Stesura Seveso 99Archivio Italiano di Urologia e Andrologia 2014; 86, 2 ORIGINAL PAPER Urolithiasis in Italy: An epidemiological study Domenico Prezioso 1, Ester Illiano 1, Gaetano Piccinocchi 2, Claudio Cricelli 2, Roberto Piccinocchi 3, Alberto Saita 4, Carla Micheli 5, Alberto Trinchieri 6 1 Department of Neuroscience, Reproductive Sciences and Dentistry, University Federico II of Naples, Naples, Italy; 2 SIMG, Italian Society of General Medicine; 3 University “Campus Biomedico” of Rome, Rome, Italy; 4 Department of Urology, “Vittorio Emanuele Hospital”, University of Catania, Catania, Italy; 5 Department of Urology and Andrology, Santa Maria della Misericordia Hospital, University of Perugia, Perugia, Italy; 6 Department of Urology Alessandro Manzoni Hospital of Lecco, Lecco, Italy. Objectives: Worldwide the urolithiasis is the third most frequent urological disease affecting both males and females. In literature there are not recent Italian epidemiological data about stone disease. The objective of this study is the evaluation of current epi- demiology of urolithiasis in Italy using the Health Search/CSD Longitudinal Patient Database (HS) database. Material and methods: An observational, descriptive, retro- spective trial was conducted. Inclusion criteria were: family physician- assisted Italian living population member of HS database within 31 December 2012, both genders, age over 17 years, at least two years of clinical history recorded from the beginning the trial. Data were collected by HS database and elaborated by its software Millewin®. Results: In Italy prevalence of urolithiasis in 2012 was 4.14%, it was higher in males than in females (4.53% versus 3.78%) with a positive relation with increasing age. The highest prevalence rate of urolithiasis was reported in the region Campania (6.08%). The general incidence was 2.23 *1000, with the highest incidence in the region Sicilia (3.15 *1000). Incidence was higher in group age 65-74 years (3.18 *1000). Conclusions: In Italy the incidence and prevalence of urolithiasis is increasing with particular distribution in relation to gender, age and regional position. KEY WORDS: Urolithiasis, prevalence; Incidence; Epidemiological trial. Submitted 26 January 2014; Accepted 31 March 2014 Summary INTRODUCTION Urolithiasis is a major clinical and economic burden for healthcare systems; infact is a highly prevalent condition with a high recurrence rate that has a large impact on the quality of life of those affected (1). In 1994 in Italy the National Institute of Statistics (ISTAT) database showed the prevalence as 1.7% and the incidence as 0.17 case/1000 patient with 95000 new cases/year. A national study of fam- ily physicians of the Società Italiana di Me dicina Generale (SIMG) in 2006 showed that 19% patients with urolithiasis undergo urologic visit, 4.6% hospitalization, 48.8% ultra- No conflict of interest declared. sonography (US), 7.2% urography, 2.6% non-contrast enhanced computed tomography (NCCT), 3.4% kidney- ureter-bladder radiography (KUB) (2). International epi- demiological data suggest that the incidence and preva- lence of stone disease is increasing (3-11) and an increase is recorded mainly in industrialized countries, as well in western countries probably resulting from improvements in clinical-diagnostic procedures and changes in nutrition- al and environmental factors (12). Many population-based studies investigated prevalence and incidence rates of urolithiasis in different countries. Nevertheless it is impor- tant to emphasize that precise data on the epidemiology of a disease or disorder can only be determined if geographi- cal position, race, age and sex, climate, nutrition and other environmental factors are also taken in consideration. When analysing the literature, we can highlight the scarci- ty of new Italian epidemiological data about stone disease. These epidemiological data are very important in the plan- ning of health services and