The effect of the presence of NGAL and KIM-1 in the bronchial aspiration fluid on mortality in intubated patients followed in the intensive care unit
Öz
Aim: Sepsis continues to be an important cause of mortality and morbidity in intensive care units. Therefore, it is important to predict the development of mortality in sepsis at an early stage. The search for prognostic markers that can be used to predict mortality in intensive care follow-up is still ongoing. This study was conducted to examine the effect of the presence of NGAL and KIM-1 in alveolar neutrophils on mortality.
Material and methods: Cell blocking was performed on bronchoalveolar lavage (BAL) fluid taken from 56 non-Covid-19 sepsis patients we followed up and stained with immunohistochemical staining.
Results: The mean age of the patients was 70.13±13, and the mean follow-up period in the intensive care unit was 27.5±18.3 days. NGAL protein was detected in macrophages or neutrophils in 19 (33.9%) patients. In chi-square analysis, no statistically significant correlation was found between the presence of NGAL expression and gender (p=0.931), the presence of sepsis (p=0.293), and survival (p=0.134). When patients with severe sepsis with more than 3% PNL cells in the BAL sample were analyzed (only 39 patients), there was no statistical difference between the presence of NGAL expression and gender (p=0.250), presence of sepsis (p=0.206) and survival (p=0.151). No significant relationship was found. KIM-1 expression was faintly positive in epithelial cells in the material of only 2 cases, and there was no statistical significance.
Conclusion: Sepsis is a common cause of death in intensive care units and causes systemic complications that can lead to multi-organ failure. Acute renal failure (ARF) is one of the most common complications and a cause of mortality. Although we think that monitoring of NGAL and KIM-1 proteins, which are early indicators of kidney damage, in lung fluids may give us an idea about mortality, we could not detect a significant statistical relationship in our study, probably due to the small number of cases. We think it is essential to investigate the relationship we question in large series.
Kaynakça
- 1.Seymour CW, Liu VX, Iwashyna TJ, Brunkhorst FM, Rea TD, Scherag A, et al. Assessment of clinical criteria for sepsis: for the third international consensus definitions for sepsis and septic shock (Sepsis-3). JAMA. 2016;315(8):762.
- 2.Fleischmann C, Scherag A, Adhikari NKJ, Hartog CS, Tsaganos T, Schlattmann P et al. Assessment of global incidence and mortality of hospital-treated sepsis current estimates and limitations. Am J Respir Crit Care Med. 2016;193:259–72.
- 3.Salomão R, Ferreira BL, Salomão MC, Santos SS, Azevedo LCP, Brunialti MKC. Sepsis: Evolving concepts and challenges. Brazilian J Med Biol Res. 2019;52:e8595.
- 4.Santiago-Sánchez GS, Pita-Grisanti V, Quiñones-Díaz B, Gumpper K, Cruz-Monserrate Z, Vivas-Mejía PE. Biological functions and therapeutic potential of lipocalin 2 in cancer. Int J Mol Sci. 2020;21:4365.
- 5.Crescenzi E, Leonardi A, Pacifico F. NGAL as a potential target in tumor microenvironment. Int J Mol Sci. 2021;22:12333.
- 6. Candido S, Maestro R, Polesel J, Catania A, Maira F, Signorelli SS et al. Roles of neutrophil gelatinase-associated lipocalin (NGAL) in human cancer. Oncotarget. 2014;5:1576–94.
- 7.Bolignano D, Donato V, Lacquaniti A, Fazio MR, Bono C, Coppolino G et al. Neutrophil gelatinase-associated lipocalin (NGAL) in human neoplasias: A new protein enters the scene. Cancer Lett. 2010;288:10–6.
- 8.Li Yang, Craig R Brooks, Sheng Xiao, Venkata Sabbisetti, Melissa Y Yeung, Li-Li Hsiao et al. KIM-1-mediated phagocytosis reduces acute injury to the kidney J Clin Invest. 2015;125:1620-36.
- 9.Liu L, Song Z, Zhao Y, Li C, Wei H, Ma J et al. HAVCR1 expression might be a novel prognostic factor for gastric cancer. PLoS One. 2018;13:e0206423.
- 10.Zheng X, Xu K, Chen L, Zhou Y, Jiang J. Prognostic value of TIM-1 expression in human non-small-cell lung cancer. J Transl Med. 2019;17:178.
- 11.Al-Bataineh MM, Kinlough CL, Mi Z, Jackson EK, Mutchler SM, Emlet DR et al. KIM-1-mediated anti-inflammatory activity is preserved by MUC1 induction in the proximal tubule during ischemia-reperfusion injury. Am J Physiol - Ren Physiol. 2021;321:F135–48.
