Correlation Analysis of Serum Uric Acid and Uric Acid Creatinine Ratio With Sarcopenia in the Elderly

ABSTRACT

Objectives

Sarcopenia is a progressive and systemic skeletal muscle disease. Uric acid is a powerful endogenous antioxidant and an indicator reflecting the nutritional status in the human body. Serum uric acid creatinine ratio (UCR) is serum uric acid (SUA) corrected by renal function. The relationship between SUA, UCR, and sarcopenia remains underexplored. This study explored the correlation between SUA, UCR, and sarcopenia in elderly patients.

Methods

This study included 214 elderly patients (aged > 65 years) who were hospitalized in Xiangya Second Hospital from March 2022 to July 2023. T test, U test, or chi‐squared test was used to compare the differences between groups. Spearman correlation analysis was used to analyze the correlation between SUA, UCR, and skeletal muscle mass index (SMI) and handgrip strength. The relationship between SUA, UCR, and sarcopenia was estimated by a multivariate logistic regression model. ROC curve was drawn to test the diagnostic efficacy of SUA and UCR for sarcopenia.

Results

The levels of SUA and UCR were significantly lower in participants with sarcopenia. Spearman correlation analysis showed that SUA and UCR were positively correlated with handgrip strength and skeletal muscle mass index. Multivariate logistic regression analysis showed that, after adjusting for relevant confounding factors, UCR remained significantly associated with sarcopenia, while SUA didn't. The AUC of SUA combined with UCR in diagnosing sarcopenia in males was 0.744. In females, the progressive significance of SUA was not statistically significant. The AUC of UCR was 0.658.

Conclusion

In the elderly, SUA and UCR are related to sarcopenia, but there are certain gender differences.

In the elderly, SUA and UCR are related to sarcopenia, but there are certain gender differences.

Abbreviations

ALB

albumin

AST/ALT

aspartate aminotransferase/alanine aminotransferase ratio

BMI

the body mass index

BUN

blood urea nitrogen

Ca

serum calcium

CHOL

total cholesterol

CIs

confidence intervals

CR

creatinine

HDL‐C

high‐density lipoprotein cholesterol

HGB

hemoglobin

IP

serum phosphorus

LDL‐C

low‐density lipoprotein cholesterol

MNA‐SF

Mini Nutritional Assessment Short‐Form

ORs

odds ratios

PLT

platelet count

ROC

Receiver Operating Characteristic

ROS

reactive oxygen species

SMI

skeletal muscle mass index

SUA

serum uric acid

SUA

serum uric acid

TG

triglycerides

UA

uric acid

UCR

serum uric acid creatinine ratio

WBC

white blood cell count

1. Introduction

Sarcopenia is a systemic skeletal muscle disease, which is mainly characterized by progressiveness and extensiveness. It can manifest as decreased muscle mass, impaired muscle function, and/or reduced physical function. The development of sarcopenia is correlated with an elevated prevalence of adverse outcomes, including falls, diminished functionality, frailty, and mortality, among patients [1]. However, the precise pathogenesis of sarcopenia remains unclear at present. Current research suggests that various mechanisms such as oxidative stress, mitochondrial dysfunction, neuromuscular junction disorders, inflammation, autoimmune responses, and imbalances in protein synthesis and degradation homeostasis may be associated with the development of sarcopenia [2, 3, 4, 5].

Uric acid (UA) is the end product of purine metabolism in humans. While excessively high serum uric acid (SUA) levels can lead to the development of gout and a range of metabolic diseases, recent studies have increasingly demonstrated that UA serves as a potent endogenous antioxidant within the human body [6, 7, 8]. Elevated SUA levels within the normal reference range contribute to antioxidant defense mechanisms in the body, mitigating oxidative stress. Furthermore, SUA levels are also considered as an indicator that can reflect the nutritional status [9, 10].

Current studies observed that the pathogenesis of sarcopenia has a close relationship with oxidative stress. This intimate association primarily stems from the strong reliance of skeletal muscle cells on oxidative metabolism, which renders skeletal muscle highly susceptible to the deleterious effects of excessive production of reactive oxygen species (ROS), a byproduct of metabolism [1]. A previous study has indicated that hyperuricemia may be associated with the occurrence and progression of sarcopenia [11]. However, recent literature has suggested that moderately elevated SUA levels exhibit a certain correlation with sarcopenia‐related assessment indicators such as grip strength and muscle mass and may contribute to delaying the onset of sarcopenia [12, 13]. This observation contradicts the conclusions of previous studies.

UA in the human body is excreted through the kidneys, and SUA levels are closely related to renal function. There is a high incidence of renal insufficiency in the elderly population due to aging or the presence of multiple comorbidities. Therefore, the use of SUA as a single indicator for assessment has certain limitations. The uric acid creatinine ratio (UCR), as a standardized SUA indicator for renal function, may serve as a better assessment tool for sarcopenia [14]. Therefore, we aimed to determine the relationship between sarcopenia, SUA, and the UCR in elderly people.

2. Materials and Methods

2.1. Study Design and Participants

This study is a cross‐sectional study. The participants were enrolled in the Geriatric Medicine Department of Second Xiangya Hospital from March 2022 to July 2023. The inclusion criteria were patients aged over 65 years, with their consent obtained.

