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Vascular OnlineFirst, published on May 12, 2015 as doi:10.1177/1708538115586917
Original Article
The association of simple renal cysts with abdominal aortic aneurysms and their impact on renal function after endovascular aneurysm repair
Vascular 0(0) 1–7 ! The Author(s) 2015 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav DOI: 10.1177/1708538115586917 vas.sagepub.com
Konstantinos Spanos1, Christos Rountas2, Vasileios Saleptsis1, Athanasios Athanasoulas1, Ioannis Fezoulidis2 and Athanasios D Giannoukas1
Abstract We validated the association of simple renal cysts with abdominal aortic aneurysm and other cardiovascular factors and assessed simple renal cysts’ impact on renal function before and after endovascular abdominal aortic aneurysm repair. A retrospective analysis of prospectively collected data was conducted. Computed tomography angiograms of 100 consecutive male patients with abdominal aortic aneurysm who underwent endovascular abdominal aortic aneurysm repair (Group 1) were reviewed and compared with 100 computed tomography angiogram of aged-matched male patients without abdominal aortic aneurysm (Group 2). Patients’ demographic data, risk factors, abdominal aortic aneurysm diameter, the presence of simple renal cyst and laboratory tests were recorded. No difference was observed between the two groups in respect to other cardiovascular risk factors except hyperlipidemia with higher prevalence in Group 1 (p < 0.05). Presence of simple renal cysts was independently associated with age (p < 0.05) and abdominal aortic aneurysm (p ¼ 0.0157). There was no correlation between simple renal cysts and abdominal aortic aneurysm size or preoperative creatinine and urea levels. No difference was observed in post-operative creatinine and urea levels either immediately after endovascular abdominal aortic aneurysm repair or in 12-month follow-up. In male patients, the presence of simple renal cysts is associated with abdominal aortic aneurysm and is increasing with age. However, their presence is neither associated with impaired renal function pre-endovascular abdominal aortic aneurysm repair and post-endovascular abdominal aortic aneurysm repair nor after 12-month follow-up.
Keywords Simple renal cyst, abdominal aortic aneurysm, endovascular aortic aneurysm repair
Introduction The prevalence of abdominal aortic aneurysm (AAA) is 8.2% in men and 1.7% in women.1,2 Associated risk factors for AAA are age, male sex, smoking and familial history of AAA. Additionally, there are weaker and inconsistent associations with other manifestations of cardiovascular disease and risk factors such as hypertension (HT) and hyperlipidemia (HL).3 AAAs’ morphology is evaluated with computed tomography angiograms (CTAs) in order to define whether endovascular approach is indicated.4,5 On the CT scan, incidental associated findings such as renal cysts may be discovered. There are only a few published data reporting on the frequency of simple renal
cysts (SRCs).6–8 Nevertheless, the role of such frequency of SRCs in patients with AAA has not been thoroughly investigated not only in respect to a 1
Department of Vascular Surgery, University Hospital of Larissa, Faculty of Medicine, School of Health Sciences, University of Thessaly, Larissa, Greece 2 Department of Radiology, University Hospital of Larissa, Faculty of Medicine, School of Health Sciences, University of Thessaly, Larissa, Greece Corresponding author: Konstantinos Spanos, Department of Vascular Surgery, University Hospital of Larissa, Faculty of Medicine, School of Health Sciences, University of Thessaly, Larissa, Greece. Email: [email protected]
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potential interrelated mechanism between SRCs and AAA development but also concerning their impact on the renal function after endovascular abdominal aortic aneurysm repair (EVAR) because of the use of nephrotoxic contrast agents.9,10 SRCs are considered to be acquired and harmless lesions, consisting of a disease different from hereditary polycystic kidney disease. In contrast, autosomal dominant polycystic kidney disease (ADPKD) is a prevalent and inherited condition which is clearly related to mutation in polycystic kidney disease genes (PKD1and/or PKD2), and thus, it is an entity entirely different from the SRCs.11 It appears though that there is lack of evidence regarding the existence of any common pathogenetic pathway between the development of SRCs and AAA. The aim of our study was to evaluate how strong is the association between the presence of SRCs and AAA, to assess their impact on renal function pre-, immediately post-EVAR and during 12-month follow-up, and whether the presence of SRCs consists a relative contraindication for EVAR.
