Urine neutrophil gelatinase-associated lipocalin: a diagnostic and prognostic marker for acute kidney injury (AKI) in hospitalized cirrhotic patients with AKI-prone conditions

BMC Gastroenterology

Pisit Tangkijvanich¹  Piyawat Komolmit³  Khajohn Tiranathanagul²  Sasipim Sallapant³  Veeravich Jaruvongvanich³  Amornpun Wongkarnjana³  Sombat Treeprasertsuk³ 

[1] Department of Biochemistry, Faculty of Medicine, and King Chulalongkorn Memorial Hospital, Chulalongkorn University, Bangkok 10330, Thailand;Division of Nephrology, Department of Medicine, Faculty of Medicine, and King Chulalongkorn Memorial Hospital, Chulalongkorn University, Bangkok 10330, Thailand;Division of Gastroenterology, Department of Medicine, Faculty of Medicine, and King Chulalongkorn Memorial Hospital, Chulalongkorn University, Rama4 Road, Pathumwan District 10330, Bangkok, Thailand

关键词: Prognostic marker;    Diagnostic marker;    Acute kidney injury;    Cirrhosis;    Urine neutrophil gelatinase-associated lipocalin;   

Others  :  1234337
DOI  :  10.1186/s12876-015-0372-5

 received in 2015-06-16, accepted in 2015-10-08,  发布年份 2015

【 摘 要 】

Background

Acute kidney injury (AKI) is known to increase mortality in hospitalized cirrhotic patients; therefore early identification is utmost significance. There are only a few studies evaluating the cut-off level of urine neutrophil gelatinase-associated lipocalin (uNGAL) for diagnosing AKI and its prognostic value in cirrhotic patients. We aimed to determine the accuracy of uNGAL as a biomarker for early identification of AKI and to determine the cut-off level of uNGAL for diagnosing AKI in hospitalized cirrhotic patients; and (2) to explore the association of 30-day liver-related mortality with uNGAL level.

Methods and Material

We prospectively enrolled cirrhotic patients admitted at the King Chulalongkorn Memorial Hospital during May 1, 2011 to Dec 31, 2013. UNGAL levels were measured within 24 h after admission. Clinical and laboratory data were obtained. Patients were followed up to 30 days.

Results

Of 137 cirrhotic hospitalized patients, 121 cirrhotic patients (88.3 %) with AKI-prone conditions were included with mean age of 57.3 ± 14.7 years. Thirty-five patients (29 %) developed AKI within 72 h of admission. The causes of AKI were prerenal azotemia (68.6 %), acute tubular necrosis (25.7 %), hepatorenal syndrome (5.7 %), respectively. The mean uNGAL level was significantly higher in the patients who developed AKI compared with those who did not (290.6 ± 356.3 vs. 54.4 ± 73.7 ng/mL; P = 0.0001). The AUC of uNGAL for diagnosing AKI was 0.83 (95 % [CI]: 0.76–0.91) with the optimal cut-off level of 56 ng/mL, providing 77.1 % sensitivity and 73.3 % specificity. Fourteen percent of subjects died during the 30-day follow-up period. The mean uNGAL levels were significantly higher in the mortality group. The AUC of uNGAL in predicting mortality was 0.75 (95 % [CI]: 0.66–0.85), with a best cut-off level of 72 ng/mL providing 70.6 % sensitivity and 69.2 % specificity. However, in multivariate logistic regression analysis, uNGAL is not an independent factor for 30-day liver-related mortality prediction.

Conclusions

uNGAL is a valid marker for the early detection of AKI in hospitalized cirrhotic patients with AKI-prone conditions; however, its level could not independently predict 30-day liver-related mortality.

【 授权许可】

   
2015 Treeprasertsuk et al.

【 图 表 】

Fig. 1.

Fig. 2.

