Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Critical Care
Published in: Critical Care 1/2018

Open Access 01-12-2018 | Research

Urinary biomarkers predict advanced acute kidney injury after cardiovascular surgery

Authors: Jian-Jhong Wang, Nai-Hsin Chi, Tao-Min Huang, Rory Connolly, Liang Wen Chen, Shih-Chieh Jeff Chueh, Wei-Chih Kan, Chih-Cheng Lai, Vin-Cent Wu, Ji-Tseng Fang, Tzong-Shinn Chu, Kwan-Dun Wu

Published in: Critical Care | Issue 1/2018

Login to get access

Abstract

Background

Acute kidney injury (AKI) after cardiovascular surgery is a serious complication. Little is known about the ability of novel biomarkers in combination with clinical risk scores for prediction of advanced AKI.

Methods

In this prospectively conducted multicenter study, urine samples were collected from 149 adults at 0, 3, 6, 12 and 24 h after cardiovascular surgery. We measured urinary hemojuvelin (uHJV), kidney injury molecule-1 (uKIM-1), neutrophil gelatinase-associated lipocalin (uNGAL), α-glutathione S-transferase (uα-GST) and π-glutathione S-transferase (uπ-GST). The primary outcome was advanced AKI, under the definition of Kidney Disease: Improving Global Outcomes (KDIGO) stage 2, 3 and composite outcomes were KDIGO stage 2, 3 or 90-day mortality after hospital discharge.

Results

Patients with advanced AKI had significantly higher levels of uHJV and uKIM-1 at 3, 6 and 12 h after surgery. When normalized by urinary creatinine level, uKIM-1 in combination with uHJV at 3 h post-surgery had a high predictive ability for advanced AKI and composite outcome (AUC = 0.898 and 0.905, respectively). The combination of this biomarker panel (normalized uKIM-1, uHJV at 3 h post-operation) and Liano’s score was superior in predicting advanced AKI (AUC = 0.931, category-free net reclassification improvement of 1.149, and p <  0.001).

