Tubular and Glomerular Biomarkers of Acute Kidney Injury in Newborns

Author(s): Monika Kamianowska*, Marek Szczepański, Anna Wasilewska.

Journal Name: Current Drug Metabolism

Volume 20 , Issue 5 , 2019

Become EABM
Become Reviewer

Graphical Abstract:


Background: Acute Kidney Injury (AKI) is a sudden decrease in kidney function. In the early period, the highest percentage of AKI occurs among newborns hospitalized in the neonatal intensive care units, especially premature neonates. The prognosis of AKI depends on the type and severity of the cause of an injury, the accuracy and the time of diagnosis and treatment. The concentration of serum creatinine is still the main diagnostic test, although it changes in the course of AKI later than glomerular filtration rate GFR. In addition, the reliability of the determination of creatinine level is limited because it depends on many factors. New studies have presented other, more useful laboratory markers of renal function that can be measured in serum and/or in urine.

Objective: The aim of the work was to present the latest data about tubular and glomerular biomarkers of acute kidney injury in newborns.

Methods: We undertook a structured search of bibliographic databases for peer-reviewed research literature by using focused review topics. According to the conceptual framework, the main idea of research literature has been summarized and presented in this study.

Results: The concentrations of some novel biomarkers are higher in serum and/or urine of term and preterm newborns with AKI, especially in the course of perinatal asphyxia.

Conclusion: In this systematic review of the literature, we have highlighted the usefulness of biomarkers in predicting tubular and/or glomerular injury in newborns. However, novel biomarkers need to prove their clinical applicability, accuracy, and cost-effectiveness prior to their implementation in clinical practice.

Keywords: Acute kidney injury, tubular biomarkers, glomerular biomarkers, newborns, risk factor, conventional biomarkers.

