Daily Mean Temperature Affects Urolithiasis Presentation in Seoul: a Time-series Analysis

The relationship between seasonal variation and urolithiasis attack is reported in several studies (1, 2, 3, 4). Urolithiasis incidence increases during summer and decreases during winter. It is generally attributed to the effect of seasonal variations in temperature on urinary volume, due to excessive perspiration and dehydration. Low urine volume is an important factor mostly of an environmental nature that directly increases the urinary saturation of stone-forming salts.

These studies on the effect of temperature on urolithiasis were usually based on data from a limited area of the country or on inadequate climatic data due to minimal temperature changes over 4 seasons. Seoul, the capital city of Korea, has 4 distinct seasonal changes and an average annual temperature of 13°C comparable to cities in Europe. The conditions are more acceptable in studying the association of climate and urolithiasis. Moreover, these studies were limited by assessment of temperatures only in summer or extreme conditions, and assessment of lag periods between exposure and outcome that may have missed significant delayed association between high daily temperatures and urolithiasis presentation. The precise relationship between temperature and urolithiasis thus remains uncertain.

The precise relationships between temperature and urolithiasis differ by region, age, and gender. It is critical to policies for preventing the health impacts of heat wave, as it is used as an indicator for initiating public health response actions to heat waves or issue heat wave warnings. The rate of increase of urolithiasis above temperature can also be used as an assessment of vulnerability and the evaluation of public health response (5). Heat-related urolithiasis was reported to increase steeply above a certain level, with similar outcomes for health impact. Nevertheless, the pattern of incidence of urolithiasis and its relationship with temperature have rarely been investigated in Korea.

Therefore, we tested the hypothesis that urolithiasis is etiologically influenced and/or determined by temperature trends in association to other meteorological factors. Additionally, we defined the overall cumulative exposure-response and the lag response relationships between daily temperature and urolithiasis presentation in Seoul.

Our study identified the effect of seasonal variation of urolithiasis presentation. Mean daily temperature and relative humidity were significant factors associated with urolithiasis presentation among the climate parameters. We observed that as daily temperatures increased to > 13°C, the risk of urolothiasis presentation over next 20 days also increased in all groups except males older than 60 years old. The lag between high daily temperatures and the risk of urolithiasis presentation was short, with the maximum risk occurring within 5 days of temperature exposure. Our estimations suggested that there is a graded increase and that time between hot days and urolithiasis presentation is short.

We hypothesized that the estimated RRs of urolithiasis presentation across a range of temperatures represent patients presenting with calcium-based urolithiasis, the most common type of stones in Korea and other developed countries. Dehydration, the proposed casual mechanism through which high temperatures would act, increases the supersaturation of calcium and uric acid, thus promoting calcium stone formation on the apatite deposits. Modeling and laboratory experiments suggested that stones grow over a span of hours in the proper urinary environment and that growth rates are dramatically increased by increasing urinary supersaturation of calcium (7, 8).

There were 4 main findings in our study. First, the existence of an association was confirmed between relative humidity, and the number of urolithiasis presentations, however it did not exist in the overall cumulative exposure-response relationship. The hypothesis supports that dry climate increases in urolithiasis formation is mainly dependent on dehydration. There are conflicting reports on whether humidity correlates with urolithiasis formation and presentation rate (1, 3, 5, 6). Acute disruption of skin from environments with relative humidity as low as 10%, produce an initial increase in transdermal water loss (TEWL) (9, 10). Cravello and Ferri (11) exposed human subjects to variable ambient temperature and relative humidity to determine the dependency of each variable on average skin temperature. They showed a greater influence on skin temperature by ambient temperature with a minor contribution by relative humidity. Furthermore, TEWL was more dependent on ambient temperature than relative temperature in the temperature range. The limited variation of humidity of Seoul might explain why temperature overwhelms humidity in distributed lag nonlinear models. Moreover, it would be interesting to examine not only the role of climate but the role of a specific location in relation to climate and time spent outdoors.

