The present study employed a cross-national dual-cohort design, incorporating data from the NHANES from 2011 to 2018 and the clinical database of the Changzhou Third People’s Hospital, China, from 2018 to 2023. The original data set of the US cohort comprised 39,156 participants, derived from four consecutive cycles of the NHANES cross-sectional survey. This study design was approved by the Ethics Review Board of the National Center for Health Statistics (NCHS), with all participants providing written informed consent. The study was deemed exempt from secondary ethical review of the NHANES data by the Ethics Committee of Changzhou Third People’s Hospital, based on the ethical guidelines of the Declaration of Helsinki and the public nature of the NHANES data. The protocol of the Chinese cohort study was formally reviewed and approved by the Ethics Committee of Changzhou Third People’s Hospital. The Chinese cohort data utilized in this study were obtained from outpatient patients undergoing routine follow-up at Changzhou Third People’s Hospital between 2018 and 2023. All participants were in the outpatient routine management phase, except those who had experienced acute hospitalization or critical illness. The Chinese cohort included 10,477 participants who underwent a nutritional assessment, and after screening with uniform exclusion criteria (age< 20 years, pregnancy, missing key data, and non-CKD patients), 827 cases were finally retained for the US cohort, and 1,038 eligible samples were retained for the Chinese cohort ( Figure 1 ).

To assess the state of renal function, the urine albumin-to-creatinine ratio (UACR) and estimated glomerular filtration rate (eGFR) were employed as the core assessment indexes in this study. The eGFR was calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula (21). The diagnosis of CKD was made in strict accordance with international consensus criteria based on a combined assessment of the UACR and the eGFR. Specifically, a UACR of at least 30 mg/g and/or an eGFR of less than 60 mL/min/1.73m² was defined as CKD (9). Patients were classified into five stages of CKD based on disease severity, according to the Kidney Disease Quality Outcome Initiative (K/DOQI) CKD classification. Stage 1: eGFR ≥ 90 mL/min/1.73m²; Stage 2: eGFR 60–89 mL/min/1.73m²; Stage 3: eGFR 30–59 mL/min/1.73m²; Stage 4: eGFR 15–29 mL/min/1.73m²; Stage 5: eGFR< 15 mL/min/1.73m² (22).

The appendicular skeletal muscle mass (ASM) of the extremities was measured using dual-energy X-ray absorptiometry (DXA) in the US cohort and bioelectrical impedance analysis (BIA) in the Chinese cohort, respectively. Standardized assessment was performed by calculating the extremity skeletal muscle mass index (ASMI=ASM/BMI). The diagnostic thresholds for sarcopenia were referenced in the guidelines of the Foundation for the National Institutes of Health (FNIH). Specifically, the ASMI was required to be less than 0.789 for males and less than 0.512 for females to be considered sarcopenia (23).

TG and FPG testing was completed by a professional team after subjects had fasted for at least 8 hours and was measured using a fully automated biochemical analyzer. The TyG index was calculated using the following formula (13):

To control for potential confounders, a multivariate correction model was constructed to include covariates such as gender, age, marital status (cohabitation and solitude), smoking, alcohol consumption, and chronic diseases (diabetes, hypertension, and metabolic syndrome). Diabetes mellitus (DM) was defined as having been diagnosed by a medical professional with an FPG level of ≥126 mg/dL or glycosylated hemoglobin (HbA1c) level of ≥6.5% or treatment with glucose-lowering medication; hypertension was defined as a self-reported history of the disease or use of antihypertensive medication; and metabolic syndrome was diagnosed when participants met at least three of the following five criteria (1): TG levels of no less than 150 mg/dL (2); high-density lipoprotein cholesterol (HDL-c) levels of less than 40 mg/dL (men) or 50 mg/dL (women) (3). FPG levels of 110 mg/dL or more (4); WC of more than 102 cm (men) or 88 cm (women) (5); Systolic blood pressure of more than 130 mmHg or diastolic blood pressure of more than 85 mmHg, or both (24).

Continuous variables were expressed as median (interquartile range), and comparisons between groups were made using the Mann-Whitney U test. Categorical variables were described in terms of frequency and percentage, and differences between groups were assessed using the chi-square test. Multi-model logistic regression was used to analyze the association between the TyG index and sarcopenia. Model 1 was unadjusted for any variables, Model 2 was adjusted for age and gender, and Model 3 was further adjusted for marital status, smoking, alcohol consumption, comorbidity status, and eGFR. The dose-response relationship between the TyG index and sarcopenia was explored using restricted cubic spline (RCS) modeling, and subgroup analyses and interaction tests were performed based on variables such as gender and comorbidity status. Statistical significance was defined as a two-sided P value of less than 0.05, and all analyses were conducted using R 4.4.0, with SPSS 23.0, and data visualization performed using GraphPad Prism 9.0.

