C3-Epimer of 25-Hydroxyvitamin D3 as a Superior Marker for Predicting the Severity of Chronic Kidney Disease in Rheumatoid Arthritis Patients

Abstract

Objective. 25-hydroxyvitamin D3 (25[OH]D3) is involved in oxidative stress regulation by upregulating the expression of antioxidant genes except for mineral homeostasis physiological role. C3-epimer of 25(OH)D3 (C3-epi-25[OH]D3) is a form of vitamin D metabolite with low bioaffinity in vivo, but little is known about the relationship between C3-epi-25(OH)D3 and diseases. This study was aimed at investigating the relationship between C3-epi-25(OH)D3 and the severity of chronic kidney disease (CKD) in patients with rheumatoid arthritis (RA). Method. A total of 318 RA inpatients were enrolled and divided into mild ( $n=247$ ), moderate ( $n=46$ ), and severe ( $n=25$ ) CKD groups according to the CKD prognosis criterion of the Kidney Disease Improving Global Outcomes guidelines. Serum levels of 25(OH)D2, 25(OH)D3, C3-epi-25(OH)D3, and free 25(OH)D (F25[OH]D) were measured, and the value of 25(OH)D was calculated. The relationship and changing trend of the indexes based on CKD severity were analyzed. Results. The serum levels of 25(OH)D, 25(OH)D3, and F25(OH)D showed a decreasing trend ( $z=-2.781–-3.996$ , $P<0.01$ ) in RA patients with CKD progression from mild to severe, while C3-epi-25(OH)D3 showed an increasing trend ( $z=6.741$ , $P<0.001$ ) and 25(OH)D2 showed no significant difference among the groups ( $z=0.976$ , $P=0.329$ ). Only levels of C3-epi-25(OH)D3 presented significant differences between adjacent CKD severity groups in RA patients (mild to moderate: $z=3.963$ , $Padj<0.001$ ; moderate to severe: $z=3.269$ , $Padj=0.002$ ). Multiple logistic regression analysis showed that 25(OH)D3 and C3-epi-25(OH)D3 were significant predictors for CKD progression in RA patients, and C3-epi-25(OH)D3 had a better predictive advantage (moderate vs. mild: $\text{OR}=4.79$ , $P<0.001$ ; severe vs. mild: $\text{OR}=17.85$ , $P<0.001$ ). Conclusions. To the best of our knowledge, this is the first study to reveal that C3-epi-25(OH)D3 is a dominant predictor of CKD severity in RA patients. Further studies are needed to explore the relationship between C3-epi-25(OH)D3 and other diseases.