Sauna bathing, renal function and chronic kidney disease: Cross‐sectional and longitudinal findings from the KIHD study

It is uncertain if passive heat therapies are associated with adverse renal outcomes. We sought to evaluate the cross‐sectional and longitudinal associations of the frequency of sauna bathing with renal function measures and chronic kidney disease (CKD).


| INTRODUCTION
Passive heat therapy or 'thermal therapy' is characterized by exposure to a high environmental temperature for a brief period. A range of passive heat therapies exist, which include repeated hot water immersion, waterperfused suits, microwave diathermy, infrared-ray sauna, Waon therapy and Turkish bath; however, the most widely used and studied till date are the Finnish saunas. Sauna bathing, a tradition embedded in the Finnish culture, has mainly been used for thousands of years for leisure and relaxation purposes. Sauna bathing is becoming a popular global lifestyle activity given its link with a myriad of health benefits. 1 In the seminal study by Laukkanen and colleagues, frequent sauna bathing (4-7 sessions/ week) was demonstrated to be associated with a reduced risk of several adverse cardiovascular outcomes including all-cause mortality, compared with 1 sauna session/ week. 2 Since then, a wealth of observational and interventional data suggests that frequent sauna bathing (i) reduces the risk of other cardiovascular outcomes including stroke, 3,4 hypertension, 5 dementia, 6 and venous thromboembolism, 7 as well as lung diseases [8][9][10] and psychotic disorders; 11 (ii) improves the severity of musculoskeletal disorders such as osteoarthritis, rheumatoid arthritis, and fibromyalgia, 12,13 COVID-19, 14 and lung conditions such as asthma, chronic bronchitis, and chronic obstructive pulmonary disease; [15][16][17] and (iii) extends the life span. 18,19 Anecdotal evidence has also suggested that passive heat therapies may be linked with adverse health effects. For instance, there were reports linking infrared sauna use with an increased risk of cancer. 20 We have, however, recently shown that life-long Finnish sauna bathing is not associated with the risk of several types of cancer. 21 Given that sauna use causes sweating and changes in body fluid balance and has the potential to cause dehydration, there have been some isolated reports of a link to renal impairments including acute renal failure. 22 Poyhonen et al. 23 recently evaluated the effect of sauna bathing on lower urinary tract symptoms in a Finnish population-based cohort and found no clear evidence of an association.
Whether frequent and regular sauna bathing causes long-term impairment in renal function or increases the risk of renal disease is uncertain. Using a population-based prospective cohort study comprising of 2071 middle-aged and older men with normal kidney function at baseline, we sought to evaluate the cross-sectional and longitudinal associations of the frequency of sauna bathing with measures of renal function including estimated glomerular filtration rate (GFR) and serum concentrations of creatinine, potassium (K) and sodium (Na) and the risk of chronic kidney disease.

| Study population and assessment methods
Reporting of the study conforms to broad EQUATOR guidelines 24 and was conducted according to STROBE (strengthening the reporting of observational studies in epidemiology) guidelines for reporting observational studies in epidemiology (Supplementary Material S1). The study cohort for this analysis was part of the ongoing Finnish Kuopio Ischemic Heart Disease (KIHD) prospective cohort study. The KIHD study was initially based on a cohort of 2682 general population-based Caucasian men aged 42-61 years recruited in Eastern Finland between March 1984 and December 1989 (Cohort 1). 25 At the 11-year follow-up examination of Cohort 1, another cohort based on a sample of 1774 men and women aged 53 to 74 years were recruited (Cohort 2). They had baseline examinations carried out between March 1998 and December 2001. Cohort 1 has mainly been used in most evaluations (including the current analysis) because of the larger sample size, availability of measurements on a comprehensive list of lifestyle factors, blood-based biomarkers and outcomes and longer follow-up. 3 Self-administered lifestyle and health questionnaires were used to assess prevalent medical conditions and lifestyle characteristics such as smoking, alcohol consumption, physical activity, socioeconomic status (SES) and the weekly frequency of traditional Finnish sauna sessions. 3,5,25 Participants were categorized into three sauna bathing frequency groups (1, 2-3 and 4-7 sessions per week) as used in previous reports. 3,5,25 A history of coronary heart disease was defined as previous myocardial infarction, angina pectoris, the use of nitroglycerin for chest pain ≥ once a week or chest pain. Alcohol consumption was assessed using the Nordic Alcohol Consumption Inventory. The assessment of SES involved the creation of a summary index comprising relevant indicators such as income, education, occupational prestige, material standard of living and housing conditions. The composite SES index ranged from 0 to 25, with higher values indicating lower SES. Resting blood pressure was measured on three occasions between 8:00 and 10:00 am following a supine rest of 5 min using a randomzero sphygmomanometer, and the mean of all available measurements was calculated. Estimated GFR and serum concentrations of creatinine, K and Na were measured at baseline with repeated measurements of K and Na at 11 years. Repeat measurements were only made for some blood-based markers and for a random sample of study participants due to logistical reasons. Supplementary Material S2 provides further details on the number of participants who had complete data on outcome measures evaluated in this analysis. For blood biomarkers measurements, participants were required to fast overnight and abstain from drinking alcohol for at least 3 days and from smoking for at least 12 h before blood samples were taken between 8:00 and 10:00 am. Serum creatinine concentrations were measured by the colorimetric Jaffe method using a Konelab 20XT automatic analyser (Thermo Fisher Scientific).
Estimated GFR was calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation 26 using the formula: 141 × (creatinine in mg/ dL/.9) −1.209 × .993 Age . Chronic kidney disease was defined as kidney damage (e.g. albuminuria) or estimated GFR lower than 60 mL/min per 1.73 m 2 (or both) for 3 months or longer based on the National Kidney Foundation Kidney Disease Outcomes Quality Initiative (KDOQI) guidelines. 27 All incident chronic kidney disease cases that occurred from study entry to 31 December 2014 were included. Chronic kidney disease outcomes were collected from the National Hospital Discharge Register data by computer linkage and a comprehensive review of hospital records. The diagnoses of chronic kidney disease were validated by two physicians.