- 12.Singer M, Deutschman CS, Seymour C, Shankar-Hari M, Annane D, Bauer M et al. The third international consensus definitions for sepsis and septic shock (Sepsis-3). JAMA. 2016;315:801-10.
- 13.Lisowska-Myjak B. Serum and urinary biomarkers of acute kidney injury. Blood Purif. 2010;29:357-65.
- 14.Kjeldsen L ,Johnsen AH, Sengeløv H, Borregaard N. Isolation and primary structure of NGAL, a novel protein associated with human neutrophil gelatinase. J Biol Chem. 1993;268:10425-32.
- 15.Hvidberg V, Jacobsen C, Strong RK, Cowland JB, Moestrup SK, Borregaard N. The endocytic receptor megalin binds the iron transporting neutrophil-gelatinase-associated lipocalin with high affinity and mediates its cellular uptake. FEBS Lett. 2005;579:773-7.
- 16.Goetz DH , Holmes MA, Borregaard N, Bluhm ME, Raymond KN, Strong RK. The neutrophil lipocalin NGAL is a bacteriostatic agent that interferes with siderophore-mediated iron acquisition. Mol Cell. 2002;10:1033-43.
- 17.Chakraborty S, Kaur S, Guha S, Batra SK. The multifaceted roles of neutrophil gelatinase associated lipocalin (NGAL) in inflammation and cancer. Biochim Biophys Acta. 2012;1826:129-69.
- 18.Laxminarayana R Devireddy , Claude Gazin, Xiaochun Zhu, Michael R Green. A cell-surface receptor for lipocalin 24p3 selectively mediates apoptosis and iron uptake. Cell. 2005;123:1293-305.
- 19.Schmidt-Ott KM, Mori K, Li JY, Kalandadze A, Cohen DJ, Devarajan P et al. Dual action of neutrophil gelatinase–associated lipocalin. J Am Soc Nephrol. 2007;18:407-13.
- 20.Yang J, Goetz D, Li J, Wang W, Mori K, Setlik D, et al. An iron delivery pathway mediated by a lipocalin. Mol Cell. 2002;10:1045-56.
- 21.Fjaertoft G, Foucard T, Xu S, Venge P. Human neutrophil lipocalin (HNL) as a diagnostic tool in children with acute infections: A study of the kinetics. Acta Paediatr. 2007;94:661–6.
- 22.Katano M, Okamoto K, Arito M, Kawakami Y, Kurokawa MS, Suematsu N et al. Implication of granulocyte-macrophage colony-stimulating factor induced neutrophil gelatinase-associated lipocalin in pathogenesis of rheumatoid arthritis revealed by proteome analysis. Arthritis Res Ther. 2009;11:R3
- 23.Moniaux N , Chakraborty S, Yalniz M, Gonzalez J, Shostrom VK, Standop J. Early diagnosis of pancreatic cancer: neutrophil gelatinase-associated lipocalin as a marker of pancreatic intraepithelial neoplasia. Br J Cancer. 2008;98:1540-7.
- 24.Yndestad A, Landrø L, Ueland T, Dahl CP, Flo TH, Vinge LE et al. Increased systemic and myocardial expression of neutrophil gelatinase-associated lipocalin in clinical and experimental heart failure. Eur Heart J. 2009;30:1229-36.
- 25.Huo W, Zhang K, Nie Z, Li Q, Jin F. Kidney injury molecule-1 (KIM-1): a novel kidney-specific injury molecule playing potential double-edged functions in kidney injury. Transplant Rev (Orlando). 2010;24:143-6.
- 26.Bailly V , Zhang Z, Meier W, Cate R, Sanicola M, Bonventre JV. Shedding of kidney injury molecule-1, a putative adhesion protein involved in renal regeneration. J Biol Chem. 2002;277:39739-48.
- 27.Vaidya VS, Ramirez V, Ichimura T, Bobadilla NA, Bonventre J V. Urinary kidney injury molecule-1: A sensitive quantitative biomarker for early detection of kidney tubular injury. Am J Physiol Renal Physiol. 2006;290:F517-29.
