Onur SAYDAM, Ercan TÜRKMEN, Oytun PORTAKAL, Mustafa ARICI, Rıza DOĞAN, Metin DEMİRCİN, İlhan PAŞAOĞLU, Mustafa YILMAZ

Emerging biomarker for predicting acute kidney injury after cardiac surgery: cystatin C

Background/aim: Cardiopulmonary bypass (CPB)-associated acute kidney injury (AKI) is a common situation and rapid diagnosis and risk classification are important in the prevention and management of AKI. Changes in serum creatinine (SCr) levels in the current consensus criteria do not allow clinicians to diagnose CPB-associated AKI until 48 h after surgery. Materials and methods: We conducted a prospective single center study involving 57 patients who underwent cardiac surgery with CBP to compare serum beta-trace protein (BTP), neutrophil gelatinase-associated lipocalin-2 (NGAL), and cystatin C (CysC) levels with SCr for early diagnosis of CPB associated AKI. We defined AKI according to KDIGO criteria. Results: AKI was diagnosed in 24 (42.1%) patients. Mean duration of postoperative intensive care unit stay was 4.79 (± 6.12) days for the AKI+ group and 2.15 (± 0.56) days for the AKI- group. The average length of hospital stay was 8.13 (± 5.75) days for the AKI+ group and 7.21 (± 3.68) days for the AKI- group, which was significantly longer in the AKI+ group (P < 0.001, P = 0.011). Unlike other biomarkers, a significant increase in postoperative CysC levels was always found in patients with AKI during follow-up when compared to patients in whom AKI did not develop (P < 0.001). Conclusion: Increase in serum CysC levels showed a significant positive correlation with increase in SCr levels. We have not seen this correlation between other biomarkers and SCr. According to our study, serum CysC was a reliable biomarker that may aid in the early detection and follow-up of AKI after cardiac surgery.

Keywords:

