Combination of Urinary Neutrophil Gelatinase-associated Lipocalin, Kidney Injury Molecular-1, and Angiotensinogen for the Early Diagnosis and Mortality Prediction of Septic Acute Kidney Injury
- Authors: Li N.1, Zhang X.1, Wan P.2, Yu M.2, Min J.1
-
Affiliations:
- Department of Critical Care Medicine, Dangyang Renmin Hospital of Hubei Province
- Department of Critical Care Medicine, The First College of Clinical Medical Science, China Three Gorges University (Yichang Central People's Hospital)
- Issue: Vol 27, No 7 (2024)
- Pages: 1033-1045
- Section: Chemistry
- URL: https://vietnamjournal.ru/1386-2073/article/view/644935
- DOI: https://doi.org/10.2174/0113862073263073231011060142
- ID: 644935
Cite item
Full Text
Abstract
Background:Acute kidney injury (AKI) is one of the most severe complications of sepsis. This study was conducted to analyze the role of urinary neutrophil gelatinase-associated lipocalin (uNGAL), urinary kidney injury molecular-1 (uKIM-1), and urinary angiotensinogen (uAGT) in the early diagnosis and mortality prediction of septic AKI.
Methods:The prospective study enrolled 80 sepsis patients in the ICU and 100 healthy individuals and divided patients into an AKI group and a non-AKI group. uNGAL, uKIM-1, uAGT, serum creatinine/procalcitonin/C-reaction protein, and other indicators were determined, and clinical prediction scores were recorded. The sensitivity and specificity of uNGAL, uKIM-1, and uAGT in diagnosis and mortality prediction were analyzed by the receiver operator characteristic (ROC) curve and the area under the curve (AUC).
Results:uNGAL, uKIM-1, and uAGT levels were higher in sepsis patients than healthy controls, higher in AKI patients than non-AKI patients, and higher in AKI-2 and AKI-3 patients than AKI-1 patients. At 0 h after admission, the combined efficacy of three indicators in septic AKI diagnosis (ROC-AUC: 0.770; sensitivity: 82.5%; specificity: 70.0%) was better than a single indicator. At 24 h, uNGAL, uKIM-1, and uAGT levels were higher in sepsis non-survivals than survivals and higher in septic AKI non-survivals than septic AKI survivals. The combined efficacy of three indicators in the prediction of sepsis/septic AKI mortality (ROC-AUC: 0.828/0.847; sensitivity: 71.4%/100.0%; specificity: 82.7%/66.7%) was better than a single indicator.
Conclusion:uNGAL, uKIM-1, and uAGT levels were increased in septic AKI, and their combination helped the early diagnosis and mortality prediction.
Keywords
About the authors
Na Li
Department of Critical Care Medicine, Dangyang Renmin Hospital of Hubei Province
Email: info@benthamscience.net
Xuelian Zhang
Department of Critical Care Medicine, Dangyang Renmin Hospital of Hubei Province
Email: info@benthamscience.net
Peng Wan
Department of Critical Care Medicine, The First College of Clinical Medical Science, China Three Gorges University (Yichang Central People's Hospital)
Email: info@benthamscience.net
Min Yu
Department of Critical Care Medicine, The First College of Clinical Medical Science, China Three Gorges University (Yichang Central People's Hospital)
Email: info@benthamscience.net
Jinyi Min
Department of Critical Care Medicine, Dangyang Renmin Hospital of Hubei Province
Author for correspondence.
