Predicting Cardiac Surgery-Associated Acute Kidney Injury Using a Combination of Clinical Risk Scores and Urinary BiomarkersFunding This is an investigator-initiated study without external funding. The study was conducted by a team consisting of one physician and one medical student. The NephroCheck device and test kits are in routine use in our institution and were purchased using funds from operation.
04 October 2018
03 January 2019
11 February 2019 (online)
Background Prediction, early diagnosis, and therapy of cardiac surgery-associated acute kidney injury (CSA-AKI) are challenging. We prospectively tested a staged approach to identify patients at high risk for CSA-AKI combining clinical risk stratification and early postoperative quantification of urinary biomarkers for AKI.
Methods All patients, excluding those on chronic hemodialysis, undergoing scheduled surgery with cardiopulmonary bypass between August 2015 and July 2016 were included. First, patients were stratified by calculating the Cleveland clinic score (CCS) and the Leicester score (LS). In high-risk patients (defined as LS > 25 or CCS > 6), urinary concentrations of biomarkers for AKI ([TIMP-2]*[IGFBP-7]) were evaluated 4 hours postoperatively. CSA-AKI was observed until postoperative day 6 and classified using the Kidney Disease: Improving Global Outcomes criteria.
Results AKI occurred in 352 of613 patients (54%). In high-risk patients, AKI occurred more frequently than in low-risk patients (66 vs. 49%; p = 0.001). In-hospital mortality after AKI stage 2 (15%) or AKI stage 3 (49%) compared with patients without AKI (1.8%; p = 0.001) was increased. LS was predictive for all stages of AKI (area under the curve [AUC] 0.601; p < 0.001) with a poor or fair accuracy, while CCS was only predictive for stage 2 or 3 AKI (AUC 0.669; p < 0.001) with fair accuracy. In 133 high-risk patients, urinary [TIMP-2]*[IGFBP-7] was significantly predictive for all-stage AKI within 24 hours postoperatively (AUC 0.63; p = 0.017). However, for the majority of AKI (55%), which occurred beyond 24 hours postoperatively, urinary [TIMP-2]*[IGFBP-7] was not significantly predictive. Sensitivity for all-stage AKI within 24 hours was 0.38 and specificity was 0.81 using a cutoff value of 0.3.
Conclusion CSA-AKI is a relevant and frequent complication after cardiac surgery. Patients at high risk for CSA-AKI can be identified using clinical prediction scores, however, with only poor to fair accuracy. Due to its weak test performance, urinary [TIMP-2]*[IGFBP-7] quantification 4 hours postoperatively does not add to the predictive value of clinical scores.
The study was approved by the ethical committee of the Faculty of Medicine at Justus Liebig University Giessen, Germany. The trial was designed and conducted in accordance to the declaration of Helsinki. Patients gave consent to collection and analysis of their data for scientific purposes prior to operation.
- 1 Lagny M-G, Jouret F, Koch J-N. , et al. Incidence and outcomes of acute kidney injury after cardiac surgery using either criteria of the RIFLE classification. BMC Nephrol 2015; 16: 76
- 2 Reents W, Hilker M, Börgermann J. , et al. Acute kidney injury after on-pump or off-pump coronary artery bypass grafting in elderly patients. Ann Thorac Surg 2014; 98 (01) 9-14 , discussion 14–15
- 3 Lassnigg A, Schmidlin D, Mouhieddine M. , et al. Minimal changes of serum creatinine predict prognosis in patients after cardiothoracic surgery: a prospective cohort study. J Am Soc Nephrol 2004; 15 (06) 1597-1605
- 4 Hobson CE, Yavas S, Segal MS. , et al. Acute kidney injury is associated with increased long-term mortality after cardiothoracic surgery. Circulation 2009; 119 (18) 2444-2453
- 5 Chertow GM, Levy EM, Hammermeister KE, Grover F, Daley J. Independent association between acute renal failure and mortality following cardiac surgery. Am J Med 1998; 104 (04) 343-348
- 6 O'Neal JB, Shaw AD, Billings IV FT. Acute kidney injury following cardiac surgery: current understanding and future directions. Crit Care 2016; 20 (01) 187
- 7 Mao H, Katz N, Ariyanon W. , et al. Cardiac surgery-associated acute kidney injury. Cardiorenal Med 2013; 3 (03) 178-199
- 8 Olivero JJ, Olivero JJ, Nguyen PT, Kagan A. Acute kidney injury after cardiovascular surgery: an overview. Methodist DeBakey Cardiovasc J 2012; 8 (03) 31-36
- 9 Zou H, Hong Q, Xu G. Early versus late initiation of renal replacement therapy impacts mortality in patients with acute kidney injury post cardiac surgery: a meta-analysis. Crit Care 2017; 21 (01) 150
- 10 Karvellas CJ, Farhat MR, Sajjad I. , et al. A comparison of early versus late initiation of renal replacement therapy in critically ill patients with acute kidney injury: a systematic review and meta-analysis. Crit Care 2011; 15 (01) R72
