Association between Circulating Ectodysplasin A and Diabetic Kidney Disease

Abstract

Background: Ectodysplasin A (EDA), a member of the TNF family, plays important roles in ectodermal development, while recent studies expanded its regulatory effects on insulin resistance and lipid metabolism. This study was the first time to investigate the correlation between circulating EDA and albuminuria in patients with T2DM.

Methods: A total of 189 T2DM and 59 healthy subjects were enrolled in the study. We analyzed the concentrations of EDA by ELISA. Plasma glucose, insulin, HbA1c, lipids, creatinine, BUN, and UACR were also measured. Insulin resistance and pancreatic cell function were assessed by HOMA.

Results: Circulating EDA concentration was significantly increased in T2DM patients and increased with the degree of albuminuria. EDA was positively correlated with age, FIns, HOMA-IR, HOMA-β, Scr, and UACR, and negatively correlated with eGFR. Linear stepwise regression showed that FIns, HOMA-β, and UACR were independent influencing factors of EDA. Logistic regression analysis showed that EDA was independently associated with the occurrence of albuminuria in T2DM. ROC curve showed that EDA had an area under the receiver operating curve of 0.701 [95%CI = (0.625 - 0.777), P < 0.001].

Conclusion: EDA is positively correlated with the degree of albuminuria in patients with T2DM and may be involved in the occurrence and progression of diabetic kidney disease (DKD).

Figure 1

Circulating EDA concentration between different subgroups.

Figure 2

Correlation between serum EDA levels and UACR levels in subjects. (a). Correlation between serum EDA levels and UACR levels in all subjects (r = 0.249, P < 0.001). (b). Correlation between serum EDA level and UACR level in T2DM patients (r = 0.220, P = 0.002). The logarithm-transformed values of UACR are used for analysis. (r = 0.703, P < 0.001).

Figure 3

Receiver operating characteristic (ROC) curves for the ability of EDA to discriminate the presence of albuminuria. The ability of the ROC curve based on EDA levels to predict the presence of albuminuria was 0.701 (0.625-0.777). Optimal cutoff points for EDA were 310.47 pg/mL and sensitivity and specificity were 72.8% and 60.3%, respectively.