Serum Elabela/Toddler Levels Are Associated with Albuminuria in Patients with Type 2 Diabetes

BACKGROUND/AIMS: Elabela (ELA) or Toddler is a recently identified hormone that plays a crucial role in embryonic development through the activation of the apelin receptor (APJ). Our previous study indicated that ELA is highly expressed in adult kidney and the ELA receptor signaling pathway is functional in mammalian systems. Whereas nothing is yet known regarding ELA and diabetic kidney disease (DKD). Here, we evaluated the relationship between serum ELA levels and albuminuria in patients with type 2 diabetes (T2D). METHODS: An observational study involving 80 patients divided into groups according to their baseline urinary albumin/creatinine ratio (ACR): Group 1 (ACR ≤ 29 mg/g), Group 2 (ACR = 30-299 mg/g), Group 3 (ACR ≥ 300 mg/g with normal serum creatinine), and Group 4 (ACR ≥ 300 mg/g with increased serum creatinine). The demographic, clinical, and biochemical variables including serum ELA were obtained or measured through disease history, physical examination, or laboratory evidence. RESULTS: The results showed that the serum ELA levels decreased gradually with the deterioration of DKD from the stages of normal albuminuria, microalbuminuria, macroalbuminuria, to macroalbuminuria and elevated serum creatinine. In addition, ELA had a significantly negative correlation with ACR (r = -0.561, P < 0.001), retinopathy (r = -0.424, P < 0.001), serum creatinine (r = -0.269, P = 0.016), SBP (r = -0.249, P = 0.026), DBP (r = -0.261, P = 0.020) and a positive correlation with eGFR (r = 0.318, P = 0.004). Furthermore, stepwise multiple linear regression analysis showed that ACR, retinopathy, and LDL-C were considered the most relevant variables to ELA, and ELA, retinopathy, eGFR, and age were important predictors for ACR (t = -4.546, P = 0.000). CONCLUSIONS: To our knowledge, this is the first study to explore the clinical relationship between ELA levels and CKD. Decreased serum ELA levels might be a significant clinical predictor in patients with DKD or even as a promising agent for treating CKD patients.