Ottonello, G.; Dessì, A.; Neroni, P.; Trudu, M.E.; Manus, D.; Fanos, V. Acute kidney injury in neonatal age. J. Pediatr. Neonat. Individual. Med., 2014, 3, 1-7.
Marin, T.; DeRossett, B.; Bhatia, J. Urinary biomarkers to predict neonatal acute kidney injury: A review of the science. J. Perinat. Neonatal Nurs., 2018, 32, 266-274.
Selewski, D.T.; Charlton, J.R.; Jetton, J.G.; Guillet, R.; Mhanna, M.J.; Askenazi, D.J.; Kent, A.L. Neonatal Acute Kidney Injury. Pediatrics, 2015, 136, e463-e473.
McMahon, G.M.; Waikar, S.S. Biomarkers in Nephrology. Am. J. Kidney Dis., 2013, 62, 165-178.
Liu, X.; Guan, Y.; Xu, S.; Li, Q.; Sun, Y.; Han, R.; Jiang, C. Early predictors of acute kidney injury: A narrative review. Kidney Blood Press. Res., 2016, 41, 680-700.
Greenberg, J.H.; Parikh, C.R. Biomarkers for diagnosis and prognosis of AKI in children: One size does not fit all. Clin. J. Am. Soc. Nephrol., 2017, 12, 1551-1557.
Ostermann, M.; Joannidis, M. Acute kidney injury 2016: Diagnosis and diagnostic workup. Crit. Care, 2016, 20, 299.
Askenazi, D.J.; Griffin, R.; McGwin, G.; Carlo, W.; Ambalavanan, N. Acute kidney injury is independently associated with mortality in very low birthweight infants: A matched case-control analysis. Pediatr. Nephrol., 2009, 24, 991-997.
Mehta, R.L.; Kellum, J.A.; Shah, S.V.; Molitoris, B.A.; Ronco, C.; Warnock, D.G. Acute kidney injury network: report of an initiative to improve outcomes in acute kidney injury. Crit. Care, 2007, 11, R31.
Khwaja, A. KDIGO clinical practice guidelines for acute kidney injury. Nephron Clin. Pract., 2012, 120, c179-c184.
Jetton, J.G.; Askenazi, D.J. Update on acute kidney injury in the neonate. Curr. Opin. Pediatr., 2012, 24, 191-196.
Ricci, Z.; Ronco, C. Neonatal RIFLE. Nephrol. Dial. Transplant., 2013, 28, 2211-2214.
Askenazi, D.; Saeidi, B.; Koralkar, R.; Ambalavanan, N.; Griffin, R.L. Acute changes in fluid status affect the incidence, associative clinical outcomes, and urine biomarker performance inpremature infants with acute kidney injury. Pediatr. Nephrol., 2016, 31, 843-851.
Abosaif, N.Y.; Tolba, Y.A.; Heap, M.; Russell, J.; El Nahas, A.M. The outcome of acute renal failure in the intensive care unit according to RIFLE: Model application, sensitivity, and predictability. Am. J. Kidney Dis., 2005, 46, 1038-1048.
Stapleton, F.B.; Jones, D.P.; Green, R.S. Acute renal failure in neonates: incidence, etiology and outcome. Pediatr. Nephrol., 1987, 1, 314-320.
Hentschel, R.; Lodige, B.; Bulla, M. Renal insufficiency in the neonatal period. Clin. Nephrol., 1996, 46, 54-58.
Agras, P.I.; Tarcan, A.; Baskin, E.; Cengiz, N.; Gurakan, B.; Saatci, U. Acute renal failure in the neonatal period. Ren. Fail., 2004, 26, 305-309.
Koralkar, R.; Ambalavanan, N.; Levitan, E.B.; McGwin, G.; Goldstein, S.; Askenazi, D. Acute kidney injury reduces survival in very low-birth-weight infants. Pediatr. Res., 2011, 69, 354-358.
Gleason, Ch.; Ballard, R. Avery’s Disease of the Newborn, 8th ed; USA: Saunders, 2004, pp. 1689-1690.
Toth-Heyn, P.; Drukker, A.; Guignard, J.P. The stressed neonatal kidney: From pathophysiology to clinical management of neonatal vasomotor nephropathy. Pediatr. Nephrol., 2000, 14, 227-239.
Sulemanji, M.; Vakili, K. Neonatal renal physiology. Semin. Pediatr. Surg., 2013, 22, 195-198.
Burke, M.; Pabbidi, M.R.; Farley, J.; Roman, R.J. Molecular mechanisms of renal blood flow autoregulation. Curr. Vasc. Pharmacol., 2014, 12, 845-858.
Martin, R.J.; Fanaroff, A.A.; Walsh, M.C. Fanaroff and Martin’s Neonatal-Perinatal Medicine: Diseases of the Fetus and Infant, 9th ed; USA: Elsevier Mosby, 2011, p. 1690.
Basile, D.P.; Anderson, D.; Sutton, T.A. Pathophysiology of acute kidney injury. Compr. Physiol., 2012, 2, 1303-1353.
Sancho-Martínez, S.M.; López-Novoa, J.M.; López-Hernández, F.J. Pathophysiological role of different tubular epithelial cell death modes in acute kidney injury. Clin. Kidney J., 2015, 8, 548-559.
Lopez-Novoa, J.M.; Quiros, Y.; Vicente, L.; Morales, A.I.; Lopez-Hernandez, F.J. New insights into the mechanism of aminoglycoside nephrotoxicity: An integrative point of view. Kidney Int., 2011, 79, 33-45.
Roszkowska-Blaim, M.; Kisiel, A. Role of biomarkers in the early diagnosis of acute kidney injury in neonates. Postepy Nauk Med., 2013, 16, 138-143.
Ringer, S.A. Acute renal failure in the neonate. NeoRevievs, 2010, 11, e243.