The exclusion criteria were:

1. Subjects with incomplete data for SUA, body composition analysis, creatinine, grip strength, sit‐to‐stand tests, and other key data.

2. Individuals with high SUA levels (SUA > 428 μmol/L, based on the laboratory test results and reference range of The Second Xiangya Hospital).

3. People who have a long‐term history of alcohol consumption or have used medications that affect uric acid metabolism, such as urate‐lowering drugs and thiazide diuretics.

4. People with severe musculoskeletal disorders or neurological diseases that impair normal physical activity.

5. People with severe renal insufficiency or those undergoing regular hemodialysis (eGFR ≤ 15 mL/min 1.73m²).

Ultimately, 214 participants were included in the study. All included participants signed informed consent forms. At the time of admission, baseline clinical characteristics of the study participants were collected through detailed self‐report questionnaires, including gender, age, past medical history, and medication usage. Patients who met the inclusion criteria underwent routine blood tests, body composition analysis, standardized examination of muscle strength and physical function, and nutritional risk screening. The nutritional risk screening was conducted using the Mini Nutritional Assessment Short‐Form (MNA‐SF) score [15]. Based on the MNA‐SF score, patients were categorized into three groups: normal (score ≥ 12), at risk of malnutrition (11 ≥ score ≥ 8), and malnourished (score ≤ 7). The at‐risk of malnutrition and malnourished groups were defined as having nutritional risk. The Body Mass Index (BMI) is calculated by dividing the weight in kilograms (kg) by the square of the height in meters (m). Hypertension is defined as a non‐consecutive three‐time measurement of non‐invasive blood pressure in the brachial artery of the right upper limb with a systolic blood pressure and/or diastolic blood pressure ≥ 140/90 mmHg, or an ambulatory blood pressure monitoring with an average blood pressure > 130/80 mmHg, or a history of hypertension with long‐term use of antihypertensive medication.

2.2. Diagnosis and Assessment of Sarcopenia

For the diagnosis of sarcopenia, we adopted the Asian Working Group for Sarcopenia version 2 (AWGS2) diagnostic criteria [16]: The presence of reduced muscle mass combined with decreased muscle strength and/or impaired physical function can be used to diagnose sarcopenia. Diagnostic methods and cut‐off points: Reduced muscle strength is measured by decreased handgrip strength (handgrip strength < 28 kg for males and < 18 kg for females). The handgrip strength dynamometer used is the CAMRY EH101 electronic model. The subject is seated with both feet naturally placed on the ground, knees and hips flexed at 90°, shoulders in an adducted and neutral position. The elbows are flexed at 90°, forearms in a neutral position, and wrists flexed between 0° and 30°, with a slight ulnar deviation of 0° to 15° maintained. The subject adjusts the handle of the dynamometer as needed to ensure that the base rests on the first metacarpal bone (palm base), and the handle is positioned in the middle of the four fingers, with the middle phalanx of the middle finger maintained at a 90° bend. Then, the patient squeezes the hand dynamometer with maximum isometric force for at least 5 s. Decreased muscle mass is measured by the skeletal muscle mass index (SMI) obtained from the body composition analyzer (InBody S10 model), which is calculated as the appendicular skeletal muscle mass divided by the square of the height (kg/m²). A reduced SMI value (SMI < 7.0 kg/m² for males and SMI < 5.7 kg/m² for females) indicates decreased muscle mass. Impaired physical function is measured by an extended time in the 5‐times sit‐to‐stand test (time > 12 s). The test is administered and quality‐controlled by professionally trained personnel.

2.3. Laboratory Data Collection

Fasting venous blood samples are collected in the morning and sent to our hospital's laboratory department for a complete set of tests, including blood routine examination, lipid profile, liver function tests, renal function tests, and electrolyte panel. Laboratory data collection will include the following parameters: triglycerides (TG, mmol/L), total cholesterol (CHOL, mmol/L), high‐density lipoprotein cholesterol (HDL‐C, mmol/L), low‐density lipoprotein cholesterol (LDL‐C, mmol/L), aspartate aminotransferase/alanine aminotransferase ratio (AST/ALT), albumin (ALB, g/L), blood urea nitrogen (BUN, mmol/L), creatinine (CR, μmol/L), serum uric acid (SUA, μmol/L), serum calcium (Ca, mmol/L), serum phosphorus (IP, mmol/L; all of the above parameters will be measured using enzymatic colorimetric methods), white blood cell count (WBC, ×10⁹/L; the following measured using the XE‐2100 automated hematology analyzer), hemoglobin (HGB, g/L), platelet count (PLT, ×10⁹/L), and further calculation of UCR.

