Urinary netrin-1 and KIM-1 as early biomarkers for septic acute kidney injury

Abstract

Background: Acute kidney injury (AKI) during sepsis is associated with poor outcome. However, diagnosis of AKI with serum creatinine (SCr) level change is neither highly sensitive nor specific. Therefore, identification of novel biomarkers for early diagnosis of AKI is desirable. Aims: To evaluate the capacity of combining urinary netrin-1 and human kidney injury molecule type 1 (KIM-1) in the early diagnosis of septic AKI. Methods: We prospectively recruited 150 septic patients from Jun 2011 to Jun 2013 at Zhejiang Provincial People's Hospital, China. SCr, urinary netrin-1, and KIM-1 levels were recorded at 0, 1, 3, 6, 24, and 48 h of ICU admission and compared between AKI and non-AKI patients. In addition, we investigated the prognostic value of netrin-1 and KIM-1 between non-survivors and survivors in septic AKI patients. Results: SCr levels started to show elevation after 24 h of ICU admission. However, netrin-1 levels increased significantly as early as 1 h, peaked at 3-6 h and remained elevated up to 48 h of ICU admission in septic AKI patients. KIM-1 increased significantly by 6 h, peaked at 24 h and remained significantly elevated until 48 h of ICU admission. Furthermore, we observed significant higher urinary KIM-1 levels at 24 h and 48 h in non-survivors compared to survivors in AKI patients. Conclusions: Our results suggest that both netrin-1 and KIM-1 are clinically useful as early biomarkers in the diagnosis of septic AKI. In addition, persistent elevation of urinary KIM-1 level may be associated with poor prognosis.

Sepsis-Associated Acute Kidney Injury

“…66 In a separate prospective evaluation of 150 septic patients, urinary netrin-1 and kidney injury molecule-1 were increased within 3 hours of admission for patients with AKI. 67 In initial studies, serum NGAL levels showed only marginal prediction for AKI in children with sepsis (AUC, 0.68). A recent study, however, showed the ability of NGAL to improve the prediction of severe AKI afforded by the clinical context model of the renal angina index (AUC increased from 0.72 to 0.84).…”

Effect of continuous renal replacement therapy on kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin in patients with septic acute kidney injury

“…In hospitalized patients with AKI, urinary Kim-1 has been shown to predict adverse clinical outcomes such as mortality (29). NGAL is a 25-kDa protein originally isolated from neutrophil secondary granules (30) and is a classic biomarker for the early diagnosis and short-term outcome of AKI.…”

Diagnostic Value of Matrix Metalloproteinase-9 and Tissue Inhibitor of Matrix Metalloproteinase-1 in Sepsis-Associated Acute Kidney Injury

“…Current diagnostic criteria for AKI, serum creatinine levels and diuresis, have serious limitations (Khwaja 2012). Diagnostic value of certain novel biomarkers of AKI, neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1), is evident in cardiac surgery (Shao et al 2014;Zhou et al 2015) and sepsis (Tu et al 2014;Dai et al 2015) but not so much in abdominal surgery (Shavit et al 2011;Cullen et al 2014). The quest for new diagnostic biomarkers of AKI remains ongoing.…”