Environmental heat exposure has increasingly been recognized as an important determinant of renal distress [1–3]. Much of the accumulated evidence linking heat to renal injury has centered on agricultural populations in Mesoamerica, where chronic dehydration, intense physical exertion, and extreme temperatures have contributed to the emergence of Mesoamerican nephropathy (MeN) or chronic kidney disease of unknown etiology (CKDu) [2–6]. These conditions have been widely regarded as region-specific, occupationally driven disorders, largely affecting male manual laborers. However, emerging studies now suggest that heat-related kidney dysfunction is not confined to this geographic or occupational context. Reports from non-Mesoamerican regions and from general, non-agricultural populations indicate that heat-associated renal impairment may represent a broader and increasingly global public health concern rather than an endemic phenomenon restricted to a single region or workforce [7–9].

Despite the growing recognition of heat-related renal risks, sex-specific patterns have been insufficiently explored. Existing Mesoamerican evidence consistently identifies men as the higher-risk group, reinforcing the view that male agricultural laborers are uniquely susceptible to heat-related kidney injury [3–6]. Yet outside agricultural contexts and beyond the Mesoamerican region, the extent to which gender and sex modifies the relationship between heat exposure and various renal outcomes remains unclear. Biological, occupational, behavioral, and sociocultural factors may differentially influence heat vulnerability among men and women, but these pathways have not been systematically synthesized across global populations [10]. Clarifying sex-specific differences in heat–renal associations is essential for understanding disease mechanisms, identifying at-risk groups, and informing mitigation strategies under accelerating climate change.

The objectives of this scoping review are to provide a comprehensive overview of evidence on environmental heat exposure and renal health beyond the Mesoamerican context. This review focuses on (Population) studies conducted among non-agricultural general adult populations, (Concept) examining the effects of environmental heat exposure on renal health and/or renal diseases, and (Context) with particular attention to studies from non-Mesoamerican regions that report gender-specific differences. Specifically, this review seeks to answer the following research questions:

What is the nature and extent of heat–renal associations across non-Mesoamerican settings, particularly among non-agricultural and general populations, and how consistently are these associations reported across studies?

By addressing these questions, this review aims to understand the global relevance of heat-related renal vulnerability and to inform future research and climate resilience strategies.

This study is a scoping review of original research examining the association between extreme heat and renal health, with a particular focus on sex differences. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) to guide the development and conduct of this review [11]. An a priori protocol of this study was registered with the Open Science Framework (OSF; https://osf.io/ts9h5) and is currently under embargo [12]. Ethical approval was not required for this study, as it involved the review of previously published literature, contained no individual human data, and was conducted in full alignment with the Bioethics and Safety Act (Act Number 15188) and the Ordinance of the Ministry of Health and Welfare on the Bioethics and Safety Act (Ordinance number 1048) of the Republic of Korea.

The basic characteristics of the articles included in the review are presented in Table 1. The included studies were conducted in Australia (n = 6), China (n = 3), the Republic of Korea (n = 2), the United States (n = 4), and Germany, Brazil, Taiwan, New Zealand, Switzerland, and Thailand (n = 1 each). Environmental heat exposure was defined using percentile-based thresholds in most studies (n = 10), typically comparing the 90th percentiles of daily mean or maximum temperature to minimum-risk or reference temperatures. Continuous temperature metrics (n = 5), such as per 1 °C increases in daily mean or minimum temperature, were also frequently applied. Fixed thresholds (n = 4), including definitions such as ≥30 °C–35 °C for ≥3 consecutive days or a calculated flexion point (e.g., 28.8 °C), were also used. Renal outcomes fell into two broad categories: (1) renal diseases, including total renal diseases (n = 11), acute kidney injury (n = 11), chronic kidney disease (n = 6), urinary tract infection (n = 7), nephrolithiasis (n = 3), urolithiasis (n = 8), and other renal conditions (n = 5); and (2) physiologic biomarkers of renal dysfunction (n = 4), such as the internationally recognized cutoff for reduced kidney function (e.g., estimated Glomerular Filtration Rate [eGFR] <60 mL/min/1.73 m²). Because individual studies often reported more than one renal outcome, these counts represent overlapping categories rather than mutually exclusive classifications. Study populations were drawn from the general population in most studies, with the exception of a few studies that targeted specific groups such as healthy young adult volunteers undergoing controlled passive heating, older institutionalized adults, or employed urban workers.

This scoping review identified a consistent trend of increased renal morbidity associated with heat exposure in non–Central American settings, suggesting that the relationship between heat exposure and renal impairment extends beyond the agricultural populations of previously recognized hotspot regions (e.g., Central America, India, Sri Lanka) and may also apply to general populations in cosmopolitan contexts. Although not included in this review, several studies from North America and Europe have demonstrated that high temperatures are associated with increased hospital admissions for renal dysfunction, supporting the relevance of heat–renal pathways in cosmopolitan populations [7–9, 34, 35].

