The decreased glomerular filtration rate (GFR) is a characteristic of chronic kidney disease (CKD) and is associated with clinical prognosis such as metabolic disease and cardiovascular mortality [1,2]. Recently, the prevalence of CKD has been increasing due to the high numbers of individuals with obesity, hypertension (HTN), and diabetes mellitus (DM), placing a financial burden on the public economy [3,4]. Common health conditions related to CKD include high blood pressure (BP), malnutrition, and heart and vessel diseases. In addition, CKD is frequently associated with adverse changes to body composition and musculoskeletal health. Protein-energy or muscle wasting syndrome that appears to be an accelerated form of sarcopenia is also one of the conditions related to CKD [5]. Several previous studies have suggested that there might be an association between sarcopenia and kidney dyfunction [6-8].

Sarcopenia, a term proposed by Rosenberg [9] in 1989, is a syndrome characterized by the progressive loss of skeletal muscle mass and strength with a risk of adverse outcomes such as physical disability, poor quality of life, and mortality [10]. In patients with sarcopenia, the loss of muscle tissue is accompanied by infiltration with fat and connective tissue, a condition known as myosteatosis in which sarcopenia is combined with obesity, so-called sarcopenic obesity (SO), causing chronic inflammation and catabolic cytokine production [11]. Sarcopenia and obesity share several pathophysiological mechanisms and may potentiate each other. Patients with SO have a higher risk of insulin resistance and metabolic syndrome than those with obesity or sarcopenia alone [12]. Therefore, populations that have both obesity and sarcopenia should be considered. However, few studies have been conducted to evaluate the relationship between SO and CKD.

An aging population is an important concern around the world. The elderly population in South Korea has been increasing, and more than 30% of Korean women are older than 50 years, which is the mean age of menopause. Several studies have suggested that menopause is associated with increased visceral fat mass and decreased skeletal muscle mass because of the natural decline in estrogen [13-15].

In this epidemiological study, we examined the association between SO and decreased GFR after adjusting for multiple confounding variables in a representative sample of the postmenopausal Korean women using data from the Korea National Health and Nutrition Examination Surveys (KNHANES).

This study aimed to examine the association between SO and kidney function decline in postmenopausal Korean women based on data from the KNHANES. In our study, the SO group was associated with independently decreased eGFR, even after adjusting for the confounding variables. These results suggest that postmenopausal women with SO had a higher risk of CKD than those with normal BMI and SMI. However, obesity or sarcopenia alone were not significantly associated with increased CKD risk.

Body composition of fat mass and muscle mass is affected by age, ethnicity, exercise, external factors such as nutrition, and several chronic conditions such as CKD, DM, and cardiovascular disease. Obesity, defined as excess adiposity, is related to a risk factor of CKD and is highly prevalent in patients with CKD. Sarcopenia, defined as low muscle mass, is common among the elderly and patients with chronic wasting disease [19]. Previous studies have suggested an association between body composition and kidney function. Foley et al. [7] reported that sarcopenia is common in community-dwelling adults with CKD in the United States. Furthermore, Zhou et al. [20] found that loss of appendicular skeletal muscle was significantly related to GFR decline. In contrast, the present study found that there was no significant association between decreased eGFR and sarcopenia or obesity. This controversial finding may be explained by different population characteristics, such as sex and ethnic differences. It is possible that women are less affected by sarcopenia relating to CKD than men in the Korean population. Moon et al. [8] suggested that sarcopenia is associated with the stage of CKD in men but not women in Korean adults. Huh et al. [21] reported that the peak muscle mass was reached at 40–59 years of age in Korean women, while it was reached at 20–39 years of age in Korean men because of the lack of physical activity and the changing body image among young Korean women. In addition, Jang et al. [22] indicated that obesity showed no clear association with CKD in the Korean population, whereas a number of studies in the United States and Iran have indicated that obesity is associated with CKD. Moreover, BMI cannot be used to accurately assess the fat distribution in Asians, who have a relatively higher proportion of body fat than other ethnic groups [23,24]. Shankar et al. [25] suggest that among Asians, there is an association in BMI and kidney disease among men, whereas among women, this association either appeared to be absent or of very low magnitude if present. Therefore, CKD risk cannot be associated with obesity based on body weight only; further evaluations concerning the appropriate index to measure obesity are required for Asian people in future studies.