Bennett, M.R.; Devarajan, P. Characteristics of an ideal biomarker of kidney diseases.In:Biomarkers of Kidney Disease; Edelstein, Ch., L. Academic Press/Elsevier: Massachusetts. , 2010, pp. 1-24.
Rehberg, P.B. Studies on kidney function: The rate of filtration and reabsorption in the human kidney. Biochem. J., 1926, 20, 447-460.
Perrone, R.D.; Madias, N.E.; Levey, A.S. Serum creatinine as an index of renal function: New insights into old concepts. Clin. Chem., 1992, 38, 1933-1953.
Oberbauer, R. Biomarkers-a potential route for improved diagnosis and management of ongoing renal damage. Transplant. Proc., 2008, 40, S44-S47.
Hoseini, R.; Otukesh, H.; Rahimzadeh, N.; Hoseini, S. Glomerular function in neonates. Iran. J. Kidney Dis., 2012, 6, 166-172.
Lolekha, P.H.; Jaruthunyaluck, S.; Srisawasdi, P. Deproteinization of serum: another best approach to eliminate all forms of bilirubin interference on serum creatinine by the kinetic Jaffe reaction. J. Clin. Lab. Anal., 2001, 15, 116-121.
Perazella, M.A.; Coca, S.G.; Hall, I.E.; Iyanam, U.; Koraishy, M.; Parikh, C.R. Urine microscopy is associated with severity and worsening of acute kidney injury in hospitalized patients. Clin. J. Am. Soc. Nephrol., 2010, 5, 402-408.
Levey, A.S.; de Jong, P.E.; Coresh, J.; El Nahas, M.; Astor, B.C.; Matsushita, K.; Gansevoort, R.T.; Kasiske, B.L.; Eckardt, K.U. The definition, classification, and prognosis of chronic kidney disease: A KDIGO controversies conference report. Kidney Int., 2011, 80, 17-28.
Mohammadjafari, H.; Rafiei, A.; Abedi, M.; Aalaee, A.; Abedi, E. The role of urinary TIMP1 and MMP9 levels in predicting vesicoureteral reflux in neonates with antenatal hydronephrosis. Pediatr. Nephrol., 2014, 29, 871-878.
Vaidya, V.S.; Ferguson, M.A.; Bonventre, J.V. Biomarkers of acute kidney injury. Annu. Rev. Pharmacol. Toxicol., 2008, 48, 463-493.
Muramatsu, Y.; Tsujie, M.; Kohda, Y.; Pham, B.; Perantoni, A.O.; Zhao, H.; Jo, S.K.; Yuen, P.S.; Craig, L.; Hu, X.; Star, R.A. Early detection of Cysteine Rich Protein 61 (CYR61, CCN1) in urine following renal ischemic reperfusion injury. Kidney Int., 2002, 62, 1601-1610.
Ochieng, J.; Chaudhuri, G. Cystatin superfamily. J. Health Care Poor Underserved, 2010, 21, 51-70.
Laterza, O.F.; Price, C.P.; Scott, M.G.; Cystatin, C. An improved estimator of glomerular filtration rate? Clin. Chem., 2002, 48, 699-707.
Li, Y.; Fu, C.; Zhou, X.; Xiao, Z.; Zhu, X.; Jin, M.; Li, X.; Feng, X. Urine interleukin-18 and cystatin-C as biomarkers of acute kidney injury in critically ill neonates. Pediatr. Nephrol., 2012, 27, 851-860.
Novo, A.C.; Sadeck Ldos, S.; Okay, T.S.; Leone, C.R. Longitudinal study of cystatin C in healthy term newborns. Clinics (São Paulo), 2011, 66, 217-220.
Sweetman, D.U.; Onwuneme, C.; Watson, W.R.; O’Neill, A.; Murphy, J.F.; Molloy, E.J. Renal function and novel urinary biomarkers in infants with neonatal encephalopathy. Acta Paediatr., 2016, 105, e513-e519.
Askenazi, D.J.; Koralkar, R. Patil; Halloran, B.; Ambalavanan, N.; Griffin, R. Acute kidney injury urine biomarkers in very low-birth-weight infants. Clin. J. Am. Soc. Nephrol., 2016, 11, 1527-1535.
El-Gamasy, M.A. Early predictors of Acute Kidney Injury (AKI) in a sample of Egyptian full term neonates. Med. Clin. Rev., 2017, 3, 12.
Abdelaal, N.A.; Shalaby, S.A.; Khashana, A.K.; Abdelwahab, A.M. Serum cystatin C as an earlier predictor of acute kidney injury than serum creatinine in preterm neonates with respiratory distress syndrome. Saudi J. Kidney Dis. Transpl., 2017, 28, 1003-1014.
Song, Y.; Sun, S.; Yu, Y.; Li, G.; Song, J.; Zhang, H.; Yan, C. Diagnostic value of neutrophil gelatinase-associated lipocalin for renal injury in asphyxiated preterm infants. Exp. Ther. Med., 2017, 13, 1245-1248.
El-Gammacy, T.M.; Shinkar, D.M.; Mohamed, N.R.; Al-Halag, A.R. Serum cystatin C as an early predictor of acute kidney injury in preterm neonates with respiratory distress syndrome. Scand. J. Clin. Lab. Invest., 2018, 22, 1-6.
Nakamura, T.; Takahashi, T.; Fukui, M.; Ebihara, I.; Osada, S.; Tomino, Y.; Koide, H. Enalapril attenuates increased gene expression of extracellular matrix components in diabetic rats. J. Am. Soc. Nephrol., 1995, 5, 1492-1497.
Carome, M.A.; Striker, L.J.; Peten, E.P.; Moore, J.; Yang, C.W.; Stetler-Stevenson, W.G.; Striker, G.E. Human glomeruli express TIMP-1 mRNA and TIMP-2 protein and mRNA. Am. J. Physiol., 1993, 264, F923-F929.
