Enhanced Detection of Cardiac Surgery-Associated Acute Kidney Injury by a Composite Biomarker Panel in Patients with Normal Preoperative Kidney Function
Abstract
1. Introduction
2. Materials and Methods
2.1. Study Population
2.2. Cardiac Procedure Protocol
2.3. Blood Samples Collection
2.4. Statistical Analysis
3. Results
4. Discussion
4.1. Neutrophil Gelatinase-Associated Lipocalin
4.2. Cystatin C
4.3. Creatinine
4.4. Combined Model
4.5. Strengths and Limitations
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
- Conlon, P.J.; Stafford-Smith, M.; White, W.D.; Newman, M.F.; King, S.; Winn, M.P.; Landolfo, K. Acute Renal Failure Following Cardiac Surgery. Nephrol. Dial. Transplant. 1999, 14, 1158–1162. Available online: http://www.ncbi.nlm.nih.gov/pubmed/10344355 (accessed on 17 October 2018). [CrossRef] [PubMed]
- Hobson, C.E.; Yavas, S.; Segal, M.S.; Schold, J.D.; Tribble, C.G.; Layon, A.J.; Bihorac, A. Acute Kidney Injury Is Associated With Increased Long-Term Mortality after Cardiothoracic Surgery. Circulation 2009, 119, 2444–2453. [Google Scholar] [CrossRef] [PubMed]
- Hansen, M.; Gammelager, H.; Mikkelsen, M.; Hjortdal, V.; Layton, J.; Johnsen, S.; Christiansen, C. Post-operative acute kidney injury and five-year risk of death, myocardial infarction, and stroke among elective cardiac surgical patients: A cohort study. Crit. Care. 2013, 17, R292. [Google Scholar] [CrossRef] [PubMed]
- Huen, S.C.; Parikh, C.R. Predicting Acute Kidney Injury after Cardiac Surgery: A Systematic Review. Ann. Thorac. Surg. 2012, 93, 337–347. [Google Scholar] [CrossRef] [PubMed]
- Coca, S.G.; Yusuf, B.; Shlipak, M.G.; Garg, A.X.; Parikh, C.R. Long-term Risk of Mortality and Other Adverse Outcomes after Acute Kidney Injury: A Systematic Review and Meta-analysis. Am. J. Kidney Dis. 2009, 53, 961–973. [Google Scholar] [CrossRef] [PubMed]
- Mizuguchi, K.A.; Huang, C.-C.; Shempp, I.; Wang, J.; Shekar, P.; Frendl, G. Predicting kidney disease progression in patients with acute kidney injury after cardiac surgery. J. Thorac. Cardiovasc. Surg. 2018, 155, 2455–2463.e5. [Google Scholar] [CrossRef] [PubMed]
- Bellomo, R.; Ronco, C.; Kellum, J.A.; Mehta, R.L.; Palevsky, P. Acute Dialysis Quality Initiative workgroup, 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, R204–R212. [Google Scholar] [CrossRef] [PubMed]
- Nadim, M.K.; Forni, L.G.; Bihorac, A.; Hobson, C.; Koyner, J.L.; Shaw, A.; Arnaoutakis, G.J.; Ding, X.; Engelman, D.T.; Gasparovic, H.; et al. Cardiac and Vascular Surgery–Associated Acute Kidney Injury: The 20th International Consensus Conference of the ADQI (Acute Disease Quality Initiative) Group. J. Am. Heart Assoc. 2018, 7, e008834. [Google Scholar] [CrossRef] [PubMed]
- Vogt, F.; Zibert, J.; Bahovec, A.; Pollari, F.; Sirch, J.; Fittkau, M.; Bertsch, T.; Czerny, M.; Santarpino, G.; Fischlein, T.; et al. Improved creatinine-based early detection of acute kidney injury after cardiac surgery, Interact. Cardiovasc. Thorac. Surg. 2021, 33, 19–26. [Google Scholar] [CrossRef]