In this study, a total of 827 patients with CKD from a US cohort were analyzed, comprising 711 individuals without sarcopenia and 116 patients with sarcopenia. The results demonstrated that patients in the sarcopenia group exhibited a markedly higher proportion of males than those in the non-sarcopenia group (62.93% vs. 40.08%, P< 0.001) and were older (50.00 years vs. 45.00 years, P< 0.001). No significant differences between the two groups were observed in marital status, smoking, or drinking habits (P > 0.05). However, the prevalence of DM (43.10% vs. 29.11%, P=0.003) and metabolic syndrome (54.31% vs. 41.63%, P=0.011) was significantly higher in the sarcopenia group than in the non-sarcopenia group. Furthermore, patients in the sarcopenia group exhibited significantly elevated BMI, WC, FPG, HbA1c, total cholesterol (TC), TG, and uric acid levels compared to those in the non-sarcopenia group. Conversely, the HDL-c levels were diminished (P< 0.05). No significant differences were observed in blood creatinine, blood urea nitrogen (BUN), and eGFR between the two groups (P > 0.05). Notably, the TyG index was significantly higher in the sarcopenia group (P< 0.001) ( Table 1 ).

Additionally, the study analyzed 1,038 patients with CKD in a Chinese cohort, comprising 860 individuals without sarcopenia and 178 with sarcopenia. The results demonstrated that patients in the sarcopenia group exhibited a markedly higher proportion of males than those in the non-sarcopenia group (76.40% vs. 56.16%, P< 0.001) and were significantly older (52.00 years vs. 44.00 years, P< 0.001). Regarding lifestyle habits, the prevalence of smoking was found to be significantly higher in the sarcopenia group than in the non-sarcopenia group (52.25% vs. 42.09%, P=0.013). However, no significant difference was observed in drinking habits (P=0.418). The prevalence of DM (34.83% vs. 24.30%, P=0.004) and metabolic syndrome (53.93% vs. 37.56%, P< 0.001) was significantly higher in the sarcopenia group than in the non-sarcopenia group. Furthermore, the sarcopenia group exhibited significantly elevated BMI, WC, FPG, HbA1c, TC, TG, and uric acid levels compared to the non-sarcopenia group (P< 0.05). Additionally, blood creatinine and BUN levels were significantly higher in the sarcopenia group than in the non-sarcopenia group (P values of 0.029 and 0.004, respectively). However, there was no significant difference in UACR and eGFR. TyG was significantly higher in the sarcopenia group (P< 0.001) ( Table 2 ).

The proportion of males in the Chinese cohort (59.6%) was significantly higher than that in the US cohort (43.3%, P<0.001). Furthermore, Chinese participants were more likely to cohabit (70.7% vs. 56.8%, P<0.001). There was no statistically significant difference in smoking between the two cohorts (P=0.514). However, the prevalence of alcohol consumption was significantly lower in the Chinese cohort than in the US cohort (19.2% vs. 68.8%, P<0.001). The Chinese cohort exhibited a higher prevalence of hypertension (62.1% vs. 44.3%, P< 0.001) and a lower prevalence of diabetes (26.1% vs. 31.1%, P=0.018), while the prevalence of metabolic syndrome remained comparable (P=0.185). Moreover, Chinese participants exhibited significantly lower BMI, WC, HbA1c, TC, TG, and HDL-C levels compared to the US cohort (all P< 0.05), yet higher BUN and uric acid levels (P< 0.001). There were no significant differences between the two cohorts in the prevalence of sarcopenia (P=0.066) or TyG index (P=0.213) ( Supplementary Table S1 ).

The relationship between TyG and sarcopenia was examined using three distinct models in the US cohort. The unadjusted model (Model 1) demonstrated a significant association between TyG and sarcopenia (OR 1.61, 95% CI 1.32-1.97, P< 0.001). After adjustment for gender and age (Model 2), the correlation exhibited a slight decline but remained statistically significant (OR 1.43, 95% CI 1.16-1.77, P< 0.001). Following further adjustment for marital status, smoking, alcohol consumption, hypertension, DM, metabolic syndrome, and eGFR (Model 3), the association between TyG and sarcopenia remained significant (OR 1.49, 95% CI 1.10-2.01, P=0.010). Furthermore, an analysis of TyG quartiles revealed a progressive increase in sarcopenia with elevated TyG levels. In comparison to the lowest TyG quartile, the risk of sarcopenia in the highest quartile was found to be 4.81 times higher (95% CI: 2.41-9.61, P< 0.001), 3.46 times higher (95% CI: 1.70-7.06, P< 0.001), and 4.01 times higher (95% CI: 1.66-9.66, P=0.002), respectively ( Table 3 ).