social-health; in clinical gover- nance and in assessing the quality of services performed and their impact in terms of both clinical benefits as well as financial savings. To achieve these goals is needed to draw the real dimension of problem, especially the epidemiolog- ical dimension. In the latter part of the 20th century and in the early of 21th century a growing application of epidemi- ological methods was observed, with well-structured analy- sis of prescriptive profile and flow chart. In Italy this system was combined with an evolution in the management of health informatics systems from the collection and storage of performance data and the related reimbursement by the regional health system (eg. hospitalizations, outpatient spe- cialist care, pharmaceutical prescriptions). These are busi- ness systems, however are used as economic, clinical and epidemiological database also. This study seeks to evaluate current Italian epidemiological situation about stone dis- ease using Health Search/CSD Longitudinal Patient Database (HS) database used by SIMG. MATERIAL AND METHODS The study was designed as a observational, descriptive, retrospective trial. The objective is the evaluation of total DOI: 10.4081/aiua.2014.2.99 Archivio Italiano di Urologia e Andrologia 2014; 86, 2 D. Prezioso, E. Illiano, G. Piccinocchi, C. Cricelli, R. Piccinocchi, A. Saita, C. Micheli, A. Trinchieri 100 prevalence and incidence of urolithiasis in Italian population in 2012 divided by region, age and gender. Inclusion criteria were: family physician- assisted Italian living population members included in HS database within 31 December 2012 of both genders, aged over 17 years, with at least two years of clinical history recorded from the beginning the trial. The physicians par- ticipating to the study were 650 and were considered the most reliable among 1000 family physicians using HS. In fact in 1998 1000 Italian family- physicians were involved in a project of electronic medical recording (EMR) in order to create a large HS database. In 2009, 650 Italian family-physicians out of the total 1000 Italian family-physi- cian initially involved were selected according to their geographical distri- bution (Northeast, Northwest, Central, South, Islands). This group of “selected” 650 family physicians is composed by family physicians who ensured the best quality of reporting in epidemiological research. In order to select this group a quality score was calculated for each family physician. The geographical dis- tribution of patients of these family physicians is similar to general Italian population census by ISTAT, without significant differences both in geo- graphical location and age distribution. Registered informations were: demo- graphic informations and clinical infor- mations such as Body Mass Index (BMI), smoking, pressure blood value, bio- chemistry data, imaging, hospitaliza- tion, drugs etc. Each patient was labelled with a nameless code, so all informations of each patient were reported with equivalent code. The nomenclature of was concordant with Official Journal, drug’s names were concordant with coding of Anatomical Therapeutic Chemical Classification System (ATC) and diseases were con- cordant with coding of International Classification of Diseases 9° Edition (ICD-9). Data were collected by the database Health Search and elaborated by its software Millewin®. RESULTS The examined population is 900.994 with a regional allocation showed in Table 1. This table shows the numbers (and rates) of family physician-assisted Italian living population members included in HS database within 31 Total Male Female Region N % N % N % Piemonte/Aosta 61701 6.85 29756 6.87 31945 6.82 Liguria 29791 3.31 14081 3.25 15710 3.36 Lombardia 140973 15.65 69138 15.97 71835 15.34 Trentino/FVG 46451 5.16 22196 5.13 24255 5.18 Veneto 72553 8.05 35135 8.12 37418 7.99 Emilia Romagna 54403 6.04 25421 5.87 28982 6.19 Toscana 46800 5.19 22555 5.21 24245 5.18 Umbria 