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Article

Hair Cortisol and Fe-BARQ: Evaluating Chronic Stress and Behavior in Cats with Chronic Kidney Disease

by
Ga-Hee Kim
1,
Kyuyoung Lee
2,
Han-Sol Choi
3,
Jin Soo Han
4 and
Sun-A Kim
5,*
1
Department of Laboratory Animal Medicine, College of Veterinary Medicine, Konkuk University, Seoul 05029, Republic of Korea
2
Department of Microbiology, Institute for Viral Diseases, College of Medicine, Korea University, Seoul 02841, Republic of Korea
3
Department of Companion Animal, Shingu College, Seongnam-si 13174, Republic of Korea
4
Department of Laboratory Animal Medicine, Institute for the 3Rs & Animal Welfare, College of Veterinary Medicine, Konkuk University, Seoul 05029, Republic of Korea
5
Duffield Institute for Animal Behavior, Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA
*
Author to whom correspondence should be addressed.
Animals 2025, 15(6), 889; https://doi.org/10.3390/ani15060889
Submission received: 18 February 2025 / Revised: 18 March 2025 / Accepted: 19 March 2025 / Published: 20 March 2025
(This article belongs to the Section Companion Animals)
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Simple Summary

Chronic kidney disease (CKD) significantly reduces cats’ quality of life; however, its association with stress is not fully understood. This study aimed to investigate stress and behavioral changes in cats with CKD. Herein, we measured cortisol levels in fur samples from cats with CKD and healthy cats and surveyed behavioral changes. Higher cortisol levels, along with specific behavioral changes, in cats with more severe CKD were observed, suggesting a complex relationship between CKD and stress in cats. The findings of this study highlight the importance of considering behavioral changes and stress management in the care and treatment of cats with CKD.

Abstract

This study used hair cortisol concentration (HCC) and the Feline Behavioral Assessment and Research Questionnaire as indicators of chronic stress status and behavioral changes in cats, respectively. Few studies have simultaneously employed both indices to examine cats with chronic kidney disease (CKD). This study aimed to evaluate HCC and questionnaire data from control group cats (n = 21) and those with CKD (n = 21). Additionally, we investigated the correlation between HCC and living environment. For this study, hair samples were collected from the cats’ abdomens and analyzed for HCC. Owners completed questionnaires to provide information on their cats’ behavior, demographics, environmental factors, and household characteristics over 3 months. Cats in the late-stage CKD group had significantly higher HCC levels than those in the early-stage CKD and control groups. We observed different associations between behavioral patterns, living environments, and HCC depending on the stage of CKD progression. The consistency between the HCC findings and questionnaire results, including the higher HCC levels in the late-stage CKD group and behavioral changes in the CKD group, suggests the possibility of a complex interaction between CKD progression and chronic stress.

1. Introduction

Widely recognized as the gold standard for measuring stress in mammals, cortisol is a primary stress hormone that plays a crucial role in the physiological mechanisms associated with stress [1,2]. Studies in humans have demonstrated a correlation between chronic stress and various diseases. Prolonged exposure to elevated cortisol levels due to chronic stress can impair immune function and exacerbate inflammation, contributing to various diseases, such as chronic obstructive pulmonary disease, inflammatory bowel disease, and metabolic disorders [3,4,5]. Although research on companion cats is limited, recent studies have increasingly identified a significant correlation between chronic stress and disease in feline populations [6,7]. Notably, studies on feline idiopathic cystitis have revealed that chronic stress plays a significant role in both initiating and worsening the disease [8,9,10,11]. These findings suggest that the physiological mechanisms underlying stress-related diseases in humans may also apply to companion cats, warranting further investigation. Chronic stress is a major contributor to behavioral changes in cats, often leading to increased aggression, anxiety, and inappropriate elimination [12,13,14,15]. These chronic stress-induced health and behavioral issues negatively impact the human–animal bond, resulting in poor welfare and quality of life for companion cats, including relinquishment and euthanasia [16,17,18].
Assessing biochemical indicators, such as cortisol levels, along with systematic observation of behavioral changes, is crucial for a comprehensive understanding of stress in cats. When evaluating stress, it is essential to monitor changes in various behaviors (e.g., play, elimination, and appetite) [14,19,20]. However, most previous studies have focused on short-term behavioral observations or have been conducted on shelter cats, leaving a gap in the evidence regarding comprehensive chronic stress in companion cats [1,21,22]. Stress assessment questionnaires based on the living environment and behavior of cats have been criticized for issues with inter-observer reliability and their limited correlation with biochemical indicators. Additionally, these questionnaires have limitations as long-term stress measurement tools because they assess behavior over short periods (e.g., one week) [21,23,24,25,26]. Short-period assessments may not account for the variability in behavior that can occur due to temporary stressors or environmental changes [27]. However, evaluating behavior over an extended period of several months provides a more representative and accurate reflection of chronic stress, as it captures cumulative and subtle behavioral changes that shorter assessments might miss [28]. Consequently, the Fe-BARQ, a validated questionnaire that reliably evaluates 100 specific behavioral items over a period of months, was selected for this study [29,30,31,32]. To obtain comprehensive and objective data on chronic stress in companion cats, it is necessary to combine biochemical measurements, such as cortisol levels, with behavioral assessments using the Fe-BARQ, among other tools.
Cortisol has been used as a representative biochemical indicator in cat stress assessment studies and is measured primarily through blood (plasma and serum), saliva, urine, and fecal samples in studies on stress in cats [6,7,33,34,35,36,37,38,39,40,41,42,43,44,45,46]. However, stress responses due to restraint during the sampling procedure are likely to elevate blood (plasma, serum) cortisol levels, and factors such as diurnal patterns and activity levels may confound the results [34,35,36]. Conversely, saliva is an excellent sample for noninvasive cortisol measurement, but it is not ideal for assessing chronic stress, as it only reflects values from the last few minutes [44,47]. Urine and fecal samples are also noninvasive biomarkers for cortisol measurement, with the additional benefit of relatively easy collection. However, cortisol concentrations in urine can only be measured 9 ± 3 h after the stress exposure and in feces 24 ± 4 h later, indicating that these samples are unsuitable for providing representative cortisol levels over an extended period, making them less reliable for reflecting chronic stress [48]. In contrast, hair cortisol concentration (HCC) has recently emerged as a valuable tool for studying chronic stress. The HCC sampling process is noninvasive, less likely to induce stress, and can even be measured from shed hair [49]. This is particularly advantageous because hair samples can be stored at room temperature without requiring immediate refrigeration or freezing after sampling [50].
The simplicity of collection in comparison to alternative samples, along with the ability to assess cortisol levels over time make HCC particularly well-suited for chronic stress research [1,6,7,46,51].
Various studies have confirmed the association between chronic kidney disease (CKD) and chronic stress. Chronic stress is suspected to contribute to CKD progression by inducing allostatic overload through persistent activation of the hypothalamic-pituitary-adrenal (HPA) axis and sympathetic nervous system [51]. This leads to excessive cortisol secretion, promoting inflammation, oxidative stress, and vascular dysfunction, while chronic sympathetic activation exacerbates hypertension and metabolic dysfunction—key factors driving kidney damage and CKD progression [52,53,54]. CKD is a progressive and irreversible syndrome characterized by a gradual loss of kidney function. Advanced stages of the disease often result in severe complications, such as uremia, which causes neurological and gastrointestinal symptoms that significantly reduce the quality of life in affected cats [55,56,57]. Despite extensive research on treatment strategies, nutritional interventions, and physiological changes in feline CKD, the impact of chronic stress on this disease remains underexplored [58,59,60]. Previous studies have identified differences in voiding habits between CKD cats and healthy cats [61,62] or partially assessed behavior in CKD cats using quality-of-life assessment tools [58]; however, they have been limited by the lack of a comprehensive evaluation of behavioral changes. A recent study categorized cats based on CKD severity and revealed a significant correlation between HCC and International Renal Interest Society (IRIS) stages. However, that study relied on survey instruments to assess the quality of life in cats and did not evaluate a range of behavioral changes [7]. Since the assessment of behavioral changes is crucial for determining feline stress, it would be beneficial to combine HCC and Fe-BARQ with CKD assessments in cats. This approach can help clarify the relationship between CKD and chronic stress. Therefore, using objective data to precisely evaluate chronic stress levels in cats with CKD, along with exploring their correlations, is necessary for disease management and improving quality of life.
This study aimed to compare HCC levels and Fe-BARQ assessment results in CKD and healthy cats to determine the association between chronic stress levels and feline CKD and to evaluate the potential of these measures as objective tools for data collection. We formulated the following null hypotheses: (1) HCC levels do not differ between CKD and healthy cats, and (2) Behavioral changes do not differ between CKD and healthy cats.

