Vol 13 No 01 January-February 2016 2471Vol 13 No 01 January-February 2016 2569 MISCELLANEOUS Simple Renal Cysts: Prevalence, Associated Risk Factors and Follow-Up in a Health Screening Cohort Bora Özveren,1* Efe Onganer,2 Levent N. Türkeri1 Purpose: To investigate the prevalence of simple renal cysts in an adult health-screening cohort, and to evaluate clinical characteristics, associated risk factors and the natural course. Materials and Methods: Between April and November 2008, a thousand individuals diagnosed with simple renal cyst by ultrasonography in a check-up program were chart-reviewed for demographic-clinical characteristics and cyst features. Follow-up was done via electronic patient records. Univariate and multivariate analyses to evaluate the relationship of outcomes and correlation analysis were done to measure the degree of association between parameters. Results: The prevalence was 7.7%. There were 123 cysts in 77 patients, followed for 3.5 years (mean). Individ- uals with cysts were older (P < .01). Prevalence rates were 2.7% in individuals younger than 40 years and 23.9% in older than 60. The cysts were predominantly (94.8%) detected in males and most (63.6%) were solitary. No relation with Body Mass Index and total cholesterol levels was found but serum creatinine values were signifi- cantly increased in individuals with cysts (P < .01). There was no difference in the diagnosis of hypertension and microscopic hematuria in patients with renal cysts, however diabetes/hyperglycemia were more common and in- creasing age correlated with higher number of cysts (all P < .05). Follow-up revealed that the number of cysts were increased and/or the same in 86.5%; the sizes of cysts were larger and/or the same in 78.4% of patients, while in 14% of patients the cyst disappeared. Conclusion: In a cohort of adults undergoing a health-screening, the prevalence of simple renal cyst was found 7.7% by ultrasonography. Renal cysts were more common in males and elders, and associated with increased lev- els of serum creatinine and diabetes. Keywords: kidney diseases, cystic; complications; epidemiology; etiology; prevalence; Turkey. 1 Department of Urology, Acibadem University School of Medicine, Istanbul 34752, Turkey. 2 Department of Family Medicine, Acibadem University School of Medicine, Istanbul 34752, Turkey. *Correspondence: Department of Urology, Acibadem University School of Medicine Acibadem Kadikoy Hospital, Istanbul 34718, Turkey. Tel: +90 216 5444276. Fax: +90 216 4284444. E-mail: ozverenb@yahoo.com; bora.ozveren@acibadem.edu.tr. Received: July 2015 &Accepted: September 2015 INTRODUCTION Simple renal cysts are the most common types of ac- quired renal cysts. The majority are detected inciden- tally at the time of radiological imaging for non-renal conditions and do not have associated clinical symp- toms. The prevalence of simple cysts differs according to sex and increases with age.(1-3) Clinical observations have revealed that most are unilocular, and since they arise from the cortex, they may distort the renal con- tour. Although most simple cysts probably remain sta- ble in size and feature, some may enlarge with time and occasionally cause subtle flank discomfort and fullness on physical examination. Intervention for simple renal cysts is seldom warranted. Although renal cysts are generally regarded as of minor clinical significance, detection and awareness of these lesions may entail anxiety in patients. Besides, recent studies have associated simple cyst incidence with hy- pertension, atherosclerotic vascular diseases and renal dysfunction.(4-9) Usually, renal cysts are typical “inci- dental” findings in imaging studies for various medical purposes. Likewise, “check-up” programs which aim for early detection of chronic conditions and malignant diseases represent a way of discovering this kidney pa- thology. Patients may naturally be concerned about its relevance to general health, natural course and need rec- ommendations on how to deal with this finding. In the present study we aimed to investigate the prev- alence of simple renal cysts in a cohort of adults who went through a “health-screening”, and to evaluate their clinical characteristics, associated risk factors and the natural course in our population. MATERIALS AND METHODS Study Population The study was performed retrospectively by reviewing the electronic charts of 1380 individuals (905 men, 475 women; mean age, 38.74 years; age range, 18–77 years) who presented for a health check-up program between April and November 