Reserch progress on novel prognostic predictors of acute renal injure in intensive care unit_West China Medical Journal

Authors：

CHEN Yi , XIA Zijing , FENG Yanhuan ,  FU Ping

Department of Nephrology / Kidney Research Institute, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P. R. China;

Corresponding author：

FU Ping, Email: fupinghx@scu.edu.cn

Keywords：

Acute kidney injury; Intensive care unit; Novel outcome predictor; Hemodialysis; Neutrophil gelatinase associated lipocalin; Interleukin-18; Kidney injury molecule-1; Cystatin-C

DOI：

10.7507/1002-0179.201806123

Video：

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Abstract Full text Figures/Tables Video References Cited by

Although the recent studies have concerned the pathogenesis and therapeutic strategies of acute kidney injury (AKI), the mortality of AKI is still terribly high, and it is still one of the most important death factors in the intensive care unit. There is no doubt that early verdict of AKI, is good for a more aggressive treatment and can promise an improved prognosis for AKI patients. Serum creatinine level, serving as the gold standard for diagnosis of kidney injury, cannot meet current clinical work in its sensitivity and specificity of diagnosis of early AKI. Over the past decades, researchers worked to find and verify novel AKI biomarkers, including neutrophil gelatinase associated lipocalin, interleukin-18, kidney injury molecule-1 and cystatin-C, which were proved to be the potential reliable predictor of AKI development and prognosis, and were of great importance to the early diagnosis and clinical monitoring of AKI. This paper reviews the main studies on these novel prognostic predictors of AKI over the decades and evaluates their roles and limitations in early diagnosis and clinical prognosis prediction.

Citation： CHEN Yi, XIA Zijing, FENG Yanhuan, FU Ping. Reserch progress on novel prognostic predictors of acute renal injure in intensive care unit. West China Medical Journal, 2018, 33(7): 900-904. doi: 10.7507/1002-0179.201806123 Copy

