Reduced risk for chronic kidney disease after recovery from metabolic syndrome: A nationwide population-based study

Abstract

Background: Metabolic syndrome (MetS) is linked to various chronic comorbidities, including chronic kidney disease (CKD). However, few large studies have addressed whether recovery from MetS is associated with reduction in the risks of such comorbidities.

Methods: This nationwide population-based study in Korea screened 10,664,268 people who received national health screening ≥ 3 times between 2012 and 2016. Those with a history of major cardiovascular events or preexisting CKD were excluded. We classified study groups into four, according to the course of MetS state, as defined by the harmonizing criteria. The main study outcome was incidental CKD (estimated glomerular filtration rate < 60 mL/min/1.73 m² which was persistent until the last health exams). The study outcomes were investigated using multivariable logistic regression analysis, which was adjusted for clinical variables and the previous severity of MetS.

Results: Four study groups included 6,315,301 subjects: 4,537,869 people without MetS, 1,034,605 with chronic MetS, 438,287 who developed MetS, and 304,540 who recovered from preexisting MetS. Those who developed MetS demonstrated higher risk of CKD (adjusted odds ratio [OR], 1.26 [1.23-1.29]) than did those who did not develop MetS. In contrast, MetS-recovery was associated with decreased risk of CKD (adjusted OR, 0.84 [0.82-0.86]) than that in people with chronic MetS. Among the MetS components, change in hypertension was associated with the largest difference in CKD risk.

Conclusion: Reducing or preventing MetS may reduce the burden of CKD on a population-scale. Clinicians should consider the clinical importance of altering MetS status for risk of CKD.

Keywords: Chronic kidney diseases; Diabetes mellitus; Dyslipidemia; Hypertension; Metabolic syndrome; Obesity.

Figure 1. Study population criteria and representative scenarios.

The diagram shows the process of study population selection. Below is the most common scenario of the study groups among five national health examinations included in the study. The black squares (MetS+) indicate the MetS-present state, while the gray rounds (MetS-) indicate the MetS-absence state. The majority of the study subjects received three health examinations biennially. Therefore, the inclusion date (indicated with the triangle) was the second health examination for them. The detailed method to define each subgroup is described in the main text. MACE, major adverse cardiovascular event; MetS, metabolic syndrome.

Figure 2. Possible exclusion scenarios.

Above, the figure demonstrates the graphical description for the time-windows when information was collected. In the MetS-developed and MetS-recovery groups, the inclusion date was the date of the health examination when MetS developed or recovered. For the MetS-free and MetS-chronic groups, the date of confirmation of consistency, or the second examination date, was the inclusion date. The outcomes were assessed during later exams. Below, the figure demonstrates several possible scenarios of exclusion, as follows: 1) those who had fewer than three health examinations; 2) those with transient changes in their MetS statuses; 3) cases with fluctuating changes; 4) cases with alterations in MetS statuses at the last exam were excluded, because designating the baseline at the time of change would not secure the persistency of the change during the follow-up period. CKD, chronic kidney disease; MetS, metabolic syndrome.

Figure 3. Risk of incidental chronic kidney disease (CKD) and albuminuria in the study groups.

The y-axes indicate the adjusted odds ratios, and the x-axes indicate the study groups. The vertical lines indicate the confidence intervals. Model 1 was adjusted for age, sex, baseline estimated glomerular filtration rate, aspartate aminotransferase/alanine aminotransferase, hemoglobin and the presence of dipstick albuminuria. In model 2, the presence of low-income status was added to the multivariable model 1. In model 3, the baseline Charlson comorbidity index scores and body mass index were added to multivariable model 2. MetS, metabolic syndrome; OR, odds ratio.

Figure 4. Changes in metabolic syndrome (MetS) components and their associations with the risks of the study outcomes.

Comparisons were performed between the MetS-recovery vs. MetS-chronic groups and between the MetS-developed vs. MetS-free groups. We analyzed whether the change in each component, which persisted until the last health exam, had a different risk on the study outcomes compared to those who maintained states. The y-axes indicate the adjusted odds ratios (ORs) in log 2 scale. The vertical lines indicate the confidence intervals. Multivariable analysis was adjusted with the following variables at the inclusion date: age, sex, low-income status, body mass index, and baseline laboratory parameters (including estimated glomerular filtration rate, aspartate aminotransferase/alanine aminotransferase, hemoglobin), and the presence of dipstick albuminuria. BP, blood pressure; CKD, chronic kidney disease; HDL, high-density lipoprotein; IFG, impaired fasting glucose; Tg, triglycerides; WC, waist circumference.