2008. Inclusion criteria: Among them, 1000 patients who had an abdominal ultrasonographic evaluation as part of a routine screening were included in this study. This study focused on simple renal cysts (category I accord- ing to Bosniak classification) diagnosed by ultrasonog- raphy (USG). Procedures and Evaluations: All cases underwent an abdominal USG by staff radiologists. The presence and characteristics of simple renal cysts were reported. The number, site (lower, middle or upper part of kidney), and maximum diameter of cysts were recorded. Patient records were also reviewed for evaluation of potential risk factors. These parameters included age, sex, Body Mass Index (BMI; kg/m2), history of diabetes and hyper- tension, blood pressure measurement. For the purposes of this study hypertension was defined as a systolic blood pressure of > 140 mmHg, a diastolic blood pres- sure of > 90 mmHg, or current use of antihypertensive medication. Biochemical variables included in analysis were serum total cholesterol, fasting glucose and serum creatinine levels. Results of urine analysis were record- ed and microscopic hematuria was defined as > 3 red blood cells per high-powered field. Patients with renal cysts were followed from electronic records for a mean of 3.5 (range: 1-6) years and sequential changes in num- ber and size of the cysts were documented. Statistical Analysis Analyses were performed by using NCSS (Number Cruncher Statistical System) 2007 & PASS (Power Analysis and Sample Size) 2008 Statistical Software® program (Utah, USA). Means, medians, ranges, and frequencies were recorded as descriptive statistical pa- rameters. Univariate analyses were performed by Fish- er’s exact test, Student’s t-test, and Yates’ Continuity Correction test (Yates’ chi-squared test). Spearman’s correlation analysis was conducted to measure the de- gree of association between parameters. Multivariate analysis of risk predictors for the presence of renal cysts was assessed by logistic regression. P values < .01 and < .05 were considered statistically significant. RESULTS The study group was comprised of 36% female (n = 363) and 64% male (n = 637) individuals with a mean age of 42.76 years. A total of 77 patients (7.7%) were diagnosed with simple renal cysts. Table 1 compares the demographic and clinical features of individuals with and without simple cysts. Of total, 5.5% had a history/diagnosis of hypertension and 9.6% had a history/diagnosis of diabetes. The mean total cho- lesterol level was 195.14 mg/dL (range: 80 to 475 mg/ dL). Urine analyses showed microscopic hematuria in 5% of the cohort. The mean serum creatinine was 0.76 mg/dL (range: 0.34 to 1.5). The overall prevalence of simple cysts was 7.7% (77/1000). There were a total of 123 cysts in these 77 patients. The mean largest diameter of renal cysts was Variables Total Cyst (-) Cyst (+) Univariate Multivariate (n = 1000) (n = 923) (n = 77) P Value OR (95% CI), P Value Mean ± SD Mean ± SD Mean ± SD Age, year 42.76 ± 10.89 41.97 ± 10.51 52.26 ± 10.91 a.001** 1.10 (1.07-1.14), P < .001** Gender (Male); n (%) 637 (63.7) 564 (61.1) 73 (94.8) b.001** 6.61 (2.08-20.99), P = .001** BMI, kg/m2 26.71 ± 4.41 26.65 ± 4.48 27.45 ± 3.28 a.078 0.98 (0.91-1.06), P = .673 Creatinine, mg/dL 0.76 ± 0.17 0.75 ± 0.17 0.87 ± 0.16 a.001** 8.61 (1.08-68.34), P = .042* Total Cholesterol, mg/dL 95.14 ± 40.04 195.05 ± 39.95 196.23 ± 41.39 a.804 ----- Hypertension, n (%) 55 (5.5) 49 (5.3) 6 (7.8) c.306 ----- Diabetes mellitus n (%) 96 (9.6) 82 (8.9) 14 (18.2) b.014* 1.43 (0.68-3.01), P = .348 Microhematuria, n (%) 50 (5.0) 49 (5.3) 1 (1.3) c.170 ----- Table 1. Demographic and clinical characteristics of the cohort. Abbreviations: BMI, Body Mass Index; SD, standard deviation; OR, odds ratio, CI, confidence interval. a, Student t-test; b, Yates’ continuity correction test; c, Fisher’s exact test. *P < .05; **P < .01. Simple Renal Cyst Prevalence-Ozveren et al. Miscellaneous 2570 Vol 13 No 01 January-February 2016 2571 27.86 mm with a range of 5 to 66 mm. The mean num- ber of cysts per individual was 1.59 cysts (range 1-7). In majority of patients (63.6%) a solitary renal cyst was detected. Of patients with multiple cysts, 3.9% had more than five cysts. Table 2 summarizes the descriptive characteristics of all 123 simple cysts with respect to laterality, number and localization. Individuals with simple renal cysts were significant- ly older than those without cysts (P < .01). When the cohort was sorted in age groups, the prevalence rates emerged as 2.7% in individuals younger than 40 