Methodology Study design and data collection A retrospective study was undertaken including the review of CTA of 100 consecutive male patients with an AAA with diameter >50 mm (Group 1). These CTA were compared with those from 100 male aged-matched consecutive patients who underwent a CTA for a reason other than an AAA (Group 2) in the same period of two years (2011–2013) and were retrieved from Radiology Department database. All patients in Group 1 had an EVAR procedure, and their operative data were retrieved from the prospectively kept database of Vascular surgery Department in our hospital. Patients’ demographic data along with their risk factors, such as HT, HL, diabetes mellitus (DM), coronary artery disease (CAD) and chronic obstructive pulmonary disease (COPD) and laboratory tests such as creatinine (Cr) and urea levels (pre- and immediately post-operatively), as well as the presence or absence of SRCs on CTA were recorded and retrieved from University Hospital of Larisa database. EVAR was performed in a single centre. All patients had oneyear follow-up, so CTA was conducted in Group 1 as it is recommended.12 Renal function assessment with Cr and urea levels of each patient was necessary before performing the CTA, and it was recorded. This study was an observational study in which research involved the collection of existing data, and diagnostic tests that have been recorded in such a manner that subjects could not be identified, either directly or through identifiers linked to the subject. However,
this study was conducted with the approval of the institutional review board.
Definitions The presence of AAA requiring treatment was set based on the aortic diameter >50 mm and were treated according to the guidelines.12 The absence of AAA was defined as aortic diameter 140 mmHg, elevated total cholesterol (>180 mg/dL) and LDL (>130 mg/dL) were recorded on the admission day into the hospital. COPD was confirmed when patients were on inhaler treatment. History of previous myocardial infraction or angina or coronary intervention confirmed the presence of CAD, while diabetes mellitus was confirmed when the patient was on antidiabetic treatment.
Statistical analysis To assess the effect of all observed factors and covariates on renal cyst, each one was initially examined
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separately, and the significant predictors at significance level p1 ¼ 0.20 were identified. These were used in a binary logistic regression model. The formerly non-significant factors were then reexamined at level p2 ¼ 0.10. Interactions between the main effects of the final model were also considered. The enter method with significance level p3 ¼ 0.05 was used to obtain p values and odds ratios for the main effects and interactions of the final model. Analysis was carried out using SPSS v 21.0. The chi-square (c2) test was used to evaluate the differences between the groups of patients for categorical variables (c2 for independent groups, two-tailed p value). In addition, post hoc power calculations were carried out using G-power 3.0.17
Results The demographic data and comorbidities present in the patients included in our study are depicted in Table 1. HL was the only factor significantly higher in the AAA group (p < 0.05). The mean age of the patients was 72.12 (2.2). In Group 1, the presence or absence of SRCs was not statistically significantly related to any of the atherosclerotic risk factors (DM, HT and HL), CAD or COPD. No family history relation of SRCs was detected among patients with SRCs. In Group 1, no statistical significance was observed regarding AAA size, Cr levels pre- and immediately post-EVAR (Figures 1 and 2) and contrast volume used in relation to presence or absence of SRCs (Table 2). The mean volume of contrast agent is also displayed in Table 2. There was no AKI in any patient immediately postEVAR according to KDIGO guidelines.16 Most of the patients had undergone EVAR with a suprarenal fixation stent graft system (60/100) while the rest of the patients with an infrarenal one (40/100). However, the stent graft’s fixation system did not influence renal function (Cr and urea levels between normal
range)18 either immediately post-operatively or after 12 months, thus no further analysis was conducted. The prevalence of SRCs in Group 1 (AAA) was 63% (63/100) and in Group 2 (without AAA) was 45% (45/ 100). AAA (p ¼ 0.0157) and age (p < 0.05) were the only factors which were statistically associated with the presence of SRCs. For each year of age, the possibility of SRC’s presence increased by 10.8%, while for patients suffering from AAA the possibility of SRC’s presence was almost doubled (increased by 99.6%) in relation to those without AAA. However, after a power calculation analysis, the presence of SRCs was only indicative for the coexistence of an AAA (power-uncorrected: 0.7270). On the other hand, the increase of age was statistically significant and directly correlated with the presence of AAA (power: 0.9892). One-year follow-up CTA was conducted in every patient who had undergone EVAR as it is recommended.12 All patients had undergone blood test for Cr and urea levels before performing the CTA. There was no renal impairment in any patient post-EVAR according to KDIGO guidelines,14 and thus Cr and urea levels were within the normal limits in both groups of patients (Cr EVAR patients with SRCs: 1.12 0.23 mg/dL vs. Cr EVAR patients without SRCs: 1.09 0.19 mg/dL) except in one patient with SRCs and DM who developed 10-month post-EVAR mild renal impairment (Cr 2.0 mg%) not requiring dialysis.