25127 2.79 11996 2.77 13131 2.80 Marche 24930 2.77 12249 2.83 12681 2.71 Lazio 79945 8.87 37788 8.73 42157 9.00 Abruzzo/Molise 29723 3.30 14035 3.24 15688 3.35 Campania 77616 8.61 37134 8.58 40482 8.65 Puglia 65505 7.27 31682 7.32 33823 7.22 Basilicata/Calabria 41207 4.57 20052 4.63 21155 4.52 Sicilia 81595 9.06 38830 8.97 42765 9.13 Sardegna 22666 2.52 10765 2.49 11901 2.54 Total 900.994 100.00 432816 100.00 468178 100.00 FFVG: Friuli Venezia Giulia. HS: Health Search/CSD Longitudinal Patient Database. N: Number. Table 1. Family physician-assisted Italian living population member of database HS within 31 December 2012 by Italian region and gender. Total Male Female Region N % N % N % Piemonte/Aosta 2237 3.63 1241 4.17 996 3.12 Liguria 1104 3.71 634 4.50 470 2.99 Lombardia 4413 3.13 2547 3.68 1866 2.60 Trentino/FVG 1216 2.62 699 3.15 517 2.13 Veneto 2119 2.92 1222 3.48 897 2.40 Emilia Romagna 2486 4.57 1436 5.65 1050 3.62 Toscana 1756 3.75 1063 4.71 693 2.86 Umbria 960 3.82 592 4.94 368 2.80 Marche 1334 5.35 770 6.29 564 4.45 Lazio 3160 3.95 1635 4.33 1525 3.62 Abruzzo/Molise 1306 4.39 659 4.70 647 4.12 Campania 4718 6.08 2105 5.67 2613 6.46 Puglia 3072 4.69 1461 4.61 1611 4.76 Basilicata/Calabria 2107 5.11 977 4.87 1130 5.34 Sicilia 4355 5.34 2135 5.50 2220 5.19 Sardegna 966 4.26 446 4.14 520 4.37 Total 37316 4.14 19626 4.53 17690 3.78 FFVG: Friuli Venezia Giulia. HS: Health Search/CSD Longitudinal Patient Database. N: Number. Table 3. Prevalence of urolithiasis in family physician-assisted Italian living population member of database HS within 31 December 2012 by Italian region and gender. Total Male Female Age N % N % N % 15-24 92113 10.22 47883 11.06 44230 9.45 25-34 121663 13.50 60975 14.09 60688 12.96 35-44 160896 17.86 79737 18.42 81159 17.34 45-54 163813 18.18 80216 18.53 83597 17.86 55-64 135266 15.01 66156 15.29 69110 14.76 65-74 114032 12.66 54314 12.55 59718 12.76 75-84 80967 8.99 33309 7.70 47658 10.18 ≥ 85 32244 3.58 10226 2.36 22018 4.70 HS: Health Search/CSD Longitudinal Patient Database. N: Number. Table 2. Family physician-assisted Italian living population member of database HS within 31 December 2012 by class age and gender. December 2012 divided by Italian re gion and gender (432.816 male versus 468.178 female) while Table 2 shows the same population divided by class age (64.55% 25-64 years, while 12.57% ≥ 75 years) and gender (66.33% 25- 64 years males versus 62.92% 25-64 years females). Patients members of HS database within 31 December 2012 with urolithiasis were 37.316, 4.14% of total family physician-assisted Italian living popula- tion members of HS database within 31 December 2012 (Table 3). This table shows an higher prevalence in males compared to females (M 4.53% versus F 3.78%) also, while table 4 shows a pos- itive relation with increasing age. The highest prevalence (6.08%) of urolithia- sis was observed in Campania (Table 3), followed by Marche 5.35% and Sicilia 5.34% whereas the lowest was recorded in Trentino/Friuli Ve ne zia Giulia 3.15% (Table 3). In almost all the Italian regions the prevalence of stone disease is higher in males (Table 3), but in some regions such as Campania (M 5.67% vs F 6.46%), Puglia (M 4.61% vs F 4.76%), Basilicata/Cala bria (M 4.87% vs F 5.34%), and Sar degna (M 4.14% vs F 4.37%) the prevalence is higher in females (Table 3). The higher preva- lence was observed in 65-74 years class age (Table 4), rating 6.71% (M 8.02% and F 5.51%), follo wed by the 75-84 years (6.35%) and 55-64 years (5.92%) age groups (Table 4). In ci dence of urolithiasis in family physician-assist- ed Italian living population member of HS database within 31 December 2012 was 2.23 *1000, with the highest rate in Sicilia (3.15 *1000) (Table 5). In Emilia Romagna an higher incidence was recorded among males (3.43 *1000), while in Sicilia among females (3.49 *1000) (Table 5). As well as the preva- lence, the incidence was higher in 65-74 years group age (3.18 *1000) (Table 6). Female