Conclusions

When added to Liano’s score, normalized uHJV and uKIM-1 levels at 3 h after cardiovascular surgery enhanced the identification of patients at higher risk of progression to advanced AKI and composite outcomes.
Appendix
Available only for authorised users
Literature
1.
Siew ED, Davenport A. The growth of acute kidney injury: a rising tide or just closer attention to detail? Kidney Int. 2015;87(1):46–61.CrossRefPubMed
2.
Lameire N, Van Biesen W, Vanholder R. Acute renal failure. Lancet (London, England). 2005;365(9457):417–30.CrossRef
3.
Chertow GM, Burdick E, Honour M, Bonventre JV, Bates DW. Acute kidney injury, mortality, length of stay, and costs in hospitalized patients. J Am Soc Nephrol. 2005;16(11):3365–70.CrossRefPubMed
4.
Zarbock A, Kellum JA, Schmidt C, Van Aken H, Wempe C, Pavenstadt H, Boanta A, Gerss J, Meersch M. Effect of early vs delayed initiation of renal replacement therapy on mortality in critically ill patients with acute kidney injury: the ELAIN randomized clinical trial. JAMA. 2016;315(20):2190–9.CrossRefPubMed
5.
Dennen P, Douglas IS, Anderson R. Acute kidney injury in the intensive care unit: an update and primer for the intensivist. Crit Care Med. 2010;38(1):261–75.CrossRefPubMed
6.
Mishra J. Identification of neutrophil gelatinase-associated lipocalin as a novel early urinary biomarker for ischemic renal injury. J Am Soc Nephrol. 2003;14(10):2534–43.CrossRefPubMed
7.
Mishra J, Dent C, Tarabishi R, Mitsnefes MM, Ma Q, Kelly C, Ruff SM, 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(9466):1231–8.CrossRefPubMed
8.
Young GH, Huang TM, Wu CH, Lai CF, Hou CC, Peng KY, Liang CJ, Lin SL, Chang SC, Tsai PR, et al. Hemojuvelin modulates iron stress during acute kidney injury: improved by furin inhibitor. Antioxid Redox Signal. 2014;20(8):1181–94.CrossRefPubMedPubMedCentral
9.
Siew ED, Ware LB, Ikizler TA. Biological markers of acute kidney injury. J Am Soc Nephrol. 2011;22(5):810–20.CrossRefPubMed
10.
Koyner JL, Garg AX, Coca SG, Sint K, Thiessen-Philbrook H, Patel UD, Shlipak MG, Parikh CR. Biomarkers predict progression of acute kidney injury after cardiac surgery. J Am Soc Nephrol. 2012;23(5):905–14.CrossRefPubMedPubMedCentral
11.
Krawczeski CD, Goldstein SL, Woo JG, Wang Y, Piyaphanee N, Ma Q, Bennett M, Devarajan P. Temporal relationship and predictive value of urinary acute kidney injury biomarkers after pediatric cardiopulmonary bypass. J Am Coll Cardiol. 2011;58(22):2301–9.CrossRefPubMedPubMedCentral
12.
Katagiri D, Doi K, Honda K, Negishi K, Fujita T, Hisagi M, Ono M, Matsubara T, Yahagi N, Iwagami M, et al. Combination of two urinary biomarkers predicts acute kidney injury after adult cardiac surgery. Ann Thorac Surg. 2012;93(2):577–83.CrossRefPubMed
13.
Hall IE, Coca SG, Perazella MA, Eko UU, Luciano RL, Peter PR, Han WK, Parikh CR. Risk of poor outcomes with novel and traditional biomarkers at clinical AKI diagnosis. Clin J Am Soc Nephrol. 2011;6(12):2740–9.CrossRefPubMedPubMedCentral
14.
Arthur JM, Hill EG, Alge JL, Lewis EC, Neely BA, Janech MG, Tumlin JA, Chawla LS, Shaw AD. Evaluation of 32 urine biomarkers to predict the progression of acute kidney injury after cardiac surgery. Kidney Int. 2014;85(2):431–8.CrossRefPubMed
15.
Alge JL, Arthur JM. Biomarkers of AKI: a review of mechanistic relevance and potential therapeutic implications. Clin J Am Soc Nephrol. 2015;10(1):147–55.CrossRefPubMed
16.
Shaw M. The use of histologically defined specific biomarkers in drug development with special reference to the glutathione S-transferases. Cancer Biomark. 2005;1(1):69–74.CrossRefPubMed
17.
Srisawat N, Wen X, Lee M, Kong L, Elder M, Carter M, Unruh M, Finkel K, Vijayan A, Ramkumar M, et al. Urinary biomarkers and renal recovery in critically ill patients with renal support. Clin J Am Soc Nephrol. 2011;6(8):1815–23.CrossRefPubMedPubMedCentral
18.
Ohnuma T, Uchino S, Toki N, Takeda K, Namba Y, Katayama S, Kawarazaki H, Yasuda H, Izawa J, Uji M, et al. External validation for acute kidney injury severity scores: a multicenter retrospective study in 14 Japanese ICUs. Am J Nephrol. 2015;42(1):57–64.CrossRefPubMed
19.
Varricatt VP, Rau NR, Attur RP, Baig WW. Validation of Liano score in acute renal failure: a prospective study in Indian patients. Clin Exp Nephrol. 2009;13(1):33–7.CrossRefPubMed
20.
Thakar CV, Arrigain S, Worley S, Yared JP, Paganini EP. A clinical score to predict acute renal failure after cardiac surgery. J Am Soc Nephrol. 2005;16(1):162–8.CrossRefPubMed
21.