Hörstrup, J.H.; Gehrmann, M.; Schneider, B.; Plöger, A.; Froese, P.; Schirop, T.; Kampf, D.; Frei, U.; Neumann, R.; Eckardt, K.U. Elevation of serum and urine levels of TIMP-1 and tenascin in patients with renal disease. Nephrol. Dial. Transplant., 2002, 17, 1005-1013.
Stetler-Stevenson, W.G. Tissue inhibitors of metalloproteinases in cell signaling: metalloproteinase-independent biological activities .Sci. Signal., 2008, 8 1, re6.
Swisshelm, K.; Ryan, K.; Tsuchiya, K.; Sager, R. Enhanced expression of an insulin growth factor-like binding protein (mac25) in senescent human mammary epithelial cells and induced expression with retinoic acid. Proc. Natl. Acad. Sci. USA, 1995, 92, 4472-4476.
Meersch, M.; Schmidt, C.; Van Aken, H.; Martens, S.; Rossaint, J.; Singbartl, K.; Gorlich, D.; Kellum, J.A.; Zarbock, A. Urinary TIMP-2 and IGFBP7 as early biomarkers of acute kidney injury and renal recovery following cardiac surgery. PLoS One, 2014, 9, e93460.
Bihorac, A.; Chawla, L.S.; Shaw, A.D.; Al-Khafaji, A.; Davison, D.L.; Demuth, G.E.; Fitzgerald, R.; Gong, M.N.; Graham, D.D.; Gunnerson, K.; Heung, M.; Jortani, S.; Kleerup, E.; Koyner, J.L.; Krell, K.; Letourneau, J.; Lissauer, M.; Miner, J.; Nguyen, H.B.; Ortega, L.M.; Self, W.H.; Sellman, R.; Shi, J.; Straseski, J.; Szalados, J.E.; Wilber, S.T.; Walker, M.G.; Wilson, J.; Wunderink, R.; Zimmerman, J.; Kellum, J.A. Validation of cell-cycle arrest biomarkers for acute kidney injury using clinical adjudication. Am. J. Respir. Crit. Care Med., 2014, 15, 932-939.
Westhoff, J.H.; Tönshoff, B.; Waldherr, S.; Pöschl, J.; Teufel, U.; Westhoff, T.H.; Fichtner, A. Urinary Tissue Inhibitor of Metalloproteinase-2 (TIMP-2) Insulin-like Growth Factor-Binding Protein 7 (IGFBP7) predicts adverse outcome in pediatric acute kidney injury. PLoS One, 2015, 25, e0143628.
Kamianowska, M.; Szczepański, M.; Kulikowska, E.E.; Bebko, B.; Wasilewska, A. Do serum and urinary concentrations of kidney injury molecule-1 in healthy newborns depend on birth weight, gestational age or gender? J. Perinatol., 2017, 37, 73-76.
Ichimura, T.; Bonventre, J.V.; Bailly, V.; Wei, H.; Hession, C.A.; Cate, R.L.; 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, 13, 4135-4142.
Chaturvedi, S.; Farmer, T.; Kapke, G.F. Assay validation for KIM-1: Human urinary renal dysfunction biomarker. Int. J. Biol. Sci., 2009, 5, 128-134.
Sabbisetti, V.S.; Ito, K.; Wang, C.; Yang, L.; Mefferd, S.C.; Bonventre, J.V. Novel assays for detection of urinary kim-1 in mouse models of kidney injury. Toxicol. Sci., 2013, 131, 13-25.
Stojanović, V.D.; Barišić, N.A.; Vučković, N.M.; Doronjski, A.D.; Peco Antić, A.E. Urinary kidney injury molecule-1 rapid test predicts acute kidney injury in extremely low-birth-weight neonates. Pediatr. Res., 2015, 78, 430-435.
Genc, G.; Ozkaya, O.; Avci, B.; Aygun, C.; Kucukoduk, S. Kidney injury molecule-1 as a promising biomarker for acute kidney injury in premature babies. Am. J. Perinatol., 2013, 30, 245-252.
Cao, X.Y.; Zhang, H.R.; Zhang, W.; Chen, B. Diagnostic values of urinary netrin-1 and kidney injury molecule-1 for acute kidney injury induced by neonatal asphyxia. Zhongguo Dang Dai Er Ke Za Zhi, 2016, 18, 24-28.
Jansen, D.; Peters, E.; Heemskerk, S.; Koster-Kamphuis, L.; Bouw, M.P.; Roelofs, H.M.; Van Oeveren, W.; Van Heijst, A.F.; Pickkers, P. Tubular injury biomarkers to detect gentamicin-induced acute kidney injury in the neonatal intensive care unit. Am. J. Perinatol., 2016, 33, 180-187.
Kamianowska, M.; Wasilewska, A.; Szczepański, M.; Kulikowska, E.; Bebko, B.; Koput, A. Health term-born girls had higher levels of urine neutrophil gelatinase-associated lipocalin than boys during the first postnatal days. Acta Paediatr., 2016, 105, 1105-1108.
Malyszko, J. Biomarkers of acute kidney injury in different clinical settings: a time to change the paradigm? Kidney Blood Press. Res., 2010, 33, 368-382.
Suchojad, A.; Tarko, A.; Smertka, M.; Majcherczyk, M.; Brzozowska, A.; Wroblewska, J.; Maruniak-Chudek, I. Factors limiting usefulness of serum and urinary NGAL as a marker of acute kidney injury in preterm newborns. Ren. Fail., 2015, 37, 439-445.
Mårtensson, J.; Xu, S.; Bell, M.; Martling, C.R.; Venge, P. Immunoassays distinguishing between HNL/NGAL released in urine from kidney epithelial cells and neutrophils. Clin. Chim. Acta, 2012, 413, 1661-1667.