Several possible mechanisms could account for the relationship between SO and decreased kidney function. Sarcopenia often coexists with an increased fat mass. SO is defined by the combination of sarcopenia and fat deposition, which refers to muscle loss associated with pathological accumulation of adipose tissue. This condition may be associated with the cumulative risk because of the double metabolic burden due to low muscle mass (sarcopenia) and high fat mass (obesity). The clinical outcome of sarcopenic obese patients with chronic diseases is worse than that of obese patients with normal muscle mass. Obesity can influence muscle strength due to lipid infiltration in muscle tissues, impairing the incorporation of amino acids and reducing the synthesis of muscle proteins [26]. Moreover, an increase in visceral fat may lead to accelerated secretion of pro-inflammatory adipokines that further promote metabolic abnormalities, insulin resistance, and systemic inflammation as well as potentially having a direct catabolic effect on muscle. In other words, muscle loss is not isolated, but is accompanied by an increase in fat mass. This mechanism leads to a vicious cycle between muscle loss and fat gain [27,28]. The combined effect of obesity and muscle mass is related to accelerated functional decline and higher risk of diseases and mortality. Risk for frailty and disability in obese subjects with low muscle mass has been reported to be significantly higher than that observed in non-obese counterparts with similar muscle alterations. This could appear as contradictory to the socalled “obesity paradox,” but it means that obesity does not protect from chronic disease-related mortality when it is associated with sarcopenia. Indeed low muscle mass is emerging as a negative prognostic factor associated with higher morbidity and mortality in obese patients with chronic diseases [29,30]. The combination of sarcopenia and obesity may potentiate each other to determine clinical adverse consequences in the elderly [31]. Therefore, we suggest that obesity, when it was accompanied by sarcopenia, might increase the risk of decreased renal function. However, it is often under-recognized whether SO is associated with kidney dysfunction. Thus, this nationally representative cross-sectional study explored the effects of obesity and sarcopenia on the renal function. We confirmed that SO is closely related to an increased CKD risk among postmenopausal Korean women.

This study also found that SO is associated with several comorbidities (dyslipidemia, HTN, DM, and myocardial infarction/angina pectoris), metabolic measurements (fasting glucose, HOMA-IR, triglyceride, BP), and inflammatory markers (white blood cell, vitamin D). Furthermore, the coexistence of obesity and sarcopenia may have had an effect on the metabolic and inflammatory conditions in our analysis.

This study has several limitations. First, because of the cross-sectional nature of the study, it is impossible to evaluate the cause-effect relationships among variables. Second, the standard definition for sarcopenia and SO is unclear internationally. The European Working Group on Sarcopenia in Older People (EWGSOP) defined sarcopenia as ASM/height² for 2SD below the mean of young adults. However, in the Korean population, the height-adjusted definition was observed to underestimate the prevalence of sarcopenia and SO, and the weight-adjusted definition was more closely correlated with metabolic factors compared to the height-adjusted definition. The weight-adjusted definition might be better for defining sarcopenic status in Korean individuals [18]. In addition, we did not evaluate muscle strength and physical performance for the assessment of sarcopenia, which was described by the EWGSOP, because the information of muscle function was not available. Third, we did not exclude postmenopausal women who were undergoing hormone replacement therapy or taking oral contraceptives. Forth, because the sample size of premenopausal women with decreased eGFR was small, we did not analyze differences in eGFR between pre- and postmenopausal women in this study. In addition, it was difficult to confirm the effects of estrogen levels on body composition because sex hormones were not measured. Finally, we used the CKD-EPI equation to estimate eGFR. The use of a creatinine-based eGFR equation would result in high eGFR in patients with sarcopenia, because serum creatinine is influenced by muscle mass. The cystatin-C-based eGFR formula may be more accurate than the creatinine-based eGFR formula. Despite these limitations, this study showed strong evidence for a close relationship between SO and decreased eGFR in postmenopausal women after adjusting for confounders.

In conclusion, the present study demonstrated that SO was independently associated with decreased eGFR among postmenopausal Korean women. Additionally, there was no significant association between decreased eGFR and sarcopenia or obesity. Further prospective studies with a large cohort and with adjustment for several factors related to kidney function are needed for assessing the relationship between SO and CKD. Furthermore, public health care and interventions are required to prevent and treat SO and CKD in postmenopausal women.