Discussion SRCs are the most common incidental finding during ultrasound or CTA, and their incidence increases with age. In CT studies, the prevalence ranges from 24% to 27% in patients older than 50 years.19,20 There is a suspicion that their presence is correlated with the development of AAA disease.6–8 In an autopsy study
Table 1. Demographics and co-morbidities of patients in Group 1 and Group 2. AAA – Group 1
PT Age DM HT HL CAD COPD
No AAA – Group 2
Renal cyst
No cyst
Renal cyst
No cyst
p
63/100 73 1.4 14 (22%) 55 (87%) 44 (70%) 22 (35%) 9 (14%)
37/100 68 2.1 6 (16%) 32 (86.4%) 26 (70%) 16 (43%) 4 (11%)
45/100 73 1.5 15 (33.3%) 40 (88.8%) 15 (33.3%) 16 (35.5%) 7 (15.5%)
55/100 70 1.3 13 (23.6%) 46 (83.6%) 17 (31%) 19 (34.5%) 7 (12.7%)
na ns ns ns 50 mm (p < 0.023) and age (p < 0.05) was the only statistically significant factor that had direct association with the presence of SRCs. Because of the small numbers included in our study, post hoc power calculation analysis was undertaken in order to assess the strength of the associations. This analysis showed that the correlation between the presence of SRCs and AAA was indicative and almost reached the power to draw strong conclusions. However, further studies with larger numbers are needed to confirm our observation. In case that an association of SRCs with AAA is confirmed, it may have a useful implication as incidentally found SRCs may justify regular ultrasonic followup for early diagnosis of AAA in future or even consist a tool for screening programs.25,26 In our study, each patient’s renal function was assessed according to the European Renal Best Practice and KDIGO guidelines.16 In a previous report,24 it has been shown that in patients younger than 60 years, the presence of SRCs has been associated
with impaired renal function as defined by changes in the serum Cr levels and Cr clearance; however, this relation did not apply for patients over 60 years. Our results remain in the line of this report,24 and the presence of SRCs in our patients who were all over 60 years (one of the inclusions criteria) was not associated with renal impairment. Additionally, we assessed whether the presence of SRCs in patients who underwent EVAR was associated with any renal function impairment immediately post-operatively and after 12 months. To the best of our knowledge, our study is the first to report that the presence of renal cysts does not have any impact on the renal function and is not associated with AKI or susceptibility in CIN immediately post-EVAR (Table 2). Thus, it was demonstrated that the renal function of patients with SRCs were not affected, although potential nephrotoxic contrast agent was used.9,10 Additionally, no association between renal impairment and the type of stent graft fixation (suprarenal vs. infrarenal) was found immediately or one-year post-operatively. This remains in the line with previous reports in which suprarenal endograft fixation was not causing any renal impairment after EVAR when comparing with infrarenal endograft fixation.27–31 In contrast, there are other reports that have demonstrated that suprarenal fixation was associated with renal function deterioration 12-month postEVAR.32,33 Therefore, it appears that this issue is still controversial, and larger studies are needed for clarification. Finally, there is lack of evidence regarding the existence of any common pathogenetic pathway between the development of SRCs and AAA. Speculatively, it could be suspected an interrelation in the metabolism of collagen and elastin that may be implicated in both entities, but this requires further research. Potential limitations of our study are the small number of samples included as well as the fact that it was of retrospective nature. Additionally as we included only male individuals, the extrapolation of our findings to females does not apply.