1.	Bagshaw SM, George C, Bellomo R, et al. A comparison of the RIFLE and AKIN criteria for acute kidney injury in critically ill patients. Nephrol Dial Transplant, 2008, 23(5): 1569-1574.
2.	Hoste EA, Kellum JA. Acute kidney injury: epidemiology and diagnostic criteria. Curr Opin Crit Care, 2006, 12(6): 531-537.
3.	Ali T, Khan I, Simpson W, et al. Incidence and outcomes in acute kidney injury: a comprehensive population-based study. J Am Soc Nephrol, 2007, 18(4): 1292-1298.
4.	Uchino S, Kellum JA, Bellomo R, et al. Acute renal failure in critically ill patients: a multinational, multicenter study. JAMA, 2005, 294(7): 813-818.
5.	Amdur RL, Chawla LS, Amodeo S, et al. Outcomes following diagnosis of acute renal failure in US. veterans: focus on acute tubular necrosis. Kidney Int, 2009, 76(10): 1089-1097.
6.	Hsu CY, Chertow GM, McCulloch CE, et al. Nonrecovery of kidney function and death after acute on chronic renal failure. Clin J Am Soc Nephrol, 2009, 4(5): 891-898.
7.	Ishani A, Xue JL, Himmelfarb J, et al. Acute kidney injury increases risk of ESRD among elderly. J Am Soc Nephrol, 2009, 20(1): 223-228.
8.	Lo LJ, Go AS, Chertow GM, et al. Dialysis-requiring acute renal failure increases the risk of progressive chronic kidney disease. Kidney Int, 2009, 76(8): 893-899.
9.	Coca SG, Yusuf B, Shlipak MG, et al. 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(6): 961-973.
10.	Paganini EP, Marshall MR. Acute renal replacement therapy in the intensive care unit//Feehally J, Floege J, Johnson R. Comprehensive clinical nephrology. 3th ed. Philadelphia: Mosby Elsevier, 2007.
11.	Baldwin I, Naka T, Koch B, et al. A pilot randomised controlled comparison of continuous veno-venous haemofiltration and extended daily dialysis with filtration: effect on small solutes and acid-base balance. Intensive Care Med, 2007, 33(5): 830-835.
12.	De Vriese AS, Colardyn FA, Philippé JJ, et al. Cytokine removal during continuous hemofiltration in septic patients. J Am Soc Nephrol, 1999, 10(4): 846-853.
13.	Bellomo R, Kellum JA, Ronco C. Defining acute renal failure: physiological principles. Intensive Care Med, 2004, 30(1): 33-37.
14.	Coca SG, Parikh CR. Urinary biomarkers for acute kidney injury: perspectives on translation. Clin J Am Soc Nephrol, 2008, 3(2): 481-490.
15.	Biomarkers Definitions Working Group. Biomarkers and surrogate endpoints: preferred definitions and conceptual framework. Clin Pharmacol Ther, 2001, 69(3): 89-95.
16.	Singhal N, Saha A. Bedside biomarkers in pediatric cardio renal injuries in emergency. Int J Crit Illn Inj Sci, 2014, 4(3): 238-246.
17.	Noto A, Cibecchini F, Fanos V, et al. NGAL and metabolomics: the single biomarker to reveal the metabolome alterations in kidney injury. Biomed Res Int, 2013: 612032.
18.	Mishra J, Ma Q, Prada A, 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): 2534-2543.
19.	Zappitelli M, Washburn KK, Arikan AA, et al. Urine neutrophil gelatinase-associated lipocalin is an early marker of acute kidney injury in critically ill children: a prospective cohort study. Crit Care, 2007, 11(4): R84.
20.	Supavekin S, Zhang W, Kucherlapati R, et al. Differential gene expression following early renal ischemia/reperfusion. Kidney Int, 2003, 63(5): 1714-1724.
21.	Yuen PS, Jo SK, Holly MK, et al. Ischemic and nephrotoxic acute renal failure are distinguished by their broad transcriptomic responses. Physiol Genomics, 2006, 25(3): 375-386.