Yoğun Bakımda Takip Edilen Entübe Hastalarda Bronşial Aspirasyon Sıvında NGAL ve KIM-1 Varlığının Mortalite Üzerine Etkisi
Öz
Amaç: Akut böbrek yetersizliği sepsisde en sık görülen komplikasyonlardan biridir ve mortalite nedenlerindendir. Böbrek hasarının erken göstergelerinden olan nötrofil jelatinaz ilişkili lipokalin (NGAL) ve böbrek hasarı molekül-1 (KIM-1) proteinlerinin akciğer sıvılarında izlenmesinin sepsiste mortalite gelişimini erken dönemde öngörebileceği düşünülmektedir. Bu çalışmada; alveolar nötrofillerde NGAL ve KIM-1 varlığı ile sepsiste böbrek hasarına bağlı mortalite arasındaki ilişki araştırılmıştır. Gereç ve Yöntemler: Takibini yaptığımız Covid-19 olmayan hastalardan alınan trakeal aspirasyon sıvısına hücre bloklaması yapılmış ve immunohistokimyasal boyama ile boyanmıştır. Bulgular: Çalışmaya toplam 56 hasta alınmıştır. Hastaların yaş ortalaması 70,13±13 yıl, yoğun bakımda ortalama takip süresi 27.5±18.3 gündür. Hastaların 19’unda (%33.9) makrofajlarda veya nötrofillerde NGAL proteini saptandı. NGAL ekspresyonunun varlığı ile cinsiyet (p=0,931), sepsis varlığı (p=0,293) ve sağ kalım arasında istatistiksel olarak anlamlı bir ilişki saptanmadı (p=0,134). Trakeal aspirasyon örneğinde %3’ün üzerinde şiddetli yangı hücresi varlığı olan şiddetli sepsisteki hastalar incelendiğinde (n=39), NGAL ekspresyonunun varlığı ile cinsiyet (p=0,250), sepsis varlığı (p=0,206) ve sağ kalım (p=0,151) arasında istatistiksel olarak anlamlı bir ilişki bulunamadı. KIM-1 ekspresyonu sadece 2 olgunun materyalindeki epitel hücrelerinde soluk pozitif olup, istatistiksel anlamlılık yoktu. Sonuç: Sepsis, yoğun bakım ünitelerinde sık karşılaşılan ölüm nedenlerinden olup, çoklu organ yetersizliğine gidebilen sistemik komplikasyonlara yol açar. Akut böbrek yetersizliği en sık görülen komplikasyonlardan biridir ve mortalite nedenlerindendir. Böbrek hasarının erken göstergelerinden olan NGAL ve KIM-1 proteinlerinin akciğer sıvılarında izlenmesinin mortalite hakkında fikir verebileceğini düşünsek de muhtemelen olgu sayısının azlığı nedeniyle çalışmamızda anlamlı istatistiksel ilişki saptayamadık. Sorguladığımız ilişkinin geniş serilerde araştırılmasının önemli olduğunu düşünüyoruz.
Anahtar Kelimeler
Kaynakça
- 1.Seymour CW, Liu VX, Iwashyna TJ, Brunkhorst FM, Rea TD, Scherag A, et al. Assessment of clinical criteria for sepsis: for the third international consensus definitions for sepsis and septic shock (Sepsis-3). JAMA. 2016;315(8):762.
- 2.Fleischmann C, Scherag A, Adhikari NKJ, Hartog CS, Tsaganos T, Schlattmann P et al. Assessment of global incidence and mortality of hospital-treated sepsis current estimates and limitations. Am J Respir Crit Care Med. 2016;193:259–72.
- 3.Salomão R, Ferreira BL, Salomão MC, Santos SS, Azevedo LCP, Brunialti MKC. Sepsis: Evolving concepts and challenges. Brazilian J Med Biol Res. 2019;52:e8595.
- 4.Santiago-Sánchez GS, Pita-Grisanti V, Quiñones-Díaz B, Gumpper K, Cruz-Monserrate Z, Vivas-Mejía PE. Biological functions and therapeutic potential of lipocalin 2 in cancer. Int J Mol Sci. 2020;21:4365.
- 5.Crescenzi E, Leonardi A, Pacifico F. NGAL as a potential target in tumor microenvironment. Int J Mol Sci. 2021;22:12333.
- 6. Candido S, Maestro R, Polesel J, Catania A, Maira F, Signorelli SS et al. Roles of neutrophil gelatinase-associated lipocalin (NGAL) in human cancer. Oncotarget. 2014;5:1576–94.
- 7.Bolignano D, Donato V, Lacquaniti A, Fazio MR, Bono C, Coppolino G et al. Neutrophil gelatinase-associated lipocalin (NGAL) in human neoplasias: A new protein enters the scene. Cancer Lett. 2010;288:10–6.
- 8.Li Yang, Craig R Brooks, Sheng Xiao, Venkata Sabbisetti, Melissa Y Yeung, Li-Li Hsiao et al. KIM-1-mediated phagocytosis reduces acute injury to the kidney J Clin Invest. 2015;125:1620-36.
- 9.Liu L, Song Z, Zhao Y, Li C, Wei H, Ma J et al. HAVCR1 expression might be a novel prognostic factor for gastric cancer. PLoS One. 2018;13:e0206423.
- 10.Zheng X, Xu K, Chen L, Zhou Y, Jiang J. Prognostic value of TIM-1 expression in human non-small-cell lung cancer. J Transl Med. 2019;17:178.