years, 10% in ages between 40-60, and 23.9% in older than 60 (Figure 1). The cysts were predominantly (94.8%) detected in male individuals. Simple renal cysts were observed in 11.45% of the men and 1.10% of the women in our cohort. Thus, the male-to-female ratio was 10.41. The higher prevalence of renal cysts in male gender was sta- tistically significant (P < .01). Analysis revealed a sta- tistically significant increase in the mean serum creati- nine values of patients with simple renal cysts (P < .01). Multivariate logistic regression analysis showed that older age, male gender and a higher serum creatinine level were significant independent predictors for the presence of renal cysts (P < .001, P = .001, P = .042, respectively) (Table 1). There were no statistically significant differences in BMI values and total cholesterol levels in individuals with or without renal cysts. No significant difference was found in the incidence of hypertension and micro- scopic hematuria in either group (P > .05). However, in patients with renal cysts, history/diagnosis of diabetes and presence of hyperglycemia were significantly more common (P < .05) (Table 1). In patients with renal cysts, statistical analysis revealed a significant but weak positive correlation of increas- ing age with the number of cysts (P < .05) (Figure 2). BMI and serum creatinine parameters did not correlate with the number of cysts (P > .05) (Table 3). Of the 77 patients who had simple renal cysts, only 43 were available for follow-up for a mean 3.5 years from elec- tronic-chart review. In the following 1 to 6 years, four of these patients had abdominal magnetic resonance imaging (MRI) and the rest had USG results that could be utilized for further evaluation of the previously di- agnosed cysts. In six patients no renal cyst was found in further evaluations. Overall, 7 cysts were previously documented in these patients with a mean age of 43.67 years (range: 34-61). The mean diameter of the “van- ished” cysts was 10.79 mm (range: 9-13.5). In others, the number of cysts was found to be increased in 15, the same in 17, and decreased in 5 patients. During the follow-up of 37 patients, the diameters of cysts were increased in 14, decreased in 8, and the size remained Simple Renal Cyst Prevalence-Ozveren et al. Table 2. Descriptive characteristics of all 123 cysts in a total of 77 indi- viduals. Cyst no. % Right side 24 31.1 Left side 38 49.4 Bilateral 15 19.5 Solitary 49 63.6 Multiple 28 36.4 Lower pole 31 25.2 Mid 65 52.8 Lower pole 26 21.1 Parapelvic 1 0.8 Variables Cyst (+) (n = 77) d r (95% CI) P Value Age, year* Number of cysts 0.290 (0.055-0.495) .010* BMI, kg/m2* Number of cysts -0.061 (-0.302-0.203) .637 Serum creatinine, mg/dL* 0.058 (-0.311-0.237) .614 Number of cysts Table 3. Evaluation of clinical characteristics according to number of re- nal cysts. Abbreviations: BMI, Body Mass Index; CI, confidence interval. d, Spearman’s correlation coefficient; *P < .05. Figure 1: Age-related prevalence of renal cysts the same in 15 patients. DISCUSSION In the current study, the prevalence of simple renal cysts was 7.7% in an adult health-screening cohort. Simple cysts were found as more common in males and elderly individuals in our study. The results of sever- al published series report the prevalence of simple re- nal cysts in a range from 5% to 40%.(2,10-16) Incidence of simple renal cysts between birth and age 18 is only 0.2 percent. By contrast, autopsy series have revealed that 50% of patients older than 50 years have grossly recognizable renal parenchymal cysts.(3) Studies which discovered higher prevalence rates (19.9 – 41%) have mostly assessed incidental computerized tomography (CT) findings.(1,10,11) Superior imaging quality of CT or MRI improves the detection of small cystic lesions and therefore may explain higher rates found in some studies. Yet, most of the published prevalence studies have utilized USG in diagnosis due to its non-invasive characteristics and feasibility. Aside from dependence on the technical qualities of the imaging modality used, the prevalence rates may also alter according to the screened population. There are several prevalence studies from different parts of the world where varied patient databases were used (Table 4). These results suggest that there may be geographi- cally determined variations in the prevalence rates.(4,12- 18) Additionally, cysts are seen more frequently in “renal patients” as opposed to “non-renal” subjects. Marumo and colleagues reported the incidence of renal cysts as 32.6% for ages 60 years or older in patients referred for asymptomatic microscopic hematuria.