- Kalisnik, J.M.; Bauer, A.; Vogt, F.A.; Stickl, F.J.; Zibert, J.; Fittkau, M.; Bertsch, T.; Kounev, S.; Fischlein, T. Artificial intelligence-based early detection of acute kidney injury after cardiac surgery. Eur. J. Cardio-Thoracic Surg. 2022, 5, 6. [Google Scholar] [CrossRef] [PubMed]
- Zhou, F.; Luo, Q.; Wang, L.; Han, L. Diagnostic value of neutrophil gelatinase-associated lipocalin for early diagnosis of cardiac surgery-associated acute kidney injury: A meta-analysis. Eur. J. Cardio-Thoracic Surg. 2016, 49, 746–755. [Google Scholar] [CrossRef]
- Doi, K.; Urata, M.; Katagiri, D.; Inamori, M.; Murata, S.; Hisagi, M.; Ono, M.; Matsubara, T.; Ishii, T.; Yahagi, N.; et al. Plasma neutrophil gelatinase-associated lipocalin in acute kidney injury superimposed on chronic kidney disease after cardiac surgery: A multicenter prospective study. Crit. Care. 2013, 17, R270. [Google Scholar] [CrossRef]
- Kališnik, J.M.; Hrovat, E.; Hrastovec, A.; Žibert, J.; Jerin, A.; Skitek, M.; Santarpino, G.; Klokocovnik, T. Creatinine, Neutrophil Gelatinase-Associated Lipocalin, and Cystatin C in Determining Acute Kidney Injury after Heart Operations Using Cardiopulmonary Bypass. Artif. Organs. 2017, 41, 481–489. [Google Scholar] [CrossRef]
- Svensson, A.S.; Kovesdy, C.P.; Kvitting, J.-P.E.; Rosén, M.; Cederholm, I.; Szabó, Z. Comparison of serum cystatin C and creatinine changes after cardiopulmonary bypass in patients with normal preoperative kidney function. Int. Urol. Nephrol. 2013, 45, 1597–1603. [Google Scholar] [CrossRef][Green Version]
- Kidher, E.; Harling, L.; Ashrafian, H.; Naase, H.; Chukwuemeka, A.; Anderson, J.; Francis, D.P.; Athanasiou, T. Pulse wave velocity and neutrophil gelatinase-associated lipocalin as predictors of acute kidney injury following aortic valve replacement. J. Cardiothorac. Surg. 2014, 9, 89. [Google Scholar] [CrossRef]
- Collins, G.S.; Reitsma, J.B.; Altman, D.G.; Moons, K.G.M. Transparent reporting of a multivariable prediction model for individual prognosis or diagnosis (TRIPOD): The TRIPOD Statement. BMC Med. 2015, 13, 148–158. [Google Scholar] [CrossRef]
- Kalisnik, J.M.; Fischlein, T.; Santarpino, G. Cardiac surgery–associated neutrophil gelatinase–associated lipocalin score for postoperative acute kidney injury: What is the clinical implication? J. Thorac. Cardiovasc. Surg. 2017, 154, 938. [Google Scholar] [CrossRef][Green Version]
- Meersch, M.; Schmidt, C.; Hoffmeier, A.; van Aken, H.; Wempe, C.; Gerss, J.; Zarbock, A. Prevention of cardiac surgery-associated AKI by implementing the KDIGO guidelines in high risk patients identified by biomarkers: The PrevAKI randomized controlled trial. Intensive Care Med. 2017, 43, 1551–1561. [Google Scholar] [CrossRef]
- Luckraz, H.; Giri, R.; Wrigley, B.; Nagarajan, K.; Senanayake, E.; Sharman, E.; Beare, L.; Nevill, A. Reduction in acute kidney injury post cardiac surgery using balanced forced diuresis: A randomized, controlled trial. Eur. J. Cardiothorac. Surg. 2021, 59, 562. [Google Scholar] [CrossRef]
