms in the operative repair group included flank pain in four and uncontrolled hypertension in one. The mean overall diameter of the RAAs was 1.22 6 0.49 cm. The diameter of operatively repaired and observed RAAs was 1.84 6 0.55 cm and 1.21 6 0.48 cm, respectively (P ¼ .002). Operative repair included four coil embolizations and one open resection. There were no renal function changes in any of these patients after operation and no other complications. Mean follow-up was 41 6 35 months for patients in the group that was observed; 18 of these RAAs were >2 cm, and none ruptured. On multivariable regression analysis, female sex (P ¼ .0001), smoking history (P ¼ .00007), left-sided RAA (P ¼ .03), and main renal artery location (P ¼ .03) were inversely related to growth, whereas a history of hypertension was directly related to growth rate (P ¼ .01). The mean growth rate for RAAs was 0.017 6 0.052 cm/y. Conclusions: RAAs tend to have a benign natural history. Although previous reports have not identified any factors that contribute to RAA growth, we observed that RAA location, sex, smoking history, and hypertension may have an impact on growth rates. No ruptures were observed. Operative repair at our institution was rare, with no morbidity or mortality. Observation of RAAs over time seems feasible in the asymptomatic patient with a small RAA. (J Vasc Surg 2018;68:137-44.)
Renal artery aneurysms (RAAs) are extremely rare, with a reported incidence of 0.01% to 0.09% in autopsy studies.1,2 However, more recent angiographic and cross-sectional imaging studies have reported the incidence of RAA to be closer to 1%.3,4 Although multiple reports recommend surgical intervention at a diameter >2 cm, there is no consensus regarding the treatment of RAAs because few studies have analyzed the natural history of these aneurysms.5-7 The prevention of RAA
rupture, which most likely occurs in <3% of cases,1,5,8 is the chief concern, given that rupture leads to an estimated nongestational mortality rate of 10%.1,5,8-10 However, many authors believe that there is not sufficient evidence to support the contention that larger RAAs rupture at higher rates.1,5,8,11,12 Whereas several series have observed patients with RAAs over time without rupture,3,13-15 only three studies have evaluated RAA growth rates to date.16-18 The
From the Aortic Institute at Yale-New Haven Hospital,a and the Section of
Poster presentation at the 2017 Vascular Annual Meeting of the Society for
Vascular and Endovascular Surgeryb and Department of Radiology and
Vascular Surgery, San Diego, Calif, May 31-June 3, 2017.
Biomedical Imaging, Division of Interventional Radiology,e Yale School of
Correspondence: John A. Elefteriades, MD, Aortic Institute at Yale-New Haven
Medicine, New Haven; the Department of Political Science and Economics,
Hospital, Yale University School of Medicine, 789 Howard Ave, Clinic Bldg
Rowan University, Glassboroc; the Department of Economics and Depart-
CB317, New Haven, CT 06519 (e-mail: [email protected]).
ment of Family, Population and Preventive Medicine, Stony Brook University,
The editors and reviewers of this article have no relevant financial rela-
Stony Brookd; and the Department of Surgical Diseases #2, Kazan State Med-
tionships to disclose per the JVS policy that requires reviewers to
ical University, Kazan.f A.J.B. was supported by the Richard K. Gershon, MD, Student Research Fellowship and the Yale University School of Medicine Medical Student Research Fellowship. Author conflict of interest: none.
decline review of any manuscript for which they may have a conflict of interest. 0741-5214 Copyright Ó 2018 by the Society for Vascular Surgery. Published by Elsevier Inc. https://doi.org/10.1016/j.jvs.2017.10.086
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largest of these studies reported a mean growth rate of 0.086 6 0.08 cm/y for 454 RAAs observed during a mean period of 49 months.16 Given the limited knowledge of the natural history of RAAs in the literature, the objectives of our study were to evaluate outcomes of treated RAAs (open and endovascular) and to delineate the growth and rupture rates of those RAAs managed nonoperatively at Yale-New Haven Hospital.
