HealthResJ, health, medicine, nursing, research

Biomarkers of acute kidney injury in a mixed ICU population. a narrative review

Vol 5, No 4 (2019)
Published: Oct 29, 2019
Acute kidney injury biomarkers renal failure ICU
Dimitrios Panagidis
Serafim Nanas
Stelios Kokkoris

Introduction: Acute kidney injury is a severe complication occurring in critically ill patients treated in the intensive care units, which has a significant impact on morbidity and mortality in these patients. Moreover, despite technological and pharmaceutical advances during the last decades, acute kidney injury is still associated with markedly increased morbidity and mortality. Creatinine, the most common renal dysfunction biomarker in use, has poor predictive accuracy for renal injury due to time delay in its increase and the influence by other factors on its serum concentration such as age, gender, muscle mass etc. Therefore, the need for better renal biomarkers in order to early detect and intervene for acute kidney injury prevention is imperative. During the last years several new acute kidney injury biomarkers have been discovered and validated to improve early detection of patients in risk groups for progressive renal failure, need for renal replacement therapy or death.

Aim: The purpose of the present article is to review the studies that have tested the predictive ability of those biomarkers (in urine and/or plasma) for early detection of acute kidney injury in the mixed adult intensive care unit population. 

Material and Method: We searched Medline (PubMed) using the keywords: acute kidney injury, biomarkers, renal failure, ICU.

Results: The most relevant articles were included in this review.

Conclusions: During the past decade, multiple AKI biomarkers have been studied and viewed as promising. Further studies are needed to determine their clinical utility.

