Temperature as a risk factor of emergency department visits for acute kidney injury: a case-crossover study in Seoul, South Korea
Previous studies show that escalations in ambient temperature are among the risk factors for acute kidney injury (AKI). However, it has not been adequately studied in our location, Seoul, South Korea. In this study, we aimed to examine the association between ambient temperatures and AKI morbidity using emergency department (ED) visit data.
We obtained data on ED visits from the National Emergency Medical Center for 21,656 reported cases of AKI from 2010 to 2014. Time-stratified case-crossover design analysis based on conditional logistic regression was used to analyze short-term effects of ambient temperature on AKI after controlling for relevant covariates. The shape of the exposure–response curve, effect modification by individual demographic characteristics, season, and comorbidities, as well as lag effects, were investigated.
The odds ratio (OR) per 1 °C increase at lag 0 was 1.0087 (95% confidence interval [CI]: 1.0041–1.0134). Risks were higher during the warm season (OR = 1.0149; 95% CI: 1.0065–1.0234) than during the cool season (OR = 1.0059; 95% CI: 1.0003–1.0116) and even higher above 22.3 °C (OR = 1.0235; 95% CI: 1.0230–1.0239).
This study provides evidence that ED visits for AKI were associated with ambient temperature. Early detection and treatment of patients at risk is important in both clinical and economic concerns related to AKI.
KeywordsAmbient temperature Acute kidney injury Emergency department visit Case-crossover design Exposure-response curve
Acute Kidney Injury
Automated Synoptic Observing System
Chronic Kidney Disease
International Classification of Disease
Institutional Review Board
Kidney Disease Improving Global Outcomes
Korean Meteorological Administration
National Emergency Department Information System
National Emergency Medical Center
Organization for Economic Co-operation and Development
Increasing recognition of climate change and global warming has led to a growing interest of researchers in assessing the potential mechanisms by which it may influence health . The adverse impacts of ambient temperature on health have been described in numerous epidemiological studies [2, 3, 4], and some studies have reported that escalations in temperature or heat (waves) are among the risk factors for acute kidney injury (AKI) [5, 6, 7, 8, 9, 10].
The primary underlying mechanism for pre-renal AKI is a series of impairment in renal autoregulation related to pre-glomerular arteriolar vasodilation, by prostaglandin I2 and nitric oxide and post-glomerular arteriolar vasoconstriction, by angiotensin II [20, 21]. True hypovolemia or a reduction in the effective circulating volume, such as decreased cardiac output, systemic vasodilation, or intra-renal vasoconstriction results in impaired renal autoregulation, leading to decreased glomerular filtration rate, which is proportional to the level of hypoperfusion [22, 23]. Dehydration due to exposure to high temperature may lead to decreased intravascular volume, increased vascular resistance, or low cardiac output, which eventually lead to hemodynamically mediated (pre-renal) AKI . Moreover, acute volume depletion leads to increased proximal reabsorption, which affects tubulo-glomerular feedback, resulting in a pre-renal reduction in glomerular filtration rate .
Numerous studies have investigated the association between ambient temperature and morbidity, particularly renal function. Most of these studies have utilized hospital admission data to demonstrate that renal morbidity rates are associated with temperature increases [5, 7, 8, 26, 27]. However, at our location, hospital admissions would not be appropriate for assessing the acute short-term association in a time transient study because most admissions are scheduled in Seoul. Inclusion of scheduled admissions could attenuate observed associations with ambient temperature, due to inclusion of admissions for which timing of the event was not caused by ambient temperature. Therefore, in this research, emergency department (ED) data for unscheduled visits were used as the outcome measure to gain a better understanding of the relationship between ambient temperature and AKI morbidity in Seoul, a city with a temperate climate with distinct seasons. We performed a time-stratified case-crossover analysis based on conditional logistic regression to investigate the association. In addition, we examined the shape of the associations as well as lag effects. To our knowledge, this is the first study to assess the generalizability of the association between ambient temperature and AKI using ED visit data in Seoul.