Conclusions The prevalence of SRCs is increasing with the age. In male patients especially in those over 60 years, the presence of AAA is associated with SRCs. Early diagnosis of SRCs may help to select individuals at high risk to develop AAA in future and in whom a regular ultrasonic follow-up could be justified. EVAR in the presence of SRCs is not associated with any additional burden to renal function even after mid-term followup. Future research is needed to investigate whether there is any common pathway in the development of SRCs and AAA.
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Conflict of interest None declared.
Funding This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.
13. 14.
References
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1. Singh K, Bønaa KH, Jacobsen BK, et al. Prevalence of and risk factors for abdominal aortic aneurysms in a population-based study. The Tromsø study. Am J Epidemiol 2001; 154: 236–244. 2. Barba A´, Vega de Ce´niga M, Estallo L, et al. Prevalence of abdominal aortic aneurysm is still high in certain areas of southern Europe. Ann Vasc Surg 2013; 27: 1068–1073. DOI: 10.1016/j.avsg.2013.01.017. 3. Norman PE and Powell JT. Abdominal aortic aneurysm: the prognosis in women is worse than in men. Circulation 115: 2865–2869. 4. IMPROVE Trial Investigators, Powell JT, Sweeting MJ, et al. Endovascular or open repair strategy for ruptured abdominal aortic aneurysm: 30 day outcomes from IMPROVE randomized trial. BMJ 2014; 348: f7661. DOI: 10.1136/bmj.f7661. 5. Goshima S, Kanematsu M, Kondo H, et al. Preoperative planning for endovascular aortic repair of abdominal aortic aneurysms: feasibility of nonenhanced MR angiography versus contrast-enhanced CT angiography. Radiology 2013; 267: 948–955. DOI: 10.1148/radiol. 13121557. 6. Yaghoubian A, De Virgilio C, White RA, et al. Increased incidence of renal cysts in patients with abdominal aortic aneurysms: a common pathogenesis? Ann Vasc Surg 2006; 20: 787–791. 7. Ito T, Kawaharada N, Kurimoto Y, et al. Renal cysts as strongest association with abdominal aortic aneurysm in elderly. Ann Vasc Dis 2010; 3: 111–116. 8. Pitoulias G, Donas KP, Chatzimavroudis G, et al. The role of simple renal cysts, abdominal wall hernia, and chronic obstructive pulmonary disease as predictive factors for aortoiliac aneurysmatic disease. World J Surg 2012; 36: 1953–1957. 9. Parfrey PS, Griffiths SM, Barrett BJ, et al. Contrast material-induced renal failure in patients with diabetes mellitus, renal insufficiency, or both. A prospective controlled study. N Engl J Med 1989; 320: 143–149. 10. Lee J, Cho JY, Lee HJ, et al. Contrast-induced nephropathy in patients undergoing intravenous contrast-enhanced computed tomography in Korea: a multi-institutional study in 101487 patients. Korean J Radiol 2014; 15: 456–463. DOI: 10.3348/kjr.2014.15.4.456. 11. Takiar V and Caplan MJ. Polycystic kidney disease: pathogenesis and potential therapies. Biochim Biophys Acta 2011; 1812: 1337–1343. DOI: 10.1016/ j.bbadis.2010.11.014 (review). 12. Walker G, Kalva SP, Yeddula K, et al. Clinical practice guidelines for endovascular abdominal aortic aneurysm repair: written by the Standards of Practice Committee
