Identification of a sensitive urinary biomarker, selenium-binding protein 1, for early detection of acute kidney injury

Abstract

Acute kidney injury (AKI) is associated with increased mortality rate in patients but clinically available biomarkers for disease detection are currently not available. Recently, a new biomarker, selenium-binding protein 1 (SBP1), was identified for detection of nephrotoxicity using proteomic analysis. The aim of this study was to assess the sensitivity of urinary SBP1 levels as an early detection of AKI using animal models such as cisplatin or ischemia/reperfusion (I/R). Sprague-Dawley rats were injected with cisplatin (6 mg/kg, once i.p.) and sacrificed at 1, 3, or 5 days after treatment. Ischemia was achieved by bilaterally occluding both kidneys with a microvascular clamp for 45 min and verified visually by a change in tissue color. After post-reperfusion, urine samples were collected at 9, 24, and 48 hr intervals. Urinary excretion of protein-based biomarkers was measured by Western blot analysis. In cisplatin-treated rats, mild histopathologic alterations were noted at day 1 which became severe at day 3. Blood urea nitrogen (BUN) and serum creatinine (SCr) levels were significantly increased at day 3. Levels of urinary excretion of SBP1, neutrophil gelatinase-associated lipocalin (NGAL), and a tissue inhibitor of metalloproteinase-1 (TIMP-1) were markedly elevated at day 3 and 5 following drug treatment. In the vehicle-treated I/R group, serum levels of BUN and SCr and AST activity were significantly increased compared to sham. Urinary excretion of SBP1 and NGAL rose markedly following I/R. The urinary levels of SBP1, NGAL, TIMP-1, and KIM-1 proteins excreted by AKI patients and normal subjects were compared. Among these proteins, a marked rise in SBP1 was observed in urine of patients with AKI compared to normal subjects. Based upon receiver-operator curves (ROC), SBP1 displayed a higher area under the curve (AUC) scores than levels of SCr, BUN, total protein, and glucose. In particular, SBP1 protein was readily detected in small amounts of urine without purification. Data thus indicate that urinary excretion of SBP1 may be useful as a reliable biomarker for early diagnosis of AKI in patients.

Protective Effects of Dendropanax morbifera against Cisplatin-Induced Nephrotoxicity without Altering Chemotherapeutic Efficacy

“…Similar to the changes in BUN and sCr, the levels of KIM-1, NGAL, TIMP-1, and SBP1 were markedly reduced in CDDP-treated rats following DM administration. These results are consistent with those of our previous study showing that the urinary excretion of AKI biomarkers was significantly elevated after CDDP exposure [29]. These protein-based biomarkers were observed in the urine following injury to the proximal tubule, in which the loss of reabsorption is generally indicative of injury to the tubular epithelium [30,31,32].…”

Selenium-Binding Protein 1 Indicates Myocardial Stress and Risk for Adverse Outcome in Cardiac Surgery

“…Heart tissue is not the only potential source of extracellular SELENBP1, as urinary SELENBP1 was described as a new biomarker of heavy metal-induced kidney injury, where the protein increased strongly in the renal cortex after mercury administration in a rodent model of nephrotoxicity [36]. The authors propose urinary SELENBP1 as a novel sensitive and specific biomarker for early stages of kidney injury before irreversible damage has taken place [29,36]. Accordingly, serum SELENBP1 may indicate severe and acute noxae to cardiomyocytes at an early time point before the onset of necrosis, i.e., at a time when protective measures may possibly reverse the path to cell death.…”

“…Information on the role and regulation of extracellular SELENBP1 is sparse. A recent report identified the protein in urine as a novel and early biomarker of acute kidney injury [29] and we described increased SELENBP1 concentrations in patients with acute coronary syndrome at high risk of major cardiac events [30]. Cardiac surgery negatively affects Se status and Se deficiency increases the risk of ischaemic heart disease [31] and promotes organ dysfunction after cardiac surgery [32].…”

The future role of proteomics in the understanding of acute kidney injury

“…Once again, they found SBP1 to be a sensitive and tissue specific biomarker of AKI, as hepatotoxic agent exposure led to no increase in SBP1 levels. These results have since been replicated both in another model of cisplatin induced nephrotoxicity and in models of ischemia reperfusion injury (IRI), indicating that SBP1 may be another tubular marker of AKI in numerous contexts [9]. While SBP1 was elevated in the urine of the IRI group at 9 h post IRI, it is not known whether it is elevated any earlier like NGAL, which peaks at between 2 and 6 h post IRI [10].…”