In the Chinese cohort, the relationship between TyG and sarcopenia in CKD patients was similarly analyzed. The results demonstrated a significant correlation between TyG and sarcopenia (OR 1.77, 95% CI 1.44-2.16, P< 0.001) in the unadjusted model (Model 1). In Model 2, the correlation decreased slightly (OR 1.60, 95% CI 1.30-1.97, P< 0.001) and remained significant (OR 1.62, 95% CI 1.20-2.18, P=0.002) after further adjustment for other confounders (Model 3). Similarly, analysis of TyG quartiles demonstrated that as the level of TyG increased, the risk of sarcopenia also increased. In comparison to the lowest TyG quartile, the risk of sarcopenia in the highest quartile was found to be increased by 4.32-fold (95% CI: 2.50-7.44, P< 0.001), 3.31-fold (95% CI: 1.89-5.80, P< 0.001), and 3.25-fold (95% CI: 1.64-6.46, P< 0.001), respectively. These findings further substantiate the role of TyG levels in predicting the risk of sarcopenia in patients with CKD, with consistent results across diverse geographical populations ( Table 4 ).

In this study, we employed restricted cubic spline fitting to analyze the relationship between TyG and sarcopenia in CKD patients, with assessments conducted separately for the US and Chinese cohorts. To more accurately assess the relationship, we adjusted for potential confounding variables, including gender, age, marital status, smoking, alcohol consumption, hypertension, DM, metabolic syndrome, and eGFR. The results demonstrated that in the US cohort ( Figure 2A ), there was a significant and positive association between TyG levels and sarcopenia, with a p-value of 0.002 and a nonlinear p-value of 0.007. Similarly, in the Chinese cohort ( Figure 2B ), there was a significant and positive association between TyG levels and sarcopenia, with a p-value of less than 0.001 and a nonlinear p-value of 0.023. The critical thresholds were determined to be 9.3 (US) and 9.2 (China), respectively. When the TyG index falls below these thresholds, a significant positive correlation with sarcopenia is indicated. However, beyond these thresholds, the risk growth rate slows down. This pattern is consistent across both cohorts, suggesting a saturation effect in the predictive value of the TyG index for sarcopenia risk.

In the US cohort, after adjusting for potential confounding variables, including gender, age, marital status, smoking and drinking habits, hypertension, DM, metabolic syndrome, and eGFR, the results demonstrated that in the overall CKD population, TyG levels were significantly and positively associated with sarcopenia, with an adjusted odds ratio of 1.49 (95% CI: 1.10, 2.01, P=0.010). Further subgroup analyses revealed that the association between TyG levels and sarcopenia in the different subgroups of gender, smoking, hypertension, DM, and metabolic syndrome exhibited some differences. For instance, the correlation between TyG levels and sarcopenia was more pronounced in the male cohort (OR=1.79, 95% CI: 1.22, 2.64, P=0.003), whereas no notable correlation was observed in the female cohort (OR=0.98, 95% CI: 0.57, 1.70, P=0.956). Furthermore, the correlation between TyG levels and sarcopenia was more pronounced in non-smokers, those without hypertension, those without diabetes, and those without metabolic syndrome (P< 0.05). Notably, no significant interactions were identified in any subgroup analyses, indicating that the observed association between TyG and sarcopenia remained consistent across all subgroups (P for interaction > 0.05) ( Figure 3 ).

In the Chinese cohort, the results of the subgroup analyses further demonstrated this association’s variability across populations after adjusting for various potential confounding variables. In the smoking and hypertension subgroups, TyG levels were significantly associated with sarcopenia regardless of whether or not the subjects smoked and irrespective of whether or not they had hypertension (P< 0.05). Furthermore, no significant interactions were found between the groups (P for interaction > 0.05). In both the gender and the drinking subgroups, TyG levels were significantly associated with sarcopenia in both males and non-drinkers (P< 0.05). Conversely, no significant associations were observed in females and the drinking subgroups. However, no significant interactions were found between groups (P for interaction > 0.05). Notably, significant interactions were observed in the subgroup analyses of patients with DM and metabolic syndrome (P for interaction< 0.05). The association between TyG levels and sarcopenia was more pronounced in patients without DM and in patients without metabolic syndrome (P< 0.001) ( Figure 4 ).