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for the Society of Interventional Radiology and endorsed by the Cardiovascular and Interventional Radiological Society of Europe and the Canadian Interventional Radiology Association. J Vasc Interv Radiol 2010; 21: 1632–1655. Bosniak MA. The current radiological approach to renal cysts. Radiology 1986; 158: 1–10. Whelan TF. Guidelines on the management of renal cyst disease. Can Urol Assoc J 2010; 4: 98–99. Paravastu SC, Jayarajasingam R, Cottam R, et al. Endovascular repair of abdominal aortic aneurysm. Cochrane Database Syst Rev 2014; 23: CD004178. DOI: 10.1002/14651858.CD004178.pub2, (review). Fliser D, Laville M, et al Ad-hoc working group of ERBP. A European Renal Best Practice (ERBP) position statement on the Kidney Disease Improving Global Outcomes (KDIGO) clinical practice guidelines on acute kidney injury: part 1: definitions, conservative management and contrast-induced nephropathy. Nephrol Dial Transplant 2012; 27: 4263–4272. DOI: 10.1093/ndt/ gfs375. Faul F, Erdfelder E, Lang AG, et al. G*Power 3: a flexible statistical power analysis program for the social, behavioral, and biomedical sciences. Behav Res Methods 2007; 39: 175–191. Israni AK and Kasiske BL. Laboratory assessment of kidney disease: glomerular filtration rate, urinalysis, and proteinuria. In: Taal MW, Chertow GM, Marsden PA, et al. (eds) Brenner and Rector’s the kidney. 9th ed. Philadelphia, PA: Elsevier Saunders, 2011, chap 25. Laucks SP Jr and McLachlan MS. Aging and simple cysts of the kidney. Br J Radiol 1981; 54: 12–14. Tada S, Yamagishi J, Kobayashi H, et al. The incidence of simple renal cyst by computed tomography. Clin Radiol 1983; 34: 437–439. Kurata A, Inoue S, Ohno S, et al. Correlation between number of renal cysts and aortic circumferences measured using autopsy material. Pathol Res Pract 2013; 209: 441–447. Lee CT, Yang YC, Wu JS, et al. Multiple and large simple renal cysts are associated with prehypertension and hypertension. Kidney Int 2013; 83: 924–930. DOI: 10.1038/ki.2012.481. Hong S, Lim JH, Jeong IG, et al. What association exists between hypertension and simple renal cyst in a screened population? J Hum Hypertens 2013; 27: 539–544. DOI: 10.1038/jhh.2013.12. Al-Said J, Brumback MA, Moghazi S, et al. Reduced renal function in patients with simple renal cysts. Kidney Int 2004; 65: 2303–2308. Cosgrove DO, Meire HB, Lim A, et al. Ultrasound: general principles. In: Adam A, Dixon AK (eds) Grainger & Allisonn’s diagnostic radiology: a textbook of medical imaging. 5th ed. New York, NY: Churchill Livingstone, 2008, chap 3. Bergqvist D, Bjo¨rck M and Wanhainen A. Abdominal aortic aneurysm and new WHO criteria for screening. Int Angiol 2013; 32: 37–41. Parmer SS and Carpenter JP Endologix Investigators. Endovascular aneurysm repair with suprarenal vs
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infrarenal fixation: a study of renal effects. J Vasc Surg 2006; 43: 19–25. 28. Alsac JM, Zarins CK, Heikkinen MA, et al. The impact of aortic endografts on renal function. J Vasc Surg 2005; 41: 926–930. 29. Davey P, Rose JD, Parkinson T, et al. The mid-term effect of bare metal suprarenal fixation on renal function following endovascular abdominal aortic aneurysm repair. Eur J Vasc Endovasc Surg 2006; 32: 516–522. 30. Lau LL, Hakaim AG, Oldenburg WA, et al. Effect of suprarenal versus infrarenal aortic endograft fixation on renal function and renal artery patency: a comparative study with intermediate follow-up. J Vasc Surg 2003; 37: 1162–1168.
31. Alric P, Hinchliffe RJ, Picot MC, et al. Long-term renal function following endovascular aneurysm repair with infrarenal and suprarenal aortic stent-grafts. J Endovasc Ther 2003; 10: 397–405. 32. Saratzis A, Sarafidis P, Melas N, et al. Suprarenal graft fixation in endovascular abdominal aortic aneurysm repair is associated with a decrease in renal function. J Vasc Surg 2012; 56: 594–600. 33. Kouvelos GN, Boletis I, Papa N, et al. Analysis of effects of fixation type on renal function after endovascular aneurysm repair. J Endovasc Ther 2013; 20: 334–344. DOI: 10.1583/12-4177MR.1.