- Husain-Syed, F.; Ferrari, F.; Sharma, A.; Danesi, T.H.; Bezerra, P.; Lopez-Giacoman, S.; Samoni, S.; de Cal, M.; Corradi, V.; Virzì, G.M.; et al. Preoperative Renal Functional Reserve Predicts Risk of Acute Kidney Injury after Cardiac Operation. Ann. Thorac. Surg. 2018, 105, 1094–1101. [Google Scholar] [CrossRef]
- Mishra, J.; Dent, C.; Tarabishi, R.; Mitsnefes, M.M.; Ma, Q.; Kelly, C.; Ruff, S.M.; Zahedi, K.; Shao, M.; Bean, J.; et al. Neutrophil gelatinase-associated lipocalin (NGAL) as a biomarker for acute renal injury after cardiac surgery. Lancet 2005, 365, 1231–1238. [Google Scholar] [CrossRef]
- 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. Int. J. Biochem. Lab. Med. 2014, 51, 335–351. [Google Scholar] [CrossRef]
- Haase-Fielitz, A.; Bellomo, R.; Devarajan, P.; Story, D.; Matalanis, G.; Dragun, D.; Haase, M. Novel and conventional serum biomarkers predicting acute kidney injury in adult cardiac surgery—A prospective cohort study. Crit. Care Med. 2009, 37, 553–560. [Google Scholar] [CrossRef]
- Parikh, C.R.; Devarajan, P.; Zappitelli, M.; Sint, K.; Thiessen-Philbrook, H.; Li, S.; Kim, R.W.; Koyner, J.L.; Coca, S.G.; Edelstein, C.L.; et al. TRIBE-AKI Consortium, Postoperative Biomarkers Predict Acute Kidney Injury and Poor Outcomes after Pediatric Cardiac Surgery. J. Am. Soc. Nephrol. 2011, 22, 1737–1747. [Google Scholar] [CrossRef]
- de Geus, H.R.H.; Ronco, C.; Haase, M.; Jacob, L.; Lewington, A.; Vincent, J.-L. The cardiac surgery–associated neutrophil gelatinase-associated lipocalin (CSA-NGAL) score: A potential tool to monitor acute tubular damage. J. Thorac. Cardiovasc. Surg. 2016, 151, 1476–1481. [Google Scholar] [CrossRef]
- Kiessling, A.-H.; Dietz, J.; Reyher, C.; Stock, U.A.; Beiras-Fernandez, A.; Moritz, A. Early postoperative serum cystatin C predicts severe acute kidney injury following cardiac surgery: A post-hoc analysis of a randomized controlled trial. J. Cardiothorac. Surg. 2014, 9, 10. [Google Scholar] [CrossRef]
- Zhang, Z.; Lu, B.; Sheng, X.; Jin, N. Cystatin C in Prediction of Acute Kidney Injury: A Systemic Review and Meta-analysis. Am. J. Kidney Dis. 2011, 58, 356–365. [Google Scholar] [CrossRef]
- McIlroy, D.R.; Farkas, D.; Matto, M.; Lee, H.T. Neutrophil Gelatinase–Associated Lipocalin Combined With Delta Serum Creatinine Provides Early Risk Stratification for Adverse Outcomes after Cardiac Surgery. Crit. Care Med. 2015, 43, 1043–1052. [Google Scholar] [CrossRef] [PubMed]
- Wang, X.; Lin, X.; Xie, B.; Huang, R.; Yan, Y.; Liu, S.; Zhu, M.; Lu, R.; Qian, J.; Ni, Z.; et al. Early serum cystatin C-enhanced risk prediction for acute kidney injury post cardiac surgery: A prospective, observational, cohort study. Biomarkers 2019, 25, 20–26. [Google Scholar] [CrossRef] [PubMed]
- Haase, M.; Bellomo, R.; Devarajan, P.; Ma, Q.; Bennett, M.R.; Möckel, M.; Matalanis, G.; Dragun, D.; Haase-Fielitz, A. Novel Biomarkers Early Predict the Severity of Acute Kidney Injury after Cardiac Surgery in Adults. Ann. Thorac. Surg. 2009, 88, 124–130. [Google Scholar] [CrossRef] [PubMed]
