Concentrations of neutrophil gelatinase-associated lipocalin are increased in serum and peritoneal fluid from horses with inflammatory abdominal disease and non-strangulating intestinal infarctions.
Abstract: Neutrophil gelatinase-associated lipocalin (NGAL) is produced in response to inflammation in horses, but it has not yet been investigated as a biomarker in horses with the abdominal disease. Objective: To investigate NGAL in serum and peritoneal fluid in horses with the abdominal disease. Methods: Retrospective clinical study. Methods: Data from medical records of 270 horses admitted with acute abdominal disease (simple obstructions [n = 43], strangulating obstructions [n = 104], inflammatory abdominal disease [n = 99], non-strangulating intestinal infarction [NSII, n = 24]) and 9 healthy control horses were reviewed, and serum and peritoneal fluid samples were retrieved from a biobank. NGAL was measured in serum and peritoneal fluid by ELISA. Differences in NGAL concentrations between groups were assessed. Results: Healthy horses had low serum and peritoneal fluid concentrations of NGAL (median = 21.0 and 9.5 μg/L, respectively). Neither serum nor peritoneal fluid NGAL concentrations (median serum, peritoneal fluid) differed between healthy horses and horses with simple (28.1 μg/L, 13.0 μg/L) and strangulating intestinal obstructions (34.7 μg/L, 38.4 μg/L). Horses with NSII (308.0 μg/L, 2163.0 μg/L) and inflammatory abdominal disease (171.1 μg/L, 314.1 μg/L) had higher serum and peritoneal fluid concentrations of NGAL than the other groups (p < 0.001). Peritoneal fluid NGAL concentrations in horses with NSII were higher than in horses with inflammatory abdominal disease (p = 0.03). Conclusions: Retrospective study design; small group of control horses. Conclusions: NGAL is a marker of inflammation in horses with the abdominal disease. The high peritoneal fluid concentration of NGAL in horses with NSII compared to all other groups may render NGAL useful for identifying this condition, which is otherwise difficult to differentiate from other types of peritonitis. Thereby, NGAL may potentially facilitate timely surgical intervention in this group of patients. The results of this study must be evaluated in larger, and preferably prospective, studies to obtain a more comprehensive evaluation of the diagnostic utility of NGAL. Unassigned: Lipocalina associada à gelatinase de neutrófilos (NGAL) é produzida em resposta à inflamação em equinos, mas ainda não foi investigada como biomarcador de equinos com doenças abdominais. Objective: Investigar a NGAL no soro e líquido peritoneal (LP) de equinos com doenças abdominais. Unassigned: Estudo retrospectivo. Methods: Informação de prontuários médicos de 270 equinos com doença abdominal (obstrução simples [n = 43], obstrução estrangulante [n = 104], doença abdominal inflamatória [n = 99], lesão de infarto não estrangulante [NSII, n = 24]) e nove equinos saudáveis como controle foram revisados, e o soro e LP foram obtidos de um biobank. NGAL foi mensurado no soro e LP através de ELISA. Diferenças na concentração de NGAL entre os grupos foi avaliada. Results: Cavalos saudáveis tiveram concentração de NGAL baixas no soro e no LP (mediana = 21.0 e 9.5 μg/L, respectivamente). A concentração de NGAL no soro e no LP não diferiram entre cavalos saudáveis e cavalos com obstrução simples (28.1,13.0) e obstrução estrangulante (34.7, 38.4). Cavalos com NSII (308.0, 2163.0) e doença abdominal inflamatória (171.1314.1) tiveram concentrações mais altas de NGAL no soro e LP quando comparados aos outros grupos (p < 0.001). A concentração de NGAL no LP em cavalos com NSII foi mais alta do que em cavalos com doença abdominal inflamatória (p = 0.03). PRINCIPAIS LIMITAÇÕES: Delineamento de estudo retrospectivo e pequeno grupo de equinos controle. CONCLUSÕES: NGAL é um marcador de inflamação em cavalos com doença abdominal. A concentração alta de NGAL no LP de cavalos com NSII comparado com os outros grupos indica que NGAL pode ser útil em identificar essa condição, o que é usualmente difícil de diferenciar de outros tipos de peritonite. Contudo, NGAL tem o potencial de facilitar a decisão rápida da necessidade de intervenção cirúrgica nesse grupo de pacientes. Os resultados deste estudo devem ser avaliados em uma população maior (e preferencialmente prospectiva) para obter uma melhor avaliação compreensiva da utilidade diagnóstica do NGAL.
The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.
The research article investigates the potential of Neutrophil gelatinase-associated lipocalin (NGAL) as a biomarker in horses with abdominal disease. The results suggest that increased levels of NGAL in serum and peritoneal fluid can signify inflammation, and might be especially useful for the detection of non-strangulating intestinal infarction.