2.4. Statistical Analysis

This study employed a cross‐sectional research design, and data analysis was performed using SPSS (version 26.0 Inc., Chicago, IL, USA). In statistics, for the description of measurement data, the Kolmogorov–Smirnov test is first applied to verify its normality. Continuous variables with normal distribution are presented as mean ± standard deviation (SDs), while those with non‐normal distribution are presented as median (interquartile range). Categorical variables are represented by frequencies and percentages (%). Due to the differences in uric acid levels between genders, we conducted separate analyses for males and females. For continuous variables, t‐tests (with equal variances) or Mann–Whitney U tests (with unequal variances) are used to compare differences between groups when the data follow a normal distribution. For data that do not follow a normal distribution, Welch t‐test and the Mann–Whitney U test are employed to compare differences between groups. For categorical variables, the chi‐squared test is used to compare differences between groups. A p‐value less than 0.05 (p < 0.05) is considered statistically significant. The correlation between serum uric acid, UCR, and various indicators of sarcopenia was determined using Spearman's correlation analysis. The relationship between serum uric acid, UCR, and sarcopenia was estimated using a multivariate logistic regression model to derive odds ratios (ORs) and 95% confidence intervals (CIs). Lastly, receiver operating characteristic (ROC) curves were constructed to compare the specificity and sensitivity of SUA and UCR in diagnosing sarcopenia.

3. Result

3.1. Characteristics of Participants by Gender

The characteristics of participants by gender were shown in Table 1. This study enrolled 214 participants, including 103 males and 111 females. The average age of the participants was 81.19 years, with an average age of 80.80 years for males and 81.56 years for females. Participants were classified into sarcopenia and non‐sarcopenia groups based on SMI, handgrip strength, and 5‐times sit‐to‐stand test data. Among male participants, no significant differences were observed between the sarcopenia and non‐sarcopenia groups in terms of age, and the prevalence of tumor, coronary heart disease, or cerebral apoplexy. However, compared to the sarcopenia group, participants in the non‐sarcopenia group had significantly higher prevalences of hypertension and diabetes (p < 0.05) and lower nutritional risk and higher BMI levels (p < 0.001). Among female participants, no significant differences were observed in age, prevalence of tumors, coronary heart disease, diabetes, or cerebral apoplexy between the two groups. However, compared to the sarcopenia group, participants in the non‐sarcopenia group had significantly higher prevalence of hypertension, lower nutritional risk (p < 0.05), and higher BMI levels (p < 0.001).

TABLE 1.

Table characteristics of participants by gender.

Variables	Total (n = 214)	Male (n = 103)				Female (n = 111)
		Total (n = 103)	Non‐sarcopenia group (n = 67)	Sarcopenia group (n = 36)	p	Total (n = 111)	Non‐sarcopenia group (n = 62)	Sarcopenia group (n = 49)	p
Age (years)	81.19 ± 5.95	80.80 ± 6.60	80.18 ± 5.65	81.94 ± 8.06	0.247	81.56 ± 5.28	80.71 ± 5.03	82.63 ± 5.45	0.560
Handgrip strength (kg)	21.61 ± 7.86	27.02 ± 6.55	28.72 ± 5.54	23.86 ± 7.16	< 0.001**	16.59 ± 5.21	18.73 ± 4.84	13.90 ± 4.38	< 0.001**
SMI (kg/m2)	6.41 ± 1.25	7.31 ± 0.97	7.83 ± 0.72	6.35 ± 0.53	< 0.001**	5.58 ± 0.83	6.16 ± 0.44	4.84 ± 0.58	< 0.001**
5‐times sit‐to‐stand test	166 (77.6%)	74 (71.8%)	44 (65.7%)	30 (83.3%)	0.057	92 (82.9%)	47 (75.8%)	45 (91.8%)	0.026*
Nutritional risk	106 (49.5%)	43 (41.7%)	19 (28.4%)	24 (66.7%)	< 0.001**	63 (56.8%)	30 (48.4%)	33 (67.3%)	0.045*
Tumor	31 (14.5%)	20 (19.4%)	10 (14.9%)	10 (27.8%)	0.116	11 (9.9%)	7 (11.3%)	4 (8.2%)	0.584
Coronary heart disease	135 (63.1%)	66 (64.1%)	46 (68.7%)	20 (55.6%)	0.186	69 (62.2%)	43 (69.4%)	26 (53.1%)	0.079
Hypertension	153 (71.5%)	72 (69.9%)	54 (80.6%)	18 (50.0%)	0.001*	81 (73.0%)	50 (80.6%)	31 (63.3%)	0.041*
Diabetes mellitus	70 (32.7%)	38 (36.9%)	30 (44.8%)	8 (22.2%)	0.024*	32 (28.8%)	21 (33.9%)	11 (22.4%)	0.187
Cerebral apoplexy	43 (20.1%)	18 (17.5%)	15 (22.4%)	3 (8.3%)	0.073	25 (22.5%)	17 (27.4%)	8 (16.3%)	0.165
BMI (kg/m2)	22.99 ± 3.49	23.70 ± 3.35	25.13 ± 2.77	21.03 ± 2.64	< 0.001**	22.33 ± 3.51	23.83 ± 3.03	20.43 ± 3.16	< 0.001**

Note: Quantitative data with normal distribution are expressed as means ± standard deviation (SD), quantitative data with non‐normal distribution are expressed as median (interquartile range), and categorical variables are expressed as frequency (n, %).

Abbreviations: BMI, body mass index; SMI, skeletal muscle mass index.

