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

Abstract

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.

APELA/ELA32 Reduces Iodixanol-induced Apoptosis, Inflammatory Response and Mitochondrial and DNA Damage in Renal Tubular Epithelial Cells

“…The crucial roles of inflammatory genes in renal I/R injury have been suggested (16,17). Apela has been found to reduce renal inflammation and fibrosis markers and lead to improvement in renal pathology and kidney dysfunction in an animal model of Type 1 diabetes mellitus (13). Here, we found that iodixanol induced cytotoxicity and apoptosis in renal tubular epithelial cells.…”

“…Apela 32 (ELA32) is a 32residue peptide that is specifically expressed in the kidney in adult mice and humans (10)(11)(12). ZHANG et al have shown that the level of Apela (ELA) in diabetic nephropathy gradually decreased with an increase in albuminuria and serum creatinine (13). In the renal ischemia-reperfusion mice model, both endogenous and exogenous Apela significantly inhibited DNA damage, apoptosis and inflammatory response of renal tubular cells (14).…”

The Elabela-APJ axis: a promising therapeutic target for heart failure

“…In an observational clinical study, 80 patients with type 2 diabetes were divided into different arms according to their baseline urinary albumin/creatinine ratio (ACR). ELA has been shown to be a significantly negative correlation with the ACR, and the serum ELA levels might be a novel clinical predictor of diabetic nephropathy [64]. This clinical evidence indirectly verified the protective effects of ELA on renal function in the diabetes population.…”

The interaction partners of (pro)renin receptor in the distal nephron

“…Several clinical studies have reported that lower levels of circulating ELA and apelin in patients with hypertension [102][103][104][105] and kidney disease. [106][107][108][109] This phenomenon in clinical studies has been recapitulated by the animal experiments. A reduced serum apelin concentration, and markedly decreased apela, apln, and aplnr mRNA expression in the heart, aorta, and kidney, were observed in the multiple hypertensive models such as hypertensive rats, 110 DOCAsalt hypertensive rats, 111 two-kidney, one-clip (2K1C) Goldblatt hypertension rats, 112,113 and Dahl salt-sensitive rats.…”