Stesura Seveso Archivio Italiano di Urologia e Andrologia 2024; 96(1):12181 1 ORIGINAL PAPER Considering the urolithiasis-related epidemiological fac- tors as an important parameter, gender-based prevalence has been subjected to several studies where the male-to- female ratio ranged from 1.3 to 3 (3). On the other hand, as a precious predictive factor, positive family history is a significant risk factor for stone formation in individu- als with family members suffering from urolithiasis (4). Geographic conditions are also important, and factors including climate, socioeconomic status, diet, and comorbidities may further affect the prevalence of stone formation (2, 5). Components of metabolic syndrome like diabetes mellitus, hypertension, or obesity have also been implicated in constituting an additional risk for uri- nary stone formation (6). Related to metabolic problems, in addition to less fluid intake, hypercalciuria, hyperox- aluria, hyperuricosuria, and hypocitraturia are the most common urinary stone-forming risk factors identified, particularly in recurrent cases (7, 8). The dietary habits of the community, both in developing countries and in developed ones, are essential in stone formation by alter- ing urine composition and increasing relevant risk status (9, 10). Lastly, despite some contradictory reports, edu- cation might play a role in urolithiasis. Some studies show that a lower education level may be a possible rea- son for stone formation (11, 12). In this present study, we aimed to assess certain clinical and metabolic factors to update epidemiological risk fac- tors in the Turkish population in a regional evaluation- based manner. METHODS Ethics committee approval was obtained for the study from the Local Ethics Committee with the number 2023/4203 on 17 February 2023. While conducting this study, the Declaration of Helsinki and international ethical standards were taken into consideration at every stage. A total of 2348 adult patients referring to the urology departments of different hospitals in the same region with sonography and/or computed tomography-proven stones were included in the study program. Following close col- laborative work with epidemiologists, our team designed a simple questionnaire and conducted a face-to-face sur- vey. Staff nurses and resident doctors in urology wards Objective: To evaluate the metabolic and clinical characteristics of adult cases with stone disease from a regional part of Turkey. Methods: The study included 2348 adult patients with sonogra- phy and/or computed tomography-proven urinary stones. All cases were given a questionnaire about the epidemiological fea- tures of urolithiasis. Aside from the type and severity of stone- forming risk factors, both patient (age, gender, BMI, associated comorbidities, first onset of stone disease, positive family histo- ry, educational level) and stone-related (size, number, location, chemical composition, previous stone attacks) factors have been thoroughly assessed. The data were evaluated in multiple aspects to outline the epidemiological features. Results: The overall mean age value of the cases was 43.3 years, and the M/F ratio was 1.34. The first onset of the disease was found to vary between 15-57 years, with a mean value of 32.4 years. While most of the stones were located in kidney and ureter, calcium-containing stones constituted the most common type (CaOx 69%, CaOxPO4 7%). More than 42% of the cases suffered from multiple stone attacks; positive family history waspresent in 31.6%. Among the associated comorbidities, hypertension was the most common pathology (45.8%), and the BMI index value was > 30 in 31.3% of the cases. 57.7% of the patients had just one stone attack, and 42.2% had recurrent stone formation. Conclusions: Our findings clearly show that important implica- tions may be extracted from epidemiologic data acquired from local scale research to implement an effective preventative pro- gram and closely monitor the patients. KEY WORDS: Urinary stones; Epidemiology; Kidney stones. Submitted 11 December 2023; Accepted 25 December 2023 INTRODUCTION As an endemic problem in certain parts of the world, urolithiasis constitutes an evident risk to the healthcare system and a certain burden on the economy. The etiolo- gy of the disease is multifactorial, and an increase in inci- dence and prevalence ranging from 7% to 13% in North America, 5-8 % in Europe, and 1-5% in Asia has been reported (1). Environmental and dietary factors, lifestyle, and some individual personal factors, such as age, gender, body mass index (BMI), and familial anamnesis, seem to play a critical role in the course of the disease (2). Clinical characteristics of adult cases with urolithiasis from Turkey: A regional epidemiological study Mehmet Ezer 1, Rasim Güzel 2, Mehmet Uslu 1, Selçuk Güven 3, Kemal Sarica 4, 5 1 Department of Urology, Kafkas University, Kars, Turkey; 