22.	Charlton JR, Portilla D, Okusa MD. A basic science view of acute kidney injury biomarkers. Nephrol Dial Transplant, 2014, 29(7): 1301-1311.
23.	Kuwabara T, Mori K, Mukoyama M, et al. Urinary neutrophil gelatinase-associated lipocalin levels reflect damage to glomeruli, proximal tubules, and distal nephrons. Kidney Int, 2009, 75(3): 285-294.
24.	Nickolas TL, O’rourke MJ, Yang J, 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): U21-810.
25.	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.
26.	Devarajan P. Neutrophil gelatinase-associated lipocalin (NGAL): a new marker of kidney disease. Scand J Clin Lab Invest Suppl, 2008, 241: 89-94.
27.	Mori K, Lee HT, Rapoport D, et al. Endocytic delivery of lipocalin-siderophore-iron complex rescues the kidney from ischemia-reperfusion injury. J Clin Invest, 2005, 115(3): 610-621.
28.	Waikar SS, Bonventre JV. Biomarkers for the diagnosis of acute kidney injury. Curr Opin Nephrol Hypertens, 2007, 16(6): 557-564.
29.	Adiyanti SS, Loho T. Acute kidney injury (AKI) biomarker. Acta Med Indones, 2012, 44(3): 246-255.
30.	Cruz DN, Gaiao S, Maisel A, et al. Neutrophil gelatinase-associated lipocalin as a biomarker of cardiovascular disease: a systematic review. Clin Chem Lab Med, 2012, 50(9): 1533-1545.
31.	Cho E, Kim SC, Kim MG, et al. The incidence and risk factors of acute kidney injury after hepatobiliary surgery: a prospective observational study. BMC Nephrol, 2014, 15: 169.
32.	Sanjeevani S, Pruthi S, Kalra S, et al. Role of neutrophil gelatinase-associated lipocalin for early detection of acute kidney injury. Int J Crit Illn Inj Sci, 2014, 4(3): 223-228.
33.	De Geus HR, Bakker J, Lesaffre EM, et al. Neutrophil gelatinase-associated lipocalin at ICU admission predicts for acute kidney injury in adult patients. Am J Respir Crit Care Med, 2011, 183(7): 907-914.
34.	Cruz DN, De Cal M, Garzotto F, et al. Plasma neutrophil gelatinase-associated lipocalin is an early biomarker for acute kidney injury in an adult ICU population. Intensive Care Med, 2010, 36(3): 444-451.
35.	Yilmaz A, Sevketoglu E, Gedikbasi A, et al. Early prediction of urinary tract infection with urinary neutrophil gelatinase associated lipocalin. Pediatr Nephrol, 2009, 24(12): 2387-2392.
36.	Gracie JA, Robertson SE, McInnes IB. Interleukin-18. J Leukoc Biol, 2003, 73(2): 213-224.
37.	Lochner M, Förster I. Anti-interleukin-18 therapy in murine models of inflammatory bowel disease. Pathobiology, 2002, 70(3): 164-169.
38.	Gonzalez F, Vincent F. Biomarkers for acute kidney injury in critically ill patients. Minerva Anestesiol, 2012, 78(12): 1394-1403.
39.	Melnikov VY, Faubel S, Siegmund B, et al. Neutrophil-independent mechanisms of caspase-1- and IL-18-mediated ischemic acute tubular necrosis in mice. J Clin Invest, 2002, 110(8): 1083-1091.
40.	Luo Q, Zhou F, Dong H, et al. Implication of combined urinary biomarkers in early diagnosis of acute kidney injury following percutaneous coronary intervention. Clin Nephrol, 2013, 79(2): 85-92.
41.	Zheng JY, Xiao YY, Yao Y, et al. Comparison of urinary biomarkers for early detection of acute kidney injury after cardiopulmonary bypass surgery in infants and young children. Pediatr Cardiol, 2013, 34(4): 880-886.