ARTICLE HIGHLIGHTS d
d
METHODS Patient cohort. RAAs were defined as focal dilations >50% of the normal diameter of the renal artery.19 The Yale radiology database was searched with specific search terms, including “renal artery aneurysm” and “renal aneurysm,” from January 1, 1999, through December 31, 2016, for patients who received a computed tomography (CT) diagnosis of RAA by a radiologist at Yale-New Haven Hospital. Patients were also identified by International Classification of Diseases, Ninth Revision disease codes 442.1 (aneurysm of renal artery) and 442.89 (aneurysm of other specified artery). Data collection included details of each patient’s clinical presentation, comorbidities, management, and followup data as identified through retrospective chart review (Table I). Consistent with prior reports, symptomatic patients were defined as those with flank pain, abdominal pain, hematuria, or difficult-to-control hypertension1,18 without other evident causes. Our primary outcomes included morbidity and mortality of operatively repaired RAAs and aneurysm growth rate and risk of rupture in those patients managed nonoperatively. Consent of individual patients for study inclusion was not obtained or required, and this study received approval from the Yale Institutional Review Board (HIC No. 1411014866) as a retrospective chart review. Imaging data and growth rate calculation. All CT scans were reanalyzed to collect data about aneurysm characteristics, including aneurysm laterality, RAA location (proximal renal artery, mid renal artery, distal renal artery, renal artery bifurcation, or within the renal pelvis), aneurysm calcification, and aneurysm diameter, as well as to identify the presence of other arterial aneurysms. Aneurysm diameter was determined by directly measuring aneurysm size from outer wall to outer wall. Observed growth rates were calculated for all patients with two or more CT scans, as follows: (diameter at last CT scanediameter at initial CT scan)/time interval between CT scans. In addition, estimated growth rates for RAAs were calculated with an instrumental variables approach. This method uses a variable (the time interval between imaging studies) that is measured accurately and correlates with changes in aneurysm size because patients with longer time intervals between CT scans should demonstrate greater true aneurysm growth.20 The estimates were obtained by means of regression
d
Type of Research: Single-center retrospective cohort study Take Home Message: In 241 patients with 259 renal artery aneurysms who were observed for a mean of 41 months, five required intervention for symptoms of flank pain (4) or uncontrolled hypertension (1); others remained asymptomatic with mean rate of growth of 0.017 cm/y. Recommendation: This study suggests that renal artery aneurysms are very slow growing and rarely require repair.
analysis in which aneurysm growth followed an exponential path. In particular, the natural logarithm of the last measured size to the first measured size was related to the time interval between the two tests and the disturbance term. Because the dependent variable has been transformed to the natural log form, we use Duan’s smearing estimator to calculate the expected value of the untransformed dependent variable. This method, which has been previously described,21 has been shown to be more accurate for both measuring aneurysm growth rates and estimating risk factors for aneurysm growth than simply calculating mean growth rate.21 This method was employed to minimize the impact of measurement errors on RAA growth rate calculations and to guard against disproportionately overweighting data of patients with stable aneurysms, who may have many repeated aneurysm measurements. Statistical analysis. Our primary outcomes were morbidity and mortality of all operatively repaired RAAs and aneurysm growth rate and risk of rupture in those patients managed nonoperatively. Data are reported using means and standard deviations for continuous variables or frequencies for categorical variables. Student t-tests were used to analyze the difference in aneurysm size between operatively repaired and nonoperatively managed groups. Fisher exact tests were used to compare comorbidity rates between nonoperatively managed and operatively repaired groups. Multivariable regression analysis was used to evaluate the impact of comorbidities and aneurysm characteristics on growth rate. Statistical analyses were performed using R (R Foundation for Statistical Computing, Vienna, Austria) and Social Science Statistics (www.socscistatistics.com).