Askenazi, D.J.; Koralkar, R.; Levitan, E.B.; Goldstein, S.L.; Devarajan, P.; Khandrika, S.; Mehta, R.L.; Ambalavanan, N. Baseline values of candidate urine acute kidney injury biomarkers vary by gestational age in premature infants. Pediatr. Res., 2011, 70, 302-306.
Huynh, T.K.; Parravicini, E.; Lorenz, J.M.; Nemerofsky, S.L.; Sise, M.E.; Bowman, T.M.; Polesana, E.; Barasch, J.M. Reference values of urinary neutrophil gelatinase-associated lipocalin in very low birth weight infants. Pediatr. Res., 2009, 66, 528-532.
Lavery, A.P.; Anderson, E.; Ma, Q.; Bennett, M.R.; Devarajan, P.; Schibler, K.R. Urinary NGAL in premature infants. Pediatr. Res., 2008, 64, 423-428.
Krawczeski, C.D.; Woo, J.G.; Wang, Y.; Bennett, M.R.; Ma, Q.; Devarajan, P. Neutrophil gelatinase- associated lipocalin concentrations predict development of acute kidney injury in neonates and children after cardiopulmonary bypass. J. Pediatr., 2011, 158, 1009-1015.
Parravicini, E.; Nemerofsky, S.L.; Michelson, K.A.; Huynh, T.K.; Sise, M.E.; Bateman, D.A.; Lorenz, J.M.; Barasch, J.M. Urinary neutrophil gelatinase-associated lipocalin is a promising biomarker for late onset culture-positive sepsis in very low birth weight infants. Pediatr. Res., 2010, 67, 636-640.
Essajee, F.; Were, F.; Admani, B. Urine neutrophil gelatinase-associated lipocalin in asphyxiated neonates: A prospective cohort study. Pediatr. Nephrol., 2015, 30, 1189-1196.
Pejović, B.; Erić-Marinković, J.; Pejović, M.; Kotur-Stevuljević, J.; Peco-Antić, A. Detection of acute kidney injury in premature asphyxiated neonates by serum Neutrophil Gelatinase-associated Lipocalin (sNGAL)-sensitivity and specificity of a potential new biomarker. Biochem. Med. (Zagreb), 2015, 15, 450-459.
Abdelhady, S.; Gawad, E.R.A.; Haie, O.M.A.; Mansour, A.I. Usefulness of serum and urinary neutrophil gelatinase - associated lipocalin in detecting acute kidney injury in asphyxiated neonates. Int. J. Med. Health Sci., 2016, 5, 230-236.
Baumert, M.; Surmiak, P.; Więcek, A.; Walencka, Z. Serum NGAL and copeptin levels as predictors of acute kidney injury in asphyxiated neonates. Clin. Exp. Nephrol., 2017, 21, 658-664.
Chandrashekar, C.; Venkatkrishnan, A. Clinical utility of serum Neutrophil Gelatinase Associated Lipocalin (NGAL) as an early marker of acute kidney injury in asphyxiated neonates. J. Nepal Paediatr. Soc., 2016, 36, 121.
Kuribayashi, R.; Suzumura, H.; Sairenchi, T.; Watabe, Y.; Tsuboi, Y.; Imataka, G.; Kurosawa, H.; Arisaka, O. Urinary neutrophil gelatinase-associated lipocalin is an early predictor of acute kidney injury in premature infants. Exp. Ther. Med., 2016, 12, 3706-3710.
Oncel, M.Y.; Canpolat, F.E.; Arayici, S.; Alyamac, D.E.; Uras, N.; Oguz, S.S. Urinary markers of acute kidney injury in newborns with perinatal asphyxia. Ren. Fail., 2016, 38, 882-888.
Tanigasalam, V.; Bhat, B.V.; Adhisivam, B.; Sridhar, M.G.; Harichandrakumar, K.T. Predicting severity of acute kidney injury in term neonates with perinatal asphyxia using urinary neutrophil gelatinase associated lipocalin. Indian J. Pediatr., 2016, 83, 1374-1378.
El Frargy, M.S.; Soliman, N.A. Urinary neutrophil gelatinase associated lipocalin and interleukin-18 as early predictors of kidney injury in neonates. J. Mol. Biomark. Diagn., 2016, 8, 308.
Hanna, M.; Brophy, P.D.; Giannone, P.J.; Joshi, M.S.; Bauer, J.A.; Ramachandra, R.S. Early urinary biomarkers of acute kidney injury in preterm infants. Pediatr. Res., 2016, 80, 218-223.
Sellmer, A.; Bech, B.H.; Bjerre, J.V.; Schmidt, M.R.; Hjortdal, V.E.; Esberg, G.; Rittig, S.; Henrikse, T.B. Urinary neutrophil gelatinase-associated lipocalin in the evaluation of patent ductus arteriosus and AKI in very preterm neonates: A cohort study. BMC Pediatr., 2017, 17, 7.
Wawrocki, S.; Druszczynska, M.; Kowalewicz-Kulbat, M.; Rudnicka, W. Interleukin 18 (IL-18) as a target for immune intervention. Acta Biochim. Pol., 2016, 63, 59-63.
Leslie, J.A.; Meldrum, K.K. The role of interleukin-18 in renal injury. J. Surg. Res., 2008, 145, 170-175.
Miklaszewska, M.; Korohodai, P.; Kwinta, P.; Tomasik, T.; Zachwieja, K.; Klich, B.; Tkaczyk, M.; Droźdź, D.; Pietrzyk, J.A. Clinical validity of urinary interleukin 18 and interleukin 6 determinations in preterm newborns. Przegl. Lek., 2015, 72, 589-596.