From a physiological perspective, exposure to high environmental heat leads to dehydration, renal vasoconstriction, and elevated urinary osmolarity, resulting in transient reductions in glomerular filtration rate [14, 15]. Repeated episodes of heat-induced acute kidney injury may progress to chronic tubulointerstitial damage and fibrosis over time [15, 19]. Dehydration-related hormonal and metabolic responses (e.g., vasopressin activation, increased fructose metabolism, oxidative stress, urate accumulation) further exacerbate tubular injury, providing a biologically plausible mechanism for heat-related renal injury [19, 25]. Likewise, several studies included in this review demonstrated significant changes in physiological biomarkers—such as reductions in eGFR and increases in tubular stress markers—indicating that subclinical renal injury may occur even in the absence of clinically diagnosed renal disease [26, 33].

The findings of this review on nephro- and urolithiasis align with existing evidence from non-Mesoamerican regions reporting that heat exposure is associated with increased kidney stone events [34]. Existing evidence also suggests regional and seasonal variation within single countries, with elevated risks during periods of higher ambient temperatures and longer sunshine duration, further supporting the role of environmental factors in stone formation [14, 15, 22, 23, 34]. Increased exposure to sunlight is suggested to enhance vitamin D activation and, in turn, intestinal calcium absorption, contributing to hypercalciuria. Simultaneously, high ambient temperatures promote lower urine volume through heat-related dehydration, resulting in higher urinary concentrations of stone-forming solutes such as calcium, oxalate, uric acid, and phosphate [15, 27, 28].

The evidence base for heat–UTI associations remains much smaller than for other renal outcomes such as acute kidney injury or nephrolithiasis. One study included in our review that found an association between UTI risk and extreme heat exposure also reported that this association was transient and limited to lag days 0 through 2, in contrast to acute kidney injury and nephrolithiasis, which tend to exhibit more consistent and cumulative heat-related effects [25]. Age-related effect modification, along with varying definitions of UTI across studies, may contribute to the relatively inconsistent or less robust associations observed for UTIs. From a physiological standpoint, chronic low urine output caused by heat-related dehydration is thought to increase bacterial concentration, elevate urine osmolality and acidity, and reduce the mechanical flushing of bacteria due to decreased urinary volume—offering a plausible explanation for heat-related increases in UTI risk, despite limited and inconsistent empirical evidence [14, 23, 27, 28].

As for CKD, our review found inconsistent associations with heat exposure, and when stratified by sex, only one study demonstrated statistically significant associations in men [15]. Several factors may explain these inconsistent findings. Unlike acute kidney injury or kidney stone events, which typically have short latency periods and are more directly affected by dehydration and heat stress, CKD represents a long-term, multifactorial condition influenced by underlying comorbidities, lifestyle factors, and chronic exposures. One study in our review found that CKD was the only renal category that required a lag period to demonstrate a statistically significant increase in admissions [14]. Consequently, short-term variations in ambient temperature may exert less detectable effects on CKD outcomes, particularly in high-income settings where hydration access, indoor cooling, and healthcare availability can buffer heat-related risks. From a physiological perspective, elevation of vasopressin secretion induced by chronic dehydration may contribute to progressive tubulointerstitial damage and thereby increase susceptibility to CKD, yet more definitive research is needed to clarify the underlying causal mechanisms [14, 15, 36].

This review identified sex-specific differences in the associations between heat exposure and renal outcomes. A greater number of studies reported stronger and statistically significant associations among men for acute kidney injury (8 studies in men vs. 6 in women) and nephrolithiasis/urolithiasis (6 vs. 4, respectively), whereas associations between heat exposure and urinary tract infections were more consistently observed and pronounced among women (5 in women vs. 2 in men). These findings are consistent with previous reports of MeN and CKDu, in which male agricultural workers faced greater risk [4–6, 37], as well as with several non–Mesoamerican studies indicating male susceptibility to heat-related renal events [38, 39]. The result of our study suggest that the risk of heat-related AKI and kidney stone events may extend beyond the traditionally studied Mesoamerican male agricultural workforce and may also represent an emerging health concern for men in global, urban, or metropolitan settings.

Men may be more prone to heat-related AKI due to greater sweat-induced fluid losses and more pronounced heat-driven renal vasoconstriction, all of which can amplify transient reductions in glomerular filtration rate under high-heat conditions [40, 41]. For nephrolithiasis, evidence suggests that men are more likely to rapidly develop calcium and uric acid stones following acute heat exposure, as they exhibit lower urine volume than women during periods of high ambient temperature [15, 30, 32]. Another factor may be that occupational heat exposure and exertional heat stress remain higher in men than in women in many settings, potentially leading to hyperosmolarity, volume depletion, and rhabdomyolysis [42]. Likewise, one study included in our review found that male workers in physically demanding jobs experienced a substantially greater heat-related risk than those in office-based occupations, suggesting that physically intensive work, regardless of whether it involves agriculture, may contribute to heightened susceptibility to heat-related renal outcomes among men [29].