RESULTS Patients. Between January 1999 and December 2016, we identified 241 patients with 259 RAAs who underwent a CT scan of the abdomen at the Yale-New Haven Hospital. The mean age at presentation was 68.6 6 13.7 (range, 35-100) years. The majority of patients were
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Table I. Comorbidities and clinical presentation of the patients Characteristic
Total patients (N ¼ 241)
Operative repair
Observed without operation
P
Demographics Age at initial presentation, years, mean 6 SD
68.6 6 13.7 (range, 35-100)
44.9 6 7.2
69.1 6 13.4
<.0001
White race
183 (76)
3 (60)
180 (76)
.596
Female
147 (61)
4 (80)
143 (61)
.651
227 (94)
0 (0)
Presentation 227 (96)
<.0001
Flank or abdominal pain
8 (3)
d
d
d
Difficult-to-control hypertension
1 (0.4)
d
d
d
Hematuria
7 (3)
d
d
d
Asymptomatic
Comorbidities Hypertension
173 (75)
3 (60)
170 (76)
NS
Hyperlipidemia
117 (51)
2 (50)
115 (50)
NS
Smoking history
110 (50)
1 (33)
109 (50)
NS
63 (28)
NS
Diabetes mellitus
64 (28)
Coronary artery disease
50 (22)
0 (0)
1 (25)
50 (22)
NS
Chronic kidney disease
39 (17)
0 (0)
39 (17)
NS
Chronic obstructive pulmonary disease
33 (14)
0 (0)
33 (14)
NS
Atrial fibrillation
28 (12)
0 (0)
28 (12)
NS
Congestive heart failure
25 (11)
0 (0)
25 (11)
NS
History of stroke or transient ischemic attack
23 (10)
0 (0)
23 (10)
NS
History of myocardial infarction
19 (8)
0 (0)
19 (8)
NS
Peripheral arterial disease
3 (1)
0 (0)
3 (1)
NS
Connective tissue disorder (Ehlers-Danlos syndrome)
1 (0.4)
0 (0)
1 (0.4)
NS
NS, Nonsignificant; SD, standard deviation. Values are reported as number (%) unless otherwise indicated. Boldface values indicate statistical significance (P < .05).
female (61%) and white (76%). Information on a number of comorbidities (Table I) was collected, including hypertension (75%), history of smoking (50%), chronic renal insufficiency (17%), diabetes mellitus (28%), and presence of connective tissue diseases (one patient had EhlersDanlos syndrome). Additional aneurysms were identified in 61 patients (25%), of which the most common locations were aneurysms of either the same or opposite renal artery (8%), the thoracic aorta (6%), the abdominal aorta (5%), the splenic artery (5%), and the iliac artery (3%). The majority of patients were asymptomatic (Table II) at presentation (94%). Operatively repaired patients presented at a significantly younger age than nonoperatively managed patients (P < .0001). Five patients had symptoms that were attributed to an RAA, including four patients with flank pain and one patient with difficult-to-control hypertension. Nine patients had hematuria or flank pain as described in a clinical note or in the indication for CT scan in the radiology report without another evident cause, so these patients were classified as symptomatic as well. Aneurysm characteristics. The distribution and location of RAAs are depicted in Fig 1, with the mean size
for each location depicted in Table II. CT scans of patients with RAAs in each location are displayed in Fig 2. The most common location of RAA was at the renal bifurcation (32%), followed by the renal pelvis (30%), the distal renal artery (22%), the mid renal artery (13%), and the proximal renal artery (2%). The majority of RAAs were located on the right side (61%; Table II) and were calcified (76%); 15 RAAs (6%) were bilateral. The mean diameter of all RAAs was 1.22 6 0.49 cm. The mean diameter of the 5 RAAs that underwent operative repair was 1.84 6 0.55 cm, whereas the mean diameter of the 254 RAAs that were observed was 1.21 6 0.48 cm (P ¼ .002). Treated RAAs. An overview of the management of those RAAs treated during our study period is shown in Fig 3. The five patients whose symptoms were attributed to the RAA underwent operative repair. One patient underwent open aneurysmorrhaphy of a 2.2-cm distal RAA; four patients underwent endovascular repair by coil embolization for three RAAs located in the renal pelvis and one RAA located at the renal artery bifurcation (Fig 4). One of the endovascular repairs was for a 0.81-cm traumatic pseudoaneurysm of the renal artery, which was the only identified pseudoaneurysm in our cohort. There were no perioperative complications,
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Table II. Renal artery aneurysm (RAA) characteristics
Characteristic
RAAs (N ¼ 259); mean 6 SD and/or No. (%)
Laterality Right sided Bilateral
159 (61) 15 (6)
Calcification Calcified Noncalcified
198 (76) 61 (24)
Location Proximal renal artery
6 (2); 1.62 6 0.77 cm
Mid renal artery
34 (13); 1.19 6 0.43 cm
Distal renal artery
58 (22); 1.22 6 0.42 cm
Renal bifurcation
84 (32); 1.16 6 0.53 cm
Renal pelvis
77 (30); 1.27 6 0.46 cm
Overall average diameter
1.22 6 0.49 cm
SD, Standard deviation.