42.	Sirota JC, Walcher A, Faubel S, et al. Urine IL-18, NGAL, IL-8 and serum IL-8 are biomarkers of acute kidney injury following liver transplantation. BMC Nephrol, 2013, 14: 17.
43.	Parikh CR, Abraham E, Ancukiewicz M, et al. Urine IL-18 is an early diagnostic marker for acute kidney injury and predicts mortality in the intensive care unit. J Am Soc Nephrol, 2005, 16(10): 3046-3052.
44.	Liu YW, Su CT, Chang YT, et al. Elevated serum interleukin-18 level is associated with all-cause mortality in stable hemodialysis patients independently of cardiac dysfunction. PLoS One, 2014, 9(3): e89457.
45.	Nisula S, Yang R, Poukkanen M, et al. Predictive value of urine interleukin-18 in the evolution and outcome of acute kidney injury in critically ill adult patients. Br J Anaesth, 2015, 114(3): 460-468.
46.	Bailly V, Zhang Z, Meier W, et al. Shedding of kidney injury molecule-1, a putative adhesion protein involved in renal regeneration. J Biol Chem, 2002, 277(42): 39739-39748.
47.	Ichimura T, Bonventre JV, Bailly V, et al. 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): 4135-4142.
48.	Kramer AB, Van Timmeren MM, Schuurs TA, et al. Reduction of proteinuria in adriamycin-induced nephropathy is associated with reduction of renal kidney injury molecule (Kim-1) over time. Am J Physiol Renal Physiol, 2009, 296(5): F1136-F1145.
49.	Dieterle F, Sistare F, Goodsaid F, et al. Renal biomarker qualification submission: a dialog between the FDA-EMEA and Predictive Safety Testing Consortium. Nat Biotechnol, 2010, 28(5): 455-462.
50.	van Timmeren MM, van den Heuvel MC, Bailly V, et al. Tubular kidney injury molecule-1 (KIM-1) in human renal disease. J Pathol, 2007, 212(2): 209-217.
51.	Liangos O, Perianayagam MC, Vaidya VS, et al. Urinary N-acetyl-beta-(D)-glucosaminidase activity and kidney injury molecule-1 level are associated with adverse outcomes in acute renal failure. J Am Soc Nephrol, 2007, 18(3): 904-912.
52.	Lucarelli G, Mancini V, Galleggiante V, et al. Emerging urinary markers of renal injury in obstructive nephropathy. Biomed Res Int, 2014: 303298.
53.	Westhuyzen J. Cystatin C: a promising marker and predictor of impaired renal function. Ann Clin Lab Sci, 2006, 36(4): 387-394.
54.	Lassus J, Harjola VP. Cystatin C: a step forward in assessing kidney function and cardiovascular risk. Heart Fail Rev, 2012, 17(2, SI): 251-261.
55.	Shlipak MG, Sarnak MJ, Katz R, et al. Cystatin C and the risk of death and cardiovascular events among elderly persons. N Engl J Med, 2005, 352(20): 2049-2060.
56.	Conti M, Moutereau S, Zater M, et al. Urinary cystatin C as a specific marker of tubular dysfunction. Clin Chem Lab Med, 2006, 44(3): 288-291.
57.	Al-Beladi FI. Cystatin C is an early marker of contrast-induced nephropathy in patients with sepsis in the intensive care unit. Saudi J Kidney Dis Transpl, 2015, 26(4): 718-724.
58.	Chen S, Shi JS, Yibulayin X, et al. Cystatin C is a moderate predictor of acute kidney injury in the early stage of traumatic hemorrhagic shock. Exp Ther Med, 2015, 10(1): 237-240.
59.	Lagos-Arevalo P, Palijan A, Vertullo L, et al. Cystatin C in acute kidney injury diagnosis: early biomarker or alternative to serum creatinine?. Pediatric Nephrol, 2015, 30(4): 665-676.
60.	Bongiovanni C, Magrini L, Salerno G, et al. Serum cystatin C for the diagnosis of acute kidney injury in patients admitted in the emergency department. Dis Markers, 2015, 2015: 416059.