Objectives and Methodology
The primary objective of the research was to investigate the role of NGAL, a protein produced in response to inflammation, as a potential biomarker in horses with abdominal disease.
The study used a retrospective clinical approach utilizing data from medical records of 270 horses admitted with varying types of acute abdominal disease – simple obstructions, strangulating obstructions, inflammatory abdominal disease, and non-strangulating intestinal infarctions (NSII), along with 9 healthy control horses.
They retrieved serum and peritoneal fluid NGAL samples from a biobank and measured NGAL concentrations using ELISA. The concentrations between different groups were then compared for significant differences.
Results
Healthy horses confirmed low NGAL levels in both serum and peritoneal fluid.
No significant difference in NGAL concentrations was found between healthy horses and those with simple and strangulating obstructions.
However, horses with NSII and inflammatory abdominal disease showed significantly raised NGAL concentrations in both serum and peritoneal fluid.
Most notably, the peritoneal fluid NGAL concentrations in horses with NSII were higher than in those with inflammatory abdominal disease.
Conclusions
The retrospective study concluded that NGAL could serve as an inflammation marker in horses with abdominal disease.
Particularly, the high peritoneal fluid NGAL in horses with NSII as compared to all other groups may prove useful in detecting this condition. Typically, peritonitis types are challenging to differentiate, and NGAL may help in deciding for a timely surgical intervention.
The researchers caution that the results need further evaluation through larger, preferably prospective, studies for a more comprehensive assessment of NGAL’s diagnostic utility.
Limitations
One significant limitation is the study’s retrospective design, which could overlook potential confounding factors affecting the results.
Additionally, the small group of control horses may limit the generalizability of the conclusions.
Cite This Article
APA
Winther MF, Haugaard SL, Pihl TH, Jacobsen S.
(2022).
Concentrations of neutrophil gelatinase-associated lipocalin are increased in serum and peritoneal fluid from horses with inflammatory abdominal disease and non-strangulating intestinal infarctions.
Equine Vet J, 55(3), 426-434.
https://doi.org/10.1111/evj.13603
Kjeldsen L, Johnsen AH, Sengelov H, Borregaard N. Isolation and primary structure of NGAL, a novel protein associated with human neutrophil gelatinase. J Biol Chem 1993;268:10425-32.
Jayaraman A, Roberts KA, Yoon J, Yarmush DM, Duan X, Lee K. Identification of neutrophil gelatinase-associated lipocalin (NGAL) as a discriminatory marker of the hepatocyte-secreted protein response to IL-1β: a proteomic analysis. Biotechnol Bioeng 2005;91:502-15.
Cowland JB, Borregaard N. Molecular characterization and pattern of tissue expression of the gene for neutrophil gelatinase-associated lipocalin from humans. Genomics 1997;45:17-23.
Mishra J, Qing MA, Prada A, Mitsnefes M, Zahedi K, Yang J. Identification of neutrophil gelatinase-associated lipocalin as a novel early urinary biomarker for ischemic renal injury. J Am Soc Nephrol 2003;14:2534-43.
Aigner F, Maier HT, Schwelberger HG, Wallnöfer EA, Amberger A, Obrist P. Lipocalin-2 regulates the inflammatory response during ischemia and reperfusion of the transplanted heart. Am J Transplant 2007;7:779-88.
Mishra J, Dent C, Tarabishi R, Mitsnefes MM, Ma Q, Kelly C. Neutrophil gelatinase-associated lipocalin (NGAL) as a biomarker for acute renal injury after cardiac surgery. Lancet 2005;365:1231-8.
Lee Y-J, Hu Y-Y, Lin Y-S, Chang C-T, Lin F-Y, Wong M-L. Correction: urine neutrophil gelatinase-associated lipocalin (NGAL) as a biomarker for acute canine kidney injury. BMC Vet Res 2013;9:228.
Steinbach S, Weis J, Schweighauser A, Francey T, Neiger R. Plasma and urine neutrophil gelatinase-associated lipocalin (NGAL) in dogs with acute kidney injury or chronic kidney disease. J Vet Intern Med 2014;28:264-9.
Mårtensson J, Bell M, Oldner A, Xu S, Venge P, Martling C-R. Neutrophil gelatinase-associated lipocalin in adult septic patients with and without acute kidney injury. Intensive Care Med 2010;36:1333-40.
van Galen G, Jacobsen S, Vinther AM, Breinholt Laurberg M, Tvermose E, Broe-Brøndum R. 11th Annual European College of Equine Internal Medicine Congress 9-10 November, 2018. J Vet Intern Med 2019;33:1549.
Oikonomou KA, Kapsoritakis AN, Theodoridou C, Karangelis D, Germenis A, Stefanidis I. Neutrophil gelatinase-associated lipocalin (NGAL) in inflammatory bowel disease: association with pathophysiology of inflammation, established markers, and disease activity. J Gastroenterol 2012;47:519-30.