2. Materials and Methods

2.1. Animals

Overall, 47 companion cats were recruited from a cat-only veterinary clinic in Seoul, South Korea. The CKD group (n = 21) was defined by the following two criteria: (1) blood creatinine level ≥ 1.8 mg/dL and (2) identification of abnormal kidney imaging features, such as cysts, infarcts, and changes in shape, size, or echogenicity. Cats in the CKD group in this study were classified into early-stage CKD (IRIS Stage 2) or late-stage CKD (IRIS Stages 3 and 4) based on the International Renal Interest Society (IRIS) guidelines. Staging was determined using measured fasting blood creatinine concentrations and kidney damage checked with ultrasound. The following thresholds were used for classification: early-stage CKD (creatinine 1.6–2.8 mg/dL) and late-stage CKD (creatinine > 2.8 mg/dL) [63]. All CKD cats received treatment in accordance with the IRIS guidelines for their respective stages. Cats in the early-stage CKD group were managed with renal therapeutic diets and treated for hypokalemia if clinically indicated. Cats in the late-stage CKD group received additional interventions, including phosphate binders to maintain serum phosphorus levels below 6.0 mg/dL, antiemetics to manage vomiting and nausea, and subcutaneous fluids to ensure adequate hydration. The control group (n = 21) comprising cats visiting the clinic for an annual health check-up were selected based on the following criteria: (1) age ≥ 2 years, irrespective of sex or breed, (2) no history of any neoplastic, renal, endocrine, neurological, or cardiovascular system disease, (3) normal clinical and physical examination findings confirmed by a veterinarian, (4) normal blood test results, including complete blood count, blood urea nitrogen (BUN; <36 μmol/L), creatinine (<2.4 μmol/L), and symmetric dimethylarginine (SDMA; <14 μg/dL, not persistently elevated; Supplementary File S1), and (5) no abnormalities in abdominal ultrasound and X-ray imaging. Cats < 2-years-old or those with unclear blood test results were excluded from the study (Table 1).

2.2. Hair Sample Collection and Cortisol Analysis

The methods for hair collection and cortisol extraction were adapted from previous studies [64,65,66]. During preparation for the ultrasound (DIAGNOSTIC ULTRASOUND SYSTEM Aplio a MODEL CUS-AA000, Canon Medical Systems Corporation, Otawara-shi, Tochigi, Japan) and X-ray scans (ROTANODE™ E7239X, TOSHIBA ELECTRON TUBES & DEVICES Co., Ltd., Otawara-shi, Tochigi, Japan), a technician shaved the cats’ abdomens, collected the shaved hair, and placed each sample in an individual ziplock plastic bag. The samples were stored at room temperature until the investigator collected them for analysis.