- Basu, R.K.; Wong, H.R.; Krawczeski, C.D.; Wheeler, D.S.; Manning, P.B.; Chawla, L.S.; Devarajan, P.; Goldstein, S.L. Combining functional and tubular damage biomarkers improves diagnostic precision for acute kidney injury after cardiac surgery. J. Am. Coll. Cardiol. 2014, 64, 2753–2762. [Google Scholar] [CrossRef]
- de Loor, J.; Herck, I.; Francois, K.; van Wesemael, A.; Nuytinck, L.; Meyer, E.; Hoste, E.A.J. Diagnosis of cardiac surgery-associated acute kidney injury: Differential roles of creatinine, chitinase 3-like protein 1 and neutrophil gelatinase-associated lipocalin: A prospective cohort study. Ann. Intensive Care 2017, 7, 24. [Google Scholar] [CrossRef]
- Neyra, J.A.; Hu, M.C.; Minhajuddin, A.; Nelson, G.E.; Ahsan, S.A.; Toto, R.D.; Jessen, M.E.; Moe, O.W.; Fox, A.A. Kidney Tubular Damage and Functional Biomarkers in Acute Kidney Injury Following Cardiac Surgery. Kidney Int. Rep. 2019, 4, 1131–1142. [Google Scholar] [CrossRef]
- Perrotti, A.; Miltgen, G.; Chevet-Noel, A.; Durst, C.; Vernerey, D.; Bardonnet, K.; Davani, S.; Chocron, S. Neutrophil Gelatinase-Associated Lipocalin as Early Predictor of Acute Kidney Injury after Cardiac Surgery in Adults With Chronic Kidney Failure. Ann. Thorac. Surg. 2015, 99, 864–869. [Google Scholar] [CrossRef]
Non-AKI | AKI | p-Value | |
---|---|---|---|
n = 68 | n = 51 | ||
Demographic and preoperative characteristics | |||
Age (years) | 72.5 [62.9;79.0] | 75.4 [67.5;81.3] | 0.080 |
Male gender, n (%) | 44 (64.7%) | 31 (60.8%) | 0.805 |
BMI (kg/m2) | 27.0 [23.9;30.0] | 27.8 [24.7;30.3] | 0.309 |
Diabetes mellitus (non/oral/insulin) | 53/11/4 | 31/13/7 | 0.109 |
Arterial hypertension, n (%) | 53 (77.9%) | 44 (86.3%) | 0.357 |
Hypercholesterolemia, n (%) | 44 (64.7%) | 29 (56.9%) | 0.497 |
Left ventricular EF (%) | 60.0 [55.0;65.0] | 60.0 [55.0;61.5] | 0.238 |
ACEI or ARB | 41(60.3%) | 31(60.8%) | 1.000 |
Preoperative creatinine (µmol/L) | 80.0 [67.8;90.0] | 69.5 [54.8;90.8] | 0.085 |
Preoperative eGFR [mL/min/1.73 m2] | 101 [74.6;115] | 84.6 [68.5;99.9] | 0.193 |
Intraoperative and postoperative characteristics | |||
Combined surgery (AVR + CABG), n (%) | 11 (16.2%) | 16 (31.4%) | 0.102 |
CPB time (min) | 84.0 [65.0;113] | 100 [71.5;124] | 0.061 |
Cross-clamp time (min) | 62.0 [45.2;83.5] | 75.0 [55.0;97.0] | 0.029 |
Units of RBC transfusion | 0.00 [0.00;2.00] | 2.00 [1.00;4.00] | <0.001 |
Units of FFP transfusion | 0.00 [0.00;2.00] | 0.00 [0.00;3.00] | 0.104 |
Platelets transfusion, 0/1/2 (%) | 64/4/0 (94/6/0%) | 45/4/1 (90/8/2%) | 0.572 |
Respiratory support (h) | 12.0 [7.75;16.0] | 14.0 [8.00;20.5] | 0.206 |
Inotropes (h) | 0.00 [0.00;21.5] | 3.00 [0.00;46.5] | 0.247 |
ICU stay (days) | 3.00 [1.00;4.00] | 4.00 [1.00;8.50] | 0.018 |
Hospital stay (days) | 8.17 [6.25;12.1] | 9.19 [7.00;20.0] | 0.106 |
Non-AKI | AKI | p-Value | ||
---|---|---|---|---|
n = 68 | n = 51 | |||
NGAL (µg/L) | Preoperative | 60.0 [36;105] | 87.0 [59;117] | 0.085 |
End of CPB | 144 [114;190] | 196 [156;260] | 0.002 | |