are more affected in this group age (3.03 *1000), while male in 55-64 years group age (3.53 *1000) (Table 6). DISCUSSION When comparing the epidemiological data of this study with those from liter- ature, temporal references should be taken into account In fact population members of HS database were included within 31 December 2012, whereas those in the literature are related to pre- vious periods, and this condition may have influence on the epidemiology of this chronic disease whose prevalence and incidence trends in recent decades have been changing. The lifetime preva- lence of kidney stone disease is estimated at 1% to 15%, with the probability of having a stone varying according to age, gender, race, and geographic location. In previous reports the prevalence of kidney stones varied greatly between geographic locations, ranging from 8% to 19% in males and from 3% to 5% in females in Western countries (12). It has been apparent for several years that the inci- 101Archivio Italiano di Urologia e Andrologia 2014; 86, 2 Urolithiasis in Italy: An epidemiological study Total Male Female Region N *1000 N *1000 N *1000 Piemonte/Aosta 106 1.71 61 2.05 45 1.39 Liguria 77 2.54 36 2.52 41 2.55 Lombardia 296 2.05 163 2.31 133 1.80 Trentino/FVG 53 1.10 29 1.27 24 0.95 Veneto 105 1.40 57 1.58 48 1.23 Emilia Romagna 153 2.72 90 3.43 63 2.10 Toscana 78 1.44 45 1.73 33 1.17 Umbria 45 1.77 32 2.66 13 0.97 Marche 51 2.02 33 2.67 18 1.40 Lazio 230 2.72 107 2.71 123 2.73 Abruzzo/Molise 63 1.97 30 2.00 33 1.95 Campania 218 2.71 114 2.97 104 2.47 Puglia 174 2.53 78 2.36 96 2.70 Basilicata/Calabria 113 2.66 64 3.10 49 2.24 Sicilia 260 3.15 108 2.76 152 3.49 Sardegna 61 2.52 30 2.61 31 2.44 Total 2090 2.23 1082 2.42 1008 2.06 FFVG: Friuli Venezia Giulia. HS: Health Search/CSD Longitudinal Patient Database. N: Number. Table 5. Incidence of urolithiasis in family physician-assisted Italian living population member of database HS within 31 December 2012 by Italian region and gender. Total Male Female Age N *1000 N *1000 N *1000 15-24 81 0.95 34 0.77 47 1.15 25-34 184 1.49 89 1.44 95 1.54 35-44 309 1.86 179 2.18 130 1.54 45-54 438 2.56 226 2.70 212 2.42 55-64 447 3.12 246 3.53 201 2.74 65-74 388 3.18 193 3.34 195 3.03 75-84 211 2.40 100 2.75 111 2.15 ≥ 85 32 0.86 15 1.26 17 0.67 HS: Health Search/CSD Longitudinal Patient Database. N: Number. Table 6. Incidence of urolithiasis in family physician-assisted Italian living population member of database HS within 31 December 2012 by age and gender. Total Male Female Age N % N % N % 15-24 601 0.65 236 0.49 365 0.83 25-34 2303 1.89 928 1.52 1375 2.27 35-44 4903 3.05 2384 2.99 2519 3.10 45-54 7381 4.51 3941 4.91 3440 4.12 55-64 8012 5.92 4562 6.90 3450 4.99 65-74 7646 6.71 4355 8.02 3291 5.51 75-84 5142 6.35 2633 7.91 2509 5.27 ≥ 85 1328 4.12 587 5.74 741 3.37 HS: Health Search/CSD Longitudinal Patient Database. N: Number. Table 4. Prevalence of urolithiasis in family physician-assisted Italian living population member of database HS within 31 December 2012 by age and gender. Archivio Italiano di Urologia e Andrologia 2014; 86, 2 D. Prezioso, E. Illiano, G. Piccinocchi, C. Cricelli, R. Piccinocchi, A. Saita, C. Micheli, A. Trinchieri 102 dence rates of lithiasis vary dramatically, not only from con- tinent to continent, but also between adjacent regions of a country, even if one allows for differences in methodology and criteria selection among epidemiology studies (13, 14) Infact epidemiological data on the occurrence of urolithia- sis ranges between 2% and 20% worldwide (15, 16) (being most common in South and South Eastern regions of United States, as well as in Central Europe and the Me - diterranean area, India and Northern Pakistan, Northern Australia and China) (17) In our study the prevalence in 2012 in Italy is 4.14%, while the incidence is 2.23 *1000, with a geographic distribution showing higher prevalences and incidences in Southern regions. This can be easily explained, by the