2.3. Cortisol Extraction and Analysis Procedure

Hair cortisol was extracted as described by Nejad et al. [67]. In the analytical laboratory, hair samples were removed from the ziplock plastic bags. Each sample (250 mg) was weighed using a digital balance. The samples were transferred to new polypropylene tubes (15 mL conical tubes), and 5 mL isopropanol was added to each tube using a single-channel pipette. The tubes were then gently swirled for 3 min to wash off external cortisol, and this procedure was repeated twice. The hair samples were dried at room temperature (22–24 °C) for 7 days. Hair samples (50 mg) were transferred to a bead-beater tube (2 mL) containing six stainless steel balls and ground at 50 Hz for 8 min. Fifty milligrams of each hair sample were then transferred to a microtube (1.5 mL). One ml of methanol was added using a pipette to extract cortisol. The samples were placed in a tube rotator and rotated at low speed (0.026× g) for 24 h at room temperature to facilitate cortisol extraction. The samples were then centrifuged at 14,269× g for 60 s at room temperature. After centrifugation, 0.6 mL of supernatant was pipetted (Research Plus® Eppendorf pipette, Eppendorf SE, Hamburg, Germany) into a new microcentrifuge tube (1.5 mL), and the sample was dried at 38 °C using a Sanyo JP/MCO175 (Panasonic Healthcare Corporation, Tokyo, Japan) incubator to evaporate excess methanol.

2.4. Fe-BARQ

A validated questionnaire used in a previous study was translated into Korean and digitally administered using an online survey tool (Google Forms, Google LLC, Mountain View, CA, USA) [29]. Cat owners completed questionnaires during their cats’ health work-ups using an online survey tool. In the survey, the respondents were asked to complete the Fe-BARQ—a validated tool for assessing feline behavior [29]. The questionnaire asked owners to report the frequency of their cats’ behavioral tendencies, with responses recorded on a 5-point Likert scale (0 = never, 4 = always). The Fe-BARQ consists of 100 questions categorized into 24 sections. Additional data collected included demographic information (e.g., name, breed, sex, age, and acquisition details), environmental factors (e.g., number of climbing spaces, hiding places, and windows), and household characteristics (e.g., household size and sociability with other pets; Supplementary File S2). Additionally, five additional Likert-scale questions were included to evaluate the companion cat’s response to stressful situations and to gauge the owners’ perceptions of any behavioral issues in their cats.

2.5. Statistical Analysis

This study evaluated the normality of HCC distribution across three groups: the control, CKD IRIS 2 (early-stage CKD), and IRIS 3 and 4 groups (late-stage CKD). The distributions of HCC, age, and body weight in these groups failed the Shapiro–Wilk test for normality (p < 0.001). Therefore, the Kruskal–Wallis test (non-parametric analysis of variance) was used to evaluate the statistical differences in HCC, age, and body weight among the three groups. The pairwise Wilcoxon test was used to evaluate the statistical difference between each pair of groups in the post hoc analysis. Fisher’s exact test was performed to evaluate the statistical difference in sex and breed among the three groups. The Spearman correlation coefficient was calculated to assess the statistical differences in HCC with numeric, count, or ordered variables in more than three groups (e.g., Fe-BARQ score on a Likert scale). All data management, statistical analyses, and visualizations were performed using RStudio (version 4.4.0; RStudio PBC, Boston, MA, USA). Statistical significance was set at a p-value of <0.05.

3. Results

3.1. General Characteristics

Hair samples were collected from 42 cats: 21 cats in the control group, 10 in the IRIS stage 2 group, 10 in the IRIS stage 3 group, and one in the IRIS stage 4 group. For clarity, the CKD stage 2 group was referred to as the early-stage CKD group (n = 10), whereas the CKD stages 3 and 4 groups were combined into the late-stage CKD group (n = 11). The mean age was 6.14 ± 3.24 years in the control group, 11.30 ± 3.56 years in the early-stage CKD group, and 14.36 ± 4.61 years in the late-stage CKD group. The mean ages in the CKD groups was significantly higher than that of the control group (p < 0.001; Table 1). The mean body weight was 5.14 ± 1.09 kg for the control group, 4.57 ± 1.42 kg in the early-stage CKD group, and 4.50 ± 1.64 kg in the late-stage CKD group, with no significant difference among the three groups (p = 0.173; Table 1). All cats were spayed or neutered. The breed distribution was as follows: Korean Domestic Shorthair (n = 24), Persian/Exotic (n = 5), British Shorthair (n = 4), Abyssinian (n = 2), Munchkin (n = 2), and other breeds (n = 5; Table 2). Environmental factors, such as the duration of cat ownership, number of other cats and dogs in the household, and time spent interacting with the cat were evaluated (Table 2). The mean duration of cat ownership was longer in the CKD groups (10.43 ± 6.04 years in the early-stage CKD group and 12.39 ± 4.58 years in the late-stage CKD group) compared to the control group (5.61 ± 3.28 years), though the difference was not statistically significant (p = 0.411). The number of other cats and dogs in the household, as well as the average daily interaction time with cats, also showed no significant differences among the groups (p > 0.05; Table 2).

3.2. Comparison of Hair Cortisol Concentration

HCC incidence was significantly higher in the CKD group than in the control group (p < 0.001). The analysis of HCC revealed that the late-stage CKD group had the highest concentration at 20.95 ± 41.13 pg/mg, followed by the early-stage CKD group at 10.70 ± 10.64 pg/mg, and the control group at 5.55 ± 4.10 pg/mg (Table 1, Figure 1a). The Kruskal–Wallis test confirmed significant differences in HCC among the three groups (p = 0.005) (Figure 1a). Post hoc analysis revealed a statistically significant difference between the control and late-stage CKD groups (p = 0.008). However, no significant difference was observed between the early-stage CKD and control groups (p = 0.074) or between the early-stage CKD and late-stage CKD groups (p = 0.387; Figure 1a).

