Login Register Cart 0
Generic placeholder image

Combinatorial Chemistry & High Throughput Screening

Editor-in-Chief

ISSN (Print): 1386-2073
ISSN (Online): 1875-5402

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

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

Author(s): Na Li, Xuelian Zhang, Peng Wan, Min Yu and Jinyi Min*

Volume 27, Issue 7, 2024

Published on: 18 October, 2023

Page: [1033 - 1045] Pages: 13

DOI: 10.2174/0113862073263073231011060142

Price: $65

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: Sepsis, acute kidney injury, uNGAL, uKIM-1, uAGT, early diagnosis, severity assessment, mortality.

« Previous Next »
Graphical Abstract

[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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/10.1002/jcla.24358] [PMID: 35334494]

Rights & Permissions Print Cite
Article Metrics
16
2
Wayfinder Image
© 2024 Bentham Science Publishers | Privacy Policy