Adropin Predicts Chronic Kidney Disease in Type 2 Diabetes Mellitus Patients with Chronic Heart Failure

Abstract

Adropin is a multifunctional secreted protein, which is involved in the metabolic modulation of the heart-brain-kidney axis in heart failure (HF). The aim of the study was to detect the plausible predictive value of serum levels of adropin for chronic kidney disease (CKD) grades 1–3 in type 2 diabetes mellitus (T2DM) patients with chronic HF. We enrolled 417 T2DM individuals with chronic HF and subdivided them into two groups depending on the presence of CKD. The control group was composed of 25 healthy individuals and 30 T2DM patients without HF and CKD. All eligible patients underwent an ultrasound examination. Adropin was detected by ELISA in blood samples at the study baseline. We found that adropin levels in T2DM patients without HF and CKD were significantly lower than in healthy volunteers, but they were higher than in T2DM patients with known HF. The optimal cut-off point for adropin levels was 2.3 ng/mL (area under the curve [AUC] = 0.86; 95% CI = 0.78–0.95; sensitivity = 81.3%, specificity = 77.4%). The multivariate logistic regression adjusted for albuminuria/proteinuria showed that serum levels of adropin <2.30 ng/mL (OR = 1.55; p = 0.001) independently predicted CKD. Conclusions: Low levels of adropin in T2DM patients with chronic CH seem to be an independent predictor of CKD at stages 1–3.

Plausible prediction of renoprotective effects of sodium-glucose cotransporter-2 inhibitors in patients with chronic kidney diseases

“…In addition, Berezina et al. 34 reported that low serum levels of adropin (<2.30 ng/ml) predicted CKD progression in patients with T2DM and concomitant HF treated with dapagliflozin. The results of included trials are summarized in Table 2.…”

“…Indeed, SGLT2 inhibitors demonstrated their ability to reduce the levels of hepcidin, inflammatory cytokines, such as IL-6, TNF-alpha, CRP and markers of kidney injury, as well as increase the levels of hemoglobin, erythropoietin, serum uric acid, adropin, irisin, and apelin. 19,22,28,34,44–48 The majority of these studies did not report any correlations between changes in the biomarkers of glomerular/tubular injury, altered glucose and lipid metabolism, adipocyte/skeletal muscle cell dysfunction and changes in UACR, whereas benefits in their changes were closely associated with slower decline in eGFR, for instance in the CREDENCE and DAPA-CKD trials. 19,28 Moreover, SGLT2 inhibitors seem to show improving kidney function independently of their glycemic effects, 49 while they are able to reduce tubular cell glucotoxicity via inhibition of sodium transporters, modulating mitochondrial dysfunction and suppressing local and systemic inflammatory reactions.…”

“…SGLT2 inhibitors have been suggested to prevent kidney fibrosis, podocyte injury and apoptosis of glomerular cells by increasing protective adipokine expression, such as adropin, irisin and apelin, which act directly through the activation of Akt/STAT3 and tyrosine protein kinase JAK2 (JAK2)/signal transducer pathways. 34,45,48,51,52 Finally, SGLT2 inhibitors adapt metabolic homeostasis by mediating the activity of NADPH oxidase and transcription factors (nuclear factor-κB and nuclear factor erythroid 2-related factor 2) preventing advanced glycation and autophagy. 51,52 These effects are considered to be crucial in the treatment of patients with either T2DM- or non-T2DM-related CKD who have HF.…”

“…32 Segar et al 33 established that early changes in four biomarkers (HbA1c, circulating hemoglobin levels, hematocrit and serum uric acid), as well as average changes in early biomarkers, including circulating hemoglobin levels, hematocrit and serum uric acid, bodyweight, and serum albumin levels, mediated the renoprotective effects of ertugliflozin. In addition, Berezina et al 34 reported that low serum levels of adropin (<2.30 ng/ml) predicted CKD progression in patients with T2DM and concomitant HF treated with dapagliflozin. The results of included trials are summarized in Table 2.…”

“…The results of included trials are summarized in Table 2. [27][28][29]31,33,34 In recent post-hoc analysis of the randomized EMPEROR-Reduced and EMPEROR-Preserved trials, compared with placebo, the SGLT2 inhibitor empagliflozin reduced HF-related clinical outcomes, including hospital admission or CV death, regardless of albuminuria levels at baseline, as well as diminished the progression of albuminuria to proteinuria with a slower progressive decline in renal function in patients with chronic HF across a wide range of LVEF regardless of baseline NT-proBNP levels. 35 A meta-analysis of 13 SGLT2 inhibitor trials (four comprising only patients with CKD) involving 90 413 participants, showed that SGLT2 inhibitors modified the risk of worsening kidney function and acute kidney injury irrespective of baseline eGFR and etiology of CKD.…”