3.3. Behavioral Differences Among the Control, Early-Stage CKD, and Late-Stage CKD Groups

Analysis of the Fe-BARQ scores revealed significant behavioral differences among the control, early-stage CKD (IRIS 2), and late-stage CKD (IRIS 3 and 4) groups. Cats in the late-stage and early-stage CKD groups demonstrated significantly higher sociability with unfamiliar cats than those in the control group (S4Q2, p = 0.049). In contrast, the control group cats exhibited higher levels of touch sensitivity and owner-directed aggression than those in both CKD groups. The control group was more likely to scratch or bite when petted on the belly (S4Q7, p = 0.0022) and had a greater tendency to lash out unexpectedly when petted (S4Q9, p = 0.041). Cats in the early-stage CKD group displayed higher levels of aggression toward familiar dogs (S6Q1, p = 0.049; S6Q2, p = 0.036) than those in the late-stage CKD group. Notably, cats in the early-stage CKD group showed significantly higher attentiveness to their owners’ actions and words than those in both the late-stage CKD and control groups (S10Q3, p = 0.005). The CKD cats were notably more likely to closely observe and listen to everything their owners said or did (Figure 1b).

3.4. Correlation Between HCC and Fe-BARQ Results

3.4.1. Control Group (n = 21)

All 21 cat owners in the control group completed the Fe-BARQ. In the control group, higher HCC levels were associated with a reduction in behaviors such as resting or sleeping on warm appliances (Cor = −0.538, p = 0.014; Table 3 and Table 4).

3.4.2. Early-Stage CKD Group (n = 9)

Nine out of 10 owners in the early-stage CKD group completed the Fe-BARQ. In the early-stage CKD group, several significant correlations were observed between HCC and behavioral traits as measured by the Fe-BARQ. Notably, HCC exhibited strong negative correlations with various activities and social behaviors. Cats with lower HCC levels demonstrated greater curiosity toward new objects or environmental changes (S1Q2, Cor = −0.684, p = 0.042), more frequent running and jumping (S1Q4, Cor = −0.949, p < 0.001), and increased climbing on high surfaces (S1Q5, Cor = −0.769, p = 0.015; Figure 2a). Additionally, lower HCC levels were associated with more frequent toy-bringing behavior (S1Q7, Cor = −0.935, p < 0.001) and a higher likelihood of playing fetch (S15Q8, Cor = −0.819, p = 0.007; Table 3 and Table 4). Social behavior also negatively correlated with HCC. Early-stage CKD group cats with lower HCC levels were more likely to purr when sitting on someone’s lap (S3Q5, Cor = −0.712, p = 0.047), nudge family members (S3Q6, Cor = −0.744, p = 0.021), and seek physical contact with family members (S3Q7, Cor = −0.800, p = 0.01; Table 3, Figure 2b). Moreover, these cats were more responsive to being called (S10Q1, Cor = −0.829, p = 0.006; Table 3, Figure 2c). Notably, a positive correlation was observed between HCC and discomfort when held or placed on the lap (S15Q6, Cor = 0.734, p = 0.024; Table 3 and Table 4).

3.4.3. Late-Stage CKD Group (n = 10)

Ten out of 11 owners in the late-stage CKD group completed the Fe-BARQ. In this group, several significant correlations were observed between the HCC and Fe-BARQ scores. A negative correlation was revealed between HCC and the tendency to carry small objects or toys in the mouth (S1Q3, Cor = −0.686, p = 0.028; Figure 3a). Conversely, a positive correlation was observed between HCC and the cat’s responsiveness to being called (S10Q1, Cor = 0.663, p = 0.037; Figure 3b).

3.5. Correlation Between HCC and Other Factors

Environmental Factors

In the control and late-stage CKD groups, no significant correlation was observed between the number of high resting places and HCC. However, the early-stage CKD group showed a significant negative correlation (Cor = −0.763, p-value = 0.017; Figure 4a). No significant correlation was observed between the control and early-stage CKD groups and number of hiding spaces and HCC. Notably, the late-stage CKD group demonstrated a significant negative correlation (Cor = −0.729, p-value = 0.017; Figure 4b). No significant correlation was observed between daily playtime and HCC in any of the three groups. The study also found no significant correlation between the number of cats in the household and HCC levels among the groups.

3.6. Cat Owner Assessment

No significant differences were detected across the three groups between unfamiliar people, veterinary visits, or other cats. Additionally, no significant correlation was observed between HCC and the owners’ assessments of their cats’ problematic behaviors.

3.7. Biochemical Parameters

Analysis of the combined data from all three groups revealed positive correlations between HCC and biochemical markers such as BUN, creatinine (CREA), and SDMA levels. Specifically, BUN showed a moderate positive correlation with HCC (Cor = 0.458, p = 0.002; Figure 5a), as did CREA (Cor = 0.451, p = 0.003; Figure 5b) and SDMA (Cor = 0.523, p < 0.001; Figure 5c). However, when the data were analyzed separately for the control, early-stage CKD, and late-stage CKD groups, no significant correlations were observed between HCC and these biochemical indicators within each group.