2 Department of Urology, Medistate Kavacık Hospital, Istanbul, Turkey; 3 Department of Urology, Necmettin Erbakan University, Konya, Turkey; 4 Department of Urology, Sancaktepe Şehit Prof. Dr. Ilhan Varank Training and Research Hospital, Istanbul, Turkey; 5 Department of Urology, Biruni University Medical School, Istanbul, Turkey. DOI: 10.4081/aiua.2024.12181 Summary Archivio Italiano di Urologia e Andrologia 2024; 96(1):12181 M. Ezer, R. Güzel, M. Uslu, S. Güven, K. Sarica 2 completed each form after interviewing study participants prior to medical or surgical management of stones. Regarding the questions with respect to the established epi- demiological features of urinary calculi, in addition to the type and severity of stone-forming risk factors, both patient-related factors (such as age, gender, BMI, associat- ed comorbidities, the first onset of stone disease, positive family history, educational level) and stone related factors (such as size, number, location, chemical composition, pre- vious stone attacks) have all been evaluated and recorded. Obtained data were assessed from multiple aspects to out- line the epidemiological features in our patients. RESULTS Evaluation of our data revealed the following findings. The mean age value of the 2348 adult cases was 43.3 years (15-69), and the gender distribution was 1346 males and 1002 females with an M/F ratio of 1.34. The first onset of the disease was found to vary between 15-57 years, with a mean value of 32.4 years (Table 1). The majority of the stones were located in the kidney (62.3%) and ureter (35.2%), and calcium-containing stones constituted the most common type (CaOx 69%, CaOxPO4 7%) (Table 2). On referral, 57.7% of the cases had the first stone attack; 42.2% had recurrent stone formation. Regarding the previ- ous interventions for stone removal, pyelolithotomy was present in 12 patients (0,5%), cystolithotomy in 14 (0,6%), PCNL in 108 (4,6%), ureterorenoscopy in 213 (9%), and lastly SWL in 284 cases (12 %) (Table 2). A positive fami- ly history was present in 743 patients (31.6%) (Table 2). Positive family history was strongly associated with the mean age of the cases at first presentation and the dis- ease's number of stone attacks (recurrence). Stones are formed at younger ages in these cases, with more recurrent stone formation than those with no fami- ly history. Of the clinical presentation symptoms noted, while the majority of the cases referred with colic pain (n:1902, 81%), 50.3% (n:1181) of the patients had microscopic hematuria, and 7.2% (n:169) presented with macroscop- ic hematuria. High-grade hydronephrosis (Grade 3-4) was present at first presentation in 14.2% of the cases, and 53.3% had no dilatation (Table 3). Among the associated comorbidities evaluated, while hypertension was present in 45.8% of the cases, diabetes was present in 2.8%, hypercholesterolemia in 27.6%, and obesity in 31.3% (in 735 cases, BMI index value was 30- 35). While the mean BMI was 25.7 ± 8.8 in male patients, this value was 26.8±9.2 in female cases (Table 3). Table 1. Evaluation of the patient characteristics and stone-related factors by gender. Male Female Total number of cases (n) 1346 1002 Mean age of the cases (years) 42.6 ± 9.8 44.3 ± 11.3 First onset of the disease (years) 31.7 ± 10.2 33.5 ± 12.8 Stone size (mm) 1.3 ± 0.8 1.1 ± 0.6 Height (cm) 170.1 ± 9.7 165.7 ± 10.2 Body weight (kg) 75.0 ± 9.4 79.2 ± 10.2 Body mass index (BMI) (kg/m2) 25.7 ± 8.8 26.8 ± 9.2 Table 2. Urolithiasis characteristics of the patients at first presentation. Total Male Female n % n % n % Stone analysis data 1945 82.8 981 72.9 964 96.2 Calcium oxalate 1342 69 703 71.7 639 66.3 Calcium phosphate 136 7 74 7.5 62 6.4 Infection stones 233 12 86 8.8 147 15.2 Uric acid 156 8 83 8.5 73 7.6 Cystine 78 4 35 3.5 43 4.5 Number of stone episodes One episode 1355 57.7 731 54.3 624 62.3 2-4 episodes 647 27.6 388 28.8 259 25.8 5 and more 346 14.7 227 16.9 119 11.9 Stone localization at the first presentation Kidney 1463 62.3 786 58.4 677 67.5 Single 696 29.6 372 27.6 324 32.3 Multiple 767 32.7 414 30.8 353 35.2 Ureter 826 35.2 437 32.5 389 38.8 Bladder 59 2.5 59 4.4 0 0 Previous interventions Pyelolithotomy 12 0.5 7 0.5 5 0.5 Uretrorenoscopy 213 9 134 10 79 7.9 PCNL 108 4.6 53 3.9 55 5.5 Cystolithotomy 14 0.6 14 1 0 0 SWL 284 12 123 9.1 161 16.1 Family history Positive 743 31.6 331 24.5 412 41.1 Table 3. Clinical characteristics of the patients at first presentation. Total Male Female n % n % n % Total number of cases 2348 100 1346 57.9 1002 42.1 Associated morbidities Hypertension 1075 45.8 623 46.3 452 45.1 Diabetes Mellitus 66 2.8 29 2.2 37 3.7 Hypercholesterolemia 648 27.6 403 29.9 245 24.5 Obesity (BMI of > 30) 735 31.3 347 25.8 388 38.7 Presence of urinary tract infection (UTI) 802 34.2 114 8.5 688 68.6 Presence of obstruction (sonographic findings) None 1252 53.3 883 65.6 369 36.8 Grade I 356 15.2 