Acute kidney injury, biomarker, cardiac surgical procedures, cystatin C,

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Rosner MH, Okusa MD. Acute kidney injury associated with cardiac surgery. Clin J Am Soc Nephrol 2006; 1: 19-32.
Mehta RL, Kellum JA, Shah SV, Molitoris BA, Ronco C, War - nock DG, Levin A, Acute Kidney Injury Network. Acute Kid- ney Injury Network: report of an initiative to improve out- comes in acute kidney injury. Crit Care. 2007; 11: R31.
Acute Kidney Injury Work Group. Kidney Disease: Improving Global Outcomes (KDIGO) Acute Kidney Injury Work Group. KDIGO Clinical Practice Guideline for Acute Kidney Injury. Kidney Inter, Suppl 2012; 2: 1-138.
Bellomo R, Kellum JA, Ronco C. Defining acute renal failure: physiological principles. Intensive Care Med 2004; 30: 33-37.
Cholongitas E, Shusang V, Marelli L, Nair D, Thomas M, Patch D, Burns A, Sweny P, Burroughs AK. Review article: renal function assessment in cirrhosis - difficulties and alternative measurements. Aliment Pharmacol Ther 2007; 26: 969-978.
Gaygisiz U, Aydogdu M, Badoglu M, Boyaci N, Gullu Z, Gursel G. Can admission serum cystatin C level be an early marker subclinical acute kidney injury in critical care patients? Scand J Clin Lab Invest 2016: 1-8.
Dharnidharka VR, Kwon C, Stevens G. Serum cystatin C is su- perior to serum creatinine as a marker of kidney function: a meta-analysis. Am J Kidney Dis 2002; 40: 221-226.
Priem F, Althaus H, Birnbaum M, Sinha P, Conradt HS, Jung K. Beta-trace protein in serum: a new marker of glomerular filtration rate in the creatinine-blind range. Clin Chem 1999; 45: 567-568.
Bökenkamp A, Franke I, Schlieber M, Düker G, Schmitt J, Buderus S, Lentze MJ, Stoffel-Wagner B. Beta-trace protein— a marker of kidney function in children: “Original research communication-clinical investigation”. Clin Biochem 2007; 40: 969-975.
Spanaus KS, Kollerits B, Ritz E, Hersberger M, Kronenberg F, von Eckardstein A, Mild, Moderate Kidney Disease Study Group. Serum creatinine, cystatin C, and beta-trace protein in diagnostic staging and predicting progression of primary non- diabetic chronic kidney disease. Clin Chem 2010; 56: 740-749.
Mishra J, Ma Q, Prada A, Mitsnefes M, Zahedi K, Yang J, Bar - asch J, Devarajan P. Identification of neutrophil gelatinase-as- sociated lipocalin as a novel early urinary biomarker for isch- emic renal injury. J Am Soc Nephrol 2003; 14: 2534-2543.
Mishra J, Mori K, Ma Q, Kelly C, Barasch J, Devarajan P. Neu- trophil gelatinase-associated lipocalin: a novel early urinary biomarker for cisplatin nephrotoxicity. Am J Nephrol 2004; 24: 307-315.
Wagener G, Gubitosa G, Wang S, Borregaard N, Kim M, Lee HT. Urinary neutrophil gelatinase-associated lipocalin and acute kidney injury after cardiac surgery. Am J Kidney Dis 2008; 52: 425-433.
Kaseda R, Iino N, Hosojima M, Takeda T, Hosaka K, Kobayashi A, Yamamoto K, Suzuki A, Kasai A, Suzuki Y et al. Megalin- mediated endocytosis of cystatin C in proximal tubule cells. Biochem Biophys Res Commun 2007; 357: 1130-1134.
Filler G, Bokenkamp A, Hofmann W, Le Bricon T, Martinez- Bru C, Grubb A. Cystatin C as a marker of GFR—history, indi- cations, and future research. Clin Biochem 2005; 38: 1-8.
Nejat M, Pickering JW, Walker RJ, Endre ZH. Rapid detection of acute kidney injury by plasma cystatin C in the intensive care unit. Nephrol Dial Transplant 2010; 25: 3283-3289.
Aydogdu M, Gursel G, Sancak B, Yeni S, Sari G, Tasyurek S, Turk M, Yuksel S, Senes M, Ozis TN. The use of plasma and urine neutrophil gelatinase associated lipocalin (NGAL) and Cystatin C in early diagnosis of septic acute kidney injury in critically ill patients. Dis Markers 2013; 34: 237-246.
Williams JR. The Declaration of Helsinki and public health. Bull World Health Organ 2008; 86: 650-652.
Kobata M, Shimizu A, Rinno H, Hamada C, Maeda K, Fukui M, Saito K, Horikoshi S, Tomino Y. Beta-trace protein, a new marker of GFR, may predict the early prognostic stages of pa- tients with type 2 diabetic nephropathy. J Clin Lab Anal 2004; 18: 237-239.
Lagny MG, Jouret F, Koch JN, Blaffart F, Donneau AF, Albert A, Roediger L, Krzesinski JM, Defraigne JO. Incidence and outcomes of acute kidney injury after cardiac surgery using either criteria of the RIFLE classification. BMC Nephrol 2015; 16: 76.
Ortega-Loubon C, Fernandez-Molina M, Carrascal-Hinojal Y, Fulquet-Carreras E. Cardiac surgery-associated acute kidney injury. Ann Card Anaesth. 2016; 19: 687-698.
O’Neil MP, Fleming JC, Badhwar A, Guo LR. Pulsatile versus nonpulsatile flow during cardiopulmonary bypass: microcircu- latory and systemic effects. Ann Thorac Surg 2012; 94: 2046- 2053.
Sirvinskas E, Andrejaitiene J, Raliene L, Nasvytis L, Karbon- skiene A, Pilvinis V, Sakalauskas J. Cardiopulmonary bypass management and acute renal failure: risk factors and progno- sis. Perfusion 2008; 23: 323-327.
Vellinga S, Verbrugghe W, De Paep R, Verpooten GA, Janssen van Doorn K. Identification of modifiable risk factors for acute kidney injury after cardiac surgery. Neth J Med 2012; 70: 450- 454.
Charlton JR, Portilla D, Okusa MD. A basic science view of acute kidney injury biomarkers. Nephrol Dial Transplant 2014; 29: 1301-1311.
Poge U, Gerhardt TM, Stoffel-Wagner B, Palmedo H, Klehr HU, Sauerbruch T, Woitas RP. beta-Trace protein is an alterna- tive marker for glomerular filtration rate in renal transplanta- tion patients. Clin Chem 2005; 51: 1531-1533.
Bhavsar NA, Appel LJ, Kusek JW, Contreras G, Bakris G, Coresh J, Astor BC, AASK Study Group. Comparison of mea- sured GFR, serum creatinine, cystatin C, and beta-trace pro- tein to predict ESRD in African Americans with hypertensive CKD. Am J Kidney Dis 2011; 58: 886-893.
Solichova P, Novackova L, Ochmanova R, Stejskal D. Assess- ment of serum beta-trace protein (BTP) measurement in the prediction of glomerular filtration rate. Comparison with se- rum cystatin C. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 2006; 150: 83-84.
Parikh CR, Devarajan P, Zappitelli M, Sint K, Thiessen-Phil- brook H, Li S, Kim RW, Koyner JL, Coca SG, Edelstein CL et al. Postoperative biomarkers predict acute kidney injury and poor outcomes after pediatric cardiac surgery. J Am Soc Nephrol 2011; 22: 1737-1747.
Ghonemy TA, Amro GM. Plasma neutrophil gelatinase-as- sociated lipocalin (NGAL) and plasma cystatin C (CysC) as biomarker of acute kidney injury after cardiac surgery. Saudi J Kidney Dis Transpl 2014; 25: 582-588.
Momeni M, Baele P, Jacquet L, Mourad M, Waterloos H, Wal- lemacq P. Cystatin C in cardiac surgery. Acta Anaesthesiol Belg 2007; 58: 107-112.
Spahillari A, Parikh CR, Sint K, Koyner JL, Patel UD, Edel- stein CL, Passik CS, Thiessen-Philbrook H, Swaminathan M, Shlipak MG et al. Serum cystatin C- versus creatinine-based definitions of acute kidney injury following cardiac surgery: a prospective cohort study. Am J Kidney Dis 2012; 60: 922-929.