Abd El-Salam, M.; Zaher, M.M.; Abd El-Salam Mohamed, R.; Al Shall, L.Y.; A.M., Saleh R.A.M.; Hegazy, A.A. Comparison ofsome urinary biomarkers of acute kidney injury in term new born with and without asphyxia. Clin. Med. Diag., 2014, 4, 23-28.
Askenazi, D.J.; Montesanti, A.; Hunley, H.; Koralkar, R.; Pawar, P.; Shuaib, F.; Liwo, A.; Devarajan, P.; Ambalavanan, N. Urine biomarkers predict acute kidney injury and mortality in very low birth weight infants. J. Pediatr., 2011, 159, 907-912.
Safina, A.I.; Daminova, M.A.; Abdullina, G.A. Acute kidney injury in neonatal intensive care: Medicines involved. Int. J. Risk Saf. Med., 2015, 27, S9-S10.
Kamijo-Ikemori, A.; Sugaya, T.; Obama, A.; Hiroi, J.; Miura, H.; Watanabe, M.; Kumai, T.; Ohtani-Kaneko, R.; Hirata, K.; Kimura, K. Liver-type fatty acid-binding protein attenuates renal injury induced by unilateral ureteral obstruction. Am. J. Pathol., 2006, 169, 1107-1117.
Kamijo, A.; Sugaya, T.; Hikawa, A.; Yamanouchi, M.; Hirata, Y.; Ishimitsu, T.; Numabe, A.; Takagi, M.; Hayakawa, H.; Tabei, F.; Sugimoto, T.; Mise, N.; Omata, M.; Kimura, K. Urinary liver-type fatty acid binding protein as a useful biomarker in chronic kidney disease. Mol. Cell. Biochem., 2006, 284, 175-182.
Tsukahara, H.; Sugaya, T.; Hayakawa, K.; Hiraoka, M.; Hata, A.; Mayumi, M. Quantification of L-type fatty acid binding protein in the urine of preterm neonates. Early Hum. Dev., 2005, 81, 643-646.
Elnady, H.G.; Abdalmoneam, N.; Shady, M.M.A.; Hassanain, M.M.; Ibraheim, R.A.I.; Ragaa, A.R.H. Urinary liver-type fatty acid-binding protein for early detection of acute kidney injury in neonatal sepsis. Med. Res. J., 2014, 13, 21-26.
Girardi, A.C.C.; Carraro-Lacroix, L.R. Regulation of Na+/H+ exchanger isoform 3 by protein kinase Ain the renal proximal tubule In: Protein Kinases; Da Silva Xavie, G. InTech: Croatia,. , 2012, pp. 321-336.
Du Cheyron, D.; Daubin, C.; Poggioli, J.; Ramakers, M.; Houillier, P.; Charbonneau, P.; Paillard, M. Urinary measurement of Na+/H+ Exchanger Isoform 3 (NHE3) protein as new marker of tubule injury in critically ill patients with ARF. Am. J. Kidney Dis., 2003, 42, 497-506.
Miyata, T.; Jadoul, M.; Kurokawa, K.; Van Ypersele de Strihou, C. Beta-2 microglobulin in renal disease. J. Am. Soc. Nephrol., 1998, 9, 1723-1735.
Chapelsky, M.C.; Nix, D.E.; Cavanaugh, J.C.; Wilton, J.H.; Norman, A.; Schentag, J.J. Renal tubular enzyme effects of clarithromycin in comparison with gentamicin and placebo in volunteers. Drug Saf., 1992, 7, 304-309.
Dehne, M.G.; Boldt, J.; Heise, D.; Sablotzki, A.; Hempelmann, G. Tamm-Horsfall protein, alpha-1- and beta-2-microglobulin as kidney function markers in heart surgery. Anaesthesist, 1995, 44, 545-551.
Schaub, S.; Wilkins, J.A.; Antonovici, M.; Krokhin, O.; Weiler, T.; Rush, D.; Nickerson, P. Proteomic-based identification of cleaved urinary beta2-microglobulin as a potential marker for acute tubular injury in renal allografts. Am. J. Transplant., 2005, 5, 729-738.
Davey, P.G.; Gosling, P. Beta 2-microglobulin instability in pathological urine. Clin. Chem., 1982, 28, 1330-1333.
Tabel, Y.; Oncül, M.; Elmas, A.T.; Güngör, S. Evaluation of renal functions in preterm infants with respiratory distress syndrome. J. Clin. Lab. Anal., 2014, 28, 310-314.
Jaconi, S.; Rose, K.; Hughes, G.J.; Saurat, J.H.; Siegenthaler, G. Characterization of two post-translationally processed forms of human serum retinol-binding protein: Altered ratios in chronic renal failure. J. Lipid Res., 1995, 36, 1247-1253.
Roberts, D.S.; Haycock, G.B.; Dalton, R.N.; Turner, C.; Tomlinson, P.; Stimmler, L.; Scopes, J.W. Prediction of acute renal failure after birth asphyxia. Arch. Dis. Child., 1990, 65, 1021-1028.
Cataldi, L.; Mussap, M.; Verlato, G.; Plebani, M.; Fanos, V. Neonatal Nephrology Study Group of the Italian Society of Neonatology. Netilmicin effect on urinary Retinol Binding Protein (RBP) and N-acetyl-beta-D-Glucosaminidase (NAG) in preterm newborns with and without anoxia. J. Chemother., 2002, 14, 76-83.
Wu, Z.J.; Huang, S.M.; Chen, R.; Hu, B.; Chen, Y.; Zhu, Y.P.; Lu, G.J.; Han, Y.K. Value of blood apoH gene expression and urinary NAG and RBP in early diagnosis of renal function damage in neonates. Zhongguo Dang Dai Er Ke Za Zhi, 2009, 11, 649-652.
Jones, S.E.; Jomary, C. Clusterin. Int. J. Biochem. Cell Biol., 2002, 34, 427-431.
Guan, Q.; Alnasser, H.A.; Nguan, C.Y.; Du, C. From humans to experimental models: The cytoprotective role of clusterin in the kidney. Med. Surg. Urol., 2014, 3, 134.
