Genitourinary tract
Brian J Pollard, Gareth Kitchen in Handbook of Clinical Anaesthesia, 2017
The diagnosis of AKI has to date depended on detection of a decrease in kidney function by an increase in serum creatinine concentration which only occurs after a significant decrease in renal function. Earlier detection of AKI would be beneficial. A number of early biomarkers of AKI are currently being investigated. Neutrophil gelatinase-associated lipocalin (NGAL), a 25 kDa protein that is bound to neutrophils and expressed in injured epithelial cells in organs including the kidney has emerged as an accurate early biomarker of acute kidney injury. Plasma and urine NGAL have proved sensitive, specific and predictive early biomarkers of AKI after cardiac surgery. Other promising biomarkers are cystatin C, interleukin-18 and kidney injury molecule-1 (KIM-1). Further studies are required to validate the sensitivity and specificity of these biomarkers in clinical samples from large cohorts and from multiple clinical situations. Clinically relevant urinary biomarkers are summarized in Box 5.5.
Angiogenesis and Roles of Adhesion Molecules in Psoriatic Disease
Siba P. Raychaudhuri, Smriti K. Raychaudhuri, Debasis Bagchi in Psoriasis and Psoriatic Arthritis, 2017
This molecule belongs to the lipocalin family of small lipid (and other hydrophobic molecule) binding proteins, which are as ancient as gram-negative bacteria and have only structural conservation but very little sequence homology; thus, it was difficult to discover by genomic searches. The myriad names of lipocalin 2 testify to its multitude of actions. It was called a siderocalin, as it sequesters bacterial siderophores, thus restricting iron supply to bacteria. In the neutrophil granule, it binds to MPO, MMP9 β-galactosidase, and so forth, and is an important component of neutrophil intracellular traps. NGAL might protect proMMP9 from premature activation. Extracellular NGAL is internalized through several receptors, which also triggers several signaling pathways that are not yet fully elucidated. It may act as an intracellular iron metabolism regulator and also has an effect on subcellular localization of transmembrane proteins, such as cadherins and catenins. Several other lipocalins, for example, retinol binding proteins, are also potentially important for angiogenesis in psoriasis. The mother family “calycin,” to which lipocalins belong, also includes fatty acid binding proteins (FABPs), some of which, for example, FABP4 and FABP5, are important in endothelial cell function and psoriasis.
Urinary System
Pritam S. Sahota, James A. Popp, Jerry F. Hardisty, Chirukandath Gopinath, Page R. Bouchard in Toxicologic Pathology, 2018
Alterations in values of urine biomarkers must be interpreted with caution. Further testing will be necessary before there is a consensus agreement on what specific amplitude of elevation is significant for each species, what combination of markers is adequate to assess early DIKI, and what types of renal injury are best diagnosed by which marker. No single biomarker is likely to be applicable across the varied contexts and temporal presentations of all possible toxicity study designs. For instance, KIM-1 is undetectable in normal urine but upregulated in response to AKI in several species (Gautier et al. 2010; Gautier et al. 2014). However, in the dog, KIM-1 has found to be quite variable and less satisfactory as a renal biomarker than other urine analytes. β2M is unstable in acid urine, and therefore of limited value in either dogs or humans, where they have largely been replaced by the use of α1-microglobulin (Ennulat and Adler 2015). In multiple species, NGAL is rapidly and transiently upregulated in response to renal injury, but NGAL interpretation may be complicated by systemic inflammation necessitating concurrent analysis of blood levels to put urine elevations in proper context (Devarajan 2010; Ennulat and Adler 2015). Some urine analytes are constitutively expressed while others are induced after injury, and all these factors and limitations must be considered when choosing which of the available urinary biomarkers to evaluate and when interpreting results.