- 11.Al-Bataineh MM, Kinlough CL, Mi Z, Jackson EK, Mutchler SM, Emlet DR et al. KIM-1-mediated anti-inflammatory activity is preserved by MUC1 induction in the proximal tubule during ischemia-reperfusion injury. Am J Physiol - Ren Physiol. 2021;321:F135–48.
- 12.Singer M, Deutschman CS, Seymour C, Shankar-Hari M, Annane D, Bauer M et al. The third international consensus definitions for sepsis and septic shock (Sepsis-3). JAMA. 2016;315:801-10.
- 13.Lisowska-Myjak B. Serum and urinary biomarkers of acute kidney injury. Blood Purif. 2010;29:357-65.
- 14.Kjeldsen L ,Johnsen AH, Sengeløv H, Borregaard N. Isolation and primary structure of NGAL, a novel protein associated with human neutrophil gelatinase. J Biol Chem. 1993;268:10425-32.
- 15.Hvidberg V, Jacobsen C, Strong RK, Cowland JB, Moestrup SK, Borregaard N. The endocytic receptor megalin binds the iron transporting neutrophil-gelatinase-associated lipocalin with high affinity and mediates its cellular uptake. FEBS Lett. 2005;579:773-7.
- 16.Goetz DH , Holmes MA, Borregaard N, Bluhm ME, Raymond KN, Strong RK. The neutrophil lipocalin NGAL is a bacteriostatic agent that interferes with siderophore-mediated iron acquisition. Mol Cell. 2002;10:1033-43.
- 17.Chakraborty S, Kaur S, Guha S, Batra SK. The multifaceted roles of neutrophil gelatinase associated lipocalin (NGAL) in inflammation and cancer. Biochim Biophys Acta. 2012;1826:129-69.
- 18.Laxminarayana R Devireddy , Claude Gazin, Xiaochun Zhu, Michael R Green. A cell-surface receptor for lipocalin 24p3 selectively mediates apoptosis and iron uptake. Cell. 2005;123:1293-305.
- 19.Schmidt-Ott KM, Mori K, Li JY, Kalandadze A, Cohen DJ, Devarajan P et al. Dual action of neutrophil gelatinase–associated lipocalin. J Am Soc Nephrol. 2007;18:407-13.
- 20.Yang J, Goetz D, Li J, Wang W, Mori K, Setlik D, et al. An iron delivery pathway mediated by a lipocalin. Mol Cell. 2002;10:1045-56.
- 21.Fjaertoft G, Foucard T, Xu S, Venge P. Human neutrophil lipocalin (HNL) as a diagnostic tool in children with acute infections: A study of the kinetics. Acta Paediatr. 2007;94:661–6.
- 22.Katano M, Okamoto K, Arito M, Kawakami Y, Kurokawa MS, Suematsu N et al. Implication of granulocyte-macrophage colony-stimulating factor induced neutrophil gelatinase-associated lipocalin in pathogenesis of rheumatoid arthritis revealed by proteome analysis. Arthritis Res Ther. 2009;11:R3
- 23.Moniaux N , Chakraborty S, Yalniz M, Gonzalez J, Shostrom VK, Standop J. Early diagnosis of pancreatic cancer: neutrophil gelatinase-associated lipocalin as a marker of pancreatic intraepithelial neoplasia. Br J Cancer. 2008;98:1540-7.
- 24.Yndestad A, Landrø L, Ueland T, Dahl CP, Flo TH, Vinge LE et al. Increased systemic and myocardial expression of neutrophil gelatinase-associated lipocalin in clinical and experimental heart failure. Eur Heart J. 2009;30:1229-36.
- 25.Huo W, Zhang K, Nie Z, Li Q, Jin F. Kidney injury molecule-1 (KIM-1): a novel kidney-specific injury molecule playing potential double-edged functions in kidney injury. Transplant Rev (Orlando). 2010;24:143-6.
- 26.Bailly V , Zhang Z, Meier W, Cate R, Sanicola M, Bonventre JV. Shedding of kidney injury molecule-1, a putative adhesion protein involved in renal regeneration. J Biol Chem. 2002;277:39739-48.
- 27.Vaidya VS, Ramirez V, Ichimura T, Bobadilla NA, Bonventre J V. Urinary kidney injury molecule-1: A sensitive quantitative biomarker for early detection of kidney tubular injury. Am J Physiol Renal Physiol. 2006;290:F517-29.
Ayrıntılar
| Birincil Dil | Türkçe |
|---|---|
| Konular | Klinik Tıp Bilimleri |
| Bölüm | Araştırma Makaleleri |
| Yazarlar | |
| Yayımlanma Tarihi | 27 Eylül 2022 |
| Gönderilme Tarihi | 26 Temmuz 2022 |
| Yayımlandığı Sayı | Yıl 2022 Cilt: 1 Sayı: 2 |
Kaynak Göster
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.