Association of Circulating ANGPTL8 Levels With Renal Dysfunction: A Case-Control Study

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.