Fig 1. Distribution of renal artery aneurysms (RAAs) by location.
The cause of death was not identified in eight patients. During the observation period, none of the RAAs ruptured, including in 11 patients with RAAs $2.0 cm who underwent CT imaging separated by a mean period of 53 6 28 months (range, 9-97 months). The overall growth rate, which was calculated using the 171 RAAs that were observed over time, was 0.017 6 0.052 cm/y. The majority of aneurysms (76%) did not grow, so the median and mode growth rates were both 0 cm/y. The frequency distribution of observed growth rates is depicted in Fig 5. RAA estimated growth rate, calculated using the instrumental variables approach described in the Methods section, was 0.022 6 0.008 cm/y. The frequency distribution of these estimated growth rates is depicted in Fig 6. To evaluate the impact of comorbidities and aneurysm characteristics on observed growth rates, a multivariable regression analysis was conducted. As shown in Table III, five variables were found to be statistically significant (P < .05). Hypertension was significantly associated with faster growth (odds ratio [OR], 1.011; 95% confidence interval [CI], 1.003-1.019; P ¼ .01), whereas a history of smoking (OR, 0.987, 95% CI, 0.981-0.993; P < .0001), female sex (OR, 0.987; 95% CI, 0.981-0.993; P < .0001), and aneurysm location on the left side (OR, 0.993; 95% CI, 0.988-0.999; P ¼ .03) were significantly associated with slower growth. Compared with aneurysms located in the renal pelvis, aneurysms located in the mid renal artery (OR, 0.983; 95% CI, 0.973-0.993; P ¼ .001), distal renal artery (OR, 0.990; 95% CI, 0.983-0.996; P ¼ .003), and renal artery bifurcation (OR, 0.992; 95% CI, 0.984-0.999; P ¼ .03) exhibited slower growth. In addition, aneurysm calcification was almost found to be significantly associated with slower growth (OR, 0.991; 95% CI, 0.982-1.000; P ¼ .05). The other nonsignificant variables analyzed included age, presence of chronic obstructive pulmonary disease, coronary artery disease, diabetes mellitus, chronic kidney disease, history of stroke, congestive heart failure, connective tissue disease, and multiple aneurysms.
DISCUSSION including no change in renal function, and no perioperative mortality. All patients who presented with flank pain improved after intervention. However, the patient who presented with hypertension remained hypertensive after intervention. Observed RAAs. There were 236 patients with 254 RAAs who did not undergo operative repair, of whom 159 patients with 171 RAAs had two or more CT scans that were on average 41 6 35 months apart (range, 1-142 months). There were 77 patients with 83 RAAs who were considered lost to follow-up because they had only one CT scan of the abdomen. Of these 77 patients, 22 died before the study data were analyzed, 14 of whom died of a known cause unrelated to the RAA.
Only three studies to date have documented the natural history of RAAs using growth rates (Table IV).16-18 This dearth of knowledge in the literature regarding the natural history of RAAs is consequential because it has traditionally been recommended that RAAs >2.0 cm undergo repair to avert a potentially fatal rupture event.5-7,22-24 However, controversially, some current evidence indicates that a 2.0-cm threshold for intervention may be too aggressive.5,16 Given the increased use of abdominal cross-sectional imaging in recent decades,18 the incidental detection of RAAs most likely will continue to increase, prompting the question of how these patients should optimally be managed. Because of these controversies and uncertainties, our study was undertaken.
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Fig 2. Examples of renal artery aneurysms (RAAs) by location (arrow): (A) proximal renal artery, (B) mid renal artery, (C) distal renal artery, (D) renal artery bifurcation, and (E) within the renal pelvis.
Fig 3. Management of patients with renal artery aneurysms (RAAs).