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Vascular OnlineFirst, published on May 12, 2015 as doi:10.1177/1708538115586917
Original Article
The association of simple renal cysts with abdominal aortic aneurysms and their impact on renal function after endovascular aneurysm repair
Vascular 0(0) 1–7 ! The Author(s) 2015 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav DOI: 10.1177/1708538115586917 vas.sagepub.com
Konstantinos Spanos1, Christos Rountas2, Vasileios Saleptsis1, Athanasios Athanasoulas1, Ioannis Fezoulidis2 and Athanasios D Giannoukas1
Abstract We validated the association of simple renal cysts with abdominal aortic aneurysm and other cardiovascular factors and assessed simple renal cysts’ impact on renal function before and after endovascular abdominal aortic aneurysm repair. A retrospective analysis of prospectively collected data was conducted. Computed tomography angiograms of 100 consecutive male patients with abdominal aortic aneurysm who underwent endovascular abdominal aortic aneurysm repair (Group 1) were reviewed and compared with 100 computed tomography angiogram of aged-matched male patients without abdominal aortic aneurysm (Group 2). Patients’ demographic data, risk factors, abdominal aortic aneurysm diameter, the presence of simple renal cyst and laboratory tests were recorded. No difference was observed between the two groups in respect to other cardiovascular risk factors except hyperlipidemia with higher prevalence in Group 1 (p < 0.05). Presence of simple renal cysts was independently associated with age (p < 0.05) and abdominal aortic aneurysm (p ¼ 0.0157). There was no correlation between simple renal cysts and abdominal aortic aneurysm size or preoperative creatinine and urea levels. No difference was observed in post-operative creatinine and urea levels either immediately after endovascular abdominal aortic aneurysm repair or in 12-month follow-up. In male patients, the presence of simple renal cysts is associated with abdominal aortic aneurysm and is increasing with age. However, their presence is neither associated with impaired renal function pre-endovascular abdominal aortic aneurysm repair and post-endovascular abdominal aortic aneurysm repair nor after 12-month follow-up.
Keywords Simple renal cyst, abdominal aortic aneurysm, endovascular aortic aneurysm repair
Introduction The prevalence of abdominal aortic aneurysm (AAA) is 8.2% in men and 1.7% in women.1,2 Associated risk factors for AAA are age, male sex, smoking and familial history of AAA. Additionally, there are weaker and inconsistent associations with other manifestations of cardiovascular disease and risk factors such as hypertension (HT) and hyperlipidemia (HL).3 AAAs’ morphology is evaluated with computed tomography angiograms (CTAs) in order to define whether endovascular approach is indicated.4,5 On the CT scan, incidental associated findings such as renal cysts may be discovered. There are only a few published data reporting on the frequency of simple renal
cysts (SRCs).6–8 Nevertheless, the role of such frequency of SRCs in patients with AAA has not been thoroughly investigated not only in respect to a 1
Department of Vascular Surgery, University Hospital of Larissa, Faculty of Medicine, School of Health Sciences, University of Thessaly, Larissa, Greece 2 Department of Radiology, University Hospital of Larissa, Faculty of Medicine, School of Health Sciences, University of Thessaly, Larissa, Greece Corresponding author: Konstantinos Spanos, Department of Vascular Surgery, University Hospital of Larissa, Faculty of Medicine, School of Health Sciences, University of Thessaly, Larissa, Greece. Email: [email protected]
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potential interrelated mechanism between SRCs and AAA development but also concerning their impact on the renal function after endovascular abdominal aortic aneurysm repair (EVAR) because of the use of nephrotoxic contrast agents.9,10 SRCs are considered to be acquired and harmless lesions, consisting of a disease different from hereditary polycystic kidney disease. In contrast, autosomal dominant polycystic kidney disease (ADPKD) is a prevalent and inherited condition which is clearly related to mutation in polycystic kidney disease genes (PKD1and/or PKD2), and thus, it is an entity entirely different from the SRCs.11 It appears though that there is lack of evidence regarding the existence of any common pathogenetic pathway between the development of SRCs and AAA. The aim of our study was to evaluate how strong is the association between the presence of SRCs and AAA, to assess their impact on renal function pre-, immediately post-EVAR and during 12-month follow-up, and whether the presence of SRCs consists a relative contraindication for EVAR.