- 11 Thakar CV, Arrigain S, Worley S, Yared J-P, Paganini EP. A clinical score to predict acute renal failure after cardiac surgery. J Am Soc Nephrol 2005; 16 (01) 162-168
- 12 Birnie K, Verheyden V, Pagano D. , et al; UK AKI in Cardiac Surgery Collaborators. Predictive models for Kidney Disease: Improving Global Outcomes (KDIGO) defined acute kidney injury in UK cardiac surgery. Crit Care 2014; 18 (06) 606
- 13 Han WK, Wagener G, Zhu Y, Wang S, Lee HT. Urinary biomarkers in the early detection of acute kidney injury after cardiac surgery. Clin J Am Soc Nephrol 2009; 4 (05) 873-882
- 14 Kellum JA, Chawla LS. Cell-cycle arrest and acute kidney injury: the light and the dark sides. Nephrol Dial Transplant 2016; 31 (01) 16-22
- 15 Bihorac A, Chawla LS, Shaw AD. , et al. Validation of cell-cycle arrest biomarkers for acute kidney injury using clinical adjudication. Am J Respir Crit Care Med 2014; 189 (08) 932-939
- 16 Meersch M, Schmidt C, Van Aken H. , et al. Urinary TIMP-2 and IGFBP7 as early biomarkers of acute kidney injury and renal recovery following cardiac surgery. PLoS One 2014; 9 (03) e93460
- 17 Pilarczyk K, Edayadiyil-Dudasova M, Wendt D. , et al. Urinary [TIMP-2]*[IGFBP7] for early prediction of acute kidney injury after coronary artery bypass surgery. Ann Intensive Care 2015; 5 (01) 50
- 18 von Elm E, Altman DG, Egger M, Pocock SJ, Gøtzsche PC, Vandenbroucke JP. ; STROBE Initiative. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. J Clin Epidemiol 2008; 61 (04) 344-349
- 19 Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron 1976; 16 (01) 31-41
- 20 Khwaja A. KDIGO clinical practice guidelines for acute kidney injury. Nephron Clin Pract 2012; 120 (04) c179-c184
- 21 Carley S, Dosman S, Jones SR, Harrison M. Simple nomograms to calculate sample size in diagnostic studies. Emerg Med J 2005; 22 (03) 180-181
- 22 Sampaio MC, Máximo CA, Montenegro CM. , et al. Comparison of diagnostic criteria for acute kidney injury in cardiac surgery. Arq Bras Cardiol 2013; 101 (01) 18-25
- 23 Machado MN, Nakazone MA, Maia LN. Prognostic value of acute kidney injury after cardiac surgery according to Kidney Disease: Improving Global Outcomes definition and staging (KDIGO) criteria. PLoS One 2014; 9 (05) e98028
- 24 Bastin AJ, Ostermann M, Slack AJ, Diller G-P, Finney SJ, Evans TW. Acute kidney injury after cardiac surgery according to Risk/Injury/Failure/Loss/End-stage, Acute Kidney Injury Network, and Kidney Disease: Improving Global Outcomes classifications. J Crit Care 2013; 28 (04) 389-396
- 25 Petäjä L, Vaara S, Liuhanen S. , et al. Acute kidney injury after cardiac surgery by complete KDIGO criteria predicts increased mortality. J Cardiothorac Vasc Anesth 2017; 31 (03) 827-836
- 26 Rosner MH, Okusa MD. Acute kidney injury associated with cardiac surgery. Clin J Am Soc Nephrol 2006; 1 (01) 19-32
- 27 Mishra J, Dent C, Tarabishi R. , et al. Neutrophil gelatinase-associated lipocalin (NGAL) as a biomarker for acute renal injury after cardiac surgery. Lancet 2005; 365 (9466): 1231-1238
- 28 Kashani K, Al-Khafaji A, Ardiles T. , et al. Discovery and validation of cell cycle arrest biomarkers in human acute kidney injury. Crit Care 2013; 17 (01) R25
- 29 Wetz AJ, Richardt EM, Wand S. , et al. Quantification of urinary TIMP-2 and IGFBP-7: an adequate diagnostic test to predict acute kidney injury after cardiac surgery?. Crit Care 2015; 19: 3
- 30 Oezkur M, Magyar A, Thomas P. , et al. TIMP-2*IGFBP7 (Nephrocheck®) measurements at intensive care unit admission after cardiac surgery are predictive for acute kidney injury within 48 hours. Kidney Blood Press Res 2017; 42 (03) 456-467
- 31 Fuhrman DY, Kellum JA. Epidemiology and pathophysiology of cardiac surgery-associated acute kidney injury. Curr Opin Anaesthesiol 2017; 30 (01) 60-65
- 32 Bellomo R, Auriemma S, Fabbri A. , et al. The pathophysiology of cardiac surgery-associated acute kidney injury (CSA-AKI). Int J Artif Organs 2008; 31 (02) 166-178
- 33 Raja SG, Dreyfus GD. Modulation of systemic inflammatory response after cardiac surgery. Asian Cardiovasc Thorac Ann 2005; 13 (04) 382-395
- 34 Djebara S, Biston P, Fossé E. , et al. Time course of CD64, a leukocyte activation marker, during cardiopulmonary bypass surgery. Shock 2017; 47 (02) 158-164
- 35 Bahar I, Akgul A, Ozatik MA. , et al. Acute renal failure following open heart surgery: risk factors and prognosis. Perfusion 2005; 20 (06) 317-322
- 36 Arora P, Kolli H, Nainani N, Nader N, Lohr J. Preventable risk factors for acute kidney injury in patients undergoing cardiac surgery. J Cardiothorac Vasc Anesth 2012; 26 (04) 687-697
- 37 Karkouti K. Transfusion and risk of acute kidney injury in cardiac surgery. Br J Anaesth 2012; 109 (Suppl. 01) i29-i38
- 38 Meersch M, Schmidt C, Hoffmeier A. , et al. 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 (11) 1551-1561