4. Discussion

In this study, HCC and the Fe-BARQ were applied to objectively assess the relationship between chronic stress levels and behavioral changes in cats with CKD. The results revealed significantly higher levels of HCC in the cats with CKD, particularly in the late-stage CKD group, than in those in the control group. Additionally, different behavioral patterns were observed depending on the stage of CKD progression. HCC reflects cumulative stress levels over the past 1–3 months [68,69,70], while the Fe-BARQ evaluates behavioral patterns observed over several months [29]. This alignment minimizes temporal discrepancies between these tools in assessing chronic stress. However, subtle differences in the specific periods covered may influence correlations between HCC and the Fe-BARQ scores or behavioral interpretations in cats with CKD. To address this, future longitudinal studies tracking HCC levels and Fe-BARQ scores simultaneously throughout CKD progression are recommended to refine our understanding of chronic stress and its impact on feline behavior.
Although previous studies examining HCC in cats with CKD are limited, our findings are consistent with those of Rothlin-Zachrisson et al., who reported that cats with chronic diseases, including CKD, have higher HCC levels than those of healthy cats [4]. Additionally, our study revealed that elevated levels of BUN, CREA, and SDMA, which reflect typical kidney function, were associated with higher HCC levels. This suggests that as kidney function declines, stress levels may increase. Furthermore, the correlation between HCC levels and IRIS stages observed in our study supports previous research indicating that HCC levels rise as CKD progresses [7]. This finding highlights a potential bidirectional relationship between CKD progression and chronic stress: while high-stress levels may accelerate CKD progression through mechanisms such as inflammation and oxidative stress, the progression of CKD itself likely exacerbates stress due to its physiological and behavioral impacts. Notably, the elevated HCC levels observed in the late-stage CKD cats, combined with behavioral changes identified in the early-stage CKD cats, underscore the complex interactions between chronic stress and disease progression. These findings emphasize the need for further longitudinal studies to clarify the causal relationships between CKD progression and chronic stress.
Owner-directed aggression in the control group may reflect heightened stress responses during veterinary visits or unfamiliar environments, as previously reported in healthy cats [71,72]. Unlike CKD cats, who may experience reduced aggression due to lethargy or chronic discomfort, control cats are generally more active and responsive, which could amplify their defensive behaviors in stressful situations. For example, healthy cats are more likely to exhibit touch sensitivity or lash out when petted on sensitive areas like the belly, as observed in our study. This aligns with previous findings that aggression during veterinary visits is often linked to fear or discomfort rather than underlying health conditions.
The cats’ behavioral patterns varied depending on the CKD stage: Cats in the early-stage CKD group were more attentive to the actions and words of their owners, suggesting that the additional attention and care they received in the early stages of CKD might have enhanced their social behavior. Cats with illnesses tend to develop a stronger bond with their caretakers during the caregiving process [73,74,75]. This is primarily attributed to the increased interaction and attention received during treatment. Cats in the late-stage CKD group were less aggressive toward familiar dogs or unfamiliar cats than those in the early-stage CKD group. This could have resulted from decreased energy, lethargy, or chronic discomfort, which may have reduced interest in interacting with other animals as the disease progresses. Lethargy is one of the most common clinical symptoms reported by owners of cats with CKD. Previous studies suggest that cats with CKD are likely to experience chronic discomfort due to vomiting and ulcerative stomatitis, among other symptoms, caused by uremic toxins [57,76]. Notably, cats in the late- and early-stage CKD groups were more social with unfamiliar cats than those in the control group. In contrast, previous studies have revealed that sick cats are less likely to engage in intimate behaviors, such as cross-species social interactions, and affiliative behaviors (maintaining proximity and grooming) are more commonly observed among familiar or related cats [11,77]. However, chronic health conditions can alter cats’ stress response mechanisms, such as exhibiting more social behavior in response to stress [14]. Therefore, these behavioral changes can be interpreted as attempts to seek safety and comfort.
We also found that different stages of CKD progression were associated with different behavioral patterns. A comprehensive analysis of HCC levels in the early-stage CKD group revealed increased activity levels (e.g., play and climbing) and social behavior (e.g., affectionate interactions with owners and attention seeking), which were linked to lower HCC levels. These results support previous studies’ findings suggesting that stress reduces general activity, play, and positive interactions with humans in companion cats [14,78]. When cats are exposed to elevated stress levels, behaviors such as appetite, grooming, and activity tend to decrease, whereas behavioral issues such as house soiling and aggressive behavior tend to increase [79]. However, despite including relevant questions about these behaviors in the survey, no significant correlation was observed between HCC levels and behavioral changes in the early-stage CKD group. This could be due to the variability in individual responses or the subtle nature of behavioral changes at this stage.
In the late-stage CKD group, the elevated HCC level was associated with increased responsiveness to being called, suggesting a potential correlation with prior research. Companion cats can associate their names with various experiences, including positive rewards, such as food and affection, and stressful situations, such as visits to veterinary clinics. Notably, cats tend to show more dynamic or communicative responses when called during stress-inducing situations [80]. This finding aligns with the results of the present study, suggesting a multifaceted relationship between stress and responsiveness to being called in cats with CKD. As CKD progresses, the frequency of calls to veterinary clinics increases. This may strengthen the association between being called and unpleasant experiences such as medications and examinations. This may have influenced responsiveness to calling [81]. However, because late-stage CKD cats require constant care and attention, it is possible that being called is associated with positive experiences, such as food provision or attention from the owner, leading to increased reactivity to naming. However, this increase in reactivity must be considered in the context of an individual cat’s personality, previous experiences, living environment, and other factors.
In contrast, the late-stage CKD group did not demonstrate a significant correlation between HCC levels and activity-related behaviors. The absence of correlation may be attributable to several factors.
These observations could reflect symptoms of depression, such as social inhibition and anhedonia, which result from prolonged or chronic stress [82,83]. Additionally, lethargy, a common symptom of CKD in cats, obscures stress-related behavioral changes, and is frequently linked to CKD complications, such as anemia [62,82]. Therefore, it is reasonable to consider that the behavioral changes observed in the late-stage CKD group may reflect disease clinical manifestations.
The present study revealed a relationship between HCC levels and living environment. Early-stage CKD cats with lower HCC levels had more elevated spaces to climb, whereas late-stage CKD cats had more hiding spaces. This finding is consistent with a meta-analysis on indoor cat behavior and welfare by Foreman-Worsley and Farnworth [84], as well as environmental enrichment studies on shelter cats by Vinke et al. and Houser and Vitale [22,85]. This suggests a close association between environmental enrichment, which reflects natural behavioral patterns, and CKD in cats. Compared to free-roaming cats, companion cats, often raised in confined indoor environments, are under more stress. Therefore, when designing indoor spaces for cats, it is essential to prioritize quality over size [86,87,88]. Previous research on home environments for cats has recommended incorporating vertical dimensions such as shelves, climbing posts, and windowsills to reflect cats’ behavioral characteristics in monitoring their surroundings from high places [86]. The authors emphasized that hiding is a common coping behavior for cats in stressful situations and highlighted the importance of providing resting spaces where cats can hide, such as high-sided cat beds and boxes, in addition to open resting areas [86]. Therefore, environmental enrichment for early-stage CKD cats could include providing three-dimensional or vertical spaces, such as shelves and cat trees, to encourage activity and social interaction for stress management. For cats with late-stage CKD and decreased activity, the focus should shift to comfort and supportive care. It is crucial to provide a safe environment with all the necessary resources, including hiding spaces, comfortable resting areas, and feeding areas. Additionally, spending appropriate interactive enrichment time with the cat, such as positive interactions with a familiar human, can further support their well-being [89].
This study has three limitations. First, we acknowledge the potential for age-related confounding in the relationship between CKD progression and stress-related responses, as measured using HCC and the Fe-BARQ. Since CKD is an age-associated disease, the observed stress-related responses in the two CKD groups might have been influenced by age-related factors rather than CKD-related factors. However, this confounding effect would not significantly impact our findings, as the control group only included healthy adult cats aged ≥2 years. Longitudinal studies on companion cats have revealed that individual behavior differences become more stable with age owing to decreased within-individual variability and increased between-individual differences. These changes make a cat’s behavioral traits more consistent and predictable with age [90]. Furthermore, episodic secretion of cortisol and other hormones in adult cats does not demonstrate significant circadian variations, suggesting a more stable hormonal profile than that in younger cats [91].
The second limitation is the subjective nature of the owners’ observations of their cats’ behavior. While owners are generally considered the most reliable source of information on their cats’ behavior, considering the amount of time spent with them, the untrained and subjective observation of owners may not always lead to highly objective assessments. Nonetheless, the Fe-BARQ minimizes subjective bias by asking respondents to report specific, itemized stress-related behaviors rather than allowing them to draw their conclusions. Therefore, this study provides reliable results by minimizing the subjectivity of owner evaluations.
Finally, the study’s cross-sectional design limited its ability to establish causality between CKD and stress-related responses due to the timing differences between CKD onset, HCC measurement, and the Fe-BARQ. Future longitudinal studies examining HCC levels and Fe-BARQ scores throughout CKD progression may provide deeper insights into the causal relationship between CKD progression, chronic stress levels, and behavioral changes.