(19) A study from Nigeria showed a 15.4% prevalence rate of cystic kid- ney disease in adult patients from a Nephrology Unit.(20) In a group of 684 outpatients from an internal medicine clinic who had USG for various reasons, 13.7% were diagnosed with simple renal cysts.(21) The prevalence of simple cysts is well known to cor- relate with demographic factors. Renal cysts are more frequent in men and the incidence correlates with ad- vancing age.(1,3) Furthermore, cysts are observed more in number and larger in size in older individuals.(10,12,15) The prevalence rates should therefore be gaged by age groups, since any cohort comprising a greater propor- tion of older individuals would render higher average rates. Statistical analysis of our results confirm these previously established characteristics concerning age and gender. Although the overall prevalence was 7.7% in our cohort, the age-specific rate raised from 2.7% in younger than 40 year-olds to 23.9% in individuals older than 60 years (Figure 1). Our study group was com- posed of people who underwent routine health check- up; and 45% of them were younger than 40 years, and Author (year) Region Prevalence (%) Number Age Range Cohort Nko’o Amvere et al. (1991)(17) Cameroon 3.08 1527 0-82 In-patients Pedersen et al. (1993)(18) Denmark 5.2 686 30-70 Volunteers Yasuda (1993)(14) Japan 14.0 30316 8-92 In-patients Pal et al. (1997)(16) India 5.06 1500 8-86 In-patients Terada et al. (2004)(13) Japan 9.9 17914 18-92 Check-up Mosharafa et al. (2005)(12) Middle-East 4.2 8551 20->80 Check-up Chin et al. (2006)(4) Korea 7.8 6603 15-89 Check-up Chang et al. (2007)(15) Taiwan 10.7 577 20-94 Check-up Present study (2008) Turkey 7.7 1000 18-77 Check-up Table 4. Simple renal cyst prevalence studies from various parts of the world. Simple Renal Cyst Prevalence-Ozveren et al. Figure 2: Relation of age to the number of renal cysts (Spearman’s Correlation Coefficient P < .05) Miscellaneous 2572 Vol 13 No 01 January-February 2016 2573 merely 7.1% were older than 60 years. While confirm- ing the high prevalence of simple renal cysts in elder- ly individuals, the current results also reveal particu- lar information on the prevalence of this pathology in younger people. We found a significant predominance of male sex in occurrence of simple renal cyst. Though the published studies usually report high male to female ratios, we observed an even greater gender disparity in the renal cyst prevalence in our study group (male to fe- male ratio of approximately 10:1 in the present study). This disproportion is uncommon and may be associated with the relatively younger median age of our cohort compared to previous epidemiological studies. The detection of a solitary lesion in two-thirds of all the individuals with cysts and the correlation of increas- ing number of cysts with older age in the present study population is in parallel with the descriptive findings in previous epidemiological studies.(12-15) The causal and temporal relationship of renal cysts with hypertension and renal dysfunction remain controver- sial. Serum creatinine, hypertension and atherosclerotic diseases are among the main implicated risk factors in the occurrence of simple renal cysts.(4-9,12,13) Chin and colleagues have concluded that presence and character- istics of cysts were not related to decreased glomerular filtration rates.(4) Their results also suggested that num- ber, size and locations of cysts were related to hyperten- sion. In another study, Hong and colleagues, analyzing the data of 29,666 patients, confirmed the association of presence and characteristics of simple renal cysts with a significantly increased incidence of hypertension.(5) Lee and colleagues furthermore assessed the time-de- pendent relationship between cysts and incident hyper- tension, and came to a conclusion that after adjusting for confounding factors, renal cysts still significantly increased the risk of hypertension.(6) Others have addi- tionally observed an increased incidence of renal cysts in patients with abdominal aortic aneurysms and dissec- tion, signifying a commonality of connective tissue de- generation.(7-9) However, pathogenesis of simple renal cysts still remains unsubstantiated. The connection of renovascular and arterial pathologies with simple renal cysts can merely be coincidental to age-related changes in renal tubules and ducts. While origins and evolution of renal simple cysts still need to be explored, the only established link is senility.