1. Bagshaw SM, George C, Bellomo R, et al. A comparison of the RIFLE and AKIN criteria for acute kidney injury in critically ill patients. Nephrol Dial Transplant, 2008, 23(5): 1569-1574.
2. Hoste EA, Kellum JA. Acute kidney injury: epidemiology and diagnostic criteria. Curr Opin Crit Care, 2006, 12(6): 531-537.
3. Ali T, Khan I, Simpson W, et al. Incidence and outcomes in acute kidney injury: a comprehensive population-based study. J Am Soc Nephrol, 2007, 18(4): 1292-1298.
4. Uchino S, Kellum JA, Bellomo R, et al. Acute renal failure in critically ill patients: a multinational, multicenter study. JAMA, 2005, 294(7): 813-818.
5. Amdur RL, Chawla LS, Amodeo S, et al. Outcomes following diagnosis of acute renal failure in US. veterans: focus on acute tubular necrosis. Kidney Int, 2009, 76(10): 1089-1097.
6. Hsu CY, Chertow GM, McCulloch CE, et al. Nonrecovery of kidney function and death after acute on chronic renal failure. Clin J Am Soc Nephrol, 2009, 4(5): 891-898.
7. Ishani A, Xue JL, Himmelfarb J, et al. Acute kidney injury increases risk of ESRD among elderly. J Am Soc Nephrol, 2009, 20(1): 223-228.
8. Lo LJ, Go AS, Chertow GM, et al. Dialysis-requiring acute renal failure increases the risk of progressive chronic kidney disease. Kidney Int, 2009, 76(8): 893-899.
9. Coca SG, Yusuf B, Shlipak MG, et al. 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(6): 961-973.
10. Paganini EP, Marshall MR. Acute renal replacement therapy in the intensive care unit//Feehally J, Floege J, Johnson R. Comprehensive clinical nephrology. 3th ed. Philadelphia: Mosby Elsevier, 2007.
11. Baldwin I, Naka T, Koch B, et al. A pilot randomised controlled comparison of continuous veno-venous haemofiltration and extended daily dialysis with filtration: effect on small solutes and acid-base balance. Intensive Care Med, 2007, 33(5): 830-835.
12. De Vriese AS, Colardyn FA, Philippé JJ, et al. Cytokine removal during continuous hemofiltration in septic patients. J Am Soc Nephrol, 1999, 10(4): 846-853.
13. Bellomo R, Kellum JA, Ronco C. Defining acute renal failure: physiological principles. Intensive Care Med, 2004, 30(1): 33-37.
14. Coca SG, Parikh CR. Urinary biomarkers for acute kidney injury: perspectives on translation. Clin J Am Soc Nephrol, 2008, 3(2): 481-490.
15. Biomarkers Definitions Working Group. Biomarkers and surrogate endpoints: preferred definitions and conceptual framework. Clin Pharmacol Ther, 2001, 69(3): 89-95.
16. Singhal N, Saha A. Bedside biomarkers in pediatric cardio renal injuries in emergency. Int J Crit Illn Inj Sci, 2014, 4(3): 238-246.
17. Noto A, Cibecchini F, Fanos V, et al. NGAL and metabolomics: the single biomarker to reveal the metabolome alterations in kidney injury. Biomed Res Int, 2013: 612032.
18. Mishra J, Ma Q, Prada A, 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): 2534-2543.
19. Zappitelli M, Washburn KK, Arikan AA, et al. Urine neutrophil gelatinase-associated lipocalin is an early marker of acute kidney injury in critically ill children: a prospective cohort study. Crit Care, 2007, 11(4): R84.
20. Supavekin S, Zhang W, Kucherlapati R, et al. Differential gene expression following early renal ischemia/reperfusion. Kidney Int, 2003, 63(5): 1714-1724.
21. Yuen PS, Jo SK, Holly MK, et al. Ischemic and nephrotoxic acute renal failure are distinguished by their broad transcriptomic responses. Physiol Genomics, 2006, 25(3): 375-386.
22. Charlton JR, Portilla D, Okusa MD. A basic science view of acute kidney injury biomarkers. Nephrol Dial Transplant, 2014, 29(7): 1301-1311.
23. Kuwabara T, Mori K, Mukoyama M, et al. Urinary neutrophil gelatinase-associated lipocalin levels reflect damage to glomeruli, proximal tubules, and distal nephrons. Kidney Int, 2009, 75(3): 285-294.
24. Nickolas TL, O’rourke MJ, Yang J, 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): U21-810.
25. 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.
26. Devarajan P. Neutrophil gelatinase-associated lipocalin (NGAL): a new marker of kidney disease. Scand J Clin Lab Invest Suppl, 2008, 241: 89-94.
27. Mori K, Lee HT, Rapoport D, et al. Endocytic delivery of lipocalin-siderophore-iron complex rescues the kidney from ischemia-reperfusion injury. J Clin Invest, 2005, 115(3): 610-621.
28. Waikar SS, Bonventre JV. Biomarkers for the diagnosis of acute kidney injury. Curr Opin Nephrol Hypertens, 2007, 16(6): 557-564.
29. Adiyanti SS, Loho T. Acute kidney injury (AKI) biomarker. Acta Med Indones, 2012, 44(3): 246-255.
30. Cruz DN, Gaiao S, Maisel A, et al. Neutrophil gelatinase-associated lipocalin as a biomarker of cardiovascular disease: a systematic review. Clin Chem Lab Med, 2012, 50(9): 1533-1545.
31. Cho E, Kim SC, Kim MG, et al. The incidence and risk factors of acute kidney injury after hepatobiliary surgery: a prospective observational study. BMC Nephrol, 2014, 15: 169.
32. Sanjeevani S, Pruthi S, Kalra S, et al. Role of neutrophil gelatinase-associated lipocalin for early detection of acute kidney injury. Int J Crit Illn Inj Sci, 2014, 4(3): 223-228.
