Original ResearchRapid Weight Change Over Time Is a Risk Factor for Adverse Outcomes in Patients With Predialysis Chronic Kidney Disease: A Prospective Cohort Study
Introduction
Chronic kidney disease (CKD) is a disease with heavy socioeconomic burden and its prevalence is increasing worldwide.1, 2, 3, 4 The clinical importance of CKD is the risk of progression to end-stage renal disease (ESRD) and additionally, cardiovascular morbidity and mortality is increased.5, 6, 7 Therefore, identifying risk factors for adverse outcomes is important in patient with CKD to slow the progression to ESRD and prevent cardiovascular disease (CVD).
The association of nutritional status with adverse outcomes in patients with CKD has been well-studied, and body mass index (BMI) is one of the commonly used nutritional indicators.8 Previous studies have shown that being overweight and obese is correlated with both CVD morbidity and the incidence/progression of CKD.9, 10, 11, 12, 13, 14, 15, 16, 17 High blood pressure, dyslipidemia, and insulin resistance related to obesity affects outcomes in patients with CKD.13 However, being underweight is another important risk factor for adverse outcomes in patients with CKD.18,19 Since being underweight is a diagnostic indicator of protein energy wasting in patients with CKD, monitoring weight and maintaining optimal nutritional status are recommended.20 However, there are some controversies as to whether a single measurement of BMI is predictive of adverse outcomes in all patients with CKD.21, 22, 23, 24, 25 A one-time BMI measurement would give information only on the cross-sectional status of a subject and cannot provide information about changes in body composition or volume status. Therefore, information about longitudinal body weight changes over time would provide additional knowledge on nutritional status.
However, few studies have reported the effects of longitudinal weight changes on outcomes in patients with CKD. Ryu et al. showed that both rapid weight gain and loss were associated with an increased risk of developing CKD in healthy men.26 A recent study showed that >5% annual weight loss after estimated glomerular filtration rates (eGFRs) reached 35 mL/min/1.73 m2 was associated with a higher risk of mortality after progression to ESRD.27 However, it has not been determined whether longitudinal changes in weight affect the risk of ESRD occurrence or CVD in patients with CKD.
Therefore, in this study, we first analyzed longitudinal patterns in weight change according to progression of renal disease in a prospective predialysis cohort. Then, we evaluated the effects of longitudinal weight changes on adverse outcomes by examining the incidence of ESRD and composite of CVD and all-cause mortality.
Section snippets
Study Subjects
This is a study from a prospective cohort of patients with predialysis CKD in Korea, the KoreaN cohort Study for Outcomes in Patients With Chronic Kidney Disease (KNOW-CKD). The KNOW-CKD cohort is a nationwide, prospective cohort study that enrolled adult, predialysis patients between 2011 and 2016.28 Among the 2,238 subjects enrolled in the cohort study, we excluded 59 patients without further follow-up, 16 without baseline weight measurement, and 141 without follow-up weight measurement.
Results
A total of 2,022 subjects were included in the analysis (Table 1). The mean age was 53.7 ± 12.1 and 39.2% were female. The mean BMI was 24.5 ± 3.4 kg/m2 and the mean eGFR was 53.7 ± 30.2 mL/min/1.73 m2. There were 6% and 32.9% with pre-existing CVD and diabetes at study entry, respectively.
Figure 1 shows the trajectory of longitudinal body weight changes according to eGFR decline. Overall weight did not change significantly until eGFRCr reached 30 mL/min/1.73 m2 (P = .137). However, when eGFRCr
Discussion
To the best of our knowledge, this is the first report suggesting that rapid weight change over time, either weight loss or gain beyond a certain range, is independently associated with increased risk of ESRD and composite of CVD and mortality in patients with CKD. We generated weight trajectory patterns throughout all stages of CKD (G1-G5) using data from the prospective cohort over the course of follow-up. In overall population, weight did not change significantly in patients with CKD stage
Practical Application
In this study, we have shown that there are two different patterns of weight change (gain and loss) along with CKD progression. We have also reported that both rapid weight gain and loss are independent risk factors for adverse outcomes (progression to ESRD, and the composite outcome of CVD and all-cause death) and there was a U shaped-correlation between the degree of longitudinal weight change and the risk of adverse outcomes. The result of this study clearly showed that regular monitoring of
Acknowledgments
We would like to thank the KNOW-CKD investigators, clinical research coordinators and the patients included in the study.
Credit Authorship Contribution Statement
Hyunjin Ryu: Conceptualization, Methodology, Formal analysis, Writing - original draft, Visualization, Project administration. Yeji Hong: Methodology, Formal analysis, Software, Data curation. Eunjeong Kang: Conceptualization, Methodology, Writing - review & editing. Minjung Kang: Methodology, Data curation, Writing - review & editing. Jayoun Kim: Methodology, Software, Formal analysis. Yun Kyu Oh: Conceptualization, Resources, Data curation, Project administration, Writing - review & editing.
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Financial Disclosure: The authors declare that they have no relevant financial interests.
Support: This work was supported by the Research Program funded by the Korea Disease Control and Prevention Agency (2011E3300300, 2012E3301100, 2013E3301600, 2013E3301601, 2013E3301602, 2016E3300200, 2016E3300201, 2016E3300202, 2019E320100, 2019E320101, 2019E320102).