Article Details
  • Section
  • Reviews
Download data is not yet available.
Hoste EA, Bagshaw SM, Bellomo R, Cely CM, Colman R, Cruz DN, Edipidis K, Forni LG, Gomersall CD, Govil D, Honore PM, Joannes -Boyau O, Joannidis M, Korhonen AM, Lavrentieva A, Mehta RL, Palevsky P, Roessler E, Ronco C, Uchino S, Vazquez JA, Vidal Andrade E, Webb S, Kellum JA. Epidemiology of acute kidney injury in critically ill patients: the multinational AKI-EPI study . Intensive Care Med 2015; 41: 1411-23.2.
Kidney Disease: Improving Global Outcomes (KDIGO) Acute Kidney Injury Work Group. KDIGO clinical practice guideline for acute kidney injury. Kidney Int 2012; 2: 1-138.
Schetz M, Gunst J, Van den Berghe G. The impact of using estimated GFR versus creatinine clearance on the evaluation of recovery from acute kidney injury in the ICU. Intensive Care Med 2014;40(11):1709-17.
Macedo E, Bouchard J, Soroko SH, Chertow GM, Himmelfarb J, Ikizler TA, Paganini EP, Mehta RL.Fluid accummulation, recognition and staging of acute kidney injury in critically ill patients. Crit Care 2010;14R82.
Ostermann M. Diagnosis of acute kidney injury: Kidney disease Improving Global Outcomes criteria and beyond. Curr Opin Crit Care. 2014;20(6):581-7.
Bellomo R, Ronco C, Kellum JA, Mehta RL, Palevsky P. 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:R204-12.
Lehner GF, Forni LG, Joannidis M. Oliguria and biomarkers of acute kidney injury: star struck lovers or strangers in the night? Nephron. 2016;134:183-190.
Prowle JR, Liu YL, Licari E, Bagshaw SM, Egi M, Haase M, Haase- Fielitz A, Kellum JA, Cruz D, Ronco C, Tsutsui K, Uchino S, Bellomo R. Oliguria as a predictive biomarker of acute kidney injury in critically ill patients. Crit Care 2011;R172.
Md Ralib A, Pickering JW, Shaw GM, Endre ZH: The urine output definition of acute kidney injury is too liberal. Crit Care 2013; 17:R112.
Murray PT, Mehta RL, Shaw A, Ronco C, Endre Z, Kellum JA, Chawla L, Cruz D, Ince C, Okusa M. Current use of biomarkers in acute kidney injury: report and summary of recommendations from the 10th Acute Dialysis Quality Initiative consensus conference. Kidney Int. 2014;85:513-21.
Ostermann M, Joannidis M. Acute kidney injury 2016: diagnosis and dignostic workup. Crit Care 2016; 27:299.
Kokkoris S, Pipili C, Grapsa E, Kyprianou T, Nanas S. Novel biomarkers of acute kidney injury in the general adult ICU: a review. Ren Fail 2013;35(4): 579-591.
Mishra J, Ma Q, Prada A, Mitsnefes M, Zahedi K, Yang J, Barasch J, Devarajan P. Identification of neutrophil gelatinase- associated lipocalin as a novel early urinary biomarker for ischemic renal injury. J Am Soc Nephrol 2003; 14:2534-2543.
de Geus HR, Bakker J, Lesaffre EM, le Noble JL. Neutrophil gelatinase-associated lipocalin at ICU admission predicts for acute kidney injury in adult patients. Am J Respir Crit Care Med 2011; 183:907-914.
Pickering JW, Endre ZH. The clinical utility of plasma neutrophil gelatinase -associated lipocalin in acute kidney injury. Blood Purif 2013; 35(4):295-302.
Hjortrup PB, Haase N, Treschow F, Moller MH, Perner A. Predictive value of NGAL for use of renal replacement therapy in patients with severe sepsis. Acta Anaesthesiol Scand 2015; 59(1):25-34.
Linko R, Pettila V, Kuitunen A, Korhonen AM, Nisula S, Alila S, Kiviniemi O, Laru-Sompa R, Varpula T, Karlsson S. Plasma neutrophil gelatinase -associated lipocalin and adverse outcome in critically ill patients with ventilatory support. Acta Anaesthesiol Scand 2013; 57(7): 855-862.
Pickering JW, Endre ZH. Challenges facing early detection of acute kidney injury in the critically ill. World J Crit Care Med 2014; 1(3):61-66.
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.
Royakkers AA, Korevaar JC, van Suijlen JD, Hofstra LS, Kuiper MA, Spronk PE, Schultz MJ, Bouman CS. Serum and urine cystatine C are poor biomarkers for acute kidney injury and renal replacement therapy. Int Care Med 2011; 37(3):493-501.
Pipili C, Ioannidou S, Tripodaki ES, Parisi M, Douka E, Vasileiadis I, Joannidis M, Nanas S. Prediction of the renal replacement therapy requirement in mechanically ventilated critically ill patients by combining biomarkers for glomerular filtration and tubular damage. J Crit Care 2014; 29(4):692.
Liangos O, Perianayagam MC, Vaidya VS, Han WK, Wald R, Tighiouart H, MacKinnon RW, Li L, Balakrishnan VS, Pereira BJ, Bonventre JV, Jaber BL. 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; 18:904-912.
Endre ZH, Pickering JW, Walker RJ, Devarajan P, Edelstein CL, Bonventre JV, Frampton CM, Bennett MR, Ma Q, Sabbisetti VS, Vaidya VS, Walcher AM, Shaw GM, Henderson SJ, Nejat M, Schollum JB, George PM. Improved performance of urinary biomarkers of acute kidney injury in the critically ill by stratification for injury duration and baseline renal function. Kidney Int. 2011; 79(10):1119-30.
