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


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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.

Sobre autores

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

Autor responsável pela correspondência
Email: info@benthamscience.net

Bibliografia

  1. 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
  2. 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
  3. 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
  4. 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
  5. Khwaja, A. KDIGO clinical practice guidelines for acute kidney injury. Nephron Clin. Pract., 2012, 120(4), c179-c184. doi: 10.1159/000339789 PMID: 22890468
  6. 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
  7. 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
  8. 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
  9. 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
  10. 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
  11. Yang, L.; Brooks, C.R.; Xiao, S.; Sabbisetti, V.; Yeung, M.Y.; Hsiao, L.L.; Ichimura, T.; Kuchroo, V.; Bonventre, J.V. KIM-1–mediated phagocytosis reduces acute injury to the kidney. J. Clin. Invest., 2015, 125(4), 1620-1636. doi: 10.1172/JCI75417 PMID: 25751064
  12. 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
  13. 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
  14. 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
  15. Velez, J.C.Q. The importance of the intrarenal renin–angiotensin system. Nat. Clin. Pract. Nephrol., 2009, 5(2), 89-100. doi: 10.1038/ncpneph1015 PMID: 19065132
  16. 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
  17. 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
  18. 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
  19. 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
  20. 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
  21. 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.
  22. Section 2: AKI definition. Kidney Int. Suppl., 2011, 2(1), 19-36. doi: 10.1038/kisup.2011.32 PMID: 25018918
  23. 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
  24. 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
  25. 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
  26. 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
  27. 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
  28. 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
  29. 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
  30. 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
  31. 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
  32. 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
  33. 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
  34. 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
  35. 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
  36. 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
  37. Kobori, H.; Urushihara, M. Augmented intrarenal and urinary angiotensinogen in hypertension and chronic kidney disease. Pflugers Arch., 2013, 465(1), 3-12. PMID: 22918624
  38. 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
  39. 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

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