2 h after CPB | 122 [88;186] | 177 [154;224] | <0.001 | |
Δ [%] | Δ1 (End of CPB—preoperative) | 140 [64;249] | 134 [68;229] | 0.899 |
Δ2 (2 h after CPB—End of CPB) | −14.55 [−30;3] | −4.09 [−18;13] | 0.065 | |
CysC (µg/L) | Preoperative | 795 [683;922] | 857 [716;1175] | 0.125 |
End of CPB | 740 [632;886] | 851 [723;998] | 0.024 | |
2 h after CPB | 748 [649;914] | 857 [677;1086] | 0.031 | |
Δ [%] | Δ1 (End of CPB—Preoperative) | −0.53 [−20;15] | 3.18 [−14;23] | 0.317 |
Δ2 (2 h post CPB—End of CPB) | −1.36 [−19;13] | −2.36 [−16;16] | 0.740 | |
Creatinine (µmol/L) | Preoperative | 80.0 [68;90] | 69.5 [55;91] | 0.085 |
End of CPB | 71.0 [60;87] | 81.5 [65;96] | 0.128 | |
2 h after CPB | 79.0 [69;92] | 87.0 [70;100] | 0.291 | |
Δ [%] | Δ1 (End of CPB -preoperative) | −3.37 [−18;7] | 8.53 [−7;28] | <0.001 |
Δ2 (2 h post CPB- End of CPB) | 11.5 [3;21] | 7.94 [0;19] | 0.512 |
NGAL Model | CysC Model | Creatinine Model | Combined Model |
---|---|---|---|
PreopNGAL, NGAL end of CPB *, NGAL 2 h after CPB, Δ1 and Δ2 | PreopCysC *, CysC end of CPB, CysC 2 h after CPB, Δ1 * and Δ2 | PreopCREAT, CREAT end of CPB *, CREAT 2 h after CPB, Δ1 * and Δ2 | CysC end of CPB *, CysC Δ1 *, NGAL 2 h after CPB *, CREAT Δ1 * |
AUC (%): 63 | AUC (%): 59 | AUC (%): 71 | AUC (%): 77 |
Sensitivity: 74% | Sensitivity: 78% | Sensitivity: 76% | Sensitivity: 77% |
Specificity: 45% | Specificity: 38% | Specificity: 51% | Specificity: 68% |
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. |
© 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Kalisnik, J.M.; Steblovnik, K.; Hrovat, E.; Jerin, A.; Skitek, M.; Dinges, C.; Fischlein, T.; Zibert, J. Enhanced Detection of Cardiac Surgery-Associated Acute Kidney Injury by a Composite Biomarker Panel in Patients with Normal Preoperative Kidney Function. J. Cardiovasc. Dev. Dis. 2022, 9, 210. https://doi.org/10.3390/jcdd9070210
Kalisnik JM, Steblovnik K, Hrovat E, Jerin A, Skitek M, Dinges C, Fischlein T, Zibert J. Enhanced Detection of Cardiac Surgery-Associated Acute Kidney Injury by a Composite Biomarker Panel in Patients with Normal Preoperative Kidney Function. Journal of Cardiovascular Development and Disease. 2022; 9(7):210. https://doi.org/10.3390/jcdd9070210
Chicago/Turabian StyleKalisnik, Jurij Matija, Klemen Steblovnik, Eva Hrovat, Ales Jerin, Milan Skitek, Christian Dinges, Theodor Fischlein, and Janez Zibert. 2022. "Enhanced Detection of Cardiac Surgery-Associated Acute Kidney Injury by a Composite Biomarker Panel in Patients with Normal Preoperative Kidney Function" Journal of Cardiovascular Development and Disease 9, no. 7: 210. https://doi.org/10.3390/jcdd9070210
APA StyleKalisnik, J. M., Steblovnik, K., Hrovat, E., Jerin, A., Skitek, M., Dinges, C., Fischlein, T., & Zibert, J. (2022). Enhanced Detection of Cardiac Surgery-Associated Acute Kidney Injury by a Composite Biomarker Panel in Patients with Normal Preoperative Kidney Function. Journal of Cardiovascular Development and Disease, 9(7), 210. https://doi.org/10.3390/jcdd9070210