Study location and health outcomes
This study was conducted in Seoul (37.34°N, 126.59°E), which is the capital and largest metropolis of South Korea with a population of approximately 10 million . Seoul spans a land area of 605.25 km2, which is only 0.6% of the total area of South Korea, but 1/5 of the total population of South Korea live in Seoul (16,492 person/km2). Seoul has a temperate climate with distinct seasons and a wide range of temperatures across the year.
We utilized data on ED visits recorded by the National Emergency Medical Center (NEMC). The NEMC is a government-funded national ED control agency, and one of its roles is to collect data on ED visits to improve the quality of emergency medical service and health care. The collected data included patient’s information such as sex, age, type of insurance, level of consciousness, vital signs, means of transportation, emergency operative procedures, time variables (visit, discharge, and admission), critical care requirement, disposition status after the ED encounter, duration of hospitalization, and final outcomes (information regarding discharge, transfer, and death) . These data are transferred electronically from the hospitals to the NEMC via a National Emergency Department Information System (NEDIS). The agency maintains an accurate assessment system and annually reports the results to the Ministry of Health and Welfare . The NEDIS database has been widely used by broad range of epidemiological researchers due to its reliability . ED visit data were obtained from the NEDIS of the NEMC between January 1, 2010 and December 31, 2014 for this study. ED visit data were coded and classified according to the discharge diagnosis using the International Classification of Disease 10th Revision (ICD-10). Patients with ICD-10 code N17 based on the primary and secondary disease codes were considered to have AKI (Additional file 1: Table S2). Because the data were based on ED visit incidence, the onset was regarded as acute even in case of CKD, although it could be regarded as an acute exacerbation of CKD. In this sense, we examined acute renal illness as a whole. In addition, we stratified the patients with both CKD (ICD-10 code N18) and AKI (ICD-10 code N17) in the sensitivity analysis due to the possible discrepancies in the pathophysiological mechanisms of AKI with pre-existing CKD (Additional file 1: Figure S1). Patients were also stratified by sex (male and female), age (< 65 years and ≥ 65 years), and season (warm and cool) when they visited the ED. We also analyzed the comorbidities for AKI, namely, hypertension and diabetes.
Automated Synoptic Observing System (ASOS) data from 2010 to 2014 were obtained from the Korean Meteorological Administration (KMA). ASOS collects data every minute, including temperatures (°C), relative humidity (%), and air pressure (hPa), and KMA provides city-level daily average of these meteorological variables. Because air pollution has been reported to have a short-term effect on renal morbidity , we also obtained hourly concentrations of particulate matter with an aerodynamic diameter of < 10 μm (PM10) from 27 monitoring sites operated by the Korean National Institute of Environmental Research. Hourly mean concentrations across the monitoring sites were calculated by averaging monitor-specific concentrations, then we calculated the daily representative concentrations of PM10 by averaging the 24-h values from all monitoring stations in Seoul. The data were grouped into two seasons: warm (April–September) and cool (October–March).
We used a time-stratified case-crossover design based on conditional logistic regression to analyze the short-term effects of temperature on AKI-ED visits. The case-crossover design, which is a variant of the case-control design, is largely used in environmental epidemiology research  for evaluating when the outcome is acute and the exposure is transient . Comparisons were made between the case day (the day of the case visits ED) and several control days. In this way, each patient serves as his/her own control on days other than the case day with measured and unmeasured potential confounding factors such as age, sex, smoking status, and other genetic predisposition. Moreover, these are automatically controlled by perfect matching. The control days were selected as the same month and year and matched by day of week for each case. This time-stratified method of selecting comparison days avoids bias resulting from time trends in examination of the environmental exposures. Long-term and seasonal time trends and day of the week were also controlled by design . We included potential time-varying confounders, which are relative humidity and barometric pressure in the model. We also performed sensitivity analyses to examine the confounding effects of PM10 (lag 0–1).
To explore the susceptibility of groups to the influence of temperature, we modelled the interactions between temperature and each subgroup, namely, age, sex, comorbidities (hypertension and diabetes), and season, to determine whether the effects of temperature differ in these aspects because the case-crossover design cancelled out the potential confounding time-invariant variables.
A significance level of α = 0.05 was adopted for each test. Statistical analysis was conducted using R software version 3.1.0 with the survival package (R Foundation for Statistical Computing, http://www.R-project.org).