124 9.2 232 23.2 Grade II 406 17.3 226 16.8 180 18 Grade III 187 8 52 3.9 135 13.5 Grade IV 147 6.2 61 4.5 86 8.5 Presence of hematuria Microscopic 1181 50.3 671 49.9 510 50.9 Macroscopic 169 7.2 87 6.5 82 8.2 Presence of pain * No 446 18.9 253 18.8 193 19,3 Mild (VAS 1-3) 680 29 408 30.3 272 27,1 Moderate (VAS 4-6) 483 20.6 267 19.8 216 21,6 Severe (VAS ≥ 7) 739 31.5 418 31.1 321 32 * Evaluation according to visual Analogus sclala 0-10. Archivio Italiano di Urologia e Andrologia 2024; 96(1):12181 3 Clinical characteristics of adult cases with urolithiasis from Turkey When the education level of the cases was evaluated, 36.4% (n = 856) were primary school graduates, 14.3% (n = 335) were secondary school graduates, 34.5% (n = 810) were high school graduates, and 14.8% (n = 347) were college graduates. DISCUSSION Urinary system stone disease is an endemic pathology in many parts of the world, which poses an evident risk to the healthcare system with a significant burden on the economy. The etiology of the disease is multifactorial, consisting of several risk factors evaluated in detail so far. Regarding the evident differences among several regions and countries of the world, variations in specific etiolog- ic parameters like age, gender, dietary preferences, fluid consumption, the climate they live in, their occupation, level of education, socioeconomic status, and genetic and metabolic factors have been considered to be responsible (2, 9). On the other hand, the formation of new stones based on the present metabolic and other risk factors is commonly observed, particularly in recurrent stone-forming cases. Studies on this aspect have revealed that after the initial stone passage, the rate of stone recurrence in patients with previous urolithiasis was reported to be 40% at five years and 75% at 20 years, respectively (13). Considering all these facts, it is clear that data from regional epidemiological studies will help us assess the prevalence and underlying etiological factors, which will support developing policies for effective metaphylaxis and treatment of the disease appropriately. In other words, in light of reported evident geographic differences in the prevalence of urolithiasis, well-conducted local/regional studies may provide a detailed understand- ing of the disease nationwide. When we look at the studies examining the effect of gen- der on kidney stone formation, several gender-based studies have shown that although infection stones were more commonly reported in women, the general inci- dence of urinary calculi tends to be more frequent in men (14, 15). Statistics show that males tend to indulge in higher amounts of alcohol and coffee as well as meat con- sumption compared to females. Moreover, it has been observed that testosterone can increase the likelihood of stone formation, whereas estrogen plays a role in inhibit- ing stone formation by regulating the synthesis of 1.25- dihydroxy-vitamin D (5). Stone formation is often linked to anatomical factors, with infravesical obstruction being a common risk factor. This obstruction is usually caused by benign prostatic hyperplasia or urethral stricture (16). In many countries, it has been observed that the ratio in favor of females is increasing while the ratio in favor of males is decreasing. Changes observed in the living stan- dards resulting in the differences in diet, lifestyle, and occupations of the female population could be responsi- ble for the decreased ratio (17). As another important factor affecting the prevalence of stone disease, geographic conditions may also affect the occurrence of urolithiasis (2, 5). Differences in factors such as climate, socioeconomic status, race, genetics, dietary habits, and the presence of other medical condi- tions may contribute to significant variations in the preva- lence of kidney stone formation in a particular geographic or regional area. This scenario has the potential to mirror the urolithiasis problem at a national and even global level. Apart from commonly diagnosed urinary tract infections, patients with urolithiasis frequently present with the component pathologies of metabolic syndrome like dia- betes mellitus, hypertension, or obesity, which could potentially be another factor that increases the risk for urinary stone formation (2, 18). The involved patients' associated comorbidities and metabolic factors play a spe- cific role in the presence and severity of urinary stone- forming risk factors. Related to this important subject, in addition to reduced fluid intake, decreased urine output, hypercalciuria, hyperoxaluria, hyperuricosuria, and hypocitraturia are the most commonly reported risk fac- tors for stone formation in adults and children (7, 8). Based on this fact, a comprehensive metabolic evaluation seems mandatory in risk group cases prone to form recur- rent stones requiring interventional procedures for a