^* p < 0.050, indicating a statistically significant difference between groups.

^** p < 0.001, indicating a highly statistically significant difference between groups.

3.2. Comparison of SUA, UCR and Other Laboratory Parameters in Non‐Sarcopenia and Sarcopenia Groups by Gender

The comparison of SUA, UCR, and other laboratory parameters in non‐sarcopenia and sarcopenia groups by gender was summarized in Table 2. Among male participants, the non‐sarcopenia group had lower AST/ALT levels while higher levels of ALB, IP, HGB, SUA, and UCR when compared to the sarcopenia group (all p < 0.050). There were no significant differences in the levels of TG, CHOL, HDL‐C, LDL‐C, BUN, CR, Ca, WBC, and PLT between the two groups. In female participants, the non‐sarcopenia group had significantly higher levels of TG, SUA, and UCR than those of the sarcopenia group (p < 0.050). There were no significant differences in the levels of CHOL, HDL‐C, LDL‐C, AST/ALT, ALB, BUN, CR, Ca, IP, WBC, HGB, and PLT between the two groups.

TABLE 2.

Laboratory test results comparison by gender.

Variables	Male (n = 103)				Female (n = 111)
	Total (n = 103)	Non‐sarcopenia group (n = 67)	Sarcopenia group (n = 36)	p	Total (n = 111)	Non‐sarcopenia group (n = 62)	Sarcopenia group (n = 49)	p
TG (mmol/L)	1.18 (0.83, 1.62)	1.11 (0.83, 1.65)	1.20 (0.76, 1.56)	0.487	1.30 (0.90, 1.63)	1.30 (0.89, 1.62)	1.26 (0.86, 1.63)	0.015*
CHOL (mmol/L)	3.85 ± 0.98	3.80 ± 0.93	3.94 ± 1.07	0.506	4.27 ± 1.00	4.22 ± 1.00	4.32 ± 1.01	0.598
HDL‐C (mmol/L)	1.08 ± 0.36	1.05 ± 0.29	1.13 ± 0.46	0.356	1.29 ± 0.34	1.27 ± 0.32	1.32 ± 0.35	0.470
LDL‐C (mmol/L)	2.14 (1.64, 2.92)	2.14 (1.64, 2.87)	2.25 (1.61, 2.93)	0.643	2.31 (1.85, 3.03)	2.41 (1.84, 3.04)	2.46 (1.86, 3.05)	0.974
AST/ALT	1.34 (1.04, 1.77)	1.22 (0.96, 1.56)	1.47 (1.28, 2.05)	0.005*	1.48 (1.20, 1.77)	1.43 (1.21, 1.73)	1.64 (1.14, 1.96)	0.226
ALB (g/L)	36.49 ± 3.97	37.16 ± 3.44	35.25 ± 4.59	0.019*	36.81 ± 4.70	36.99 ± 4.44	36.59 ± 5.04	0.652
BUN (mmol/L)	7.16 ± 2.42	7.07 ± 2.15	7.32 ± 2.89	0.657	5.73 ± 1.98	5.53 ± 1.63	5.99 ± 2.34	0.229
CR (μmol/L)	84.40 (71.20, 102.00)	82.00 (70.20, 99.70)	85.65 (71.78, 106.50)	0.502	64.00 (57.80, 72.00)	62.70 (55.68, 71.35)	66.00 (57.95, 72.50)	0.316
Ca (mmol/L)	2.19 ± 0.12	2.19 ± 0.12	2.18 ± 0.12	0.876	2.19 ± 0.15	2.19 ± 0.13	2.19 ± 0.17	0.982
IP (mmol/L)	0.99 ± 0.13	1.01 ± 0.14	0.95 ± 0.10	0.033*	1.08 (1.01, 1.19)	1.07 (1.01, 1.21)	1.10 (1.00, 1.17)	0.960
WBC (×109/L)	5.93 ± 1.99	5.85 ± 1.95	6.07 ± 2.08	0.607	5.93 ± 1.77	5.65 ± 1.49	6.28 ± 2.03	0.062
HGB (g/L)	124.67 ± 18.60	128.12 ± 18.05	118.25 ± 18.14	0.010*	118.05 ± 14.18	118.94 ± 11.69	116.94 ± 16.88	0.464
PLT (×109/L)	170.00 (130.00, 226.00)	164.00 (131.00, 222.00)	193.50 (126.25, 242.50)	0.333	211.33 ± 61.99	203.26 ± 55.33	221.55 ± 68.73	0.123
SUA (μmol/L)	322.80 (269.20, 369.00)	343.00 (284.00, 371.00)	292.45 (234.43, 338.90)	0.008*	274.63 ± 48.90	283.00 ± 43.31	264.04 ± 53.76	0.048*
UCR	3.67 ± 0.96	3.93 ± 0.86	3.19 ± 0.95	< 0.001**	4.32 (3.62, 4.84)	4.42 (4.02, 4.90)	4.06 (3.24, 4.54)	0.004*

Note: Quantitative data with normal distribution are expressed as means±standard deviation (SD); quantitative data with non‐normal distribution are expressed as median (interquartile range).