Demographic characteristics of patients with acute kidney injury who visited the emergency department
No. of subjects
AKI with coexisting hypertension
AKI with coexisting diabetes
Descriptive statistics for environmental variables in Seoul, South Korea, 2010–2014
Mean temperature (°C)
Mean relative humidity (%)
Mean pressure (hPa)
Mean PM10 (μg/m3)
We observed a considerable increase in the risk of AKI that was associated with escalations in ambient temperature over all seasons, and the risk for AKI was particularly higher during the warm season. In addition, a noticeable nonlinear relationship with temperature was found during the warm season, indicating a severe risk for AKI associated with ambient temperatures above the threshold of 22.3 °C. Our findings are in line with those of previous studies that show evidence supporting a positive association between high temperatures and the risk of AKI. Two studies from the US and one from Australia found that hospital admissions for AKI were substantially increased during heat wave periods compared with non-heat wave periods [8, 27, 40]. In addition, a study of temperature effects on AKI hospital admissions in California reported a 7.4% increase in AKI admissions associated with each 10 °F (5.56 °C) increase in daily mean temperature , while 8.28% increase in AKI-ED visits associated with each 10 °F during the warm season in Seoul of our study. Given that our results were obtained using individual ED visit data, this study strengthens the epidemiologic evidence of an acute adverse effect of ambient temperature on AKI morbidity.
We observed considerable adverse effects of temperature on ED visits due to AKI in both warm and cool seasons as the temperature increases, but the risk was greater during the warm season than the cool season and was even greater above the threshold temperature of 22.3 °C. Many studies have focused on the health effects of heatwaves or high temperatures [8, 27, 40, 41]. However, the risk for AKI substantially increased in temperatures above 22.3 °C in the present study, suggesting that the threshold temperature is lower than that used in previous studies. This finding is consistent with that of Kovats et al.  who reported that threshold temperatures of 18 °C for diseases of the renal system and 21 °C for renal failure. Additionally, they reported that kidney stones have a considerable effect on hospital admissions for renal disease in Greater London, UK. This suggests that not only extremely hot temperatures and heatwaves, but also moderate temperatures affect health. The effects of non-extreme weather are less focused in the literature. The increased risk of AKI from outdoor exposures during the warm season places greater emphasis on the preventive aspects of AKI.
Some studies explored the temporal lag patterns of the association between temperature and health risks. For the association of temperature with morbidity, lag days were reported ranging from the same day  to a month . According to Fletcher et al. (2012), the strongest association between the mean temperature and AKI hospital admissions occurs at lag 1 (OR = 1.09, 95% CI: 1.07, 1.12), while significant associations were also observed at lags 0 and 2 (OR = 1.06, 95% CI: 1.04, 1.09 and OR = 1.06, 95% CI: 1.03, 1.08, respectively). Our result showed more acute effects of temperature on AKI-ED visits for lag 0 in both seasons. Similarly, Basu et al. found acute effects of temperature (lag 0) on ED visits in California, USA . In Atlanta, USA, Chen et al. also found that increased temperature had same-day (lag 0) effects on both all renal diseases and AKI .
PM10 was assessed in the model. Associations between PM and daily mortality , cardiovascular hospital admissions in the elderly , and infant mortality  have been identified in Korean cities. Furthermore, a recent longitudinal study among US veterans demonstrated the associations of PM concentrations with a higher risk of reducing renal function , development of CKD, and progression to end-stage renal disease . It is biologically plausible that the inflammation and oxidative stress linked to PM exposure could be an underlying mechanism for a broader number of disease outcomes , including renal disorders. Nonetheless, the effect of temperature on AKI was robust with a potential confounder of air pollutants in our analysis. Moreover, our findings remained statistically significant after adjusting for PM10. In addition, the fact that the temperature effect is robust to the adjustment for PM in our analysis suggests that PM is not solely responsible for the higher risk of AKI. Toxicity depends on the components of PM , and exposure patterns vary by seasons due to behavioral changes of individuals . Thus, the adverse effects of PM on AKI need to be further validated.