stone-free status. Considering the formation of metabolic risk factors in these cases, apart from the lifestyle playing a significant role in the formation of stones, the dietary habits of the community have a more critical role. While cereals and vegetables contain high levels of oxalate and its precur- sors are widely consumed in developing countries, in the western part of the world, a Westernized diet containing excessive protein, lipid, calcium, and sodium is also important in stone formation, changing the urine compo- sition and increasing the associated risk status (9, 19). Among the dietary risk factors evaluated so far, in addi- tion to excessive calcium and oxalate-rich food consump- tion, a high sodium intake may increase calcium absorp- tion into the blood or decrease absorption from urine into renal tubular cells, resulting in hypercalciuria. On the other hand, higher consumption of animal protein can also lead to urine acidification (10). Last but not least, education might play a role in urolithi- asis. In support of this, Data from studies in Iran and Turkey suggest that lower education levels may con- tribute to kidney stone formation (11, 20). However, some studies also show a negative relationship between the incidence of stone disease and the education level or occupation (12, 21). Taking all the above facts, we believe that significant implications could be derived from the epidemiologic data obtained from local scale studies. With this aim to update urolithiasis epidemiological data by examining certain epidemiological risk factors in the Turkish popu- lation, we conducted this study. Our findings revealed valuable data showing useful clini- cal implications that could be derived from our trial. The majority of the stones were located in the upper tract and were calcium-containing stones. The number of stone attack episodes was an important issue, and most cases did present with the first attack (57.7%), where a limited percentage had high recurrence rates with more than five attacks (14.7%). Men were affected by the disease at rela- tively younger ages than women. Hypertension was the most common co-morbidity. Additionally, as another important component of metabolic syndrome, BMI values Archivio Italiano di Urologia e Andrologia 2024; 96(1):12181 M. Ezer, R. Güzel, M. Uslu, S. Güven, K. Sarica 4 were well evaluated, and 31.3% of the cases had severe obesity with BMI values of > 30. On the first presentation, most cases presented with persistent microscopic hema- turia (50.3%), and recurrent infection, colic pain were the other presenting symptoms. 26.8% of the patients have a previous stone-related intervention. A considerable per- centage of the cases have severe (Grade III-IV) obstruc- tion at first evaluation. Last but not least, positive family history was a critical and predictive parameter noted where 1/3 of all cases did have this history, and men were more likely to have this anamnesis. This parameter affect- ed the course of the disease, and mean age at first onset was less in these cases. Also, stone attacks were higher in these cases than in patients without family history. Our study is not free of limitations. The number of patients evaluated may be limited, and the need for a con- trol group may constitute another critical drawback. However, taking limited information regarding the epi- demiological data on stone disease, particularly in a regional evaluation-based manner, we believe our find- ings will be contributive to a greater extent. Additionally, taking the endemic nature of the stone disease in our country, these values coming from a regional part of the country will give further insights into the epidemiologic features of the disease. CONCLUSIONS In light of the data published so far and our findings obtained in adult cases with urinary stones, we may say that local and regional epidemiological studies focusing on personal, environmental, and metabolic risk factors could be critical. 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Int Urol Nephrol 2010; 42:119-26. 21. Abomelha MS, al-Khader AA, Arnold J. Urolithiasis in Saudi Arabia. Urology 1990; 35:31-4. Correspondence Mehmet Ezer, MD (Corresponding Author) mehmetezer@gmail.com Department of Urology, Kafkas University, Kars, Turkey, 36100 Mehmet Uslu, MD dr.mhmtuslu@gmail.com Department of Urology, Kafkas University, Kars, Turkey Rasim Güzel, MD rasimguzel@hotmail.com Department of Urology, Medistate Kavacık Hospital, Istanbul, Turkey Selçuk Güven, MD selcukguven@hotmail.com Department of Urology, Necmettin Erbakan University, Konya, Turkey Kemal Sarıca, MD saricakemal@gmail.com Department of Urology, Sancaktepe Şehit Prof. Dr. Ilhan Varank Training and Research Hospital, Istanbul, Turkey Department of Urology, Biruni University Medical School, Istanbul, Turkey Conflict of interest: The authors declare no potential conflict of interest.