The prevalence of urinary calculi and the frequency of different types of stone can change consequently to changes of environmental factors, such as diet and climate, as well as changes of age and gender distribution of the population.
Our series confirm some findings commonly observed in epidemiological studies of urolithiasis such as higher struvite and apatite-containing stone rates in females and higher rates of uric acid containing stones in male and older patients.
Only a limited number of studies have assessed the spectrum of the composition of urinary calculi in the same population over different periods of time 1,2,11-15.
In South Australia urinary stone composition has remained relatively static over the past 30 years 11.
In Japan, from 1953 to 1984, a reduction in the frequency of struvite calculi from 20% before 1960 to 10% after 1961 was observed, although a slight tendency to increase was again detected after 1973, especially in females 12. In Massachusetts from 1990 to 2010, the frequency of struvite stones significantly decreased from 7.8% to 3.0% in females but remained stable in males ranging from 2.8% to 3.7% 13,
This trend is in accordance with our observations that show a decrease from 24% of our previously reported observations in the period 1981-9516 to the actual 1.6-6.5% value. The frequency of struvite stones was very low in the 2001-03 series in Milan (1.6%), although it is interesting to note that in the most recent period it tended to increase slightly from 3.3% to 6.5%. This can be explained by recent immigration in Italy from countries of Eastern Europe and from north and central Africa, which contributed with a relevant number of infection stone cases due to poor health conditions of those countries. In Canada, an 80.4% rate of calcium oxalate and/or calcium phosphate stones was observed with a 3.9% rate of magnesium ammonium phosphate and 7.6% of uric acid/urate stones 14. In the calcium stone group, stones with prevalent oxalate content accounted for 65% and stones with prevalent phosphate content for 16%, although from 1980-83 to 1995-1998 a relative increase in stones with prevalent oxalate and a decrease in stones with prevalent phosphate was observed. A similar trend was reported in Massachusetts with a significant decrease from 20% to 11.7% of the frequency of apatite stones in females but an increase from 9.8% to 12.5% in males 13. In our series we observed only a slight decrease of the frequency of apatite-containing stones from 15.4% to 14%, in association with an increase of the rate of COM and a decrease of COD stones.
In Texas, uric acid containing stones increased from 7% to 14% from 1980 to 2015 1. This trend was explained by an increase in age and body mass index (BMI) in the population of stone formers. However, in Minnesota 15, from 1984 to 2012, no change of uric acid stone rate was observed and, in Massachusetts, from 1990 to 2010, the rate of uric acid stones increased in females, from 7.6 to 10.8%, but not in males (11.7 vs 10.8%) 12.
In southern Italy it was also observed from the period 1983-86 to 2008-2011, a decrease in the frequency of calcium oxalate stones (from 83.9% to 76.6%) and an increase in the frequency of uric acid stones from 2.2% to 9.3% 2.
On the contrary, the results of our study do not confirm this trend, demonstrating unchanged rates of uric acid stone rates over the last 15 years even after age adjustment.
The increase of the frequency of uric acid stones in some countries could be related to different factors. The main driving force of uric acid crystallization in urine is an acidic pH that can be associated with ageing, obesity and type 2 diabetes. Ageing is a common feature of all Western populations. According to the World Population Prospects 2019 of the United Nations 17 the ratio of population aged > 65 years (old-age dependency ratio) increased in the United States from 20.9% in 2000 to 24.6% in 2015 and in Italy from 29.5% to 36.8%. Obesity is the result of chronic imbalance of energy intake and expenditure by physical activity and unhealthy diet and a sedentary lifestyle are also considered important drivers of the onset of diabetes in genetically predisposed subjects. According to NCD Risk Factor Collaboration 18, obesity prevalence (BMI > 30 kg/m2) in the United States increased from 25.5% in 2001 to 36.4% in 2016 for men and from 28.5% to 38.1% for women. Obesity rates in Italy were lower although in the same time interval they increased from 14.9% to 20.9% in men and from 16.8% to 20.4% in women. Crude prevalence of diabetes in the United States increased from 7.7% in 2001 to 9.8% in 2014 in men and from 6.9% to 8.3% in women. In Italy, a similar increase was observed from 7.5% to 9.5% of men and from 6.9% to 7.4%, although these values refer to an older population 19.
All these factors should lead to an increase in the frequency of uric acid stones which has not been uniformly observed in all the studies we have evaluated.
We must therefore assume that there is another epidemiological factor which is decisive in increasing the frequency of uric acid stones in certain geographical regions.
Different climatic conditions could be an explanation of the different trends of the epidemiology of uric acid urinary calculi observed in different studies (Figure 1).
Uric acid stones are more easily formed in a warm climate. In South Australia a greater incidence of uric stones during Summer and Autumn was observed 20 and Stuart et al showed that in the warmer months of the year there is a higher level of urinary saturation for uric acid in relation to lower urinary volumes and lower urine pH values 21.
In fact, as a result of global warming, the average annual temperatures increased by about one Celsius degree from the 1981-85 period to the 2011-2015 period in most of United States 22.
According to data collected by the National Climatic Data Center of the United States 22, average annual temperature increased from 5.2-6.4°C to 3.7-7.3°C in Minnesota, from 8.4-9.2°C to 8.7-10.7°C in Massachusetts and from 17.4-18.3 C° to 18.2-19.9°C in Texas.
In Texas, the increase of temperature may have had a greater impact on the risk of formation of uric acid stones as it occurred in a higher temperature range than in northern regions of the United States (Fig.1).
In fact, the number of days in which the risk threshold for crystallization of uric acid was exceeded was higher 13. The threshold value beyond which the risk of precipitation of uric acid in the urine is significantly increased has not been precisely defined, but it can be inferred by values of temperature associated with the risk of the onset of acute gout attacks, that according to Neogi et al could be placed at 26°C13 .
Similarly, the different climatic conditions in southern Italy may explain the discrepancy of the study of Rendina et al. 2 with the results of our study carried out in a region of northern Italy 3.
A possible bias factor in our study is the imbalance between the number of patients retrospectively reviewed in the two study periods in favor of patients observed in the most recent period. Unfortunately, in the first period the use of infrared spectrophotometry had not been routinely extended to all patients, whereas in the most recent period the analysis was carried out routinely. In addition, the volume of patients observed in the second period increased because a second institution was associated with the primary academic institution. Consequently, the populations studied were homogeneous and the increase in numbers of the second group is not attributable to an increase in the prevalence of urinary stones which, after the increase observed in the 1980s 23, has remained relatively stable in Italy over the last decade at a value of 7.5% 24.