Prediction Value of Serum NGAL in the Diagnosis and Prognosis of Experimental Acute and Chronic Kidney Injuries.

Weida Wang,Yuanyuan Chen,Xiaoguang Chen,Haijie Wu,Sen Zhang,Zhaojun Li

doi:10.3390/biom10070981

Weida Wang, Yuanyuan Chen + Show 4 more

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https://doi.org/10.3390/biom10070981

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Abstract

Sensitive and accurate serum biomarkers for monitoring acute and chronic kidney disease progression are more convenient and can better evaluate drug efficiency in pharmacological research. Neutrophil Gelatinase-associated Lipocalin (NGAL) is considered a hopeful early biomarker of acute kidney injury (AKI), but its utility in early prediction and prognosis of diabetic nephropathy (DN) and immune-mediated glomerulonephritis is still not clear. Moreover, detailed prognosis studies of NGAL in AKI are lacking, and most studies use a urine source. In the current study, through two experimental AKI and two chronic kidney injury animal models, serum NGAL (sNGAL) prediction values on diagnosis and prognosis of kidney injuries in animal disease models have been investigated thoroughly. Four experimental kidney disease models include cisplatin-induced and lipopolysaccharide (LPS)-induced AKI, streptozocin-induced diabetic nephropathy (DN), and cationized-bovine serum albumin (c-BSA)-induced membranous nephropathy (MN), respectively. The sNGAL concentration was measured at different stages of kidney injury (KI) in each experimental model, and receiver operating characteristic (ROC) analyses were performed to investigate the diagnosis efficiency of sNGAL for KI. Western blot and immunohistochemistry were used to measure the protein levels in the kidneys, and pathological analysis was used as the gold standard to confirm KI. Results suggest that sNGAL can predict early diagnosis of cisplatin-induced AKI accurately but is less powerful in later stages compared to blood urea nitrogen (BUN) and serum creatinine (Scr). sNGAL is sensitive but lacks specificity to evaluate early kidney injury for LPS-induced AKI under low-dosage LPS challenge. sNGAL is not an efficient biomarker for early diagnosis of STZ-induced DN, but sNGAL is an efficient predictor for the early diagnosis and prognosis of immune-mediated MN. In conclusion, application of sNGAL as a kidney injury biomarker to determine the diagnosis and prognosis in pharmacological studies is dependent on experimental animal models.

Highlights

Experimental kidney injury (KI) animal models are very helpful in screening potential nephrotoxic reagents and possible anti-KI compounds in vivo, and they can provide research tools to study renal pathophysiology
Because mice in the 20 mg kg−1 group began to die at 72 h after cisplatin injection, the data in the 20 mg kg−1 group at day 6 were excluded. serum NGAL (sNGAL) increased 24 h later in the cisplatin-injected mice, both at 10 mg kg−1 and 20 mg kg−1 cisplatin dosage, but it was more significant at the 20 mg kg−1 dosage (p < 0.0001)
We demonstrated that Neutrophil gelatinase-associated lipocalin (NGAL) protein levels in the kidney tissues increased in a time‐dependent manner (Figure 2D)

Summary

Introduction

Experimental kidney injury (KI) animal models are very helpful in screening potential nephrotoxic reagents and possible anti-KI compounds in vivo, and they can provide research tools to study renal pathophysiology. Traditional biomarkers measuring renal functions in the human study, such as blood urea nitrogen (BUN) and serum creatinine (Scr), are not sensitive enough to detect early or slight damages in experimental animals [1,2]. NGAL is one of the most highly induced proteins in the kidney after ischemic or nephrotoxic AKI, both in clinical studies and animal models, and it increases in urine before the rise in serum creatinine concentration [9,10]. Most research with experimental animal models lack in-depth predictions of serum NGAL (sNGAL). Several biofunctions in humans cannot be detected in rodent animals (e.g., NGAL/MMP-9 interaction is absent in rodents), and rodents are unable to form homodimers and heterodimers [12] These discrepancies limit the applicability of rodent models in discovering human biofunctions [13,14]. A comprehensive investigation of sNGAL in experimental KI animal models will benefit its usage as a biomarker in pharmacology and toxicity studies

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