well documented knowledge that the incidence of urinary stones is higher in countries with warm or hot climates, probably due to low urinary output and scant fluid intake (18). Seasonal variation in stone dis- ease is likely related to temperature by way of fluid losses through perspiration and perhaps by sunlight –induced increases in vitamin D (19). In a previous study of the SIMG (2) in 2008, the prevalence of urolithiasis in Italy was evaluated at a lower rate of 3.1%. The higher rate demon- strated in the present study confirm in our country the increasing trend reported in the rest of the world. Stone disease typically affects adult men more commonly than adult woman (12). Howerver Scales et al. (20) observed a dramatic increase from 1997 to 2002 of the adjusted rate of discharges for stone disease in females in American pop- ulation with a change from 1.7:1 to 1.3:1 of the male-to- female ratio. The increasing incidence of nephrolithiasis in women might be due to lifestyle associated risk factors, such as obesity (20). In Italy the rates in 2012 confirm the 2008 data (2) with higher prevalence in males than in females (M 3.4 vs. F 2.8%) but contrasting results were observed in southern regions.. Data from the American database National Health and Nutrition Examination Survey (NHANES) indicate that stone prevalence increased in all age groups from 1980 to 1994 though, despite more than 15,000 participants at each time point, the increase was statistically significant only for men aged 60-74 (21). In Italy hypercalciuria was more frequent in patients aged 20-39 years (50.3%) than in older patients (36%) and hyperuricosuria was lower in the younger patients (5%) than in the older patients (10%) (22). In our study the age group most affected is 65-74 years (6.71%, M 8.02% and F 5.51%), instead of the 55-64 years age group (4.5% M 5.40% and F 3.60%) in 2008 (2), however in both stud- ies a similar trend was observed. CONCLUSIONS This is the first study that evaluated prevalence and inci- dence of urolithiasis in Italy by age, gender and Italian region. These data are important for clinical workforce planning, training, service delivery and research in the field of urolithiasis. REFERENCES 1. Semins MJ. Medical evaluation and management of urolithiasis. Ther Adv Urol. 2010; 2:3-9. 2. Campo S, Pasqua A, Simonetti M, Mazzaglia G. Studio sulla nefrolitiasi nel setting delle cure primarie italiane. Rivista della Società Italiana di Medicina Generale 2011; 2:1-5. 3. Pearle M, Calhoun E, Curhan G. Urologic diseases in America project: urolithiasis J Urol. 2005; 173:848-57. 4. Romero V, Akpinar H, Assimos D. Kidney stones: a global picture of prevalence, incidence, and associated risk factors. Rev Urol. 2010; 12:86-96. 5. Stamatelou K, Francis M, Jones C, et al. Time trends in reported prevalence of kidney stones in the United States: 1976-1994. Kidney Int. 2003; 63:1817-23. 6. 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Time trends in reported prevalence of kidney stones in the USA:1976-1994. Kidney Int. 2003; 64:1817-1823. 22. Vitale C, Tricerri A, Manganaro M, et al. Clinical and metabol- ic features of renal calculi in adults in regard to age of onset. Minerva Urol Nefrol. 1999; 51:71-74. Correspondence Domenico Prezioso, MD (Corresponding Author) Ester Illiano, MD Department of Neuroscience, Reproductive Sciences and Dentistry. University Federico II of Naples, Naples, Italy Gaetano Piccinocchi, MD - SIMG. Italian Society of General Medicine Claudio Cricelli, MD - SIMG. Italian Society of General Medicine Roberto Piccinocch, MD - University “Campus Biomedico” of Rome, Italy Alberto Saita, MD - Department of Urology. “Vittorio Emanuele Hospital”. University of Catania, Italy Carla Micheli, MD - Department of Urology and Andrology. Santa Maria della Misericordia Hospital. University of Perugia, Perugia, Italy Alberto Trinchieri, MD - Department of Urology Alessandro Manzoni Hospital of Lecco, Lecco, Italy