Dear Editor,

Chronic kidney disease (CKD) is often asymptomatic even in the advanced stages; therefore, screening tests for CKD should be performed in an asymptomatic population to detect the disease at an early stage [1]. As directly measuring the glomerular filtration rate (GFR) in clinical settings is inefficient, an estimated glomerular filtration rate (eGFR) based on serum creatinine (SCr) calculated by the Chronic Kidney Disease Epidemiology Collaboration equation (hereinafter referred to as the CKD-EPI-eGFR) is widely used [2]. However, as a muscle metabolite, SCr is affected by muscle mass [2]. The CKD-EPI-eGFR corrects the SCr value using surrogate variables (sex, age, and race) rather than muscle mass [2]. However, these variables do not reflect the diet and physiological conditions, which affect muscle mass; therefore, the CKD-EPI-eGFR may be inaccurate in sarcopenic and muscular populations [3].

Skeletal muscle mass (SMM) is widely measured using bioelectrical impedance analysis (BIA) because it is a simple, inexpensive, and fast approach [4]. We aimed to determine the difference between the stage determined by the CKD-EPI-eGFR and the stage determined by the measured glomerular filtration rate (mGFR) when the SMM measured by BIA during a health checkup was outside the standard range. If the two stages do not match, CKD diagnosis may be delayed or unnecessary management may be conducted.

Between October 2021 and December 2022, 284 patients were admitted to Asan Medical Center (Seoul, Korea), and ^99mTc-diethylenetriamine pentaacetic acid was used to measure GFR (hereinafter referred to as mGFR). Among them, 152 healthy Korean potential kidney donors agreed to participate. Participants’ height, weight, SMM, SCr, CKD-EPI-eGFR, and mGFR were recorded (Table 1). The SMM was measured using an InBody770 analyzer (Inbody Co., Seoul, Korea). InBody770 calculates the standard range of SMM and judges muscularity as below, within, or above the standard based on its undisclosed algorithm. The mGFR value was considered the true GFR. As all participants were potential kidney donors, none had an mGFR <60 mL/min/1.73 m². SCr levels were measured using the rate-blanked and compensated Jaffe method. This study was approved by the Institutional Review Board of the Asan Medical Center (approval number: 2021-1813) and complied with the Declaration of Helsinki. Written informed consent was obtained from all participants.

Participants were divided by kidney function based on the CKD-EPI-eGFR and mGFR values using the same classification as in our previous study (stage 1, ≥90 mL/min/1.73 m²; stage 2, 60–89 mL/min/1.73 m²) [5]. When the CKD-EPI-eGFR and mGFR stages were the same, they were considered matched; otherwise, they were considered unmatched. The CKD-EPI-eGFR matched with the mGFR for 105 out of the 152 participants. The SMM was within the standard range (InBody770) for 108 participants. The CKD-EPI-eGFR staging results according to the SMM standard range for each group are summarized in Table 2. The proportions of CKD-EPI-eGFR and mGFR stage matching were 74.1% in the group with SMM within the standard range and 56.8% in the group with SMM outside the standard range (P=0.037).

Because age, sex, and race do not completely replace muscle mass, muscle mass should be considered in the evaluation of eGFR [6]. In a study of CKD stages 3–5, Zhou, et al. [7] reported that appendicular muscle mass measured using dual-energy X-ray absorptiometry (DEXA) showed a significant positive correlation with the GFR. Gunnarsson, et al. [8] reported a negative correlation between lean body mass measured by DEXA and eGFR in a study of community residents, although the correlation was not significant. Although DEXA is the gold standard method for measuring muscle mass, it is expensive and cumbersome, making its routine use during health checkups difficult [9]. As InBody770 is widely available in health-checkup and fitness centers in Korea, and there are reports that BIA is highly correlated with DEXA [4, 9], it may be helpful to use BIA to measure SMM in routine clinical settings. We observed no significant difference in SMM (P=0.215; Table 1) between the kidney function groups; however, SMM/SCr and SCr showed significant differences (both P<0.05; Table 1). In addition, the CKD-EPI-eGFR tended to overestimate mGFR in participants whose SMM was below the standard, compared to that in participants whose SMM was within or above standard (35.0% vs. 18.2%, P=0.082; data not shown), suggesting that the CKD-EPI-eGFR does not accurately reflect actual kidney status in patients with low muscle mass. As visual evaluation of muscle health in routine clinical practice is difficult, inappropriate staging is likely to occur when using the CKD-EPI-eGFR without SMM measurements. Therefore, when staging CKD, it is desirable to consider SMM, if possible.

In conclusion, care should be taken when interpreting the CKD-EPI-eGFR when the SMM is outside the standard range. Additional testing is recommended, as there is a possibility that the stages of the actual GFR and CKD-EPI-eGFR are different when the SMM is out of the standard range.