Budzyńska A, Nowakowska-Duława E, Gawron-Kiszka M, Spiewak J, Lesinska M, Kukla M. Serum neutrophil gelatinase-associated lipocalin correlates with Mayo Clinic score in ulcerative colitis but fails to predict activity in Crohn's disease. J Crohns Colitis 2017;11:S172-2.
Bolignano D, Della Torre A, Lacquaniti A, Costantino G, Fries W, Buemi M. Neutrophil gelatinase-associated lipocalin levels in patients with Crohn disease undergoing treatment with infliximab. J Invest Med 2010;58:569-71.
Nielsen OH, Gionchetti P, Ainsworth M, Vainer B, Campieri M, Borregaard N. Rectal dialysate and fecal concentrations of neutrophil gelatinase- associated lipocalin, interleukin-8, and tumor necrosis factor-α in ulcerative colitis. Am J Gastroenterol 1999;94:2923-8.
Axelsson L, Bergenfeldt M, Ohlsson K. Studies of the release and turnover of a human neutrophil lipocalin. Scand J Clin Lab Invest 1995;55:577-88.
Nielsen BS, Borregaard N, Bundgaard JR, Timshel S, Sehested M, Kjeldsen L. Induction of NGAL synthesis in epithelial cells of human colorectal neoplasia and inflammatory bowel diseases. Gut 1996;38:414-20.
Kjelgaard-Hansen M, Jacobsen S. Assay validation and diagnostic applications of major acute-phase protein testing in companion animals. Clin Lab Med 2011;31:51-70.
Kent J. Acute phase proteins: their use in veterinary diagnosis. Br Vet J 1992;148:279-82.
Abella V, Scotece M, Conde J, Gómez R, Lois A, Pino J. The potential of lipocalin-2/NGAL as biomarker for inflammatory and metabolic diseases. Biomarkers 2015;20:565-71.
Spanton JA, Mair TS, Sherlock CE, Fews D. Non-strangulating intestinal infarction in horses in the UK: a review of 15 cases. Equine Vet Educ 2020;32:603-10.
Southwood LL, Russell G. The use of clinical findings in the identification of equine peritonitis cases that respond favorably to medical therapy: retrospective study. J Vet Emerg Crit Care 2007;17:382-90.
Carlson M, Raab Y, Sevéus L, Xu S, Hällgren R, Venge P. Human neutrophil lipocalin is a unique marker of neutrophil inflammation in ulcerative colitis and proctitis. Gut 2002;50:501-6.
Haase-Fielitz A, Haase M, Devarajan P. Neutrophil gelatinase-associated lipocalin as a biomarker of acute kidney injury: a critical evaluation of current status. Ann Clin Biochem 2014;51:335-51.
Zhang Y, Fan Y, Mei Z. NGAL and NGALR overexpression in human hepatocellular carcinoma toward a molecular prognostic classification. Cancer Epidemiol 2012;36:294-9.
Cho HB, Kim JH. Lipocalin2 expressions correlate significantly with tumor differentiation in epithelial ovarian cancer. J Histochem Cytochem 2009;57:513-21.
Hemdahl AL, Gabrielsen A, Zhu C, Eriksson P, Hedin U, Kastrup J. Expression of neutrophil gelatinase-associated lipocalin in atherosclerosis and myocardial infarction. Arterioscler Thromb Vasc Biol 2006;26:136-42.
Law IKM, Xu A, Lam KSL, Berger T, Mak TW, Vanhoutte PM. Lipocalin-2 deficiency attenuates insulin resistance associated with aging and obesity. Diabetes 2010;59:72-882.
Moreno-Navarrete JM, Manco M, Ibá̃ez J, García-Fuentes E, Ortega F, Gorostiaga E. Metabolic endotoxemia and saturated fat contribute to circulating NGAL concentrations in subjects with insulin resistance. Int J Obes 2010;34:240-9.
Dai X, Zeng Z, Fu C, Zhang S, Cai Y, Chen Z. Diagnostic value of neutrophil gelatinase-associated lipocalin, cystatin C, and soluble triggering receptor expressed on myeloid cells-1 in critically ill patients with sepsis-associated acute kidney injury. Crit Care 2015;19:1-10.
Pedersen KR, Ravn HB, Hjortdal VE, Nørregaard R, Povlsen JV. Neutrophil gelatinase-associated Lipocalin (NGAL): validation of commercially available ELISA. Scand J Clin Lab Invest 2010;70:374-82.
Schuh MP, Nehus E, Ma Q, Haffner C, Bennett M, Krawczeski CD. Long-term stability of urinary biomarkers of acute kidney injury in children. Am J Kidney Dis 2016;67:56-61.