End-stage renal disease (ESRD) is defined as a glomerular filtration rate (GFR) of less than 15 mL/min/1.73 m², requiring kidney transplantation or hemodialysis [1]. The estimated incidence of ESRD in the United States increased from 117,162 in 2013 [2] to 124,111 in 2015 [3]. In Korea, approximately 56,396 patients (1,113.6 patients per million population) were estimated to have ESRD at the end of 2009 [4], and 70,211 patients (1,353.3 patients per million population) were estimated to have ESRD at the end of 2012 [5]. ESRD is associated with increased comorbidities, such as hypertension, cardiovascular disease (CVD), diabetes mellitus (DM), and higher mortality [6,7]. Additionally, patients with ESRD require ongoing treatment, including dialysis or kidney transplantation, creating a substantial socioeconomic burden for individuals and society alike [6,7].

Known risk factors for ESRD include smoking, exposure to nephrotoxins, socioeconomic status, acute kidney injury, hypertension, DM, and obesity [8–11]. Several studies have examined the relationship between obesity and ESRD, showing that obesity is an independent risk factor for ESRD and chronic kidney disease (CKD) [12–15]. However, other studies have reported inverse associations between obesity and ESRD [16–19], suggesting that a lower body mass index (BMI) could increase both the incidence of ESRD and mortality among ESRD patients [19,20]. Thus, conventional obesity parameters such as BMI have yielded controversial results regarding their relationship with ESRD incidence. Furthermore, studies have examined the relationship between changes in body weight and GFR, but the results have been inconsistent due to variations in the methodologies used to measure kidney function [21,22]. Recently, weight fluctuation—beyond simple weight change—has been investigated in relation to cardiovascular outcomes, demonstrating that greater weight fluctuation increases cardiovascular events and mortality [23,24]. However, to date, no studies have directly explored the relationship between weight fluctuation and the incidence of ESRD in the Korean population. Thus, this study aimed to examine the association between weight fluctuation and ESRD incidence using health checkup data from the Korean National Health Insurance Service (NHIS).

The general characteristics of subjects are summarized in Table 1. As BMI increased, weight, WC, glucose levels, SBP, DBP, total cholesterol, and triglyceride levels all significantly increased (all P<0.001). Additionally, the prevalence of DM, hypertension, dyslipidemia, and CKD increased significantly with higher BMI (all P<0.001). The eGFR decreased as BMI increased, up to a BMI of 30 kg/m², after which the eGFR slightly increased.

Table 2 shows the HRs for ESRD according to the five BMI categories and quartiles of weight ARV. After adjusting for all covariates, HRs for ESRD showed a decreasing trend with increasing BMI, exhibiting a J-shaped pattern. Regarding weight ARV quartiles, the HRs for ESRD increased progressively from the lowest quartile (Q1, reference) to the highest quartile (Q4), with HRs of 1.086, 1.132, and 1.420 for ARV Q2, Q3, and Q4, respectively. However, a statistically significant increase in HR for ESRD was observed only in the ARV Q4 group.

Fig. 1 illustrates the cumulative incidence probability of ESRD according to the quartiles of weight ARV in the overall population, as well as separately for men, women, and age groups. Compared to ARV Q1, Q2, and Q3, subjects in ARV Q4 consistently demonstrated the highest cumulative incidence probability of ESRD. This increased risk in ARV Q4 was evident in both men and women. Furthermore, ARV Q4 exhibited the highest probability of ESRD across both age groups (<65 and ≥65 years) compared to ARV Q1 to Q3.

Table 3 presents the HRs for ESRD in ARV Q4 compared to ARV Q1 to Q3, stratified by sex, age, and weight change status. Men exhibited a statistically significant increased risk of ESRD in ARV Q4 (HR, 1.372). Subjects aged <65 and ≥65 years both displayed increased ESRD risk in ARV Q4, consistent with Fig. 1 (HR of 1.337 and 1.361, respectively). Regarding weight change groups, individuals with sustained or increased weight showed significantly increased HRs for ESRD in ARV Q4 (HR of 1.222 and 1.490, respectively), whereas the weight-loss group did not show this association.

In this study, baseline BMI and body weight variability were associated with the risk of ESRD. The overall HR for ESRD decreased as BMI increased. However, weight fluctuation exhibited a J-shaped relationship with ESRD risk, with the highest weight fluctuation (ARV Q4) having a 1.42-fold increased incidence of ESRD after adjusting for confounding factors. This increased HR for ESRD in the highest weight fluctuation group (ARV Q4) was also significant in men, as well as in groups with sustained or increased weight, but not in the weight-loss group.

Several previous studies have examined the relationship between body weight or BMI and ESRD, yielding conflicting results [19,31–33]. In a study of a Chinese urban population, obesity parameters, including BMI, WC, and waist to height ratio, positively correlated with CKD risk [31]. Additionally, two US studies reported a positive association between BMI and ESRD [13,34]. Similarly, a Japanese study found that increased BMI correlated with decreased eGFR [32]. A prospective study in China also found a J-shaped association between BMI and ESRD risk [33]. Conversely, another US population study found that higher BMI was associated with a lower ESRD risk, consistent with the "obesity paradox." Furthermore, the REGARDS (Reasons for Geographic and Racial Differences in Stroke) study found no significant association between BMI and ESRD incidence after adjusting for WC [19,35].

Recent studies have investigated new predictive parameters for chronic diseases, including ESRD, to reduce comorbidities and related mortality. Several studies examined weight change or fluctuation in relation to health outcomes rather than BMI or weight at a single point. The Framingham population study showed associations between body weight fluctuation and increased all-cause mortality, coronary heart disease mortality, and morbidity [36]. Another study demonstrated that body weight fluctuation correlated with higher risks of coronary and cardiovascular events among patients with preexisting coronary heart disease [23]. In relation to kidney disease, weight gain increased the risk of CKD even among healthy Korean men with normal BMI [37].

The mechanisms underlying the associations between BMI, body weight variability, and ESRD incidence remain unclear, but several hypotheses can be considered. From a nutritional perspective, although patients with baseline chronic liver disease or ESRD were excluded and heart failure was adjusted, low BMI may indicate malnutrition due to reduced food intake or impaired protein-energy metabolism linked to unstable health conditions [38,39]. Another explanation is that low body weight does not necessarily indicate good health in Asian populations; Asians tend to have higher body fat percentages at a given BMI compared to Western populations [40,41], making them more susceptible to type 2 DM and hypertension even at lower BMIs [40]. Regarding weight variability and ESRD risk, direct mechanisms remain uncertain, but several studies indicate adverse effects on cardiovascular health, new-onset diabetes, and all-cause mortality [23,24,36], suggesting weight fluctuation negatively impacts general health. Therefore, since cardiovascular diseases and diabetes are known risk factors for ESRD, greater weight variability could increase ESRD risk. The observed sex difference in ESRD incidence with weight fluctuation might be attributed to differences in fat distribution, as men typically accumulate more central fat associated with metabolic complications compared to women’s peripheral fat distribution [42]. Further studies are required to elucidate the mechanism underlying the relationship between weight fluctuation and incidence of ESRD.