Vincent JL, Moreno R, Takala J, Willatts S, De Mendonca A, Bruining H, Reinhart CK, Suter PM, Thijs LG. The SOFA (Sepsis-related Organ Failure Assessment) score to describe organ dysfunction/failure. On behalf of the Working Group on Sepsis-Related Problems of the European Society of Intensive Care Medicine. Intensive Care Med. 1996;22(7):707–10.CrossRefPubMed
22.
Wu VC, Ko WJ, Chang HW, Chen YS, Chen YW, Chen YM, Hu FC, Lin YH, Tsai PR, Wu KD. Early renal replacement therapy in patients with postoperative acute liver failure associated with acute renal failure: effect on postoperative outcomes. J Am Coll Surg. 2007;205(2):266–76.CrossRefPubMed
23.
Wu VC, Ko WJ, Chang HW, Chen YW, Lin YF, Shiao CC, Chen YM, Chen YS, Tsai PR, Hu FC, et al. Risk factors of early redialysis after weaning from postoperative acute renal replacement therapy. Intensive Care Med. 2008;34(1):101–8.CrossRefPubMed
24.
Shiao CC, Wu VC, Li WY, Lin YF, Hu FC, Young GH, Kuo CC, Kao TW, Huang DM, Chen YM, et al. Late initiation of renal replacement therapy is associated with worse outcomes in acute kidney injury after major abdominal surgery. Crit Care. 2009;13(5):R171.CrossRefPubMedPubMedCentral
25.
Wu VC, Wang CH, Wang WJ, Lin YF, Hu FC, Chen YW, Chen YS, Wu MS, Lin YH, Kuo CC, et al. Sustained low-efficiency dialysis versus continuous veno-venous hemofiltration for postsurgical acute renal failure. Am J Surg. 2010;199(4):466–76.CrossRefPubMed
26.
Huang TM, Wu VC, Young GH, Lin YF, Shiao CC, Wu PC, Li WY, Yu HY, Hu FC, Lin JW, et al. Preoperative proteinuria predicts adverse renal outcomes after coronary artery bypass grafting. J Am Soc Nephrol. 2011;22(1):156–63.CrossRefPubMedPubMedCentral
27.
Levey AS, Coresh J, et al. K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Am J Kidney Dis. 2002;39(2 Suppl 1):S1–266.
28.
Wu VC, Huang TM, Shiao CC, Lai CF, Tsai PR, Wang WJ, Huang HY, Wang KC, Ko WJ, Wu KD, et al. The hemodynamic effects during sustained low-efficiency dialysis versus continuous veno-venous hemofiltration for uremic patients with brain hemorrhage: a crossover study. J Neurosurg. 2013;119(5):1288–95.CrossRefPubMed
29.
Young GH, Wu VC. KLOTHO methylation is linked to uremic toxins and chronic kidney disease. Kidney Int. 2012;81(7):611–2.CrossRefPubMed
30.
Wu VC, Wu CH, Huang TM, Wang CY, Lai CF, Shiao CC, Chang CH, Lin SL, Chen YY, Chen YM, et al. Long-term risk of coronary events after AKI. J Am Soc Nephrol. 2014;25(3):595–605.CrossRefPubMedPubMedCentral
31.
Wu VC, Young GH, Huang PH, Lo SC, Wang KC, Sun CY, Liang CJ, Huang TM, Chen JH, Chang FC, et al. In acute kidney injury, indoxyl sulfate impairs human endothelial progenitor cells: modulation by statin. Angiogenesis. 2013;16(3):609–24.CrossRefPubMed
32.
Palevsky PM, Liu KD, Brophy PD, Chawla LS, Parikh CR, Thakar CV, Tolwani AJ, Waikar SS, Weisbord SD. KDOQI US commentary on the 2012 KDIGO clinical practice guideline for acute kidney injury. Am J Kidney Dis. 2013;61(5):649–72.CrossRefPubMed
33.
Friedman M. The use of ranks to avoid the assumption of normality implicit in the analysis of variance. J Am Stat Assoc. 1937;32(200):675–701.CrossRef
34.
Ralib AM, Pickering JW, Shaw GM, Devarajan P, Edelstein CL, Bonventre JV, Endre ZH. Test characteristics of urinary biomarkers depend on quantitation method in acute kidney injury. J Am Soc Nephrol. 2012;23(2):322–33.CrossRefPubMed
35.
Hanley JA, McNeil BJ. The meaning and use of the area under a receiver operating characteristic (ROC) curve. Radiology. 1982;143(1):29–36.CrossRefPubMed
36.
Wu VC, Lo SC, Chen YL, Huang PH, Tsai CT, Liang CJ, Kuo CC, Kuo YS, Lee BC, Wu EL, et al. Endothelial progenitor cells in primary aldosteronism: a biomarker of severity for aldosterone vasculopathy and prognosis. J Clin Endocrinol Metab. 2011;96(10):3175–83.CrossRefPubMed
37.
Shu KH, Wang CH, Wu CH, Huang TM, Wu PC, Lai CH, Tseng LJ, Tsai PR, Connolly R, Wu VC. Urinary pi-glutathione S-transferase predicts advanced acute kidney injury following cardiovascular surgery. Sci Rep. 2016;6:26335.CrossRefPubMedPubMedCentral
38.
Hin LY, Lau TK, Rogers MS, Chang AM. Dichotomization of continuous measurements using generalized additive modelling–application in predicting intrapartum caesarean delivery. Stat Med. 1999;18(9):1101–10.CrossRefPubMed
39.
Steyerberg EW, Vickers AJ, Cook NR, Gerds T, Gonen M, Obuchowski N, Pencina MJ, Kattan MW. Assessing the performance of prediction models: a framework for traditional and novel measures. Epidemiology. 2010;21(1):128–38.CrossRefPubMedPubMedCentral
40.
Eisen MB, Spellman PT, Brown PO, Botstein D. Cluster analysis and display of genome-wide expression patterns. Proc Natl Acad Sci U S A. 1998;95(25):14863–8.CrossRefPubMedPubMedCentral