Guo, J.; Guan, Q.; Liu, X.; Wang, H.; Gleave, M.E.; Nguan, C.Y.; Du, C. Relationship of clusterin with renal inflammation and fibrosis after the recovery phase of ischemia-reperfusion injury. BMC Nephrol., 2016, 17, 133.
Kahles, F.; Findeisen, H.M.; Bruemmer, D. Osteopontin: A novel regulator at the cross roads of inflammation, obesity and diabetes. Mol. Metab., 2014, 3, 384-393.
Taub, P.R.; Borden, K.C.; Fard, A.; Maisel, A. Role of biomarkers in the diagnosis and prognosis of acute kidney injury in patients with cardiorenal syndrome. Expert Rev. Cardiovasc. Ther., 2012, 10, 657-667.
Xie, Y.; Sakatsume, M.; Nishi, S.; Narita, I.; Arakawa, M.; Gejyo, F. Expression, roles, receptors, and regulation of osteopontin in the kidney. Kidney Int., 2001, 60, 1645-1657.
Lorenzen, J.M.; Hafer, C.; Faulhaber-Walter, R.; Kümpers, P.; Kielstein, J.T.; Haller, H.; Fliser, D. Osteopontin predicts survival in critically ill patients with acute kidney injury. Nephrol. Dial. Transplant., 2011, 26, 531-537.
Abdelmagid, S.M.; Barbe, M.F.; Rico, M.C.; Salihoglu, S.; Arango-Hisijara, I.; Selim, A.H.; Anderson, M.G.; Owen, T.A.; Popoff, S.N.; Safadi, F.F. Osteoactivin, an anabolic factor that regulates osteoblast differentiation and function. Exp. Cell Res., 2008, 314, 2334-2351.
Ye, M.; Xie, X.; Peng, L.; Tan, L.; Lan, G.; Yu, S. Expression and mechanism of osteoactivin in the kidney of SD rats after acute cyclosporine A toxicity. Zhong Nan Da Xue Xue Bao Yi Xue Ban, 2011, 36, 881-888.
McMahon, B.A.; Koyner, J.L.; Murray, P.T. Urinary glutathione S-transferases in the pathogenesis and diagnostic evaluation of acute kidney injury following cardiac surgery: A critical review. Curr. Opin. Crit. Care, 2010, 16, 550-555.
Ali, R.J.; Al-Obaidi, F.H.; Arif, H.S. The role of urinary N-acetyl beta-D-glucosaminidase in children with urological problems. Oman Med. J., 2014, 29, 285-288.
Fujita, H.; Narita, T.; Morii, T.; Shimotomai, T.; Yoshioka, N.; Kakei, M.; Ito, S. Increased urinary excretion of n-acetylglucos-aminidase in subjects with impaired glucose tolerance. Ren. Fail., 2002, 24, 69-75.
Dun, X.P.; Parkinson, D.B. Role of netrin-1 signaling in nerve regeneration. Int. J. Mol. Sci., 2017, 18, 491.
Mehlen, P.; Furne, C. Netrin-1: When a neuronal guidance cue turns out to be a regulator of tumorigenesis. Cell. Mol. Life Sci., 2005, 62, 2599-2616.
Boneschansker, L.; Nakayama, H.; Eisenga, M.; Wedel, J.; Klagsbrun, M.; Irimia, D.; Briscoe, D.M. Netrin-1 augments chemokinesis in CD4+ T cells in vitro and elicits a proinflammatory response in vivo. J. Immunol., 2016, 197, 1389-1398.
Prieto, C.P.; Ortiz, M.C.; Villanueva, A.; Villarroel, C.; Edwards, S.S.; Elliott, M.; Lattus, J.; Aedo, S.; Meza, D.; Lois, P.; Palma, V. Netrin-1 acts as a non-canonical angiogenic factor produced by human Wharton’s Jelly Mesenchymal Stem Cells (WJ-MSC). Stem Cell Res. Ther., 2017, 8, 43.
Wang, W.; Reeves, W.B.; Ramesh, G. Netrin-1 and kidney injury. I. Netrin-1 protects against ischemia-reperfusion injury of the kidney. Am. J. Physiol. Renal Physiol., 2008, 294, F739-F747.
White, J.J.; Mohamed, R.; Jayakumar, C.; Ramesh, G. Tubular injury marker netrin-1 is elevated early in experimental diabetes. J. Nephrol., 2013, 26, 1055-1064.
Mussap, M.; Noto, A.; Fravega, M.; Fanos, V. Urine Neutrophil Gelatinase-Associated Lipocalin (uNGAL) and netrin-1: Are they effectively improving the clinical management of sepsis-induced acute kidney injury (AKI)? J. Matern. Fetal Neonatal Med., 2011, 24, 15-17.
Jayakumar, C.; Nauta, F.L.; Bakker, S.J.; Bilo, H.; Gansevoort, R.T.; Johnson, M.H.; Ramesh, G. Netrin-1, a urinary proximal tubular injury marker, is elevated early in the time course of human diabetes. J. Nephrol., 2014, 27, 151-157.
Al Morsy, E.A.; Mokhtar, E.R.; Ibrahim, G.E. El- Nasser, A.M; Ebrahem, E.E.; Elattar, S. Urinary metabolomic profiles and netrin-1 as diagnostics and predictors of acute kidney injury in preterm neonates. Am. J. Med. Med. Sci., 2018, 8, 79-90.
Denecke, B.; Graber, S.; Schafer, C.; Heiss, A.; Woltje, M.; Jahnen-Dechent, W. Tissue distribution and activity testing suggest a similar but not identical function of fetuin-B and fetuin-A. Biochem. J., 2003, 376, 135-145.
Zhou, H.; Pisitkun, T.; Aponte, A.; Yuen, P.S. Hoffert. J.D.; Yasuda, H.; Hu, X.; Chawla, L.; Shen, R. F.; Knepper, M.A.; Star, R.A. Exosomal fetuin-A identified by proteomics: A novel urinary biomarker for detecting acute kidney injury. Kidney Int., 2006, 70, 1847-1857.