Email: info@benthamscience.net
References
- Fernando, S.M.; Rochwerg, B.; Seely, A.J.E. Clinical implications of the third international consensus definitions for sepsis and septic shock (Sepsis-3). CMAJ, 2018, 190(36), E1058-E1059. doi: 10.1503/cmaj.170149 PMID: 30201611
- Ma, S.; Evans, R.G.; Iguchi, N.; Tare, M.; Parkington, H.C.; Bellomo, R.; May, C.N.; Lankadeva, Y.R. Sepsis‐induced acute kidney injury: A disease of the microcirculation. Microcirculation, 2019, 26(2), e12483. doi: 10.1111/micc.12483 PMID: 29908046
- Bagshaw, S.M.; Uchino, S.; Bellomo, R.; Morimatsu, H.; Morgera, S.; Schetz, M.; Tan, I.; Bouman, C.; Macedo, E.; Gibney, N.; Tolwani, A.; Oudemans-van Straaten, H.M.; Ronco, C.; Kellum, J.A. Septic acute kidney injury in critically ill patients: Clinical characteristics and outcomes. Clin. J. Am. Soc. Nephrol., 2007, 2(3), 431-439. doi: 10.2215/CJN.03681106 PMID: 17699448
- Keir, I.; Kellum, J.A. Acute kidney injury in severe sepsis: Pathophysiology, diagnosis, and treatment recommendations. J. Vet. Emerg. Crit. Care, 2015, 25(2), 200-209. doi: 10.1111/vec.12297 PMID: 25845505
- Khwaja, A. KDIGO clinical practice guidelines for acute kidney injury. Nephron Clin. Pract., 2012, 120(4), c179-c184. doi: 10.1159/000339789 PMID: 22890468
- Bellomo, R.; Ronco, C.; Kellum, J.A.; Mehta, R.L.; Palevsky, P. Acute renal failure: Definition, outcome measures, animal models, fluid therapy and information technology needs: The second international consensus conference of the acute dialysis quality initiative (ADQI) group. Crit. Care, 2004, 8(4), R204-R212. doi: 10.1186/cc2872 PMID: 15312219
- Bagshaw, S.M. Diagnosis and classification of AKI: AKIN or RIFLE? Nat. Rev. Nephrol., 2010, 6(2), 71-73. doi: 10.1038/nrneph.2009.225 PMID: 20111048
- Shum, H.P.; Yan, W.W.; Chan, T.M. Recent knowledge on the pathophysiology of septic acute kidney injury: A narrative review. J. Crit. Care, 2016, 31(1), 82-89. doi: 10.1016/j.jcrc.2015.09.017 PMID: 26475099
- Marakala, V. Neutrophil gelatinase-associated lipocalin (NGAL) in kidney injury: A systematic review. Clin. Chim. Acta, 2022, 536, 135-141. doi: 10.1016/j.cca.2022.08.029 PMID: 36150522
- Mishra, J.; Ma, Q.; Prada, A.; Mitsnefes, M.; Zahedi, K.; Yang, J.; Barasch, J.; Devarajan, P. Identification of neutrophil gelatinase-associated lipocalin as a novel early urinary biomarker for ischemic renal injury. J. Am. Soc. Nephrol., 2003, 14(10), 2534-2543. doi: 10.1097/01.ASN.0000088027.54400.C6 PMID: 14514731
- Yang, L.; Brooks, C.R.; Xiao, S.; Sabbisetti, V.; Yeung, M.Y.; Hsiao, L.L.; Ichimura, T.; Kuchroo, V.; Bonventre, J.V. KIM-1mediated phagocytosis reduces acute injury to the kidney. J. Clin. Invest., 2015, 125(4), 1620-1636. doi: 10.1172/JCI75417 PMID: 25751064
- Karmakova capital Te, C.A.C.; Sergeeva, N.S.; Kanukoev capital Ka, C.; Alekseev, B.Y.; Kaprin capital A, C. Kidney injury molecule 1 (KIM-1): A multifunctional glycoprotein and biological marker. Sovrem. Tekhnologii Med., 2021, 13(3), 64-78. doi: 10.17691/stm2021.13.3.08 PMID: 34603757
- Tu, Y.; Wang, H.; Sun, R.; Ni, Y.; Ma, L.; Xv, F.; Hu, X.; Jiang, L.; Wu, A.; Chen, X.; Chen, M.; Liu, J.; Han, F. Urinary netrin-1 and KIM-1 as early biomarkers for septic acute kidney injury. Ren. Fail., 2014, 36(10), 1559-1563. doi: 10.3109/0886022X.2014.949764 PMID: 25154466