Secondary, a heterogeneous influence of temperature was demonstrated according to patient age, in that variations of temperature were less effective in males older than 60 years old. With adjustment by the population number of age group, the rate of stone incidence was the highest in the 60-69 years old in Korea. The research had some limitations since it would be necessary to consider other potential etiological factors in addition to the meteorological variables in the statistical model. This is thought to be due to the fact that males less than 60 years old engage in outdoor activities more frequently than any other groups, and thus are more exposed to environments with high temperature. Moreover, a diet rich in animal protein is possibly associated with increased urinary calcium excretion and a decreased excretion of citrate (12, 13, 14). Metabolic syndrome had also been considered an independent risk factor in the onset of urolithiasis in Korea (15, 16). Moreover, old people have comorbidities such as hypertension and diabetes that are well-established risk factors for urolithiasis. Meterological factors might less affect old people due to their other lithogenic factors.

Third, the association with temperature was more accurate in females than males; and at below -10°C, the risk of urolithiasis presentation over the next 20 days decreased. Thus, females appear to have greater temperature variation. In general, females show greater variability in physiologic variables, including systolic blood pressure and relative plasma volume due to lower lean body mass (17, 18). The higher variability in physiologic variables seen in females suggests an overall physiology that may be more adaptable to changing circumstances. An alternative hypothesis is that female have a lower incidence of chronic diseases and males consistently have a greater prevalence of urolithiasis than females.

Fourth, the lag between high temperature and urolithiasis was short such that the risk of increasing RR of urolithiasis presentation was observed within 5 days of high temperatures. The observed lag response is strikingly similar to other studies. Tasian et al. (6) reported that the lag response was short, with the maximum risk occurring within 3 days of exposure and persistently of a mild elevated RR at 10-20 days in Philadelphia; and Fletcher et al. (19) reported at case-crossover study in which the maximum odds for admission for nephrolithiasis after high daily temperature were also observed at 3 days. Within 7-10 days of the temperature exposure, we observed that the increased RR of urolithiasis presentation was immediately followed by decreases in RR. We attributed this phenomenon to “harvesting” of urolithiasis cases in subjects who would have had urolithiasis at a future time, but for whom heat caused the event to occur earlier. Harvesting of susceptible cases possibly reflects the causal mechanism of urolithiasis formation and explains the short lag between hot days and urolithiasis presentation. In patients who are predisposed to urolithiasis formation, low urinary volume resulting from sweating on hot days may result in spontaneous urolithiasis nucleation, and/or small asymptomatic urolithiasis, and/or small asymptomatic stones that enlarge enough to become symptomatic.

RR can be fundamental to making decisions related to investing resources and implementing policies to prevent urolithiasis in a region or a population group, or in deciding when to issue a heat warning. RR can be helpful in determining vulnerable groups. In this study, the incidence of urolithiasis increased according to the temperature rise in females and males less than 60 years old. Such a trend can be changed by preventive action and management, besides un-modifiable factors such as gender and age. Therefore, preventive and management policies against heat-related urolithiasis can be evaluated based on RRs.

One of the limitations of this study was that ED visits are not representative of all urolothiasis cases in Seoul. In Korea, most patients usually visit the urology outpatient clinic and not the ED during the day, except patients with very severe pain. Therefore, patients who visited ED were a sub-group of all the urolithiasis patients. However, we controlled this confounding factor by adjustment of the day of week, and selected 4 hospitals located in the west, east, south, and north regions of Seoul. Further study on the entire population using the health care department data is expected. We acknowledge an additional limitation to this study. Temperature-dependent models presume an accurate understanding of current urolithiasis prevalence; however, such data are problematic for a variety reasons. Urolithiasis occurs intermittently and is not always readily apparent. Many patients harbor undiagnosed asymptomatic urolithiasis, whereas others require repeated hospitalizations for recurrent urolithiasis events. Consequently, true urolithiasis prevalence is difficult to determine and is likely to be routinely under estimated and occasionally overestimated. And subanalysis of stone size on CT scan was not evaluated in this study. Actually in the retrospective study, reviewing stone size on CT scan is difficult. Therefore, prospective multicenter study is necessary.

Despite these limitations, the results of our study suggested that specific periods of temperature exposure might be associated with an increased risk of urolithiasis. Additional research is needed to demonstrate whether an intervention such as increasing fluid intake among patients with increased risk for urolithiasis can reduce the frequency of urolithiasis episodes. Further research is needed to confirm these results and access potential intervention strategies during the periods of increased climate associated risk.

Urolithiasis presentation increased with high temperature with higher daily mean temperatures, with the strongest associations estimated for lags of only a few days, in Seoul, a metropolitan city in Korea. These findings further support the adverse effect of high temperature on urolithiasis.