Abbreviations: ALB, albumin; AST/ALT, aspartate aminotransferase alanine aminotransferase ratio; BUN, blood urea nitrogen; Ca, serum calcium; CHOL, total cholesterol; CR, creatinine; HDL‐C, high‐density lipoprotein cholesterol; HGB, hemoglobin; IP, serum phosphorus; LDL‐C, low‐density lipoprotein cholesterol; PLT, platelet count; SUA, serum uric acid; TG, triglycerides; UCR, serum uric acid to creatinine ratio; WBC, white blood cell count.

^* p < 0.050, indicating a statistically significant difference between groups.

^** p < 0.001, indicating a highly statistically significant difference between groups.

3.3. The Relationship Between SUA, UCR and Various Indicators of Sarcopenia by Gender

In separate gender groups, participants were categorized based on grip strength, SMI, and the 5‐times sit‐to‐stand test to investigate the differences in SUA and UCR across different subgroups. Among male participants, when grouped by handgrip strength, those in the low handgrip strength group had significantly lower SUA and UCR levels compared to the normal handgrip strength group (p < 0.050). Similarly, when grouped by SMI, participants in the low SMI group had significantly lower SUA and UCR levels compared to the normal SMI group (p < 0.050). However, when grouped by the 5‐times sit‐to‐stand test, no significant differences were observed in SUA and UCR levels between the two groups (Table 3). Among female participants, when grouped by handgrip strength, those in the low handgrip strength group had significantly lower SUA levels compared to the normal handgrip strength group (p < 0.05), and the UCR levels were significantly lower in the low handgrip strength group compared to the normal group (p < 0.001). When grouped by SMI, participants in the low SMI group had significantly lower SUA and UCR levels compared to the normal SMI group (p < 0.050). However, when grouped by the 5‐times sit‐to‐stand test, no significant differences were observed in SUA and UCR levels between the two groups (Table 4).

TABLE 3.

Relationship between SUA, UCR, and various indicators of sarcopenia in males.

	Low handgrip strength (n = 54)	Normal handgrip strength (n = 49)	p	Low SMI (n = 41)	Normal SMI (n = 62)	p	5‐times sit‐to‐stand ≥ 12 s (n = 74)	5‐times sit‐to‐stand < 12 s (n = 29)	p
SUA (μmol/L)	296.91 ± 73.96	331.88 ± 53.36	0.007*	291.53 ± 75.89	328.11 ± 56.47	0.006*	308.51 ± 68.60	326.40 ± 62.03	0.225
UCR	3.43 ± 1.08	3.94 ± 0.73	0.006*	3.28 ± 0.95	3.93 ± 0.88	0.001*	3.60 ± 0.90	3.87 ± 1.08	0.195

Abbreviations: SUA, serum uric acid; UCR, serum uric acid to creatinine ratio.

^* p < 0.05, indicating a statistically significant difference between groups.

TABLE 4.

Relationship between SUA, UCR and various indicators of sarcopenia in female.

	Low handgrip strength (n = 64)	Normal handgrip strength (n = 47)	p	Low SMI (n = 52)	Normal SMI (n = 59)	p	5‐times sit‐to‐stand ≥ 12 s (n = 92)	5‐times sit‐to‐stand < 12 s (n = 19)	p
SUA (μmol/L)	264.33 ± 51.47	288.65 ± 41.73	0.009*	264.88 ± 52.48	283.22 ± 44.19	0.048*	273.95 ± 50.65	277.90 ± 40.32	0.750
UCR	3.99 ± 0.93	4.69 ± 0.88	< 0.001**	4.05 ± 0.97	4.49 ± 0.93	0.015*	4.21 ± 1.00	4.65 ± 0.74	0.074

Abbreviations: SUA, serum uric acid; UCR, serum uric acid to creatinine ratio.

^* p < 0.05, indicating a statistically significant difference between groups.

^** p < 0.001, indicating a highly statistically significant difference between groups.

Subsequently, Spearman correlation analysis was performed separately for SUA and UCR with handgrip strength and SMI in both male and female participants (Table 5). Among male participants, SUA (r = 0.250, p = 0.011) and UCR (r = 0.283, p = 0.004) were positively correlated with handgrip strength, while SUA (r = 0.273, p = 0.005) and UCR (r = 0.349, p < 0.001) were positively correlated with SMI (Figure 1). Among female participants, SUA (r = 0.225, p = 0.018) and UCR (r = 0.338, p < 0.001) were positively correlated with handgrip strength, while SUA (r = 0.221, p = 0.026) and UCR (r = 0.204, p = 0.032) also showed positive correlations with SMI (Figure 2).

TABLE 5.

Spearman correlation analysis for SUA and UCR with handgrip strength and SMI.

	Male				Female
	Handgrip strength (kg)		SMI (kg/m2)		Handgrip strength (kg)		SMI (kg/m2)
	SUA	UCR	SUA	UCR	SUA	UCR	SUA	UCR
r	0.250	0.283	0.273	0.349	0.225	0.338	0.221	0.204
p	0.011*	0.004*	0.005*	< 0.001**	0.018*	< 0.001**	0.026*	0.032*

Abbreviations: SUA, serum uric acid; UCR, serum uric acid to creatinine ratio.

