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

Abstract

<jats:p>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.</jats:p>

Development of Canine Chronic Kidney Disease Model: A Pilot Study

“…Also, chronically damaged tubular cells produce a great quantity of NGAL (Bolignano et al 2008). Serum NGAL acts as a kidney injury biomarker but not in all experimental animal models as reported previously (Wang et al 2020). In the present study, the expression of NGAL gene increased with the increase of kidney injury.…”

Arbutus Unedo Honey and Propolis Ameliorate Acute Kidney Injury, Acute Liver Injury, and Proteinuria via Hypoglycemic and Antioxidant Activity in Streptozotocin-Treated Rats

“…The most important complications of diabetes are proteinuria and CKD. It was found that serum creatinine increases 12 weeks after STR administration and induction of hyperglycemia [51]. However, BU increased after one week indicating AKI without chronic glomerular endothelial cell injury [52].…”

A Review of Specific Biomarkers of Chronic Renal Injury and Their Potential Application in Nonclinical Safety Assessment Studies

“…In a study comparing the utility of serum NGAL in AKI and chronic kidney injury models in rats and mice, serum NGAL had variable success in detection of kidney injury across all of the models, which is not surprising given that serum NGAL can lack specificity for renal injury due to production and release by neutrophils and nonrenal epithelia (liver, bladder, lung, stomach, small intestine, pancreas, prostate gland, mammary gland, adrenal gland, thymus) in response to injury. 231,232 In a mouse ischemiareperfusion kidney injury model, serum and urine NGAL increased continuously during progression of AKI to CKD compared with serum and urine KIM-1 which peaked in the acute phase and declined during the chronic phase. 207 Similarly in humans, serum and urine NGAL were good prognostic biomarkers for predicting the progression of AKI to CKD in sepsis-associated AKI patients.…”