Abstract
Background: Chronic kidney disease (CKD) is recognized as a major public health problem with high morbidity and mortality worldwide. Recently, angiopoietin-like protein 8 (ANGPTL8) was found to regulate lipid metabolism. Previous studies suggested that serum ANGPTL8 levels increased in patients with diabetes, especially in diabetic patients with albuminuria. This study aimed to investigate the association between circulating levels of ANGPTL8 and kidney function in the general population.Methods: The subjects were patients with renal dysfunction [estimated glomerular filtration rate (eGFR) <60/min/1.73 m2] from Risk Evaluation of cAncers in Chinese diabeTic Individuals: a lONgitudinal study (the REACTION study). Each case was matched by age, sex, and body mass index (BMI) with one control whose eGFR was ≥ 90 ml/min/1.73 m2. The case and control groups were compared using a paired t-test. Binary logistic regression analysis was used to calculate the odds ratio (OR) of renal dysfunction (RD).Results: Among 135 case-control pairs, circulating ANGPTL8 levels were elevated in patients with RD compared to control subjects [799.96 (410.12-1086.44) vs. 609.58 (365.13-740.06) pg/ml, p < 0.05]. Partial correlations showed that ANGPTL8 levels were negatively correlated with eGFR (r = −0.26, p < 0.05). Multivariable-adjusted binary logistic regression analysis showed that elevated ANGPTL8 levels were associated with an increased risk of RD (OR in quartile 4 vs. 1, 3.80; 95% CI, 1.71-8.41). Interestingly, the association between ANGPTL8 levels and RD was consistent with the overall findings in both nondiabetic individuals (OR, 1.44; 95% CI, 1.09 to 1.91) and diabetic patients (OR, 2.71; 95% CI, 1.13-6.49) in the subgroup analyses. Furthermore, the estimates for this association were also significant in females (OR, 2.12; 95% CI, 1.33-3.37), individuals aged > 60 years (OR, 1.55; 95% CI, 1.16-2.07), individuals with a BMI <24 (OR, 1.66; 95% CI, 1.16-2.39), and individuals without hyperlipidaemia (OR, 1.61; 95% CI, 1.16-2.23) (all p-values <0.05).Conclusion: Elevated circulating ANGPTL8 levels were associated with increased risk of RD in the general population, especially among females, individuals aged > 60 years, individuals with a BMI < 24, individuals without diabetes mellitus, individuals with diabetes mellitus (DM), and individuals without hyperlipidaemia. This finding implies that ANGPTL8 may play a role in the pathological process of RD.
Highlights
Chronic kidney disease (CKD) is defined as kidney damage caused by a variety of factors, including diabetes, hypertension, autoimmune diseases, lipid dysregulation, and urinary tract infections [1, 2]
Among 135 case-control pairs, no significant differences in age, sex, body mass index (BMI), hemoglobin A1c (HbA1c), highdensity lipoproteins (HDL), low-density lipoproteins (LDL), total cholesterol, TG, fasting plasma glucose (FPG), 2 h postprandial blood glucose (2hPG), alanine transaminase (ALT), and AST data were detected between the case and control groups
The serum angiopoietin-like protein 8 (ANGPTL8) levels were inversely associated with the estimated glomerular filtration rate (eGFR) (r = −0.26, p < 0.05; Figure 1)
Summary
Chronic kidney disease (CKD) is defined as kidney damage caused by a variety of factors, including diabetes, hypertension, autoimmune diseases, lipid dysregulation, and urinary tract infections [1, 2]. CKD is recognized as a major public health problem with high morbidity and mortality worldwide, and it requires substantial financial and social resources [3,4,5]. According to the 2010 Global Burden of Disease study, CKD was ranked 27th in the list of causes of total global deaths in 1990 but rose to 18th in 2010, and the ranking of chronic kidney disease has risen in recent years [7, 8]. Diagnosis, and treatment are important to prevent disease progression because progressive CKD is associated with many adverse outcomes, including end-stage kidney disease, cardiovascular disease, and increased mortality [7, 8]. Chronic kidney disease (CKD) is recognized as a major public health problem with high morbidity and mortality worldwide. This study aimed to investigate the association between circulating levels of ANGPTL8 and kidney function in the general population
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