^* p < 0.05, indicating a statistically significant difference between groups.

^** p < 0.001, indicating a highly statistically significant difference between groups.

FIGURE 1.

The correlation between SUA, UCR, and various indicators of sarcopenia in males. (a) The correlation between SUA and handgrip strength in male participants. (b) The correlation between UCR and handgrip strength in male participants. (c) The correlation between SUA and SMI in male participants. (d) The correlation between UCR and SMI in male participants.

FIGURE 2.

The correlation between SUA, UCR, and various indicators of sarcopenia in females. (a) The correlation between SUA and handgrip strength in female participants. (b) The correlation between UCR and handgrip strength in female participants. (c) The correlation between SUA and SMI in female participants. (d) The correlation between UCR and SMI in female participants.

3.4. Multivariate Logistic Regression Analyses of SUA and UCR by Gender

To explore the relationship between SUA, UCR, and sarcopenia in different gender groups, multivariate logistic regression analyses were performed, respectively. The analysis among male participants showed that the correlation of UCR remained statistically significant, with an OR (95% CI) of 0.454 (0.224, 0.920) (p = 0.028), whereas SUA did not show statistical significance after adjusting for factors such as nutritional risk, hypertension prevalence, diabetes prevalence, BMI, AST/ALT, ALB, IP, and HGB (Table 6). The analysis among female participants revealed that the correlation of UCR remained statistically significant, with an OR (95% CI) of 0.519 (0.303, 0.887) (p = 0.017), whereas SUA did not demonstrate statistical significance after adjusting for factors such as nutritional risk, hypertension prevalence, triglycerides, and BMI (Table 7).

TABLE 6.

Multivariate logistic regression analyses of sarcopenia with SUA and UCR in males.

	p	OR (95% CI)		p	OR (95% CI)
UCR	0.028*	0.454 (0.224, 0.920)	SUA (umol/L)	0.180	0.993 (0.984, 1.003)
Nutritional risk	0.178	0.429 (0.125, 1.469)	Nutritional risk	0.378	0.587 (0.180, 1.917)
Hypertension	0.279	2.067 (0.555, 7.699)	Hypertension	0.122	2.761 (0.761, 10.011)
Diabetes mellitus	0.574	1.501 (0.365, 6.171)	Diabetes mellitus	0.601	1.440 (0.368, 5.638)
BMI (kg/m2)	< 0.001**	0.557 (0.411, 0.756)	BMI (kg/m2)	< 0.001**	0.559 (0.412, 0.759)
AST/ALT	0.783	1.165 (0.393, 3.453)	AST/ALT	0.557	1.374 (0.475, 3.977)
ALB (g/L)	0.616	0.953 (0.788, 1.152)	ALB (g/L)	0.593	0.951 (0.790, 1.144)
IP (mmol/L)	0.558	0.218 (0.001, 35.570)	IP (mmol/L)	0.438	0.148 (0.001, 18.594)
HGB (g/L)	0.486	1.014 (0.975, 1.055)	HGB (g/L)	0.567	1.011 (0.973, 1.051)

^* p < 0.05, indicating a statistically significant difference between groups.

^** p < 0.001, indicating a highly statistically significant difference between groups.

TABLE 7.

Multivariate logistic regression analyses of sarcopenia with SUA and UCR in female.

	p	OR (95% CI)		p	OR (95% CI)
UCR	0.017*	0.519 (0.303, 0.887)	SUA (μmol/L)	0.689	0.998 (0.988, 1.008)
Nutritional risk	0.285	1.815 (0.608, 5.418)	Nutritional risk	0.344	1.657 (0.582, 4.723)
Hypertension	0.417	1.532 (0.547, 4.292)	Hypertension	0.345	1.643 (0.586, 4.601)
TG (mmol/L)	0.157	0.637 (0.342, 1.189)	TG (mmol/L)	0.111	0.617 (0.340, 1.117)
BMI (kg/m2)	< 0.001**	0.664 (0.544, 0.809)	BMI (kg/m2)	< 0.001**	0.679 (0.563, 0.819)

^* p < 0.05, indicating a statistically significant difference between groups.

^** p < 0.001, indicating a highly statistically significant difference between groups.

3.5. The ROC of SUA and UCR Levels in Predicting the Presence of Sarcopenia by Gender

To investigate the predictive value of SUA and UCR for sarcopenia, ROC curves were plotted in different gender groups. Among male participants, the AUC of SUA was 0.660 (95% CI 0.545–0.755, p = 0.008), with a cut‐off value of 322.05 mmol/L for SUA, yielding a sensitivity of 72.2% and a specificity of 62.7%. The AUC of UCR was 0.716 (95% CI 0.610–0.823, p < 0.001), with a cut‐off value of 3.15 for UCR, resulting in a sensitivity of 50.0% and a specificity of 86.6%. The sensitivity of SUA combined with UCR in predicting sarcopenia in males was 69.4%, and the specificity was 73.1% (AUC: 0.744, 95% CI: 0.642–0.846, p < 0.001). Among female participants, the progressive significance of SUA (p = 0.065) was not statistically significant. The AUC of UCR was 0.658 (95% CI 0.555–0.762, p = 0.004), with a cut‐off value of 4.12 for UCR, yielding a sensitivity of 53.1% and a specificity of 74.2% (Figure 3).

