title: Serum Neutrophil Gelatinase Associated Lipocalin (NGAL) Outperforms Serum Creatinine in Detecting Sepsis-Induced Acute Kidney Injury, Experiments on Bilateral Nephrectomy and Bilateral Ureter Obstruction Mouse Models.
abstract: Serum neutrophil gelatinase associated lipocalin (sNGAL), a promising acute kidney injury (AKI) biomarker produced by renal and non-renal tissues, might be affected by sepsis. We evaluated sNGAL in zero glomerular filtration rate models [bilateral ureter obstruction (BUO) and bilateral nephrectomy (BiNx)] with subsequent cecal ligation and puncture (CLP)-induced sepsis in 6 to 8-week-old ICR mice. We found that sNGAL increased earlier than serum creatinine (Scr) in BiNx/BUO with and without CLP. The earliest time-point of increased sNGAL in BiNx+CLP was 1  h after surgery. Scr, but not sNGAL, was lower at 18  h after BiNx/BUO+CLP compared with BiNx/BUO alone. Compared with BUO, BiNx had higher, and equal sNGAL at 1 to 18  h and 36  h, respectively. Additionally, similar NGAL expression in internal organs (heart, lung, liver, and spleen) and survival rates indicated the comparable severity of BiNx and BUO. Serum interleukin (IL)-6 was increased and correlated with sNGAL in BiNx/BUO with and without sepsis. In summary, we demonstrated: sNGAL is an early AKI biomarker, which is not affected by sepsis; sNGAL is mainly produced by extrarenal sources as demonstrated by the comparable sNGAL in BiNx and BUO; the saturation of renal NGAL re-absorption in BUO is demonstrated by lower sNGAL in BUO at 1 to 18  h, but not at 36  h when compared with BiNx; and a correlation of sNGAL and IL-6 implied sNGAL is a good sepsis prognostic biomarker. Therefore, sNGAL is a more beneficial sepsis-AKI biomarker than Scr.
authors: *Immunology Unit, Department of Microbiology †Center of Excellence in Immunology and Immune-Mediated Diseases, Department of Microbiology, Faculty of Medicine and STAR on Craniofacial and Skeletal Disorders, Faculty of Dentistry ‡Research Affairs, Faculty of Medicine §Nephrology Unit, Department of Medicine, Chulalongkorn University, Bangkok, Thailand.
authors: Asada
authors: A
authors: Leelahavanichkul
authors: Poorichaya
authors: P
authors: Somparn
authors: Jiraphorn
authors: J
authors: Issara-Amphorn
authors: Somchai
authors: S
authors: Eiam-ong
authors: Yingyos
authors: Y
authors: Avihingsanon
authors: Nattiya
authors: N
authors: Hirankarn
authors: Nattachai
authors: N
authors: Srisawat
mesh_terms: D058186:Acute Kidney Injury / Q000097:blood* / Q000209:etiology*; D000818:Animals; D003404:Creatinine / Q000097:blood*; D004195:Disease Models, Animal; D015850:Interleukin-6 / Q000097:blood; D000071068:Lipocalin-2 / Q000097:blood*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009392:Nephrectomy; D018805:Sepsis / Q000097:blood* / Q000150:complications*
chemical_list: D015850:Interleukin-6; D000071068:Lipocalin-2; D003404:Creatinine