Our study is consistent with prior reports indicating that RAAs tend to have a benign natural history as we found no cases of RAA rupture. Also, these aneurysms grow at very slow rates. Early studies demonstrated rupture rates considerably higher (4.8% and 14% in two studies24,25) than the accepted contemporary rate of <3%.5,8 In the two largest studies to date of RAAs observed over time, no RAAs ruptured in the observed cohort in each study. Henke et al13 observed 86 RAAs during a mean followup of 72 months, whereas Klausner et al16 observed 454 aneurysms during a mean follow-up of 49 months. Henke et al and Klausner et al each reported three cases of RAA rupture at presentation, leading to overall
rupture rates of 1.2% and 0.3%, respectively. Importantly, Klausner et al observed 88 aneurysms between 2 and 3 cm that did not rupture, whereas the aneurysms that did rupture were all >3.0 cm, leading to a rupture rate of 18% for RAAs >3.0 cm. Wayne et al17 also reported no ruptures in a study of 68 RAAs observed during a median follow-up of 19.4 months, although 6 patients underwent elective repair of RAAs $2.5 cm. Moreover, Tham et al3 and Cinat et al,14 in a pooled analysis, reported no aneurysm ruptures among 69 RAAs during a mean follow-up of 4.3 years and 200 RAAs during a mean follow-up of 17 years, respectively. In our study, no ruptures among 259 RAAs occurred, including 171
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Fig 4. Renal artery aneurysm (RAA) before and after embolization. A, Saccular RAA at the renal artery bifurcation (red circle). B, Status after coil embolization of the RAA (arrow).
Fig 5. Frequency distribution of observed growth rates. RAA, Renal artery aneurysm.
RAAs that were observed for a mean follow-up between CT scans of 41 6 35 months, 11 RAAs $2.0 cm observed during a period of 53 6 28 months, and 2 RAAs of 3.0 cm in diameter. Therefore, our results are consistent with those of Klausner et al, who posited that observation of RAAs between 2.0 and 3.0 cm among asymptomatic, nonpregnant patients may be warranted.16 However, RAAs can rupture at sizes <3.0 cm and even <2.0 cm.1,2628 These findings highlight the unpredictability of behavior in some cases. In addition to simple arithmetic calculation, we employed an instrumental variables method21 to estimate RAA growth rates to reduce measurement error. This method has been demonstrated to be more accurate for calculating aneurysm growth rates than using mean growth rate.21 Table IV depicts our observed mean and estimated RAA growth rates, which were 0.017 6 0.052 cm/y and 0.022 6 0.008 cm/y, respectively, compared with growth rates observed in the three other studies in the literature.
Fig 6. Frequency distribution of estimated growth rates. RAA, Renal artery aneurysm.
Our finding that 76% of RAAs observed did not grow during the follow-up period is consistent with prior reports as the majority of RAAs reported by Wayne et al and Klausner et al remained the same size. Morita et al29 also found that among 30 RAA patients managed conservatively, only two experienced growth during a median follow-up of 65.4 months. However, our observed and estimated growth rates are four and five times slower, respectively, than the growth rate reported by Klausner et al. Because most of our patients were identified by a search of the Yale radiology database, it is more likely that we would identify RAAs incidentally. In fact, 94% of our RAAs were asymptomatic and were detected incidentally, whereas Klausner et al reported that only 75% of their patients were asymptomatic at presentation. As a result, our cohort of RAAs may be predisposed to have a benign natural history. According to the literature, approximately 70% of RAA patients have hypertension,30 which is similar to the 75% of patients we identified with hypertension.
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Table III. Multivariable regression analysis analyzing the impact of comorbidities and aneurysm characteristics on growth rate Direction of impact on renal aneurysm growth
Variable
(OR; 95% CI) P value
Hypertension
Increased
(1.011; 1.003-1.019) .01
Smoking history
Decreased
(0.987; 0.981-0.993) <.001
Female sex
Decreased
(0.987; 0.981-0.993) <.001
Mid renal artery location (relative to renal pelvis aneurysms)
Decreased
(0.983; 0.973-0.993) .001
Distal renal artery location (relative to renal pelvis aneurysms)
Decreased
(0.990; 0.983-0.996) .003
Renal artery bifurcation location (relative to renal pelvis aneurysms)
Decreased
(0.992; 0.984-0.999) .03
Left side
Decreased
(0.993; 0.988-0.999) .03
Aneurysm calcification
Decreased
(0.991; 0.982-1.000) .05
CI, Confidence interval; OR, odds ratio.