FIGURE 3.

The ROC of SUA and UCR levels in predicting the presence of sarcopenia. (a) ROC in male participants. (b) ROC in female participants.

4. Discussion

This study revealed that regardless of gender, the levels of SUA and UCR in patients with sarcopenia were significantly lower than those in the non‐sarcopenia group. This indicates that the occurrence of sarcopenia may be associated with lower SUA and UCR levels. There was no statistically significant difference in creatinine levels between the two groups, which is consistent with its nature as an indicator of renal function. The correlation analysis between SUA, UCR, and sarcopenia‐related indicators revealed that in both males and females, SUA and UCR were positively correlated with handgrip strength and SMI, but not with the positive rate of the 5‐times sit‐to‐stand test. Multivariate Logistic regression analysis suggested that in males, after adjusting for factors such as nutritional risk, prevalence of hypertension, prevalence of diabetes, BMI, AST/ALT ratio, ALB, IP, and HGB, the correlation between UCR and sarcopenia diagnosis remained statistically significant, while SUA did not. This indicates that lower UCR may be an independent risk factor for sarcopenia in males, and an increase in UCR may be a protective factor against sarcopenia in males. In the analysis of female participants, after adjusting for factors such as nutritional risk, prevalence of hypertension, triglyceride levels, and BMI, the correlation between UCR and sarcopenia diagnosis remained statistically significant, while SUA did not. This suggests that lower UCR may be an independent risk factor for sarcopenia in females, and an increase in UCR may be a protective factor against sarcopenia in females. However, this study is a small‐sample cross‐sectional study and cannot definitively establish causality. Further large‐sample prospective studies are needed to validate the findings. The ROC curve analysis revealed that both SUA and UCR have certain diagnostic value for sarcopenia in males. SUA showed better sensitivity, while UCR demonstrated better specificity. The combination of both SUA and UCR resulted in an even better AUC value for diagnosing sarcopenia in males. Uric acid is the end product of purine metabolism in the human body. Among them, endogenous purines account for 2/3, while exogenous purines obtained from food account for 1/3 [17]. Under normal physiological conditions, the production and excretion of uric acid in the human body maintain a dynamic balance. The uric acid pool in the human body is approximately 1200 mg, with approximately 750–800 mg of uric acid produced daily and approximately 500–1000 mg excreted daily. One‐third of this excretion occurs through the intestine and biliary tract, while two‐thirds is excreted through the kidneys, maintaining this dynamic balance [18]. Therefore, uric acid levels in patients with renal insufficiency will also increase. Although hyperuricemia has been proven to increase the burden on the heart, kidneys, pancreas, etc., and increase the incidence of metabolic diseases [19, 20, 21, 22]. However, uric acid, as a natural antioxidant in the human body, can scavenge superoxide anions, singlet oxygen, and hydroxyl radicals. At the same time, uric acid can prevent the inactivation of superoxide dismutase (SOD), and therefore, within a certain range, higher levels of uric acid can help improve the body's antioxidant stress capacity [23]. Furthermore, uric acid is also considered a nutritional indicator. A lower blood uric acid level can also reflect a patient's poor nutritional status [24]. Since the SUA is greatly influenced by renal function, current scholars use the renal function‐corrected SUA, known as UCR, to represent a more accurate uric acid level [14]. Given the high proportion of renal insufficiency among elderly patients, the use of UCR may be a more accurate method to assess serum uric acid levels in this population. Multiple studies have indicated that sarcopenia is associated with excessive production of ROS and reactive nitrogen species in muscles [25], antioxidant stress responses can help delay the muscle loss associated with aging. Furthermore, the maintenance of muscle mass requires a delicate balance between protein synthesis and degradation. When this homeostasis is disrupted, with increased degradation and insufficient synthesis, it can lead to a decrease in muscle mass, ultimately resulting in the development of sarcopenia [26, 27, 28]. The decline in muscle mass and muscle function is related to the imbalance in protein synthesis and degradation homeostasis, which is closely related to the nutritional status of the body. This also indicates the connection between sarcopenia and SUA as well as UCR. Previously, a study has shown that among middle‐aged and elderly individuals in western China, higher levels of blood uric acid are associated with greater muscle mass [12]. This finding is consistent with the conclusion of our study, albeit the previous study excluded patients with kidney diseases. The study conducted by Oncel Yoruk et al. investigated elderly patients and also demonstrated that high uric acid has a positive effect on preventing and delaying the development of sarcopenia [29]. In our study, we considered the population with renal insufficiency by incorporating renal function‐corrected SUA, also known as UCR [30], and we also found statistically significant results. In summary, lower levels of SUA and UCR are associated with a higher prevalence of sarcopenia, poorer grip strength, and lower SMI in elderly individuals. SUA and UCR are potential serological markers for sarcopenia in the elderly. Both SUA and UCR have diagnostic value in males, with higher diagnostic power when used in combination. In females, only UCR shows diagnostic value.