- Ganda, I.J.; Kasri, Y.; Susanti, M.; Hamzah, F.; Rauf, S.; Albar, H.; Aras, J.; Fikri, B.; Lawang, S.A.; Daud, D.; Laompo, A.; Massi, M.N. Kidney injury molecule type-1, interleukin-18, and insulin-like growth factor binding protein 7 levels in urine to predict acute kidney injury in pediatric sepsis. Front Pediatr., 2022, 10, 1024713. doi: 10.3389/fped.2022.1024713 PMID: 36545669
- Velez, J.C.Q. The importance of the intrarenal reninangiotensin system. Nat. Clin. Pract. Nephrol., 2009, 5(2), 89-100. doi: 10.1038/ncpneph1015 PMID: 19065132
- Ba Aqeel, S.H.; Sanchez, A.; Batlle, D. Angiotensinogen as a biomarker of acute kidney injury. Clin. Kidney J., 2017, 10(6), 759-768. doi: 10.1093/ckj/sfx087 PMID: 29225804
- Alge, J.L.; Karakala, N.; Neely, B.A.; Janech, M.G.; Velez, J.C.Q.; Arthur, J.M.; Investigators, S.A. Urinary angiotensinogen predicts adverse outcomes among acute kidney injury patients in the intensive care unit. Crit. Care, 2013, 17(2), R69. doi: 10.1186/cc12612 PMID: 23587112
- Alge, J.L.; Karakala, N.; Neely, B.A.; Janech, M.G.; Tumlin, J.A.; Chawla, L.S.; Shaw, A.D.; Arthur, J.M.; Investigators, S.A. Urinary angiotensinogen and risk of severe AKI. Clin. J. Am. Soc. Nephrol., 2013, 8(2), 184-193. doi: 10.2215/CJN.06280612 PMID: 23143504
- Singer, M.; Deutschman, C.S.; Seymour, C.W.; Shankar-Hari, M.; Annane, D.; Bauer, M.; Bellomo, R.; Bernard, G.R.; Chiche, J.D.; Coopersmith, C.M.; Hotchkiss, R.S.; Levy, M.M.; Marshall, J.C.; Martin, G.S.; Opal, S.M.; Rubenfeld, G.D.; van der Poll, T.; Vincent, J.L.; Angus, D.C. The Third international consensus definitions for sepsis and septic shock (Sepsis-3). JAMA, 2016, 315(8), 801-810. doi: 10.1001/jama.2016.0287 PMID: 26903338
- Rhodes, A.; Evans, L.E.; Alhazzani, W.; Levy, M.M.; Antonelli, M.; Ferrer, R.; Kumar, A.; Sevransky, J.E.; Sprung, C.L.; Nunnally, M.E.; Rochwerg, B.; Rubenfeld, G.D.; Angus, D.C.; Annane, D.; Beale, R.J.; Bellinghan, G.J.; Bernard, G.R.; Chiche, J.D.; Coopersmith, C.; De Backer, D.P.; French, C.J.; Fujishima, S.; Gerlach, H.; Hidalgo, J.L.; Hollenberg, S.M.; Jones, A.E.; Karnad, D.R.; Kleinpell, R.M.; Koh, Y.; Lisboa, T.C.; Machado, F.R.; Marini, J.J.; Marshall, J.C.; Mazuski, J.E.; McIntyre, L.A.; McLean, A.S.; Mehta, S.; Moreno, R.P.; Myburgh, J.; Navalesi, P.; Nishida, O.; Osborn, T.M.; Perner, A.; Plunkett, C.M.; Ranieri, M.; Schorr, C.A.; Seckel, M.A.; Seymour, C.W.; Shieh, L.; Shukri, K.A.; Simpson, S.Q.; Singer, M.; Thompson, B.T.; Townsend, S.R.; Van der Poll, T.; Vincent, J.L.; Wiersinga, W.J.; Zimmerman, J.L.; Dellinger, R.P. Surviving sepsis campaign: International guidelines for management of sepsis and septic shock: 2016. Intensive Care Med., 2017, 43(3), 304-377. doi: 10.1007/s00134-017-4683-6 PMID: 28101605
- Kellum, J.A.; Lameire, N.; Aspelin, P.; Barsoum, R.S.; Burdmann, E.A.; Goldstein, S.L.; Herzog, C.A.; Joannidis, M.; Kribben, A.; Levey, A.S.; MacLeod, A.M.; Mehta, R.L.; Murray, P.T.; Naicker, S.; Opal, S.M.; Schaefer, F.; Schetz, M.; Uchino, S. Kidney disease: Improving global outcomes (KDIGO) acute kidney injury work group. KDIGO clinical practice guideline for acute kidney injury. Kidney Int. Suppl., 2012, 2(1), 1-138.
