The association of simple renal cysts with abdominal aortic aneurysms and their impact on renal function after endovascular aneurysm repair

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 = 0.0157). There was no correlation between simple renal cysts and abdominal aortic aneurysm size or pre-operative 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 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 one-year 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 <30 mm.

For the definition for the presence of SRCs, we used the Bosniak classification system, and all cysts in our study belonged to Category I.¹³ Category I cysts have no malignant potential and, as such, no follow-up is required.¹⁴ Patients with ADPKD were excluded from our study.

EVAR is defined as the treatment of an AAA through imaged-guided placement of a stent-graft device (endoprosthesis) within the native abdominal aorta, securing device fixation to the vascular wall proximal and distal to the diseased aneurismal segment(s), thus eliminating AAA sac pressurization.¹⁵

Two different types of endografts were used: (a) those having a suprarenal fixation such as Endurant II (Medtronic), Ovation Prime (Trivascular) and Treovance (Bolton) and (b) those with active infrarenal fixation (Excluder, Gore). These procedures were performed in the operating theatre equipped with a moveable radiolucent surgical table and a mobile digital angiographic system using a C-arm (Philips BV Endura, Philips Medical Systems, Release 2.2.3, the Netherlands). The contrast agents used was iopromide that is a nonionic, low osmolarity, water soluble X-ray contrast.

The renal function was assessed through Cr and urea level (Cr normal ratio: 0.6–1.3 mg/dL, urea normal ratio: 7–20 mg/dL). The renal impairment [acute kidney injury (AKI) – contrast-induced nephropathy (CIN)] was defined according to the Kidney Disease Improving Global Outcomes (KDIGO) and clinical practice guidelines for AKI.¹⁶

HT and HL were defined from the history of anti-hypertensive and statin treatment or when more than four measurements of systolic blood pressure >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 anti-diabetic treatment.

Statistical analysis

To assess the effect of all observed factors and covariates on renal cyst, each one was initially examined separately, and the significant predictors at significance level p₁ = 0.20 were identified. These were used in a binary logistic regression model. The formerly non-significant factors were then reexamined at level p₂ = 0.10. Interactions between the main effects of the final model were also considered. The enter method with significance level p₃ = 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 post-EVAR according to KDIGO guidelines.¹⁶

Table 1.

Demographics and co-morbidities of patients in Group 1 and Group 2.

	AAA – Group 1		No AAA – Group 2
	Renal cyst	No cyst	Renal cyst	No cyst	p
PT	63/100	37/100	45/100	55/100	na
Age	73 ± 1.4	68 ± 2.1	73 ± 1.5	70 ± 1.3	ns
DM	14 (22%)	6 (16%)	15 (33.3%)	13 (23.6%)	ns
HT	55 (87%)	32 (86.4%)	40 (88.8%)	46 (83.6%)	ns
HL	44 (70%)	26 (70%)	15 (33.3%)	17 (31%)	<0.05
CAD	22 (35%)	16 (43%)	16 (35.5%)	19 (34.5%)	ns
COPD	9 (14%)	4 (11%)	7 (15.5%)	7 (12.7%)	ns

AAA: abdominal aortic aneurysm; PT: patients; DM: diabetes mellitus; HT: hypertension; HL: hyperlipidemia; CAD: coronary artery disease; COPD: chronic obstructive pulmonary disease; na: not applicable; ns: non-significant. Age in years.

Figure 1.

Relation between creatinine levels pre-operatively and the presence of simple renal cysts.

Figure 2.

Relation between creatinine levels immediately post-operatively and the presence of simple renal cysts.

Table 2.

Comparison between AAA patients with or without Simple renal cysts in relation to AAA size, peri-operative contrast volume, Cr levels pre- and immediate post operation.

	AAA – Group 1		p
	Renal cyst	No cyst
AAA size	57.7 ± 1.2 mm	57.3 ± 0.9 mm	ns
Contrast volume	218.7 ± 20 ml	210 ± 19 ml	ns
Cr pre	1.068 ± 0.24 mg/dL	1.05 ± 0.22 mg/dL	ns
Cr post	1.054 ± 0.21 mg/dL	1.04 ± 0.19 mg/dL	ns

AAA: abdominal aortic aneurysm; Cr pre: creatinine levels pre-operatively; Cr post: creatinine levels post-operatively; ns: non-significant.

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 = 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 on consecutive cases, it was demonstrated that the number of SRCs had been related with the aortic circumference.²¹ Along this line was our study, in which the prevalence of SRCs in patients with AAA was 63% compared with only 45% in aged-matched patients without AAA. All the aforementioned studies come from different geographic latitudes, including Asia, America and Europe, and thus, there is a speculation that no obvious relation with ethnicity should exist.

After comparison of the two aged- and gender-matched groups (Group 1: AAA vs. Group 2: without AAA), the only difference as far as it concerns the risk factors was the prevalence of HL which was higher in Group 1. Patients with SRCs had no family history of SRCs as it was anticipated.^22,23 That contradiction was probably because of the insufficient ultrasound screening for SRCs among relatives of the patients. In some previous reports, the presence of SRCs has been related to pre-HT and HT.^22,23 However, in our study, it was interesting that no difference was noticed in respect to HT between the group of patients with SRCs and without, although we cannot exclude the presence of pre-HT situation in our patients as it was not specifically investigated. That evidence complies only with one other report.²⁴ Failure to find any association between the presence of SRC and HT maybe explained by the small number of patients included in our study as compared to the previous studies^22,23 or due to the fact that HT among several other factors² play an important role in the natural history of AAA, so the prevalence of HT among study’s patients was already high.

In multivariate analysis, it was demonstrated that the presence of AAA with a diameter >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 follow-up 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 post-EVAR.^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 follow-up. Future research is needed to investigate whether there is any common pathway in the development of SRCs and AAA.

Footnotes

Declaration of conflicting interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The author(s) received no financial support for the research, authorship, and/or publication of this article.

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