5. Conclusions

The findings of this study demonstrated significant correlations between HCC levels and behavior in cats with CKD. Specifically, the high HCC levels in late-stage CKD cats and behavioral changes in those with early-stage CKD suggest the possibility of complex interactions between CKD progression and chronic stress. As discussed above, the bidirectional relationship between CKD progression and chronic stress highlights the need for further investigation into their complex interactions. In other words, while CKD progression induces stress, chronic stress may also affect CKD progression and prognosis. However, due to the cross-sectional nature of this study, it was not possible to establish a direct causal relationship between these factors. Future longitudinal studies are needed to clarify whether elevated cortisol levels act as a causative factor in CKD progression or are a compensatory response to declining kidney function. This study’s use of HCC levels to assess stress responses provides a novel approach to monitoring stress in cats with CKD. This method is incorporated into veterinary practice as a tool for tracking disease progression and stress levels over time, providing valuable information for adjusting treatment plans and ensuring better patient outcomes. Additionally, the findings that different stages of CKD are associated with varying levels of behavioral change suggest the development of personalized care strategies for cats at different disease stages. For instance, cats with early-stage CKD may benefit from increased social interaction, while those in the late stage require a more comfort-oriented approach, focusing on rest and reduced stress.

Supplementary Materials

The following supporting information can be downloaded at: https://www.mdpi.com/article/10.3390/ani15060889/s1, File S1: Table S1: Clinical characteristics of the control group; Table S2: Clinical characteristics of the CKD group. File S2: Questionnaire S1: Demographic information questionnaire.

Author Contributions

Conceptualization, G.-H.K. and S.-A.K.; methodology, G.-H.K. and S.-A.K.; software, K.L.; validation, K.L.; formal analysis, K.L.; investigation, G.-H.K. and H.-S.C.; resources, G.-H.K.; writing—original draft preparation, G.-H.K., K.L. and H.-S.C.; writing—review and editing, G.-H.K., S.-A.K., K.L. and H.-S.C.; visualization, G.-H.K. and K.L.; supervision: S.-A.K.; project administration: G.-H.K. and J.S.H. All authors have read and agreed to the published version of the manuscript.

Funding

This research received no external funding.

Institutional Review Board Statement

This study did not involve direct use of animals. The research utilized only discarded fur samples collected after routine veterinary care. Therefore, specific ethical approval was not required for this study. The research protocol adhered to all applicable institutional and national guidelines for using indirect animal materials in research.

Informed Consent Statement

Informed consent was obtained from all subjects involved in the study.

Data Availability Statement

All data generated or analyzed during this study are included in this published article and its Supplementary Materials.

Acknowledgments

The authors acknowledge CO-ANI (Kangwon national university atmospheric environment science in livestock) for conducting the HCC measurements as part of the study.

Conflicts of Interest

The authors declare no conflicts of interest.