Table IV. Studies reporting growth rates of renal artery aneurysms (RAAs) in the literature Study
No. of aneurysms Mean follow-up, Mean aneurysm Method for calculating Rupture observed months size, cm Growth rate, cm/y growth rate rate, %
Klausner et al, 201418
14
36 6 9
Wayne et al, 2014
68
19.4
1.6 6 0.64
49
Klausner et al, 201516 Yale a
454 171
41 6 35
1.4 6 0.1
0.06 6 0.016
Mean
0
0.006
Median
0
1.3 6 0.1
0.086 6 0.08
Mean
0a
1.21 6 0.48
0.017 6 0.052 (0.022 6 0.008)
Mean (estimated)
0
Three patients in this study presented with a ruptured renal artery aneurysm, leading to an overall rupture rate of 0.3%.
In addition, we observed that 61% of RAA patients were female, which is consistent with prior reports demonstrating that up to 72% of RAA patients are female, most likely attributable to the increased prevalence of fibromuscular dysplasia among women.30 Our multivariable analysis findings, including faster RAA growth among patients with hypertension and slower growth among female patients, indicate that these variables may have very small effects on RAA growth. In our cohort, operative repair was safe with no associated perioperative morbidity or mortality, although our cohort of patients who underwent RAA repair was small. Four of our patients underwent coil embolization for RAAs within the renal pelvis or at the renal bifurcation, whereas one underwent open resection of a distal RAA. As reviewed by Coleman and Stanley,30 endovascular repair and open repair both lead to low rates of morbidity and mortality and have not been shown to be significantly different from each other in terms of outcomes. The patient’s comorbidities, the aneurysm’s location and morphology, and the surgeon’s preference should all be considered in deciding the best mode for operative repair. The main limitations of this study are our small sample size and short follow-up. Our calculated growth rates should be assessed with a degree of skepticism, given these limitations. To obtain as accurate a growth rate as possible, we included only patients with CT scan imaging to minimize measurement error due to differences in
imaging modalities. Furthermore, we also used only two size measurements per patient (even when there were more available) because, in general, patients with less stable aneurysms will tend to have fewer measured sizes, as they are more likely to be eventually selected out for surgical repair. However, this potential source of bias in calculating growth rates did not apply to our study in any event as only one patient in the operatively repaired group had been observed over time and ultimately underwent repair because of the presence of symptoms as opposed to rapid RAA growth. Last, because we did not observe any aneurysm ruptures, we could not identify any risk factors for RAA rupture.
CONCLUSIONS Our single-center study is consistent with recent reports indicating that RAAs tend to have a benign natural history with extremely low rupture rates and slow growth rates. Therefore, as other authors have articulated,5,16 a size threshold of 2.0 cm may be too aggressive for asymptomatic, nonpregnant patients. Our study is the first to report significant associations with RAA growth rates, including several patient characteristics (hypertension, female sex, and smoking history) and aneurysm characteristics (laterality and location within the renal artery). The clinical significance of these findings is unclear, given that we observed no RAA ruptures, and the effects of these variables on RAA growth appear to be quite small.
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Journal of Vascular Surgery July 2018
AUTHOR CONTRIBUTIONS Conception and design: AB, YE, JE Analysis and interpretation: AB, YE, SR, YL, JR, HM, BZ, JE Data collection: AB, YE, SR, HM Writing the article: AB, YE, BZ, JE Critical revision of the article: AB, YE, SR, YL, JR, HM, BZ, JE Final approval of the article: AB, YE, SR, YL, JR, HM, BZ, JE Statistical analysis: AB, YL, JR Obtained funding: Not applicable Overall responsibility: JE AB and YE contributed equally to this article and share first authorship.
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Submitted Jul 10, 2017; accepted Oct 26, 2017.