In the present study, calcium-containing stones were the most frequent, followed by uric acid-containing stones, while struvite and cystine are less frequent. In accordance to previous reports , uric acid containing stones were more frequent in males and in older ages, whereas phosphate stones were more frequent in women.
The average age of RSFs in different countries varies but these differences reflect those that are observable in the general population of their countries, which averaged about 20 years lower. On the other hand, the average age values observed in our series overlapped to those previously reported in other series of patients with kidney stones from the same countries [6, 21-29]
Male to female (M/F) ratio is different in countries, being balanced between men and women or slightly in favor of men in the countries of North America, Europe, South America and China but heavily in favor of men in Egypt, Pakistan, India and Iraq.
This finding confirm the tendency to an increase of stone formation in women of Western countries , and more recently of China , while in Egypt, Pakistan, India and Iraq the ratio of males to females is still similar to what was observed in Western countries forty years ago . This trend may be explained by the so-called nutrition transition, that is the change in dietary habits across the world with a convergence towards an increased consumption of unhealthy foods that is the cause of the increase in non-communicable diseases in almost all regions of the world in both sexes . Consumption of unhealthy foods is still limited in some regions of North Africa and South Asia that maintain dietary patterns with a lower risk of urinary stones forming. Moreover, in some countries the characteristics of family structure and cultural rules still present a nutritional disadvantage for women .
The spectrum of composition of urinary stones is quite variable in different countries. Differences could be attributable to the different characteristics by age and gender of the populations studied, reflecting the distribution by age and gender in the general population of each country. On the other hand, the modality of stone analysis and reporting in the different centers may be a confounding factor . For this reason, the most robust data are those comparing the rates of calcium-containing with those of uric acid containing stones, whereas it is less significant to compare the results of different countries in relation to the specific crystallographic composition, which should be compared between patients whose stones have been analyzed and reported in the same laboratory.
Calcium-containing stones were the most common in most countries with a rate ranging from 52 to 91%. The highest rates of calcium-containing stones were observed in North America, South America, China, and some European countries. In most countries, calcium oxalate stones (in particular COM stones) were the more frequent calcium-containing stones, whereas calcium phosphate and mixed calcium oxalate/calcium phosphate stones were more frequent than pure calcium oxalate stones in some countries such as Egypt and India. This trend is in agreement with previous observation in North America where a tendency has been reported of an increase in oxalate stones and a decrease in phosphate stones during the last two decades .
The highest frequency rates of acid uric containing stones were observed in Iraq, Pakistan, India, Egypt and Poland and Bulgaria. In general, uric acid-containing stones should be more frequent in older male patients, but surprisingly in our study the highest rates of uric acid-containing stones were observed in two countries with the lowest mean age, namely Egypt and Iraq. The impact of environmental factors may be decisive, considering that high temperatures and high humidity cause a decrease of urinary volumes and urinary pH values resulting in an increase of urinary uric acid saturation and of the incidence of uric acid stones [37, 38]. In fact, the highest values of uric acid-containing stones were observed in countries with high mean temperatures  and tropic or hot desert climates such as Egypt, India, Pakistan and Iraq. Our data confirm previous evidence in the literature showing a high rate of uric acid-containing stones in Pakistan, Egypt, and Iraq [23,24,39]. In the present study, the prevalence of uric acid containing stones was also high in Southern India in accordance with previous reports. In fact, the frequency of uric acid-containing stones was reported as low (< 1%) in North Western India [25,26], but higher in Southern India . This difference can be explained by different regional eating habits: in the Northern and Western regions, a more traditional vegetarian diet is consumed with exclusive consumption of fruit, vegetables and legumes, whereas in the Southern regions the consumption of sweets, snacks and pork meat is common . On the other hand, in our study the lowest rate of uric acid containing stones was observed in Canada, the country with the lowest mean temperature. Intermediate rate values were observed in countries with a temperate climate, such as China and Italy.
In some countries, the high frequency of uric acid-containing stones may be explained by the effect of dietary factors that contribute to the risk of uric acid stone formation .
Although in contrast with previous findings showing lower rates of uric acid stones in a series of stones analyzed by infrared spectroscopy , the high rate of uric acid stones in Poland may be explained by high obesity rate of the population (45%) and unfavorable dietary patterns . In fact, the adherence to the traditional Polish dietary pattern, characterized by high intake of refined grains, potatoes, sugar and sweets is associated with a higher risk of abdominal obesity and hypertriglyceridemia . Similarly, in Bulgaria the frequency of uric acid-containing stones is associated with an unhealthy nutritional pattern characterized by high consumption of fatty meats and meat products, high-fat milk and a high alcohol intake .
The rate of struvite stones is generally lower than described in the past, due to improved health conditions and early diagnosis and treatment of urinary tract infections by urease-producers, although in some countries such as Pakistan and India it still accounts for a quarter of cases.
In some areas of these countries, the diagnosis and treatment of urinary infections is still inadequate and can result in chronic infections and scarring of the urinary tract promoting the formation and growth of staghorn infection stones .
Cystine stone rates are similar in all countries, with similar rates than those reported in the literature.
The strength of this study has been to have compared series from different countries according to the same evaluation parameters, but it has some limitations. A limitation was the use of wet-chemical analysis of the stones in 3 out 12 centers that participated in the study. In fact, chemical analysis of the stone has limitations in identifying all the stone components and distinguishing their crystalline forms for which most guidelines recommend analysis by infrared spectroscopy or X-ray diffractometry . Unfortunately, these methods are not available in all centers, so to extend our survey to as many countries as possible, we decided to include also centers where the stones were analyzed with wet chemical analysis. For this reason, data of the stones analyzed in Argentina, Canada and Poland may be less reliable and should be evaluated with caution.
Another possible limitation of this study was the use of frequency rate of the different types of stones as a parameter to compare the pattern of stone composition in different countries. This parameter should be corrected based on the prevalence rate of urinary calculi (all types included) in the population of each country. Unfortunately, we know the rate of prevalence of urinary calculi in the general population only for a limited number of countries.
When we calculated the specific prevalence of different types of stones, we were able to confirm the high prevalence of uric acid stones in Pakistan and, to a lesser extent, in India while we could not calculate prevalence rates of uric acid stones for Iraq, Egypt, Poland and Bulgaria where epidemiological studies were never carried out to assess the prevalence of urinary stones in the general population. The significance of the high frequency rates of uric acid-containing stones in these countries remains uncertain.
In fact, the frequency of a type of stone is not a measure of its prevalence but it is the result of the prevalence of the different types of urinary stones. In other words, a high frequency of uric acid stones may be due to an increase in the prevalence of uric acid stones but, alternatively, to a lower prevalence of other types of stones (e.g. calcium oxalate).
In conclusion, the frequency of different types of urinary stones varies from country to country. Calcium-containing stones are the most frequent in all countries, with frequencies of up to 90%. The frequency of uric acid containing stones seems to depend mainly on climatic factors, being more frequent in warmer countries with desert or tropical climates although dietary patterns can also lead to an increase in the frequency of uric acid containing stones in association with high obesity rates. Struvite stones are decreasing in most countries except India and Pakistan.