In our study, hypertension, hyperglycemia, hyperuricemia and metabolic syndrome are significantly associated with CKD in a middle-aged and elderly population in Taiwan. In several studies among different countries and races, the metabolic syndrome has been disclosed as a risk factor for developing CKD [16–20]. In Japan, Tozawa et al followed 6,371 subjects without CKD or diabetes mellitus for a 5-year period and found that the relative risk of developing CKD was 1.86 (95% CI: 1.43–2.41, p < 0.0001) in subjects with metabolic syndrome after adjusting for age, sex, current cigarette smoking and alcohol drinking habits [21]. In the United States, Kurella et al enrolled 10,096 nondiabetic participants with 9 years follow-up, also revealing that metabolic syndrome was independently associated with an increased risk for incident CKD in nondiabetic adults; the OR of incident CKD among participants with the metabolic syndrome was 1.24 (95% CI, 1.01 to 1.51) after adjusting for the subsequent development of diabetes and hypertension [22]. In the present study, metabolic syndrome also serves as an independent risk factor for the development of CKD (yes versus no, OR = 2.48, 95% CI: 1.40–4.40) in a middle-aged and elderly population in Taiwan after adjusting for age, sex, smoking, physical exercise, BMI categories, ALT, and uric acid.
Each component of metabolic syndrome can cause renal damage; however, the components may not contribute equally to the risk of developing CKD [17, 23, 24]. Many studies have further reported the gradient associations between CKD risk and the number of components of metabolic syndrome [21, 22, 24–26]. The multiple mechanisms of renal damage caused by each metabolic syndrome component and their interactions with each other are not yet thoroughly understood. In the present study, elevated blood pressure and hyperglycemia served as independent risk factors for CKD, while other components did not reach statistical significance after adjusting for confounding factors.
High-normal BP is significantly associated with microalbuminuria when compared with optimal BP, and the increase in urinary protein causes injury to tubular cells, leading to interstitial inflammation and fibrosis [27, 28]. Previous studies have also revealed that elevated blood pressure, as a component of metabolic syndrome, is an independent risk factor for the development of CKD. Cao et al. [29] enrolled 11274 subjects and found CKD risk was significantly greater (OR, 1.30; 95% CI: 1.03–1.63) in males with high-normal blood pressure than in those with optimal blood pressure. Song et al. [24] followed 75,468 urban workers for a 2-year period and found that the OR of metabolic syndrome related to reduced eGFR was 1.43 (95% CI, 1.13 to 1.83) [24]. In addition, lower blood pressure targets (i.e., 130/80 mmHg) are strongly associated with better renal outcomes [30]. Thus, aggressive blood pressure control is suggested in the management of patients with metabolic syndrome and mild renal function decline to promote a better prognosis.
Hyperglycemia, including previously diagnosed diabetes and impaired fasting glucose, is another component of metabolic syndrome that is significantly associated with CKD in the present study. Increased GFR, also called hyperfiltration, is a proposed mechanism for renal injury in diabetes, which has been hypothesized to cause intra-glomerular hypertension leading to albuminuria and then reduced GFR. Hyperfiltration also occurred in patients with impaired fasting glucose, and can be used as a predictor of diabetic nephropathy [31–34].
Hypertriglyceridemia, low HDL-C levels, and central obesity were not significantly associated with CKD in the present study. Several other studies also had similar results. Although metabolic syndrome itself is an independent risk factor associated with CKD, dyslipidemia (including both hypertriglyceridemia and low HDL-C level) is not significantly associated with the development of CKD [18, 21, 22, 25, 26, 35]. Some studies have shown that hypertriglyceridemia or low HDL-C level is only significantly associated with the development of CKD in patients with metabolic syndrome [24, 36]. However, the role of central obesity in developing CKD has not reached consensus [25, 27, 36–38]. Differences in race, large disparities in subjects’ ages, definition of CKD, and adjusted confounding factors in these studies might be other reasons for discrepancies between studies.
The present study has several limitations. First, this was a cross-sectional study, thus, the causal relationship between CKD and associated risk factors cannot be evaluated and determined. Second, the number of participants in this study was relatively small and all were recruited from only a single community. Third, volunteer bias may exist due to subjects participating on a volunteer basis. Volunteer bias is defined as the bias that comes from the fact that a particular sample contains only those participants who are actually willing to participate in the study. Those who participate and find the topic particularly interesting are more likely to volunteer, and the same is true of those who are expected to be evaluated on a positive level [39]. In addition, we recruited these volunteer subjects to join our study at gathering places in town such as temples and community centers. This means that people who require considerable assistance or frequent medical care had a lower possibility to be recruited. Volunteer bias would potentially influence the prevalence of CKD and the associated risk factors, and the association between CKD and associated risk factors in those who require substantial assistance or care might not be observed in the present study.