33. De Geus HR, Bakker J, Lesaffre EM, et al. Neutrophil gelatinase-associated lipocalin at ICU admission predicts for acute kidney injury in adult patients. Am J Respir Crit Care Med, 2011, 183(7): 907-914.
34. Cruz DN, De Cal M, Garzotto F, et al. Plasma neutrophil gelatinase-associated lipocalin is an early biomarker for acute kidney injury in an adult ICU population. Intensive Care Med, 2010, 36(3): 444-451.
35. Yilmaz A, Sevketoglu E, Gedikbasi A, et al. Early prediction of urinary tract infection with urinary neutrophil gelatinase associated lipocalin. Pediatr Nephrol, 2009, 24(12): 2387-2392.
36. Gracie JA, Robertson SE, McInnes IB. Interleukin-18. J Leukoc Biol, 2003, 73(2): 213-224.
37. Lochner M, Förster I. Anti-interleukin-18 therapy in murine models of inflammatory bowel disease. Pathobiology, 2002, 70(3): 164-169.
38. Gonzalez F, Vincent F. Biomarkers for acute kidney injury in critically ill patients. Minerva Anestesiol, 2012, 78(12): 1394-1403.
39. Melnikov VY, Faubel S, Siegmund B, et al. Neutrophil-independent mechanisms of caspase-1- and IL-18-mediated ischemic acute tubular necrosis in mice. J Clin Invest, 2002, 110(8): 1083-1091.
40. Luo Q, Zhou F, Dong H, et al. Implication of combined urinary biomarkers in early diagnosis of acute kidney injury following percutaneous coronary intervention. Clin Nephrol, 2013, 79(2): 85-92.
41. Zheng JY, Xiao YY, Yao Y, et al. Comparison of urinary biomarkers for early detection of acute kidney injury after cardiopulmonary bypass surgery in infants and young children. Pediatr Cardiol, 2013, 34(4): 880-886.
42. Sirota JC, Walcher A, Faubel S, et al. Urine IL-18, NGAL, IL-8 and serum IL-8 are biomarkers of acute kidney injury following liver transplantation. BMC Nephrol, 2013, 14: 17.
43. Parikh CR, Abraham E, Ancukiewicz M, et al. Urine IL-18 is an early diagnostic marker for acute kidney injury and predicts mortality in the intensive care unit. J Am Soc Nephrol, 2005, 16(10): 3046-3052.
44. Liu YW, Su CT, Chang YT, et al. Elevated serum interleukin-18 level is associated with all-cause mortality in stable hemodialysis patients independently of cardiac dysfunction. PLoS One, 2014, 9(3): e89457.
45. Nisula S, Yang R, Poukkanen M, et al. Predictive value of urine interleukin-18 in the evolution and outcome of acute kidney injury in critically ill adult patients. Br J Anaesth, 2015, 114(3): 460-468.
46. Bailly V, Zhang Z, Meier W, et al. Shedding of kidney injury molecule-1, a putative adhesion protein involved in renal regeneration. J Biol Chem, 2002, 277(42): 39739-39748.
47. Ichimura T, Bonventre JV, Bailly V, et al. 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): 4135-4142.
48. Kramer AB, Van Timmeren MM, Schuurs TA, et al. Reduction of proteinuria in adriamycin-induced nephropathy is associated with reduction of renal kidney injury molecule (Kim-1) over time. Am J Physiol Renal Physiol, 2009, 296(5): F1136-F1145.
49. Dieterle F, Sistare F, Goodsaid F, et al. Renal biomarker qualification submission: a dialog between the FDA-EMEA and Predictive Safety Testing Consortium. Nat Biotechnol, 2010, 28(5): 455-462.
50. van Timmeren MM, van den Heuvel MC, Bailly V, et al. Tubular kidney injury molecule-1 (KIM-1) in human renal disease. J Pathol, 2007, 212(2): 209-217.
51. Liangos O, Perianayagam MC, Vaidya VS, et al. Urinary N-acetyl-beta-(D)-glucosaminidase activity and kidney injury molecule-1 level are associated with adverse outcomes in acute renal failure. J Am Soc Nephrol, 2007, 18(3): 904-912.
52. Lucarelli G, Mancini V, Galleggiante V, et al. Emerging urinary markers of renal injury in obstructive nephropathy. Biomed Res Int, 2014: 303298.
53. Westhuyzen J. Cystatin C: a promising marker and predictor of impaired renal function. Ann Clin Lab Sci, 2006, 36(4): 387-394.
54. Lassus J, Harjola VP. Cystatin C: a step forward in assessing kidney function and cardiovascular risk. Heart Fail Rev, 2012, 17(2, SI): 251-261.
55. Shlipak MG, Sarnak MJ, Katz R, et al. Cystatin C and the risk of death and cardiovascular events among elderly persons. N Engl J Med, 2005, 352(20): 2049-2060.
56. Conti M, Moutereau S, Zater M, et al. Urinary cystatin C as a specific marker of tubular dysfunction. Clin Chem Lab Med, 2006, 44(3): 288-291.
57. Al-Beladi FI. Cystatin C is an early marker of contrast-induced nephropathy in patients with sepsis in the intensive care unit. Saudi J Kidney Dis Transpl, 2015, 26(4): 718-724.
58. Chen S, Shi JS, Yibulayin X, et al. Cystatin C is a moderate predictor of acute kidney injury in the early stage of traumatic hemorrhagic shock. Exp Ther Med, 2015, 10(1): 237-240.
59. Lagos-Arevalo P, Palijan A, Vertullo L, et al. Cystatin C in acute kidney injury diagnosis: early biomarker or alternative to serum creatinine?. Pediatric Nephrol, 2015, 30(4): 665-676.
60. Bongiovanni C, Magrini L, Salerno G, et al. Serum cystatin C for the diagnosis of acute kidney injury in patients admitted in the emergency department. Dis Markers, 2015, 2015: 416059.

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