Contrary to expectations, the temperature effects of AKI did not vary substantially across demographic characteristics. The elderly may be more vulnerable due to a reduction in thermoregulatory abilities, age-related declines in kidney function, adaptation behaviors, low self-care abilities, and health comorbidities. However, although the risk of the elderly was slightly higher among those aged ≥ 65 years than among those aged < 65 years, the difference was not statistically significant (P = 0.87). No significant difference by sex was noted in this study either (P = 0.96).
On the other hand, we also examined the susceptibility to ambient temperatures of persons with comorbidities of prevalent chronic illnesses, particularly hypertension and diabetes. Although AKI is more prevalent among individuals who already have hypertension or diabetes , our analysis of temperature-related AKI-ED visits was not significantly associated with these comorbidities. Further in-depth studies are required to clarify these discrepancies.
Even small acute changes in kidney function can result in both short- and long-term complications. Early diagnosis and appropriate treatment of AKI are associated with an increased survival rate and restore complete renal function. This results in reduced cost of treatment  because CKD patients require hemo- or peritoneal dialysis or kidney transplantation. If AKI patients without premorbid CKD survive, then most of them recover to dialysis independence . Therefore, early diagnosis and appropriate treatment is crucial to prevent subsequent CKD, end-stage renal disease, or death  in AKI patients.
This study furthers our understanding of the association between temperature and AKI in Seoul. However, our study has some limitations, including the possible misclassification of exposures intrinsic in ecological studies. The use of ambient rather than personal measurements of temperature may have resulted in bias, which probably underestimated the association. Also, differences between indoor and outdoor temperatures due to air conditioning or heating may affect the association between temperature and AKI outcomes. Similar to other environmental epidemiological studies on AKI , we used the ICD-10 code for the definition of AKI without knowing whether the standard Kidney Disease Improving Global Outcomes (KDIGO) criteria were used for diagnosis. With ICD-codes, diagnosis of AKD could be incorrectly reported or underreported . We did not have information on medication, as nephrotoxic medications contribute to a substantial proportion of AKI. Further, there may be other individual factors influencing the association between air temperature and AKI. Finally, our study was conducted in a single city; therefore, the findings may not be applicable to other target populations in other areas. To explicitly understand the effects of temperature on AKI, multi-city studies are required.
Undoubtedly, AKI is affected by more complex factors aside from ambient temperature. However, despite these limitations, we found convincing evidence supporting that temperature might be a triggering or exacerbating factor for AKI. The findings from this study have considerable public health implications because it may help elucidate the effects of ambient temperature on AKI.
Based on the estimation of the impact of temperature on ED visits of patients with AKI in Seoul, a considerable health burden at elevated temperatures was identified for this population. Projections from global climate models indicate that the variability and extremes of temperature that may affect AKI are likely to increase in the future. Thus, the relationship between temperature and AKI needs to be investigated. Our findings suggest that increases in temperatures are a risk factor for AKI. Patient management and education need to be improved as extreme temperatures become more prevalent with climate change.
The authors thank the NEMC for their data.
SK led the design of the study, performed analyses, and drafted the manuscript; HL assisted with statistical modeling and YL provided medical expertise. JK and MK made substantial contributions to acquisition of data; HK and YH supervised the study and contributed to the discussion of the findings. All authors revised the paper critically for important intellectual content and approved final approval of the version to be submitted.
This research was supported by the Climate Change Adaptation Research Program of National Institute for Environmental Studies of Japan (NIES), the Environment Research and Technology Development Fund of the Environmental Restoration and Conservation Agency of Japan [S-14-5], the Climate Change Correspondence Program of the Ministry of Environment of Republic of Korea , the National Research Foundation (NRF) of Republic of Korea [MSIP, No.2017R1C1B2002663], and the Basic Science Research Program through the NRF funded by the Ministry of Education of Korea [NRF-2018R1D1A1B07049034]. The funding source had no role in the study design; in the collection, analysis and interpretation of data; in the writing of the report; or in the decision to submit the article for publication.
Ethics approval and consent to participate
This study was approved by the Institutional Review Board (IRB) of the National Health Insurance Medical Center, Goyang, South Korea (IRB No.: NHIMC 2017–12-020). All methods were performed in accordance with the relevant guidelines and regulations. NEDIS provided the data after encryption to protect private information. Therefore, the need for informed consent was waived.