(1) We observed a significant increase in the mean serum creatinine values of individuals with renal cysts. Com- parable outcomes have previously been reported in several investigations on non-renal screening cohorts. (4) The mechanism that links kidney cysts to age and renal function is unknown but it is likely that irregu- lar tubular growth may lead to cystic changes. While renal cysts may be an early sign of renal impairment, older-age should be regarded as a confounding factor for the correlation of higher creatinine with renal cysts. (22) Nevertheless, in the current study, it would be inju- dicious to derive any association of simple renal cysts with renal parenchymal dysfunction because there was no correlation of cyst number to higher creatinine lev- els. Moreover, contrary to a common belief that simple cysts cause microscopic hematuria, we did not observe any increased incidence of microscopic hematuria in in- dividuals with cysts. Our results also showed a higher incidence of hypertension in the group with simple re- nal cysts, but statistical analysis failed to reveal a non- random association. There was also no difference in the BMI, and total cholesterol levels of individuals with and without renal cysts. However there was a significantly increased proportion of individuals with a history and/ or diagnosis of diabetes among individuals with sim- ple renal cysts. Evidently, our results do not allow us to simply deduce a correlation of simple renal cysts with a group of risk factors relating to metabolic syndrome. The natural history of simple renal cysts appears to be exceedingly benign. In addition to our prevalence study, we traced our patients with cysts. Chart review allowed us to obtain information on 43 of 77 patients with cysts, for a mean period of 3.5 years. In 6 patients, subsequent USG examinations did not show any renal simple cysts. The patients whose cysts “disappeared” in follow-up did not have any distinguishing demo- graphic feature but the average sizes of these cysts were remarkably smaller than the overall mean largest diameter. The reasons for the disappearance or shrink- age are unclear, but might include bleeding into the cyst or spontaneous rupture of the cyst into the perirenal space or the collecting system.(24) A study found that in children, diameter of renal cysts increased in 49%, decreased in 10%, unchanged in 31%, and disappeared in 10% when followed-up for a mean 2.9 years.(25) Since the present study lacks any large numbered prospective data of follow-up, we did not attempt to analyze the changes in lesion diameter. When the data was assessed on patient-basis, we found that the number of cysts in- creased or stayed the same in 86.5%; the sizes of cysts were larger or the same in 78.4% of patients. In their study of 61 patients with a mean follow-up period of 9.9 years, Terada and associates concluded that the ma- jority of simple renal cysts continued to increase in size and number, but some may involute and disappear over time. The cysts they followed had an average increase Simple Renal Cyst Prevalence-Ozveren et al. of 1.6 mm in size and 3.6% rate of enlargement, which appeared to decrease with age.(23) The main limitation of the current study lies in the ret- rospective chart-review format. We also acknowledge that the small number of our cohort makes it difficult to explain the lack of any significant change in cyst fea- tures in the follow-up data. Measurement reliability of USG should also be taken into account. A prospective fashion of follow-up would give more insight on the natural course of cyst dimensions and spontaneous dis- appearance of these lesions. We also believe that lower median age of our check-up cohort might have influ- enced the striking gender difference in the prevalence rate. CONCLUSIONS In a cohort of adults evaluated for a health-screening program, the prevalence of simple renal cyst was found to be 7.7% by ultrasonography. Simple renal cysts were more common in males and elders, and associated with increased levels of serum creatinine and diabetes in our study. ACKNOWLEDGEMENT Ms. Emire Bor, EMPIAR Statistics Consulting, assisted with statistical analysis. CONFLICT OF INTEREST None declared. REFERENCES 1. Laucks SP Jr, McLachlan MSF. Aging and simple cysts of the kidney. Br J Radiol. 1981;54:12-4. 2. Ravine D, Gibson RN, Donlan J, Sheffield LJ. An ultrasound renal cyst prevalence survey: specificity data for inherited renal cystic diseases. 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