The observed gender differences in our results can be attributed to several factors. One reason is the sharp decline in estrogen levels experienced by postmenopausal women, which is not observed in men [31]. Regarding the influence of estrogen on sarcopenia, there are several perspectives. Firstly, estrogen is known to reduce uric acid synthesis and promote uric acid excretion. In postmenopausal women, the decrease in estrogen levels leads to an elevation in baseline uric acid levels, which may not accurately reflect the body's oxidative stress level and nutritional status. Consequently, uric acid may not be as effective in diagnosing sarcopenia in this population [32]. Secondly, the decline in estrogen levels can lead to bone calcium loss and the development of osteoporosis [33], while postmenopausal osteoporosis and sarcopenia have a mutually reinforcing and interactive relationship [34, 35], forming a vicious cycle. Thirdly, the decrease in estrogen levels can lead to an increase in the secretion of inflammatory cytokines [36], such as tumor necrosis factor‐alpha or interleukin‐6 [37, 38]. These inflammatory cytokines can, in turn, increase muscle catabolism. Additionally, estrogen may play a crucial role in stimulating skeletal muscle repair and regeneration, including activating and proliferating satellite cells [39]. The rapid decline in estrogen levels may lead to impairments in muscle repair and regeneration. These factors suggest that the rapid decline in estrogen levels significantly increases the risk of sarcopenia in elderly women, which may weaken the significant association between SUA levels and sarcopenia in this population.

In our study, differences in BMI and nutritional risk were observed between groups for both males and females, and the multivariate logistic regression analysis showed statistical significance of BMI, indicating the correlation between BMI, nutritional risk, and sarcopenia, which is consistent with previous studies [24, 40]. However, due to the small number of obese patients included in the study, the research on sarcopenic obesity was not comprehensive [41], further studies with a larger sample of obese patients are needed to gain a more comprehensive understanding of sarcopenic obesity. In our study, the prevalence of hypertension was lower among patients with sarcopenia, which may be related to reduced muscle mass and impaired vasoconstriction. However, previous studies on the relationship between hypertension and sarcopenia have yielded conflicting results [42, 43], further studies with larger sample sizes and inclusion of more obese individuals are needed to clarify this relationship. It's important to note that our study is cross‐sectional, and the causal relationship between sarcopenia and hypertension remains unclear. Additionally, the statistically significant differences observed in malnutrition risk, albumin, hemoglobin, triglycerides, platelets, and diabetes prevalence in specific gender subgroups require further validation in larger sample sizes.

There are several limitations to our study. Firstly, we don't have further subgroup analysis of sarcopenic obesity patients. Secondly, patient diets were not strictly controlled prior to serum sampling, and uric acid and creatinine levels can be affected by diet, potentially impacting the study results. Lastly, our study was a single‐center, small‐sample, cross‐sectional study; further multi‐center, large‐sample, and prospective studies are needed to validate our findings.

5. Conclusion

Regardless of gender, patients with sarcopenia had lower levels of SUA and UCR compared to those without sarcopenia. In both males and females, higher SUA and UCR were associated with better grip strength and muscle mass, but not with physical function. Low UCR emerged as an independent risk factor for sarcopenia. There are certain gender differences in the diagnostic value of SUA and UCR for sarcopenia in the elderly. In males, both SUA and UCR demonstrate diagnostic value for sarcopenia, with their combination offering even higher diagnostic power. However, in females, only UCR shows certain diagnostic value, while SUA does not. Clinicians should pay attention to SUA and UCR in routine clinical practice to aid in the detection of sarcopenia. During treatment, the use of uric acid‐lowering medications should not be overcorrected, leading to excessively low uric acid levels. Due to the limitations of this study, further research with larger sample sizes is needed to validate the significance of UCR in the diagnosis of sarcopenia.

Author Contributions

Conceptualization, Yi‐Yang Liu, Yan‐Jiao Wang, and You‐Shuo Liu; data curation, Yi‐Yang Liu, Shuang Li, Jing Cai, and Yi Wang; formal analysis, Yi‐Yang Liu, Qi‐Fei Kuang, and Yan‐Jiao Wang; funding acquisition, Yan‐Jiao Wang and You‐Shuo Liu; investigation, Qi‐Fei Kuang, Shuang Li, Qun‐Yan Xiang, Yu‐Qing Ni, Chen Li, and Le Liu; software, Qun‐Yan Xiang, Jing Cai, and Yi Wang; supervision, Chen Li and Le Liu; validation, Qi‐Fei Kuang and Yan‐Jiao Wang; writing – original draft, Yi‐Yang Liu.

Funding

This study was supported by the National Natural Science Foundation of China 82071593.

Ethics Statement

All participants have given informed consent. This study adhered to the principles of the Declaration of Helsinki, and we obtained ethical clearance from the Ethics and Research Committee of the Second Xiangya Hospital of Central South University (LYEC2024‐K0156).

Conflicts of Interest

The authors declare no conflicts of interest.

Data Availability Statement

The original contributions presented in this study are included in the article/Supporting Information. Further inquiries can be directed to the corresponding author(s).