β2-Microglobulin, Neutrophil Gelatinase-Associated Lipocalin, and Endocan Values in Evaluating Renal Functions in Patients with β-Thalassemia Major
Published in Hemoglobin, 2020
Petek Uzay Cetinkaya, Fatih Mehmet Azik, Volkan Karakus, Bulent Huddam, Nigar Yilmaz
Abnormalities of glomerular filtration rate (GFR) and tubular dysfunction resulting from chronic anemia, hypoxia, iron load and nephrotoxic effects of chelators are seen in β-thal patients [4,5]. Glomerular filtration rate, urea, creatinine, creatinine clearance and serum cystatin C are frequently used to assess glomerular functions; whereas, urine density, pH, and presence of bicarbonate, phosphate, glucose and amino acids in the urine are frequently used to assess tubular functions [6]. Moreover, diagnostic and predictive values of various biomarkers have also been investigated. Among these biomarkers, β2-microglobulin (β2-MG) is a low molecular weight protein used to assess renal tubular functions. β2-Microglobulin is filtered by the glomeruli of normal kidneys, 99.9% of the β2-MG is reabsorbed, and it is excreted in negligible amounts in the urine. Elevated β2-MG level in the urine is the early indicator of proximal tubular damage [7]. Neutrophil gelatinase-associated lipocalin (NGAL) is a small protein and is minimally expressed in many tissues. Its expression increases in situations that lead to epithelial injury. Neutrophil gelatinase-associated lipocalin has a critical role as an indicator of acute renal injury [8]. Endocan is a proteoglycan secreted from the vascular endothelial cells and a marker of endothelial activation. Thus, increased endocan expression is in question in the presence of inflammatory diseases, endothelial pathologies and tumor progression [9].
Postpartum human breast milk levels of neutrophil gelatinase-associated lipocalin (NGAL) and matrix metalloproteinase-9 (MMP-9)/NGAL complex in normal and pregnancies complicated with insulin-dependent gestational diabetes mellitus. A prospective pilot case-control study
Published in Journal of Obstetrics and Gynaecology, 2020
Dimitra Metallinou, Katerina Lykeridou, Grigorios Karampas, Georgios Theodoros Liosis, Chrysanthi Skevaki, Myrto Rizou, Ioannis Papassotiriou, Demetrios Rizos
The neutrophil gelatinase-associated lipocalin (NGAL), also known as lipocalin-2, belongs to the superfamily of lipocalins, which are small extracellular proteins, structurally and functionally different in-between (Flower 1996). It is a 25 kDa protein which was first isolated as a complex covalently linked with the 92 kDa matrix metalloproteinase-9 (MMP-9) (Kjeldsen et al. 1993; Kjeldsen et al. 1994; Xu et al. 1994; Goetz et al. 2000). NGAL mRNA is normally expressed in a variety of human tissues, including the uterus, salivary gland, stomach, colon, lung, kidney and the liver, as well as in extracellular fluids such as colostrum, amniotic fluid and cervical mucus (Costantini et al. 2002; Fernandez et al 2005; Makris et al. 2012; Wenyi et al. 2012). Neutrophils, monocytes/macrophages and adipocytes are the cells with abundant NGAL expression. Consequently, NGAL seems to have a crucial role in numerous physiological and pathological pathways including antibacterial activity, embryogenesis, neoplastic growth, renal-cardiovascular disease and epithelium function (Makris et al. 2012).
Relationship between morning peak phenomenon and early renal injury NGAL in H-type hypertension
Published in Blood Pressure, 2022
Chi Zhang, Dan-Dan Zhang, Yu-Mei Feng, Zhan-Qiang Huang, Yun-BO Xie, Jian Zhou, Jun Li
The results of this study showed that CysC, β_2-MG, and NGAL levels were higher in the morning peak group than in the non-morning peak group in patients with H hypertension with BUN, Cr, and UA in the normal range. CysC is a newly discovered biomarker of endogenous renal injury, which is widely used for the detection of early and acute and chronic renal failure. CysC is neither actively secreted into the small intestine nor reabsorbed into the plasma and is completely reabsorbed and catabolized by renal tubular epithelial cells after filtration. Its concentration in serum is almost entirely dependent on renal function. There is a negative correlation between serum Cys-C and glomerular filtration rate, and serum concentrations are independent of age, muscle mass, sex, and diet. Serum CysC concentrations are extremely sensitive to changes in GFR, and serum Cys-C is elevated by minor glomerular injury and varies with disease [12,13]. Measurement of serum and urine CysC is routinely used to evaluate kidney function [14]. 12,15,16]. This study showed that NGAL was associated with CysC and 17]. NGAL can be used as an acute kidney injury biomarker because it is rapidly released in renal tubular injury.NGAL has good stability and resistance to proteases, making it a preferred biomarker for clinical use [18], and studies abroad have shown that NGAL has good sensitivity and specificity in predicting kidney injury.