Cheruvanky, A.; Zhou, H.; Pisitkun, T.; Kopp, J.B.; Knepper, M.A.; Yuen, P.S.; Star, R.A. Rapid isolation of urinary exosomal biomarkers using a nanomembrane ultrafiltration concentrator. Am. J. Physiol. Renal Physiol., 2007, 292, F1657-F1661.
Yu, Y.; Jin, H.; Holder, D.; Ozer, J.S.; Villarreal, S.; Shughrue, P.; Shi, S.; Figueroa, D.J.; Clouse, H.; Su, M.; Muniappa, N.; Troth, S.P.; Bailey, W.; Seng, J.; Aslamkhan, A.G.; Thudium, D.; Sistare, F.D.; Gerhold, D.L. Urinary biomarkers trefoil factor 3 and albumin enable early detection of kidney tubular injury. Nat. Biotechnol., 2010, 28, 470-477.
Kinoshita, K.; Taupin, D.R.; Itoh, H.; Podolsky, D.K. Distinct pathways of cell migration and antiapoptotic response to epithelial injury: Structure-function analysis of human intestinal trefoil factor. Mol. Cell. Biol., 2000, 20, 4680-4690.
Deshmane, S.L.; Kremlev, S.; Amini, S.; Sawaya, B.E. Monocyte Chemoattractant Protein-1 (MCP-1): An overview. J. Interferon Cytokine Res., 2009, 29, 313-326.
Munshi, R.; Johnson, A.; Siew, E.D.; Ikizler, T.A.; Ware, L.B.; Wurfel, M.M.; Himmelfarb, J.; Zager, R.A. MCP-1 gene activation marks acute kidney injury. J. Am. Soc. Nephrol., 2011, 22, 165-175.
Su, L.; Xie, L.; Liu, D. Urine sTREM-1 may be a valuable biomarker in diagnosis and prognosis of sepsis-associated acute kidney injury. Crit. Care, 2015, 14, 281.
Yuan, Z.K.; Fang, F.; Liu, C.J.; Li, J.; Chen, Y.F.; Xu, F. Value of urine soluble triggering receptor expressed on myeloid cells-1 in the early diagnosis of sepsis associated acute kidney injury. Zhonghua Er Ke Za Zhi, 2018, 56, 342-346.
Wasung, M.E.; Chawla, L.S.; Madero, M. Biomarkers of renal function, which and when? Clin. Chim. Acta, 2015, 438, 350-357.
McIlroy, D.R.; Wagener, G.; Lee, H.T. Neutrophil gelatinase-associated lipocalin and acute kidney injury after cardiac surgery: The effect of baseline renal function on diagnostic performance. Clin. J. Am. Soc. Nephrol., 2010, 5, 211-219.
Schmidt-Ott, K.; Mori, K.; Yi, Li. J.; Kalandadze, A.; Cohen, D.J.; Devarajan, P.; Barasch, J. Dual action of neutrophil gelatinase-associatedlipocalin. J. Am. Soc. Nephrol., 2007, 18, 407-413.
Parikh, C.R.; Mansour, S.G. Perspective on clinical application of biomarkers in AKI. J. Am. Soc. Nephrol., 2017, 28, 1677-1685.
Malhotra, R.; Siew, E.D. Biomarkers for the early detection and prognosis of acute kidney injury. Clin. J. Am. Soc. Nephrol., 2017, 6, 149-173.
National Institutes of Diabetes and Digestive and Kidney Diseases: Kidney Precision Medicine Project (KPMP), 2016; https://www. niddk.nih.gov/research-funding/research-programs/kidney-precision-medicine-project-kpmp (Accessed February 19, 2019).
Zarbock, A.; Kellum, J.A.; Schmidt, C.; Van Aken, H.; Wempe, C.; Pavenstädt, 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, 2190-2199.
Kępka, A.; Waszkiewicz, N.; Chojnowska, S.; Zalewska-Szajda, B.; Ładny, J.R.; Wasilewska, A.; Zwierz, K.; Szajda, S.D. Utility of urinary biomarkers in kidney transplant function assessment In: Current issues and future direction in kidney transplantation; Rath, T.; InTech: Rijeka,. , 2013, pp. 61-88.
Dean, P.G.; Park, W.D.; Cornell, L.D.; Gloor, J.M.; Stegall, M.D. Intragraft gene expression in positive crossmatch kidney allografts: ongoing inflammation mediates chronic antibody-mediated injury. Am. J. Transplant., 2012, 12, 1551-1563.
Scian, M.J.; Maluf, D.G.; David, K.G.; Archer, K.J.; Suh, J.L.; Wolen, A.R.; Mba, M.U.; Massey, H.D.; King, A.L.; Gehr, T.; Cotterell, A.; Posner, M.; Mas, V. MicroRNA profiles in allograft tissues and paired urines associate with chronic allograft dysfunction with IF/TA. Am. J. Transplant., 2011, 11, 2110-2122.
Srivastava, M.; Eidelman, O.; Torosyan, Y.; Jozwik, C.; Mannon, R.B.; Pollard, H.B. Elevated expression levels of ANXA11, integrins β3 and α3, and TNF-α contribute to a candidate proteomic signature in urine for kidney allograft rejection. Proteomics Clin. Appl., 2011, 5, 311-321.
Wishart, D.S. Metabolomics in monitoring kidney transplants. Curr. Opin. Nephrol. Hypertens., 2006, 15, 637-642.

Rights & PermissionsPrintExport Cite as

Article Details

Year: 2019
Page: [332 - 349]
Pages: 18
DOI: 10.2174/1389200220666190321142417
Price: $58

Article Metrics

PDF: 21