41.
42.
Lin L, Goldberg YP, Ganz T. Competitive regulation of hepcidin mRNA by soluble and cell-associated hemojuvelin. Blood. 2005;106(8):2884–9.CrossRefPubMed
43.
Shah SV, Baliga R, Rajapurkar M, Fonseca VA. Oxidants in chronic kidney disease. J Am Soc Nephrol. 2007;18(1):16–28.CrossRefPubMed
44.
Nath KA. Heme oxygenase-1: a provenance for cytoprotective pathways in the kidney and other tissues. Kidney Int. 2006;70(3):432–43.CrossRefPubMed
45.
Ichimura T, Bonventre JV, Bailly V, Wei H, Hession CA, Cate RL, Sanicola M. Kidney injury molecule-1 (KIM-1), a putative epithelial cell adhesion molecule containing a novel immunoglobulin domain, is up-regulated in renal cells after injury. J Biol Chem. 1998;273(7):4135–42.CrossRefPubMed
46.
Ichimura T, Asseldonk EJ, Humphreys BD, Gunaratnam L, Duffield JS, Bonventre JV. Kidney injury molecule-1 is a phosphatidylserine receptor that confers a phagocytic phenotype on epithelial cells. J Clin Invest. 2008;118(5):1657–68.CrossRefPubMedPubMedCentral
47.
Coca SG, Garg AX, Thiessen-Philbrook H, Koyner JL, Patel UD, Krumholz HM, Shlipak MG, Parikh CR. Urinary biomarkers of AKI and mortality 3 years after cardiac surgery. J Am Soc Nephrol. 2014;25(5):1063–71.CrossRefPubMed
48.
Endre ZH, Walker RJ, Pickering JW, Shaw GM, Frampton CM, Henderson SJ, Hutchison R, Mehrtens JE, Robinson JM, Schollum JB, et al. Early intervention with erythropoietin does not affect the outcome of acute kidney injury (the EARLYARF trial). Kidney Int. 2010;77(11):1020–30.CrossRefPubMed
49.
Gaudry S, Hajage D, Schortgen F, Martin-Lefevre L, Pons B, Boulet E, Boyer A, Chevrel G, Lerolle N, Carpentier D, et al. Initiation strategies for renal-replacement therapy in the intensive care unit. N Engl J Med. 2016;375(2):122–33.CrossRefPubMed
50.
Lannemyr L, Lundin E, Reinsfelt B, Bragadottir G, Redfors B, Oras J. Renal tubular injury during cardiopulmonary bypass as assessed by urinary release of N-acetyl-ss-D-glucosaminidase. Acta Anaesthesiol Scand. 2017;61(9):1075–83.CrossRefPubMed
51.
Wang J, Long Q, Zhang W, Chen N. Protective effects of exogenous interleukin 18-binding protein in a rat model of acute renal ischemia-reperfusion injury. Shock. 2012;37(3):333–40.CrossRefPubMed
52.
Ferguson MA, Vaidya VS, Waikar SS, Collings FB, Sunderland KE, Gioules CJ, Bonventre JV. Urinary liver-type fatty acid-binding protein predicts adverse outcomes in acute kidney injury. Kidney Int. 2010;77(8):708–14.CrossRefPubMed
53.
Prowle JR, Calzavacca P, Licari E, Ligabo EV, Echeverri JE, Bagshaw SM, Haase-Fielitz A, Haase M, Ostland V, Noiri E, et al. Combination of biomarkers for diagnosis of acute kidney injury after cardiopulmonary bypass. Ren Fail. 2015;37(3):408–16.CrossRefPubMedPubMedCentral
54.
Yang CH, Chang CH, Chen TH, Fan PC, Chang SW, Chen CC, Chu PH, Chen YT, Yang HY, Yang CW, et al. Combination of urinary biomarkers improves early detection of acute kidney injury in patients with heart failure. Circ J. 2016;80(4):1017–23.CrossRefPubMed
55.
Parikh CR, Moledina DG, Coca SG, Thiessen-Philbrook HR, Garg AX. Application of new acute kidney injury biomarkers in human randomized controlled trials. Kidney Int. 2016;89(6):1372–9.CrossRefPubMedPubMedCentral
Metadata
Title
Urinary biomarkers predict advanced acute kidney injury after cardiovascular surgery
Authors
Jian-Jhong Wang
Nai-Hsin Chi
Tao-Min Huang
Rory Connolly
Liang Wen Chen
Shih-Chieh Jeff Chueh
Wei-Chih Kan
Chih-Cheng Lai
Vin-Cent Wu
Ji-Tseng Fang
Tzong-Shinn Chu
Kwan-Dun Wu
Publication date
01-12-2018
Publisher
BioMed Central
Published in
Critical Care / Issue 1/2018
Electronic ISSN: 1364-8535
DOI
https://doi.org/10.1186/s13054-018-2035-8

Other articles of this Issue 1/2018

Critical Care 1/2018 Go to the issue

Research

Metabolic profiles in community-acquired pneumonia: developing assessment tools for disease severity

Review

Pathophysiology, echocardiographic evaluation, biomarker findings, and prognostic implications of septic cardiomyopathy: a review of the literature

Research

Intravenous ivabradine versus placebo in patients with low cardiac output syndrome treated by dobutamine after elective coronary artery bypass surgery: a phase 2 exploratory randomized controlled trial

Editorial

Treatment of central line-associated bloodstream infections

Viewpoint

High protein intake during the early phase of critical illness: yes or no?

Research

Protracted immune disorders at one year after ICU discharge in patients with septic shock