Abbreviations

The following abbreviations are used in this manuscript:
CKDchronic kidney disease
CREAcreatinine
HCChair cortisol concentration
IRISInternational Renal Interest Society
Fe-BARQFeline Behavioral Assessment & Research Questionnaire
FICfeline idiopathic cystitis
SDMAsymmetric dimethylarginine

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Animals 15 00889 g001
Figure 1. Comparison of hair cortisol concentrations and Fe-BARQ scores among the control and CKD groups. (a) Hair cortisol concentrations (HCC) in the control, early-stage CKD, and late-stage CKD groups. (b) Differences in Fe-BARQ scores among the control, early-stage CKD, and late-stage CKD groups.
Figure 1. Comparison of hair cortisol concentrations and Fe-BARQ scores among the control and CKD groups. (a) Hair cortisol concentrations (HCC) in the control, early-stage CKD, and late-stage CKD groups. (b) Differences in Fe-BARQ scores among the control, early-stage CKD, and late-stage CKD groups.
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Figure 2. Correlation between hair cortisol concentrations and behavioral characteristics in early-stage CKD cats. (a) Correlation between activity-related behaviors and HCC: S1Q2, curiosity toward new objects; S1Q4, running and jumping behavior; S1Q5, climbing to high places. (b) Correlation between social interaction behaviors and HCC: S3Q5, purring while on a lap; S3Q6, nudging family members; S3Q7: staying close to family. (c) correlation between responsiveness-related behaviors and HCC: S10Q1, coming when called.
Figure 2. Correlation between hair cortisol concentrations and behavioral characteristics in early-stage CKD cats. (a) Correlation between activity-related behaviors and HCC: S1Q2, curiosity toward new objects; S1Q4, running and jumping behavior; S1Q5, climbing to high places. (b) Correlation between social interaction behaviors and HCC: S3Q5, purring while on a lap; S3Q6, nudging family members; S3Q7: staying close to family. (c) correlation between responsiveness-related behaviors and HCC: S10Q1, coming when called.
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Figure 3. Correlation between hair cortisol concentrations and behavioral characteristics in late-stage CKD cats. (a) Correlation between playfulness-related behaviors and HCC: S1Q3, carries small objects/toys in the mouth to interact with. (b) Correlation between responsiveness to name-calling behaviors and HCC: S10Q1, coming when called.
Figure 3. Correlation between hair cortisol concentrations and behavioral characteristics in late-stage CKD cats. (a) Correlation between playfulness-related behaviors and HCC: S1Q3, carries small objects/toys in the mouth to interact with. (b) Correlation between responsiveness to name-calling behaviors and HCC: S10Q1, coming when called.
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Figure 4. Environmental factors and HCC correlation in different CKD stages. (a) Correlation between the number of high places and HCC in early-stage CKD cats. (b) Correlation between the number of hiding places and HCC in late-stage CKD cats.
Figure 4. Environmental factors and HCC correlation in different CKD stages. (a) Correlation between the number of high places and HCC in early-stage CKD cats. (b) Correlation between the number of hiding places and HCC in late-stage CKD cats.
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Figure 5. Correlation between HCC and biochemical parameters in CKD cats. (a) Correlation between blood urea nitrogen (BUN) levels and HCC in the CKD group. (b) Correlation between creatinine levels and HCC in the CKD group. (c) Correlation between symmetric dimethylarginine (SDMA) levels and HCC in the CKD group.
Figure 5. Correlation between HCC and biochemical parameters in CKD cats. (a) Correlation between blood urea nitrogen (BUN) levels and HCC in the CKD group. (b) Correlation between creatinine levels and HCC in the CKD group. (c) Correlation between symmetric dimethylarginine (SDMA) levels and HCC in the CKD group.
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Table 1. Comparison of blood and serum biochemistry parameters among groups.
Table 1. Comparison of blood and serum biochemistry parameters among groups.
Group
ControlEarly-Stage CKDLate-Stage CKD
BUN (mg/dL)21.33 ± 3.5735.40 ± 15.3369.09 ± 32.05
CRE (mg/dL)1.45 ± 0.242.40 ± 0.294.11 ± 1.19
SDMA (μg/dL)10.57 ± 2.4615.25 ± 3.1119.11 ± 5.71
Hct (%)44.96 ± 4.89--
PLT (103/μL)27.89 ± 64.53--
WBC (/μL)153.81 ± 92.91--
ALB (μg/dL)3.04 ± 0.36--
TP (g/dL)7.60 ± 0.49--
GLU (mg/dL)113.19 ± 25.44--
ALKP (U/L)35.14 ± 12.21--
ALT (U/L)52.29 ± 17.85--
Data are expressed as mean ± SD. Early-stage CKD: CKD IRIS stage 2 (creatinine 1.6–2.8 mg/dL). Late-stage CKD: CKD IRIS stages 3 and 4 (creatinine > 2.8 mg/dL). SDMA data were unavailable for the CKD cats (n = 4) owing to technical limitations in the retrospective data collection. Those cats met all other inclusion criteria for the CKD group, including elevated creatinine (≥1.8 mg/dL) and abnormal kidney imaging findings. ALB, albumin; ALKP, alkaline phosphatase; ALT, alanine aminotransferase; BUN, blood urea nitrogen; CRE, creatinine; GLU, glucose; Hct, hematocrit; PLT, platelets; SDMA, symmetric dimethylarginine; TP, total protein; WBC, white blood cell.
Table 2. Demographic, clinical characteristics, and environmental factors of the study population.
Table 2. Demographic, clinical characteristics, and environmental factors of the study population.
