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

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: OR = 4.79, P < 0.001; severe vs. mild: 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.