- Section 2: AKI definition. Kidney Int. Suppl., 2011, 2(1), 19-36. doi: 10.1038/kisup.2011.32 PMID: 25018918
- Qiu, Z.L.; Yan, B.Q.; Zhao, R.; Xu, D.W.; Shen, K.; Deng, X.; Lu, S.Q. Combination of hepcidin with neutrophil gelatinase-associated lipocalin for prediction of the development of sepsis-induced acute kidney injury. Clin. Chim. Acta, 2021, 523, 38-44. doi: 10.1016/j.cca.2021.08.029 PMID: 34480953
- Pei, Y.; Zhou, G.; Wang, P.; Shi, F.; Ma, X.; Zhu, J. Serum cystatin C, kidney injury molecule-1, neutrophil gelatinase-associated lipocalin, klotho and fibroblast growth factor-23 in the early prediction of acute kidney injury associated with sepsis in a Chinese emergency cohort study. Eur. J. Med. Res., 2022, 27(1), 39. doi: 10.1186/s40001-022-00654-7 PMID: 35272698
- Bolignano, D.; Donato, V.; Coppolino, G.; Campo, S.; Buemi, A.; Lacquaniti, A.; Buemi, M. Neutrophil gelatinase-associated lipocalin (NGAL) as a marker of kidney damage. Am. J. Kidney Dis., 2008, 52(3), 595-605. doi: 10.1053/j.ajkd.2008.01.020 PMID: 18725016
- Han, M.; Li, Y.; Wen, D.; Liu, M.; Ma, Y.; Cong, B. NGAL protects against endotoxin-induced renal tubular cell damage by suppressing apoptosis. BMC Nephrol., 2018, 19(1), 168. doi: 10.1186/s12882-018-0977-3 PMID: 29980183
- de Geus, H.R.H.; Betjes, M.G.; Schaick, R.; Groeneveld, J.A.B.J. Plasma NGAL similarly predicts acute kidney injury in sepsis and nonsepsis. Biomarkers Med., 2013, 7(3), 415-421. doi: 10.2217/bmm.13.5 PMID: 23734805
- Zhang, A.; Cai, Y.; Wang, P.F.; Qu, J.N.; Luo, Z.C.; Chen, X.D.; Huang, B.; Liu, Y.; Huang, W.Q.; Wu, J.; Yin, Y.H. Diagnosis and prognosis of neutrophil gelatinase-associated lipocalin for acute kidney injury with sepsis: A systematic review and meta-analysis. Crit. Care, 2016, 20(1), 41. doi: 10.1186/s13054-016-1212-x PMID: 26880194
- Hu, B.; Li, D.; Lu, Y.; Ling, Y.; Zhang, L.; Ling, Y.; Chen, H.; Tan, M.; Jiang, H.; Xu, X.; Shi, W. Early diagnostic value of urinary ngal in acute kidney injury in septic patients. Altern. Ther. Health Med., 2022, 28(7), 120-124. PMID: 35751900
- Lee, C.W.; Kou, H.; Chou, H.S.; Chou, H.; Huang, S.F.; Chang, C.H.; Wu, C.H.; Yu, M.C.; Tsai, H.I. A combination of SOFA score and biomarkers gives a better prediction of septic AKI and in-hospital mortality in critically ill surgical patients: A pilot study. World J. Emerg. Surg., 2018, 13(1), 41. doi: 10.1186/s13017-018-0202-5 PMID: 30214469
