Rapid Weight Change Over Time Is a Risk Factor for Adverse Outcomes in Patients With Predialysis Chronic Kidney Disease: A Prospective Cohort Study

Objective

Both obesity and being underweight are risk factors for adverse outcomes in chronic kidney disease (CKD) patients. However, the effects of longitudinal weight changes on patients with predialysis CKD have not yet been studied. In this study, we analyzed the effects of weight change over time on the adverse outcomes in predialysis CKD population.

Methods

Longitudinal data from a multicenter prospective cohort study (KNOW-CKD) were analyzed. In a total of 2,022 patients, the percent weight change per year were calculated using regression analysis and the study subjects were classified into five categories: group 1, ≤ −5%/year; group 2, −5< to ≤ −2.5%/year; group 3, −2.5< to <2.5%/year; group 4, 2.5≤ < 5%/year; and group 5, ≥5%/year. The incidences of end-stage renal disease (ESRD) and the composite outcome of cardiovascular disease (CVD) and death were calculated in each group and compared to group 3 as reference.

Results

During a median 4.4 years of follow-up, 414 ESRD, and 188 composite of CVD and mortality events occurred. Both weight gain and loss were independent risk factors for adverse outcomes. There was a U-shaped correlation between the degree of longitudinal weight change and ESRD (hazard ratio 3.61, 2.15, 1.86 and 3.66, for group 1, 2, 4 and 5, respectively) and composite of CVD and death (hazard ratio 2.92, 2.15, 1.73 and 2.54, respectively), when compared to the reference group 3. The U-shape correlation was most prominent in the subgroup of estimated glomerular filtration rate <45 mL/min/1.73 m².

Conclusion

Both rapid weight gain and weight loss are associated with high risk of adverse outcomes, particularly in the advanced CKD.

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.