In contrast, studies examining UTIs showed more significant associations among women. Several factors may explain women’s greater susceptibility to heat-related UTI risk. Women experience higher baseline rates of UTI, meaning that additional stressors such as dehydration or reduced urine flow during heat exposure may more readily cause infection [14, 15]. In addition, hormonal influences—particularly lower estrogen levels in postmenopausal women—can reduce the integrity of the urogenital epithelium and alter the vaginal and periurethral microbiota, potentially increasing vulnerability under conditions of heat-related dehydration [14, 27]. This explanation is supported by prior studies showing that heat–UTI associations tend to be stronger among elderly women [43].

Our findings suggest that although MeN and CKDu represent severe and geographically concentrated manifestations of heat-related renal injury, the fundamental biological mechanisms through which heat impairs kidney function are not restricted to these settings. Rather, they appear to operate universally, permitting heat–renal associations to emerge across diverse populations, including those outside traditional high-risk occupational environments. The results further demonstrate discernible sex-specific patterns across renal outcomes, indicating that physiological, occupational, and behavioral differences may jointly modulate susceptibility to heat-related renal dysfunction [44–48].

Despite these insights, substantial uncertainties persist. The disease entities historically described as CKDu or MeN are unlikely to be entirely mutually exclusive from the heat-related renal distress observed in non-Mesoamerican regions included in this review. The heterogeneous clinical manifestations of CKDu and MeN are not fundamentally distinct from the patterns of AKI, nephrolithiasis, and UTI documented in these studies, with the exception of a few contexts in which specific genetic predispositions (e.g., reported in Sri Lanka and India) or particular chemical exposures (e.g., aristolochic acid in Balkan endemic nephropathy) have been identified as major contributing factors [4–6]. Environmental-associated nephropathy is unlikely to arise from a single causal pathway, and the relative contributions of heat exposure and other hypothesized cofactors—such as recurrent dehydration, toxic exposures, infectious agents, water contaminants, and genetic susceptibility—remain incompletely delineated [49–51]. These considerations underscore the need for further investigation into the potential continuum between endemic CKDu and more globally distributed forms of heat-related nephropathy.

In addition, only eight studies explicitly evaluated sex-specific vulnerability by examining the interaction between sex and heat exposure [17, 20, 23–25, 30, 31, 33]. These studies showed mixed findings, with five reporting statistically significant interaction effects, and three reporting no evidence of interaction. The limited use of interaction modelling highlights an important gap in the literature. Although the results of our scoping review suggest a potential heterogeneity between sexes, the evidence yet remains inconclusive, making it difficult to determine whether observed differences reflect true effect modification or variations in study design, population characteristics, or statistical power. Also, differences in lag structures across studies may have influenced both the presence and magnitude of sex-specific associations. Given the diversity in renal outcomes (acute versus chronic) and study designs, heat-related effects may manifest as immediate responses or delayed effects over several days to weeks, and even longer-term cumulative impacts. Such variability in lag structures and outcome definitions may hinder direct comparison of findings across studies. Future studies should incorporate formal interaction analyses along with clearly defined and consistently reported lag structures to better clarify sex-based differences in heat-related renal outcomes.

Future studies should also rigorously adjust for occupational exposures, age, socioeconomic position, climate zone, season, ethnicity, and genetic predisposition; and employ longitudinal or prospective cohort designs capable of elucidating temporal and causal pathways. However, it is worth noting that while occupational exposures may contribute to observed sex differences in heat-related renal outcomes, these differences may not be solely attributable to confounding. Men and women may be differentially exposed due to occupational variations, differentially susceptible to the same level of exposure, or differentially vulnerable in a broader sense [52]. This broader vulnerability encompasses the ability to manage, adjust to, and recover from heat exposure, which can be influenced by contextual factors such as access to protective equipment, work schedule flexibility, hydration resources, and occupational autonomy—factors that may systematically differ between men and women. Future research should consider these multiple dimensions to better understand sex-related vulnerability to heat and inform targeted preventive strategies.

The limitation of this study is the relatively small number of articles that met our inclusion criteria, reflecting the limited volume of existing research on heat–renal associations outside Mesoamerica that also report gender-specific results. In addition, heterogeneity in exposure metrics and outcome definitions may limit the comparability of findings. Definitions of heat exposure and temperature thresholds varied considerably across studies, and few studies comprehensively accounted for confounders such as climate zone, comorbidities, occupational heat exposure, and ambient air pollution. These methodological inconsistencies may limit the ability to directly compare results across studies.

Despite these limitations, a major strength of this review is its focus on sex-specific associations between heat exposure and renal outcomes, an area that has been under-examined in the existing literature. The accelerating trajectory of climate change, which involve rising ambient temperatures, urban heat island effects, and extreme heat events, will likely expose larger segments of the global population to thermal conditions sufficient to induce renal stress. By synthesizing evidence across geographic regions outside Mesoamerica, our study broadens the understanding of heat-related renal vulnerability beyond traditionally recognized hotspot settings.