- Rewa, O.; Wald, R.; Adhikari, N.K.J.; Hladunewich, M.; Lapinsky, S.; Muscedere, J.; Bagshaw, S.M.; Smith, O.M.; Lebovic, G.; Kuint, R.; Klein, D.J. Whole-blood neutrophil gelatinase-associated lipocalin to predict adverse events in acute kidney injury: A prospective observational cohort study. J. Crit. Care, 2015, 30(6), 1359-1364. doi: 10.1016/j.jcrc.2015.08.019 PMID: 26421697
- Mårtensson, J.; Bellomo, R. The rise and fall of NGAL in acute kidney injury. Blood Purif., 2014, 37(4), 304-310. doi: 10.1159/000364937 PMID: 25170751
- Zhang, C.F.; Wang, H.J.; Tong, Z.H.; Zhang, C.; Wang, Y.S.; Yang, H.Q.; Gao, R.Y.; Shi, H.Z. The diagnostic and prognostic values of serum and urinary kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin in sepsis induced acute renal injury patients. Eur. Rev. Med. Pharmacol. Sci., 2020, 24(10), 5604-5617. PMID: 32495895
- de Geus, H.R.H.; Fortrie, G.; Betjes, M.G.H.; van Schaik, R.H.N.; Groeneveld, A.B.J. Time of injury affects urinary biomarker predictive values for acute kidney injury in critically ill, non-septic patients. BMC Nephrol., 2013, 14(1), 273. doi: 10.1186/1471-2369-14-273 PMID: 24321290
- Cuesta, C.; Fuentes-Calvo, I.; Sancho-Martinez, S.M.; Valentijn, F.A.; Düwel, A.; Hidalgo-Thomas, O.A.; Agüeros-Blanco, C.; Benito-Hernández, A.; Ramos-Barron, M.A.; Gómez-Alamillo, C.; Arias, M.; Nguyen, T.Q.; Goldschmeding, R.; Martínez-Salgado, C.; López-Hernández, F.J. Urinary KIM-1 correlates with the subclinical sequelae of tubular damage persisting after the apparent functional recovery from intrinsic acute kidney injury. Biomedicines, 2022, 10(5), 1106. doi: 10.3390/biomedicines10051106 PMID: 35625842
- Mu, L.; Hu, G.; Liu, J.; Chen, Y.; Cui, W.; Qiao, L. Protective effects of naringenin in a rat model of sepsis-triggered acute kidney injury via activation of antioxidant enzymes and reduction in urinary angiotensinogen. Med. Sci. Monit., 2019, 25, 5986-5991. doi: 10.12659/MSM.916400 PMID: 31401645
- Kobori, H.; Urushihara, M. Augmented intrarenal and urinary angiotensinogen in hypertension and chronic kidney disease. Pflugers Arch., 2013, 465(1), 3-12. PMID: 22918624
- Cruz-López, E.O.; Ye, D.; Wu, C.; Lu, H.S.; Uijl, E.; Mirabito Colafella, K.M.; Danser, A.H.J. Angiotensinogen suppression: A new tool to treat cardiovascular and renal disease. Hypertension, 2022, 79(10), 2115-2126. doi: 10.1161/HYPERTENSIONAHA.122.18731 PMID: 35904033
- Ji, J.; Luo, H.; Shi, J. Clinical value of serum miR‐320‐3p expression in predicting the prognosis of sepsis‐induced acute kidney injury. J. Clin. Lab. Anal., 2022, 36(5), e24358. doi: 10.1002/jcla.24358 PMID: 35334494
Supplementary files