Consent for publication
The authors declare that they have no competing interests.
- 4.Sewe MO, Bunker A, Ingole V, Egondi T, Åström DO, Hondula DM, et al. Estimated effect of temperature on years of life lost: a retrospective time-series study of low-, middle-, and high-income regions. Environ Health Perspect. 2017;126.Google Scholar
- 10.Borg M, Nitschke M, Williams S, McDonald S, Nairn J, Bi P. Using the excess heat factor to indicate heatwave-related urinary disease: a case study in Adelaide, South Australia. Int J Biometeorol. InternetInt J Biometeorol. 2019:435–47. Available from. https://doi.org/10.1007/s00484-019-01674-5.CrossRefGoogle Scholar
- 12.Pancreas VPP. Kidney and skin regeneration: Springer; 2017.Google Scholar
- 13.Basile D, Anderson M, Sutton T. Pathophysiology of acute kidney injury. Compr Physiol. 2012;2:1303–53.Google Scholar
- 20.De Nicola L, Blantz RC, Gabbai FB, Khang SJ. Nitric oxide and angiotensin II. Glomerular and tubular interaction in the rat. J Clin Invest. 1992:1248–56.Google Scholar
- 24.Tierney L, McPhee S, Papadakis M. Current medical diagnosis and treatment. Curr med diagnosis treat; 2017. p. 1124.Google Scholar
- 26.Lim Y-H, So R, Lee C, Hong Y-C, Park M, Kim L, et al. Ambient temperature and hospital admissions for acute kidney injury: a time-series analysis. Sci Total Environ. Elsevier B.V. 2018:616–617:1134–8.Google Scholar
- 28.Statistics of Korea. Korean statistical information service. 2017.Google Scholar
- 29.NEDIS. National Emergency Department Information System Statistical Yearbook. 2015.Google Scholar
- 36.Lerman PM. Fitting segmented regression models by grid search. J R Stat Soc Ser C Appl Stat. 1980;29:77–84.Google Scholar
- 37.Gronlund CJ, Zanobetti A, Wellenius GA, Schwartz JD, O’Neill MS. Vulnerability to renal, heat and respiratory hospitalizations during extreme heat among U.S. elderly. Clim change [internet]. Clim Chang. 2016;136:631–45. Available from:. https://doi.org/10.1007/s10584-016-1638-9.CrossRefGoogle Scholar
- 41.Isaksen TB, Yost MG, Hom EK, Ren Y, Lyons H, Fenske RA. Increased hospital admissions associated with extreme-heat exposure in King County, Washington, 1990-2010. Rev Environ Health. 2015;30:51–64.Google Scholar
- 44.Chen T, Sarnat SE, Winquist A, Grundstein A, Chang HH. Time-series analysis of heat waves and Emergency department visits in Atlanta, 1993 to 2012, vol. 2016. p. 1–22.Google Scholar
- 45.Hong YC, Leem JH, Ha EH, Christiani DC. PM (10) exposure, gaseous pollutants, and daily mortality in Inchon, South Korea. Environ Health Perspect. 1999;107:873–8.Google Scholar
- 47.Ha E-H, Lee J-T, Kim H, Hong Y-C, Lee B-E, Park H-S, et al. Infant susceptibility of mortality to air pollution in Seoul. South Korea Pediatrics. 2003;111:284–90.Google Scholar
- 50.Valavanidis A, Fiotakis K, Vlachogianni T. Airborne particulate matter and human health: toxicological assessment and importance of size and composition of particles for oxidative damage and carcinogenic mechanisms. J environ Sci heal - part C. Environ Carcinog Ecotoxicol Rev. 2008;26:339–62.CrossRefGoogle Scholar
- 52.Lea JP, Nicholas SB. Diabetes mellitus and hypertension: key risk factors for kidney disease. J Natl Med Assoc. 2002;94:7S–15S.Google Scholar
- 56.Chauhan V, Eskin B, Allegra JR, Cochrane DG. Effect of season, age, and gender on renal colic incidence. Am J Emerg Med. 2004.Google Scholar
Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.