| Statistical analyses
Baseline characteristics were presented as means (standard deviation, SD) or median (interquartile range, IQR) for continuous variables and percentages for categorical variables. We also assessed univariable relationships between sauna bathing and baseline characteristics using ANOVA (for continuous variables) and chi-square tests (for categorical variables). The associations of frequency of sauna bathing with baseline values of estimated GFR, creatinine, K and Na and 11-year values of K and Na were examined using multiple regression analyses with robust standard errors. Cox proportional hazard regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for incident chronic kidney disease. For this analysis, we excluded men with (i) existing kidney disease at baseline (n = 56) and (ii) missing data on the exposure or potential confounders (n = 555), which left a total of 2071 men who had complete information on sauna bathing, relevant covariates, measures of renal function and chronic kidney disease events for the analysis ( Figure 1). Given the high mortality rate in the KIHD cohort, we performed additional analyses to estimate the baseline cumulative subhazard of chronic kidney disease considering mortality as a competing outcome to chronic kidney disease. We used the competing-risks extension of the Cox proportional hazards models, as proposed by Fine and Grey. 28 In a subsidiary analysis, we also assessed the associations between sauna bathing and mortality risk. All analyses were conducted using stata version 16 (Stata Corp).

| RESULTS
The mean (SD) age of study participants at baseline was 53 (5) years. Compared to men who had one sauna session F I G U R E 1 Flow of participants in the study. CKD, chronic kidney disease. per week, participants who had 4-7 sauna sessions per week were slightly younger, more likely to be physically active, less likely to be smokers and have comorbidities such as type 2 diabetes, coronary heart disease and hypertension (Table 1). In partial correlational analyses adjusted for age, frequency of sauna bathing (as a continuous variable) was weakly and inversely correlated with baseline estimated GFR (r = −.06, p = .006), weakly and positively correlated with creatinine (r = .06, p = .011) and potassium (r = .08, p = .001), with no evidence of a correlation with Na (r = .001, p = .95). The cross-sectional and longitudinal associations of frequency of sauna bathing with levels of estimated GFR, creatinine, K and Na are presented in Table 2. Compared to a single sauna session/week, cross-sectional analyses showed that 4-7 sauna sessions/week were not associated with significant changes in levels of estimated GFR, creatinine and Na, but there was a slight increase in K .05 mmoL/L (95% CI, .00, .10; p = .033). In longitudinal analyses, however, there were no significant changes in levels of K 3.37 mmoL/L (95% CI: −1.34 to 8.08; p = .16) and Na 5.88 mmoL/L (95% CI: −4.74 to 16.51; p = .28).

