Identification of Urinary Activin A as a Novel Biomarker Reflecting the Severity of Acute Kidney Injury

Abstract

Acute kidney injury (AKI) is a common but complex condition that is associated with increased morbidity and mortality. In the present study, we examined whether urinary activin A, a member of the TGF-beta superfamily, is present in mice with ischemia-reperfusion injury and in humans with AKI, as well as its potential as a biomarker for AKI. Expression of activin A was markedly increased in ischemic mouse kidneys. In situ hybridization demonstrated that activin mRNA was expressed in tubular cells of ischemic kidneys but not of normal kidneys. Immunoreactive activin A, which was absent in normal kidneys, was detected in the cytoplasm of proximal tubular cells in ischemic kidneys. Activin A was undetectable in the urine of normal mice. In contrast, activin A was significantly increased in the urine of ischemic mice at 3 h after reperfusion. Urinary activin A levels increased according to the period of ischemia. In humans, urinary activin A was almost undetectable in healthy volunteers and in patients with pre-renal AKI, but was significantly increased in patients with renal AKI. There was no significant correlation between urinary activin A and serum activin A. Collectively, urinary activin A might be a useful biomarker reflecting the severity of AKI.

Serum Activin A Levels and Renal Outcomes After Coronary Angiography

“…Several studies had shown increased serum activin A levels in cardiovascular disease. In patients with type 2 diabetes, serum activin A levels were associated with higher incidence of cardiovascular diseases 39,40 . A comprehensive study by Yndestad et al found increased serum activin A levels in patients with CHF, concluding that abundant activin A may contribute to the pathogenesis of myocardial remodeling 27 .…”

Emerging Roles of Interleukin-33-responsive Kidney Group 2 Innate Lymphoid Cells in Acute Kidney Injury

“…However, Scr is not a sensitive marker for early AKI event, and, therefore, the development of more sensitive, accurate, and cost-effective biomarker assays for clinical AKI assessment other than Scr analysis is crucial [26]. In addition to SCr, several urine biomarkers have emerged as more sensitive indicators for early detection of AKI, such as urine levels of kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), activin A, and insulin-like growth factor-binding protein 7 (IGFBP-7) [27][28][29][30]. Urine Biomarker [(Tissue inhibitor of metalloproteinases 2) TIMP-2] × [IGFBP-7] level has also been proposed as a promising indicator for clinical AKI risk assessment [31].…”

Senescence marker activin A is increased in human diabetic kidney disease: association with kidney function and potential implications for therapy

“…In the kidney, activin A is expressed during embryonic development but not in maturity 16–18. However, activin A becomes abundantly expressed in the injured kidney in experimental models of acute kidney injury (AKI),19 20 glomerulonephritis and CKD 21–23. Circulating activin A levels doubled in unilateral ureter obstruction (UUO) rats while levels remained unchanged in unilateral nephrectomized controls with similar kidney function, suggesting the obstructed kidney as the source 24.…”

“…Circulating activin A levels doubled in unilateral ureter obstruction (UUO) rats while levels remained unchanged in unilateral nephrectomized controls with similar kidney function, suggesting the obstructed kidney as the source 24. Renal tubular cells release activin A, which acts as a paracrine factor that promotes fibroblast proliferation, contributing to kidney fibrosis and CKD progression 17 19 25. Beyond the kidney microenvironment, circulating activin A levels are 10-fold higher in a high fat-fed, lipoprotein receptor deficient (Ldlr –/– ) CKD mouse model and elevated fivefold in a mouse model of Alport syndrome compared with wild types 22.…”