Nejat M, Pickering JW, Devarajan P, Bonventre JV, Edelstein CL, Walker RJ, Endre ZH. Some biomarkers of acute kidney injury are increased in pre-renal acute injury. Kidney Int. 2012; 81:1254-1262.
Koyner JL, Vaidya VS, Bennett MR, Ma Q, Worcester E, Akhter SA, Raman J, Jeevanandam V, O’ Connor MF, Devarajan P, Bonventre JV, Murray PT. Urinary biomarkers in the clinical prognosis and early detection of acute kidney injury. Clin J Am Soc Nephrol 2010; 5:2154-2165.
Obermuller N, Geiger H, Weipert C, Urbschat A. Current developments in early diagnosis of acute kidney injury. Int Urol Nephrol 2014; 46(1):1-7.
Doi K, Negishi K, Ishizu T, Katagiri D, Fujita T, Matsubara T, Yahagi N, Sugaya T, Noiri E. Evaluation of new acute kidney injury biomarkers in a mixed intensive care unit. Crit Care Med 2011; 39:2464-2469.
Doi K, Katagiri D, Negishi K, Hasegawa S, Hamasaki Y, Fujita T, Matsubara T, Ishii T, Yahagi N, Sugaya T, Noiri E. Mild elevation of urinary biomarkers in prerenal acute kidney injury. Kidney Int 2012; 82:1114-1120.
Nisula S, Yang R, Poukkanen M, Vaara ST, Kaukonen KM, Tallgren M, Haapio M, Tenhunen J, Korhonen AM, Pettila V.
Predictive value of urine interleukin -18 in the evolution and outcome of acute kidney injury in critically adult patients. Br J Anaesth 2015; 114(3):460-468.
Tan NS, Shaw NS, Vinckenbosch N, Liu P, Yasmin R, Desvergne B, Wahli W, Noy N. Selective cooperation between fatty acid binding proteins and peroxisome proliferator-activated receptors in regulating transcription. Mol Cell Biol 2002; 22:5114-5127.
Doi K, Noiri E, Maeda-Mamiya R, Ishii T, Negishi K, Hamasaki Y, Fujita T, Yahagi N, Koide H, Sugaya T, Nakamura T. Urinary L-type fatty acid-binding protein as a new biomarker of sepsis complicated with acute kidney injury. Crit Care Med. 2010; 38:2037-2042.
Dihazi H, Koziolek MJ, Datta RR, Wallbach M, Jung K, Heise D, Dihazi GH, Markovic I, Asif AR, Muller GA. FABP1 and FABP3 have high predictive values for Renal Replacement Therapy in patients with Acute Kidney Injury. Blood Purif. 2016; 42(3):202-213.
Chindarkar NS, Chawla LS, Straseski JA, Jortani SA, Geiger DU, Orr RR, Kellum JA, Fitzgerald RL. Reference intervals of urinary acute kidney injury (AKI) markers [IGFBP7[TIMP2] in apparently healthy subjects and chronic comorbid subjects without AKI. Clin Chim Acta 2016; 452:32-37.
Kashani K, Al-khafaji A, Ardiles T, Artigas A, Bagshaw SM, Bell M, Bihorac A, Birkhahn R, Cely CM, Chawla LS, Davison DL, Feldkamp T, Forni LG, Gong MN, Gunnerson KJ, Haase M, Hackett J, Honore PM, Hoste EA, Joannes –Boyau O, Joannidis M, Kim P, Koyner JL, Laskowitz DT, Lissauer ME, Marx G, McCullough PA, Mullaney S, Ostermann M, Rimmele T, Shapiro NI, Shaw AD, Shi J, Sprague AM, Vincent JL, Vinsonneau C, Wagner L, Walker MG, Wilkerson RG, Zacharowski K, Kellum JA. Discovery and validation of cell cycle arrest biomarkers in human acute kidney injury. Crit Care 2013; 17:R25.
Bihorac A, Chawla LS, Shaw AD, Al-Khafaji A, Davison DL, Demuth GE, Fitzgerald R, Gong MN, Graham DD, Gunnerson K, Heung M, Jortani S, Kleerup E, Koyner JL,
Krell K, Letourneau J, Lissauer M, Miner J, Nguyen HB, Ortega LM, Self WH, Sellman R, Shi J, Straseski J, Szalados JE, Wilber ST, Walker MG, Wilson J, Wunderink R, Zimmerman J, Kellum JA. Validation of cell-cycle arrest biomarkers for acute kidney injury using clinical adjudication. Am J Respir Crit Care Med 2014; 189:932-939.
Hoste EA, McCullough PA, Kashani K, Chawla LS, Joannidis M, Shaw AD, Feldkamp T, Uettwiller-Geiger DL, McCarthy P, Shi J, Walker MG, Kellum JA. Derivation and validation of cutoffs for clinical use of cell cycle biomarkers. Nephrol Dial Transplant 2014; 29:2054-2061.
Koyner JL, Shaw AD, Chawla LS, Hoste EA, Bihorac A, Kashani K, Haase M, Shi J, Kellum JA. Tissue inhibitor metalloproteinase -2 (TIMP-2)IGF binding protein -7(IGFBP7) levels are associated with adverse long- term outcomes in patients with AKI. J Am Soc Nephrol 2015;26:1747-1754.
Nagy G, Gasner B, nyi ELA , Marko L, Feher E, Cseh J, Koszegi T, Betlehem J, Sulyok E, Cziraki A, Wittmann I. Selective association of endogenous ouabain with subclinical organ damage in treated hypertensive patients. J Hum Hypertens 2010; 25:122-129.
Bignami E, Casamassima N, Frati E, Lanzani C, Corno L, Alfieri O, Gottlieb S, Simonini M, Shah KB, Mizzi A, Messaggio E, Zangrillo A, Ferrandi M, Ferrari P, Bianchi G, Hamlyn JM, Manunta P.Preoperative endogenous ouabain predicts acute kidney injury in cardiac surgery patients. Crit Care Med 2013; 41:744-755.
Simonini M, Lanzani C, Bignami E, Casamassima N, Frati E, Meroni R, Messaggio E, Alfieri O, Hamlyn J, Body SC, Collard CD, Zangrillo A, Manunta P. A new clinical multivariable model that predicts postoperative acute kidney injury: impact of endogenous ouabain. Nephrol Dial Transplant 2014; 29:1696-1701.
Most read articles by the same author(s)