N=3433
During a median (IQR) follow-up of 25.7 (18.4-27.9) years, 188 chronic kidney disease cases were recorded. In analysis adjusted for age, body mass index, smoking status, systolic blood pressure, total cholesterol, histories of type 2 diabetes, hypertension and coronary heart disease, alcohol consumption, SES, and physical activity, the HR (95% CI) for chronic kidney disease was .84 (.46-1.53; p = .56) comparing 4-7 sauna sessions/week with a single sauna session per week. Following further adjustment for estimated GFR, the HR (95% CI) was .84 (.46-1.53; p = .56; Figure 2). A total of 1302 mortality events occurred during follow-up. In analyses including mortality as a competing risk event, the HR (95% CI) for chronic kidney disease was .81 (.21-3.14; p = .76), comparing 4-7 sauna sessions/ week with a single sauna session per week. In a multivariable model adjusted for age, body mass index, smoking status, systolic blood pressure, total cholesterol, histories of type 2 diabetes, hypertension and coronary heart disease, alcohol consumption, socioeconomic status, physical activity and estimated GFR, the HR (95% CI) for all-cause mortality was .78 (.62 to .98; p = .031), comparing 4-7 sauna sessions/week with a single sauna session per week (Table 3).

| DISCUSSION
Given the controversial and scanty evidence on the link between passive heat therapies and adverse renal outcomes, we evaluated the cross-sectional and longitudinal associations of frequency of Finnish sauna bathing (most commonly used and widely studied passive heat therapy 19 ) with measures of renal function and chronic kidney disease in a general population-based cohort of middleaged and older Caucasian men. Baseline cross-sectional analysis showed that men who had 4-7 sauna sessions per week were younger, more likely to be physically active, and less likely to be smokers and have cardiometabolic comorbidities; these results likely reflect the fact that these individuals were young and had fewer comorbidities and therefore more likely to be physically active and engage in leisure activities such as sauna bathing. Except for an .05 mmoL/L increase in baseline levels of K with 4-7 sauna sessions/week, there were no significant changes in levels of the other renal markers at baseline and at 11year follow-up. Furthermore, we found no evidence of an association between frequency of sauna bathing and the future risk of chronic kidney disease. We confirmed previously reported associations between frequent sauna bathing and reduced risk of all-cause mortality. 2,29 We are unable to compare and contrast these findings with previous studies as this is the first study to assess both the cross-sectional and longitudinal associations of Finnish sauna baths with measures of renal function and the future risk of chronic kidney disease. However, there are a few related studies that are worth discussing. In a before-and-after experimental study to determine the effects of a single relatively hot sauna session of 30 min duration on several blood-based parameters in 102 participants with at least one conventional cardiovascular risk factor, it was demonstrated that apart from an increase in plasma creatinine levels from 76 to 79 μmoL/L which were within normal range, levels of Na and K remained constant. 30 In a recent review of the effect of high temperature on kidney disease morbidity, the results suggested that high temperature was associated with an increased incidence of kidney stones, renal colic, acute kidney injury and hospital admissions for kidney disease. 31 The temperature exposures that were evaluated included atmospheric temperature, heat waves, stress and strain, which are not controlled and have the potential to cause kidney injury due to excessive dehydration. A recent review reported on the rising death toll from chronic kidney disease of unknown origin in the Central American region, and it has been attributed to heat exposure and dehydration. 32 Indeed, the sugarcane workers in that region who have been found to have high rates of chronic kidney disease of unknown origin typically work for several hours per day, while heavily clothed in temperatures that exceed 40°C. 32 Furthermore, exposure to heavy metals, agrochemicals, infectious agents, genetic factors and risk factors related to poverty, malnutrition, and other social determinants of health have been suggested to be contributory factors for chronic kidney disease of unknown origin.  134 (17) 135 (18) 133 (16) 135 (17) .075

Response variables
Diastolic blood pressure (mmHg) 88 (10) 89 (11) 88 (10) 90 (12) .12 Physical activity (kj/day) The current findings may seem unexpected given the emerging evidence of potential adverse effects of longterm exposure to high temperature on the kidney and the following plausible reasons: unlike infrared saunas which operate at a lower temperature and gradually heat up the body and provide a form of whole-body hyperthermia; the heat from the dry Finnish sauna rapidly increases the skin temperature to about 40°C after about 10 min in the sauna, T A B L E 2 Associations of frequency of sauna bathing with estimated glomerular filtration rate and serum levels of creatinine, potassium and sodium.