VariablesReference RangeGroupp-Values
Control (n = 21)Early-Stage CKD (n = 10)Late-Stage CKD (n = 11)
Breed-Abyssinian (1), American Shorthair (1), British Shorthair (2), Korean Shorthair (10), Mixed (1), Munchkin (3), Scottish Straight (1), Selkirk Rex (1), Siamese (1)Abyssinian (1), Exotic (1), Korean Shorthair (6), Persian (1), Russian Blue (1)Abyssinian (1), British Shorthair (1), Korean Shorthair (4), Mixed (1), Neva Masquerade (1), Persian (1), Scottish Straight (1), Siamese (1)0.478
Sex-CM (10), SF (11)CM (7), SF (3)CM (8), SF (3)0.331
Age (years)-6.14 ± 3.2411.30 ± 3.5614.36 ± 4.61<0.001
Body weight (kg)-5.14 ± 1.094.57 ± 1.424.50 ± 1.640.173
Hair cortisol concentration (pg/mg)-5.55 ± 4.1010.70 ± 10.6420.95 ± 41.130.005
Duration of cat ownership
(years)		-5.61 ± 3.2810.43 ± 6.0412.39 ± 4.580.411
Indoor/
Outdoor		-Indoor (21)Indoor (10)Indoor (11)1.0
Number of other cats-0.38 ± 0.670.67 ± 1.001.27 ± 2.940.814
Number of other dogs-0.00 ± 0.000.22 ± 0.670.00 ± 0.000.537
Spending time interacting with your cat
(minutes per day)		-23.10 ± 16.3246.22 ± 74.7530.91 ± 34.270.806
Data are expressed as mean ± SD. Age, body weight, and hair cortisol concentration were analyzed using the non-parametric ANOVA (Kruskal–Wallis test). Breed and sex distributions were analyzed using Fisher’s exact test. p < 0.05 is considered statistically significant. Sex is expressed as CM (castrated male) and SF (spayed female). Early-stage CKD: CKD IRIS stage 2. Late-stage CKD: CKD IRIS stages 3 and 4. Duration of cat ownership (years-months) was calculated based on the period from the time the cat was acquired to the date of the hair sample collection.
Table 3. Description of significant behavioral items in the Fe-BARQ questionnaire.
Table 3. Description of significant behavioral items in the Fe-BARQ questionnaire.
FactorItemDescription
Activity/PlayfulnessS1Q2Curious: actively investigates/explores new objects, sights, or changes in its environment
S1Q3Carries small objects or toys in the mouth to interact with
S1Q4Runs and jumps in the air
S1Q5Engages in active jumping and climbing on high surfaces, furniture, or curtains/drapes
S1Q7Stalks, chases, or pounces on moving objects (string, balls, soft toys) during playful activity
PurringS3Q5Purrs when sitting or lying on someone’s lap
Attention seekingS3Q6Nudges and/or nuzzles household members when they are sitting or lying down
S3Q7Seeks physical contact with household members when they are sitting or lying down
Sociability with cats and touch sensitivity/Owner-directed aggressionS4Q2Greets unfamiliar (non-household) cats visiting your home in a friendly manner (sniffs, touches nose, rubs)
S4Q7Scratches, bites, or attempts to bite (in a non-playful way) when petted on the belly
S4Q9Lashes out (scratches, bites) unexpectedly when petted
Dog AggressionS6Q1Attacks (scratches, bites, or attempts to bite) familiar dog(s)
S6Q2Growls/hisses at familiar dog(s)
TrainabilityS10Q1Comes when called
S10Q3Attends and listens closely to everything you say or do
Location preferences for resting/sleepingS12Q2Tends to sleep or rest on warm appliances (DVD player, TV, printer, computer, radiator, etc.
Miscellaneous behaviorsS15Q6Appears uncomfortable (trembles, becomes rigid/tense, struggles) when picked up/held in arms and/or when sitting on laps
S15Q8Plays “fetch” by retrieving thrown objects or toys
Fe-BARQ items were selected based on statistical significance (p < 0.05). All items were scored on a 5-point Likert scale (never to always). Behavioral categories were classified based on a validated feline ethogram.
Table 4. Correlation analysis between hair cortisol concentration and Fe-BARQ items.
Table 4. Correlation analysis between hair cortisol concentration and Fe-BARQ items.
GroupIncreased/More LikelyDecreased/Less Likely
Itemρ (p-Value)Itemρ (p-Value)
Controls--S12Q2−0.538 (0.014)
Early-stage CKDS15Q60.734 (0.024)S1Q2−0.684 (0.042)
S1Q4−0.949 (<0.001)
S1Q5−0.769 (0.015)
S1Q7−0.935 (<0.001)
S3Q5−0.712 (0.047)
S3Q6−0.744 (0.021)
S10Q1−0.829 (0.006)
S15Q8−0.819 (0.007)
S15Q12−0.853 (0.003)
Late-stage CKDS10Q10.663 (0.037)S1Q3−0.686 (0.028)
p-values < 0.05 were considered statistically significant. Positive correlation indicates behaviors that become more likely with higher HCC. Negative correlation indicates behaviors that become less likely with higher HCC. Analyses were performed separately for each group to account for disease-stage effects.
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Kim, G.-H.; Lee, K.; Choi, H.-S.; Han, J.S.; Kim, S.-A. Hair Cortisol and Fe-BARQ: Evaluating Chronic Stress and Behavior in Cats with Chronic Kidney Disease. Animals 2025, 15, 889. https://doi.org/10.3390/ani15060889

AMA Style

Kim G-H, Lee K, Choi H-S, Han JS, Kim S-A. Hair Cortisol and Fe-BARQ: Evaluating Chronic Stress and Behavior in Cats with Chronic Kidney Disease. Animals. 2025; 15(6):889. https://doi.org/10.3390/ani15060889

Chicago/Turabian Style

Kim, Ga-Hee, Kyuyoung Lee, Han-Sol Choi, Jin Soo Han, and Sun-A Kim. 2025. "Hair Cortisol and Fe-BARQ: Evaluating Chronic Stress and Behavior in Cats with Chronic Kidney Disease" Animals 15, no. 6: 889. https://doi.org/10.3390/ani15060889

APA Style

Kim, G.-H., Lee, K., Choi, H.-S., Han, J. S., & Kim, S.-A. (2025). Hair Cortisol and Fe-BARQ: Evaluating Chronic Stress and Behavior in Cats with Chronic Kidney Disease. Animals, 15(6), 889. https://doi.org/10.3390/ani15060889

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