【 参考文献 】

• [1]Garcia-Tsao G, Parikh CR, Viola A: Acute kidney injury in cirrhosis. Hepatology 2008, 48(6):2064-77.
• [2]du Cheyron D, Bouchet B, Parienti JJ, Ramakers M, Charbonneau P: The attributable mortality of acute renal failure in critically ill patients with liver cirrhosis. Intensive Care Med 2005, 31(12):1693-9.
• [3]Mehta RL, Kellum JA, Shah SV, Molitoris BA, Ronco C, Warnock DG, et al.: Acute Kidney Injury Network: report of an initiative to improve outcomes in acute kidney injury. Crit Care 2007, 11(2):R31.
• [4]Proulx NL, Akbari A, Garg AX, Rostom A, Jaffey J, Clark HD, et al. Measured creatinine clearance from timed urine collections substantially overestimates glomerular filtration rate in patients with liver cirrhosis: a systematic review and individual patient meta-analysis. Nephrol Dial Transplant. 2005;20(8):1617–22. PubMed Epub 2005/04/28. eng.
• [5]Bellomo R, Ronco C, Kellum JA, Mehta RL, Palevsky P: Acute dialysis quality initiative w. 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):R204-12.
• [6]D’Amico G, Garcia-Tsao G, Pagliaro L: Natural history and prognostic indicators of survival in cirrhosis: a systematic review of 118 studies. J Hepatol 2006, 44(1):217-31.
• [7]Haase M, Bellomo R, Devarajan P, Schlattmann P, Haase-Fielitz A, Group NM-aI, et al. Accuracy of neutrophil gelatinase-associated lipocalin (NGAL) in diagnosis and prognosis in acute kidney injury: a systematic review and meta-analysis. Am J Kidney Dis. 2009;54(6):1012–24. PubMed Epub 2009/10/24.
• [8]Mishra J, Ma Q, Prada A, Mitsnefes M, Zahedi K, Yang J, et al.: 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.
• [9]Parikh CR, Jani A, Mishra J, Ma Q, Kelly C, Barasch J, et al.: Urine NGAL and IL-18 are predictive biomarkers for delayed graft function following kidney transplantation. Am J Transplant 2006, 6(7):1639-45.
• [10]Wagener G, Jan M, Kim M, Mori K, Barasch JM, Sladen RN, et al.: Association between increases in urinary neutrophil gelatinase-associated lipocalin and acute renal dysfunction after adult cardiac surgery. Anesthesiology 2006, 105(3):485-91.
• [11]Bennett M, Dent CL, Ma Q, Dastrala S, Grenier F, Workman R, et al.: Urine NGAL predicts severity of acute kidney injury after cardiac surgery: a prospective study. Clin J Am Soc Nephrol 2008, 3(3):665-73.
• [12]Nickolas TL, O’Rourke MJ, Yang J, Sise ME, Canetta PA, Barasch N, et al.: Sensitivity and specificity of a single emergency department measurement of urinary neutrophil gelatinase-associated lipocalin for diagnosing acute kidney injury. Ann Intern Med 2008, 148(11):810-9.
• [13]Siew ED, Ware LB, Gebretsadik T, Shintani A, Moons KG, Wickersham N, et al.: Urine neutrophil gelatinase-associated lipocalin moderately predicts acute kidney injury in critically ill adults. J Am Soc Nephrol 2009, 20(8):1823-32.
• [14]Fagundes C, Pepin MN, Guevara M, Barreto R, Casals G, Sola E, et al.: Urinary neutrophil gelatinase-associated lipocalin as biomarker in the differential diagnosis of impairment of kidney function in cirrhosis. J Hepatol 2012, 57(2):267-73.
• [15]Verna EC, Brown RS, Farrand E, Pichardo EM, Forster CS, Sola-Del Valle DA, et al.: Urinary neutrophil gelatinase-associated lipocalin predicts mortality and identifies acute kidney injury in cirrhosis. Dig Dis Sci 2012, 57(9):2362-70.
• [16]Ahmed QA, El Sayed FS, Emad H, Mohamed E, Ahmed B, Heba P, et al. Urinary biomarkers of acute kidney injury in patients with liver cirrhosis. Med Arch. 2014;68(2):132–6. PubMed Epub 2014/06/19.
• [17]Slack AJ, McPhail MJ, Ostermann M, Bruce M, Sherwood R, Musto R, et al.: Predicting the development of acute kidney injury in liver cirrhosis--an analysis of glomerular filtration rate, proteinuria and kidney injury biomarkers. Aliment Pharmacol Ther 2013, 37(10):989-97.