Cross-sectional association (Baseline)
Longitudinal association ( with core body temperature ranging between 37 and 38°C. 34 This has the potential to cause substantial dehydration and even rhabdomyolysis, leading to acute kidney injury, a major risk factor for chronic kidney disease. 35 In a case study of a patient referred to the intensive care unit with acute renal failure, the cause was attributed to rhabdomyolysis following severe dehydration due to frequent visits to the sauna. 22 However, further evaluation showed the patient had a sickle cell trait; hence, the dehydration induced a vaso-occlusive crisis with resulting acute renal failure. 22 Recurrent exposure to heat stress and dehydration have been shown to induce chronic inflammation and tubular injury in mice. 36 Any renal impairments associated with sauna use are likely to be short-term and may be due to comorbidities, dehydration following excessive sauna use, and failure to rehydrate. It is well known that sauna users keep themselves hydrated the whole time when undergoing sauna bathing sessions. Overall, these new results are encouraging and provide an important public health message that regular sauna baths do not have adverse effects on renal function. Based on previous evidence and the direction of the effect estimate for the relationship between frequency of sauna bathing and chronic kidney disease risk, if there is any association at all, it would be most likely to be a protective one. The several benefits of sauna are mainly attributed to the body's responses and adaptations to heat stress. 19 There is a possibility that heat stress may not have any beneficial effect on renal function. However, this explanation is mainly speculative and whether there are any beneficial effects of sauna exposure on renal function warrants further investigation. In a comprehensive review of the role of hot baths for the treatment of chronic renal failure, the authors concluded that hot baths had the potential to clear uremic toxins by skin eccrine sweating and decrease the frequency of adverse events in patients with chronic renal failure. 37 In a rodent model of chronic kidney disease, mild systemic thermal therapy was effective at ameliorating renal dysfunction. 38 Both observational and interventional evidence suggests that sauna reduces blood pressure and the risk of hypertension, which is a major risk factor for chronic kidney disease. We have shown that life-long sauna use of 4-7 sessions/week reduces the risk of hypertension compared to a single sauna session/ week. 5 In a recent systematic review and meta-analysis, regular heat therapy compared with controls was shown to decrease both systolic and diastolic blood pressure by an average of 4 mmHg, with larger reductions in those with higher blood pressure at baseline. 39 Furthermore, we have recently demonstrated in a randomized controlled trial that 8 weeks of regular sauna bathing sessions combined with exercise produced a mean reduction in systolic blood pressure of 8 mmHg. 40 Sauna bathing has a good safety profile and few adverse effects when used prudently and it is generally tolerated by most people, including patients with stable cardiovascular disease and heart failure. 41,42 Typical hot and dry sauna sessions consist of short stays ranging from 5 to 20 min, although longer sauna bathing sessions may be used depending on the experience and comfort of the individual. 43 It is always essential to keep rehydrated during and immediately after a sauna session and avoid the use of alcohol, which increases the risk of dehydration and hypotension. Known contra-indications to sauna bathing include patients with unstable angina pectoris, recent myocardial infarction, uncontrolled hypertension, ischemic or decompensated heart failure, or severe aortic stenosis. 41,42,44 Obviously, individuals with kidney disease and those prone to dehydration need to exercise caution or avoid its use. Nevertheless, despite the lack of evidence of any associations, this is the first ever evaluation of the topic using a large-scale prospective cohort and needs to be confirmed in women, other populations and age groups. Apart from the novelty, other strengths of this study include the use of a prospective cohort design, large sample size, evaluation of several renal outcomes including their repeat measures after several years of follow-up as well as incident chronic kidney disease events, and the ability to account for several potential confounders. Important limitations which deserve consideration are the (i) lack   of repeat measurements on variables such as estimated GFR and creatinine during follow-up, which was purely due to logistical reasons; (ii) absence of data on the precise cause of chronic kidney disease and classification of chronic kidney disease; (iii) potential for misclassification of sauna assessment because it was based on self-reports; (iv) sauna bathing habits may have changed during follow-up due to changes in habits or development of diseases over the long period of time. However, any changes may be minimal as sauna bathing habits are relatively consistent within the Finnish population based on previous studies and our reproducibility studies of sauna bathing habits (regression dilution ratio of .69); 21 (v) inability to generalize findings to women and those with comorbidities such as existing kidney disease; and (vi) lack of other relevant renal disease-related measures such as urea, albuminuria, and cystatin C as well as data on the progression of renal disease.
In conclusion, frequent sauna bathing is not associated with impaired renal function or the future risk of chronic kidney disease.

AUTHOR CONTRIBUTIONS
S.K.K.: Study design, data analysis and interpretation, drafting manuscript, and revising manuscript content and approving final version of manuscript; J.K.: Study design and conduct, responsibility for the patients and data collection, and revising manuscript content and approving final version of manuscript; J.A.L.: Study design and conduct, responsibility for the patients and data collection, and revising manuscript content and approving final version of manuscript.