Identification of Nestin as a Urinary Biomarker for Acute Kidney Injury

Abstract

Objectives: Acute kidney injury (AKI) is a common complication in hospitalized patients and the incidence of AKI is rapidly increasing. Despite the advances in treatment of AKI, many patients still progress to end-stage renal disease and depend on dialysis. Therefore, early diagnosis and adequate treatment of AKI could improve prognosis. Methods: We established rat models of AKI induced by cisplatin nephrotoxicity and renal ischemia-reperfusion (I/R). Urine samples were collected, labeled with isobaric tags for relative and absolute quantification agents, and then subjected to nano-LC-MS/MS-based proteomic analysis. Results of the proteomic study were confirmed by Western blot. We also performed RNAi to silence nestin and investigate its role in renal I/R injury. We then validated its clinical application by studying urine nestin levels in AKI patients with cardiovascular surgeries. Results: Our proteomic analysis showed that fetuin-A, nestin, hamartin and T-kininogen were differentially expressed in the urine samples of rats after cisplatin or I/R treatment. Western blot confirmed the differential expression of these proteins in animal models and ELISA confirmed the differential expression of nestin in human urine samples. To explore the expression of nestin in the development of AKI, our results showed that nestin was primarily detected in the glomeruli and barely detected in tubular cells but increased in tubular cells during I/R- and cisplatin-induced AKI. The urine nestin-to-creatinine ratio increased earlier than serum creatinine in AKI patients with postcardiovascular surgeries. The role of nestin in AKI might be related to the p53 signaling pathway. Conclusions: Thus, our results demonstrated that urinary nestin could be a urinary biomarker for patients with AKI and its role in AKI might be related to the p53 signaling pathway.

Urinary Kininogen-1 and Retinol binding protein-4 respond to Acute Kidney Injury: predictors of patient prognosis?

“…To our best knowledge, urinary KNG1 has not been directly related to AKI in humans. T-Kininogen was found differentially expressed in rats after cisplatin or ischemia/reperfusion treatment 29 . In response to streptozotocin-induced diabetes in rats, kininogen, kallikrein, BK levels and BK B1- and B2-receptor expression were decreased in glomeruli and in cultured podocytes, implying a role for kallikrein-kinin system in podocyte apoptosis in diabetic conditions 30 .…”

Acute kidney injury inChina

“…Relevant substances, such as neutrophil gelatinaseassociated lipocalin, liver-type fatty acid binding protein, cystatin C, kidney injury molecule-1, N-acetyl-beta-Dglucosaminidase, nestin, and interleukin-18 have all been well studied in the clinical setting in China. [38][39][40][41][42][43] In addition to those protein or peptide biomarkers, nucleic acids such as circulating microRNA have been added to the growing list of potentially useful biomarkers of AKI. 44 In a study involving 120 adult patients undergoing cardiac surgery, urinary and plasma microRNA-21(miR-21) were identified to be associated with severe AKI and other poor postoperative outcomes of cardiac surgery, indicating their potential use as prognostic markers.…”

“…A variety of promising biomarkers for AKI have been identified in the published literature. Relevant substances, such as neutrophil gelatinase‐associated lipocalin, liver‐type fatty acid binding protein, cystatin C, kidney injury molecule‐1, N‐acetyl‐beta‐D‐glucosaminidase, nestin, and interleukin‐18 have all been well studied in the clinical setting in China . In addition to those protein or peptide biomarkers, nucleic acids such as circulating microRNA have been added to the growing list of potentially useful biomarkers of AKI .…”

Acute kidney injury: Current concepts and new insights

“…To date, several other biomarkers such as microalbumin, N-acetyl-B-D-glucosaminidase, kidney injury molecule-1, interleukin-18, liver fatty acid-binding protein, netrins and nestin have been studied for the diagnosis, severity classification and most importantly, the modification of the outcome in AKI. 29 , 30 However, more clinical studies will be required to prove the true superiority and cost effectivity of novel biomarkers over creatinine.…”