• [18]Belcher JM, Sanyal AJ, Peixoto AJ, Perazella MA, Lim J, Thiessen-Philbrook H, et al.: Kidney biomarkers and differential diagnosis of patients with cirrhosis and acute kidney injury. Hepatology 2014, 60(2):622-32.
• [19]Gungor G, Ataseven H, Demir A, Solak Y, Gaipov A, Biyik M, et al.: Neutrophil gelatinase-associated lipocalin in prediction of mortality in patients with hepatorenal syndrome: a prospective observational study. Liver Int 2014, 34(1):49-57.
• [20]Hampel H, Bynum GD, Zamora E, El-Serag HB: Risk factors for the development of renal dysfunction in hospitalized patients with cirrhosis. Am J Gastroenterol 2001, 96(7):2206-10.
• [21]Gines P, Schrier RW: Renal failure in cirrhosis. N Engl J Med 2009, 361(13):1279-90.
• [22]Martin-Llahi M, Guevara M, Torre A, Fagundes C, Restuccia T, Gilabert R, et al.: Prognostic importance of the cause of renal failure in patients with cirrhosis. Gastroenterology 2011, 140(2):488-96 e4.
• [23]Salerno F, Gerbes A, Gines P, Wong F, Arroyo V: Diagnosis, prevention and treatment of hepatorenal syndrome in cirrhosis. Postgrad Med J 2008, 84(998):662-70.
• [24]Gill N, Nally JV Jr, Fatica RA: Renal failure secondary to acute tubular necrosis: epidemiology, diagnosis, and management. Chest 2005, 128(4):2847-63.
• [25]Yilmaz A, Sevketoglu E, Gedikbasi A, Karyagar S, Kiyak A, Mulazimoglu M, et al.: Early prediction of urinary tract infection with urinary neutrophil gelatinase associated lipocalin. Pediatr Nephrol 2009, 24(12):2387-92.
• [26]Decavele AS, Dhondt L, De Buyzere ML, Delanghe JR: Increased urinary neutrophil gelatinase associated lipocalin in urinary tract infections and leukocyturia. Clin Chem Lab Med 2011, 49(6):999-1003.
• [27]Ronco C: N-GAL: diagnosing AKI as soon as possible. Crit Care 2007, 11(6):173.
• [28]Torregrosa I, Montoliu C, Urios A, Andres-Costa MJ, Gimenez-Garzo C, Juan I, et al. Urinary KIM-1, NGAL and L-FABP for the diagnosis of AKI in patients with acute coronary syndrome or heart failure undergoing coronary angiography. Heart and Vessels. 2014. PubMed Epub 2014/07/06.
• [29]Taghizadeh-Ghehi M, Sarayani A, Ashouri A, Ataei S, Moslehi A, Hadjibabaie M. Urine neutrophil gelatinase associated lipocalin as an early marker of acute kidney injury in hematopoietic stem cell transplantation patients. Renal Fail. 2015. May 6:1–5. PubMed Epub 2015/05/07.
• [30]Zwiers AJ, de Wildt SN, van Rosmalen J, de Rijke YB, Buijs EA, Tibboel D, et al.: Urinary neutrophil gelatinase-associated lipocalin identifies critically ill young children with acute kidney injury following intensive care admission: a prospective cohort study. Crit Care 2015, 19(1):181.
• [31]Salerno F, Gerbes A, Gines P, Wong F, Arroyo V: Diagnosis, prevention and treatment of hepatorenal syndrome in cirrhosis. Gut 2007, 56(9):1310-8.
• [32]Angeli P, Merkel C: Pathogenesis and management of hepatorenal syndrome in patients with cirrhosis. J Hepatol 2008, 48(Suppl 1):S93-103.
• [33]Schmidt-Ott KM: Neutrophil gelatinase-associated lipocalin as a biomarker of acute kidney injury--where do we stand today? Nephrol Dial Transplant 2011, 26(3):762-4.
• [34]Barreto R, Elia C, Sola E, Moreira R, Ariza X, Rodriguez E, et al.: Urinary neutrophil gelatinase-associated lipocalin predicts kidney outcome and death in patients with cirrhosis and bacterial infections. J Hepatol 2014, 61(1):35-42.
• [35]Moreau R, Jalan R, Gines P, Pavesi M, Angeli P, Cordoba J, et al.: Acute-on-chronic liver failure is a distinct syndrome that develops in patients with acute decompensation of cirrhosis. Gastroenterology 2013, 144(7):1426-37.
• [36]Shi Y, Yang Y, Hu Y, Wu W, Yang Q, Zheng M, et al.: Acute-on-chronic liver failure precipitated by hepatic injury is distinct from that precipitated by extrahepatic insults. Hepatology 2015, 62(1):232-42.