Methodology Study design and data collection A retrospective study was undertaken including the review of CTA of 100 consecutive male patients with an AAA with diameter >50 mm (Group 1). These CTA were compared with those from 100 male aged-matched consecutive patients who underwent a CTA for a reason other than an AAA (Group 2) in the same period of two years (2011–2013) and were retrieved from Radiology Department database. All patients in Group 1 had an EVAR procedure, and their operative data were retrieved from the prospectively kept database of Vascular surgery Department in our hospital. Patients’ demographic data along with their risk factors, such as HT, HL, diabetes mellitus (DM), coronary artery disease (CAD) and chronic obstructive pulmonary disease (COPD) and laboratory tests such as creatinine (Cr) and urea levels (pre- and immediately post-operatively), as well as the presence or absence of SRCs on CTA were recorded and retrieved from University Hospital of Larisa database. EVAR was performed in a single centre. All patients had oneyear follow-up, so CTA was conducted in Group 1 as it is recommended.12 Renal function assessment with Cr and urea levels of each patient was necessary before performing the CTA, and it was recorded. This study was an observational study in which research involved the collection of existing data, and diagnostic tests that have been recorded in such a manner that subjects could not be identified, either directly or through identifiers linked to the subject. However,
this study was conducted with the approval of the institutional review board.
Definitions The presence of AAA requiring treatment was set based on the aortic diameter >50 mm and were treated according to the guidelines.12 The absence of AAA was defined as aortic diameter 140 mmHg, elevated total cholesterol (>180 mg/dL) and LDL (>130 mg/dL) were recorded on the admission day into the hospital. COPD was confirmed when patients were on inhaler treatment. History of previous myocardial infraction or angina or coronary intervention confirmed the presence of CAD, while diabetes mellitus was confirmed when the patient was on antidiabetic treatment.
Statistical analysis To assess the effect of all observed factors and covariates on renal cyst, each one was initially examined
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separately, and the significant predictors at significance level p1 ¼ 0.20 were identified. These were used in a binary logistic regression model. The formerly non-significant factors were then reexamined at level p2 ¼ 0.10. Interactions between the main effects of the final model were also considered. The enter method with significance level p3 ¼ 0.05 was used to obtain p values and odds ratios for the main effects and interactions of the final model. Analysis was carried out using SPSS v 21.0. The chi-square (c2) test was used to evaluate the differences between the groups of patients for categorical variables (c2 for independent groups, two-tailed p value). In addition, post hoc power calculations were carried out using G-power 3.0.17
Results The demographic data and comorbidities present in the patients included in our study are depicted in Table 1. HL was the only factor significantly higher in the AAA group (p < 0.05). The mean age of the patients was 72.12 (2.2). In Group 1, the presence or absence of SRCs was not statistically significantly related to any of the atherosclerotic risk factors (DM, HT and HL), CAD or COPD. No family history relation of SRCs was detected among patients with SRCs. In Group 1, no statistical significance was observed regarding AAA size, Cr levels pre- and immediately post-EVAR (Figures 1 and 2) and contrast volume used in relation to presence or absence of SRCs (Table 2). The mean volume of contrast agent is also displayed in Table 2. There was no AKI in any patient immediately postEVAR according to KDIGO guidelines.16 Most of the patients had undergone EVAR with a suprarenal fixation stent graft system (60/100) while the rest of the patients with an infrarenal one (40/100). However, the stent graft’s fixation system did not influence renal function (Cr and urea levels between normal
range)18 either immediately post-operatively or after 12 months, thus no further analysis was conducted. The prevalence of SRCs in Group 1 (AAA) was 63% (63/100) and in Group 2 (without AAA) was 45% (45/ 100). AAA (p ¼ 0.0157) and age (p < 0.05) were the only factors which were statistically associated with the presence of SRCs. For each year of age, the possibility of SRC’s presence increased by 10.8%, while for patients suffering from AAA the possibility of SRC’s presence was almost doubled (increased by 99.6%) in relation to those without AAA. However, after a power calculation analysis, the presence of SRCs was only indicative for the coexistence of an AAA (power-uncorrected: 0.7270). On the other hand, the increase of age was statistically significant and directly correlated with the presence of AAA (power: 0.9892). One-year follow-up CTA was conducted in every patient who had undergone EVAR as it is recommended.12 All patients had undergone blood test for Cr and urea levels before performing the CTA. There was no renal impairment in any patient post-EVAR according to KDIGO guidelines,14 and thus Cr and urea levels were within the normal limits in both groups of patients (Cr EVAR patients with SRCs: 1.12 0.23 mg/dL vs. Cr EVAR patients without SRCs: 1.09 0.19 mg/dL) except in one patient with SRCs and DM who developed 10-month post-EVAR mild renal impairment (Cr 2.0 mg%) not requiring dialysis.
Discussion SRCs are the most common incidental finding during ultrasound or CTA, and their incidence increases with age. In CT studies, the prevalence ranges from 24% to 27% in patients older than 50 years.19,20 There is a suspicion that their presence is correlated with the development of AAA disease.6–8 In an autopsy study
Table 1. Demographics and co-morbidities of patients in Group 1 and Group 2. AAA – Group 1
PT Age DM HT HL CAD COPD
No AAA – Group 2
Renal cyst
No cyst
Renal cyst
No cyst
p
63/100 73 1.4 14 (22%) 55 (87%) 44 (70%) 22 (35%) 9 (14%)
37/100 68 2.1 6 (16%) 32 (86.4%) 26 (70%) 16 (43%) 4 (11%)
45/100 73 1.5 15 (33.3%) 40 (88.8%) 15 (33.3%) 16 (35.5%) 7 (15.5%)
55/100 70 1.3 13 (23.6%) 46 (83.6%) 17 (31%) 19 (34.5%) 7 (12.7%)
na ns ns ns 50 mm (p < 0.023) and age (p < 0.05) was the only statistically significant factor that had direct association with the presence of SRCs. Because of the small numbers included in our study, post hoc power calculation analysis was undertaken in order to assess the strength of the associations. This analysis showed that the correlation between the presence of SRCs and AAA was indicative and almost reached the power to draw strong conclusions. However, further studies with larger numbers are needed to confirm our observation. In case that an association of SRCs with AAA is confirmed, it may have a useful implication as incidentally found SRCs may justify regular ultrasonic followup for early diagnosis of AAA in future or even consist a tool for screening programs.25,26 In our study, each patient’s renal function was assessed according to the European Renal Best Practice and KDIGO guidelines.16 In a previous report,24 it has been shown that in patients younger than 60 years, the presence of SRCs has been associated
with impaired renal function as defined by changes in the serum Cr levels and Cr clearance; however, this relation did not apply for patients over 60 years. Our results remain in the line of this report,24 and the presence of SRCs in our patients who were all over 60 years (one of the inclusions criteria) was not associated with renal impairment. Additionally, we assessed whether the presence of SRCs in patients who underwent EVAR was associated with any renal function impairment immediately post-operatively and after 12 months. To the best of our knowledge, our study is the first to report that the presence of renal cysts does not have any impact on the renal function and is not associated with AKI or susceptibility in CIN immediately post-EVAR (Table 2). Thus, it was demonstrated that the renal function of patients with SRCs were not affected, although potential nephrotoxic contrast agent was used.9,10 Additionally, no association between renal impairment and the type of stent graft fixation (suprarenal vs. infrarenal) was found immediately or one-year post-operatively. This remains in the line with previous reports in which suprarenal endograft fixation was not causing any renal impairment after EVAR when comparing with infrarenal endograft fixation.27–31 In contrast, there are other reports that have demonstrated that suprarenal fixation was associated with renal function deterioration 12-month postEVAR.32,33 Therefore, it appears that this issue is still controversial, and larger studies are needed for clarification. Finally, there is lack of evidence regarding the existence of any common pathogenetic pathway between the development of SRCs and AAA. Speculatively, it could be suspected an interrelation in the metabolism of collagen and elastin that may be implicated in both entities, but this requires further research. Potential limitations of our study are the small number of samples included as well as the fact that it was of retrospective nature. Additionally as we included only male individuals, the extrapolation of our findings to females does not apply.
Conclusions The prevalence of SRCs is increasing with the age. In male patients especially in those over 60 years, the presence of AAA is associated with SRCs. Early diagnosis of SRCs may help to select individuals at high risk to develop AAA in future and in whom a regular ultrasonic follow-up could be justified. EVAR in the presence of SRCs is not associated with any additional burden to renal function even after mid-term followup. Future research is needed to investigate whether there is any common pathway in the development of SRCs and AAA.
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Conflict of interest None declared.
Funding This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.
13. 14.
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