Skip to main content
Erschienen in: Pediatric Nephrology 12/2016

11.06.2016 | Original Article

Urinary biomarkers for the differentiation of prerenal and intrinsic pediatric acute kidney injury

verfasst von: Jens H. Westhoff, Alexander Fichtner, Sina Waldherr, Nikolaos Pagonas, Felix S. Seibert, Nina Babel, Burkhard Tönshoff, Frederic Bauer, Timm H. Westhoff

Erschienen in: Pediatric Nephrology | Ausgabe 12/2016

Einloggen, um Zugang zu erhalten

Abstract

Background

Urinary calprotectin and neutrophil gelatinase-associated lipocalin (NGAL) have recently been identified as promising biomarkers for the differentiation of prerenal and intrinsic acute kidney injury (AKI) in adults. In the study reported here we examined the diagnostic accuracy of calprotectin, NGAL, and kidney injury molecule 1 (KIM-1) in pediatric patients.

Methods

Urinary calprotectin, NGAL, and KIM-1 concentrations were assessed in a study population of 139 pediatric subjects including 39 patients with intrinsic AKI, 14 with prerenal AKI, and 86 non-AKI subjects.

Results

Median urinary calprotectin and NGAL concentrations were higher in patients with intrinsic AKI than in those with prerenal AKI (calprotectin by 22-fold, NGAL by 9-fold). Receiver operating characteristic (ROC) curve analyses for the differentiation of intrinsic and prerenal AKI resulted in an area under the curve (AUC) of 0.90 [95 % confidence interval (CI) 0.81–0.98] for calprotectin and 0.73 (95 % CI 0.58–0.87) for NGAL. Median urinary KIM-1 concentrations were not significantly different between patients with prerenal AKI and those with intrinsic disease (P = 0.98; AUC 0.50, 95 % CI, 0.35–0.65). The AUC for the fractional excretion of sodium (FENa) and proteinuria was 0.78 (95 % CI 0.63–0.92) and 0.77 (CI 0.65–0.90), respectively.

Conclusions

Urinary calprotectin outperforms NGAL, KIM-1, FENa, and proteinuria as a biomarker for the differentiation of prerenal and intrinsic AKI in pediatric patients with a high diagnostic accuracy.
Anhänge
Nur mit Berechtigung zugänglich
Literatur
1.
Zurück zum Zitat Raimundo M, Crichton S, Martin JR, Syed Y, Varrier M, Wyncoll D, Ostermann M (2015) Increased fluid administration after early acute kidney injury is associated with less renal recovery. Shock 44:431–437CrossRefPubMed Raimundo M, Crichton S, Martin JR, Syed Y, Varrier M, Wyncoll D, Ostermann M (2015) Increased fluid administration after early acute kidney injury is associated with less renal recovery. Shock 44:431–437CrossRefPubMed
2.
Zurück zum Zitat Endre ZH, Kellum JA, Di Somma S, Doi K, Goldstein SL, Koyner JL, Macedo E, Mehta RL, Murray PT (2013) Differential diagnosis of AKI in clinical practice by functional and damage biomarkers: workgroup statements from the tenth acute dialysis quality initiative consensus conference. Contrib Nephrol 182:30–44CrossRefPubMed Endre ZH, Kellum JA, Di Somma S, Doi K, Goldstein SL, Koyner JL, Macedo E, Mehta RL, Murray PT (2013) Differential diagnosis of AKI in clinical practice by functional and damage biomarkers: workgroup statements from the tenth acute dialysis quality initiative consensus conference. Contrib Nephrol 182:30–44CrossRefPubMed
3.
Zurück zum Zitat Singer E, Elger A, Elitok S, Kettritz R, Nickolas TL, Barasch J, Luft FC, Schmidt-Ott KM (2011) Urinary neutrophil gelatinase-associated lipocalin distinguishes pre-renal from intrinsic renal failure and predicts outcomes. Kidney Int 80:405–414CrossRefPubMed Singer E, Elger A, Elitok S, Kettritz R, Nickolas TL, Barasch J, Luft FC, Schmidt-Ott KM (2011) Urinary neutrophil gelatinase-associated lipocalin distinguishes pre-renal from intrinsic renal failure and predicts outcomes. Kidney Int 80:405–414CrossRefPubMed
4.
Zurück zum Zitat Heller F, Frischmann S, Grunbaum M, Zidek W, Westhoff TH (2011) Urinary calprotectin and the distinction between prerenal and intrinsic acute kidney injury. Clin J Am Soc Nephrol 6:2347–2355CrossRefPubMedPubMedCentral Heller F, Frischmann S, Grunbaum M, Zidek W, Westhoff TH (2011) Urinary calprotectin and the distinction between prerenal and intrinsic acute kidney injury. Clin J Am Soc Nephrol 6:2347–2355CrossRefPubMedPubMedCentral
5.
Zurück zum Zitat Seibert FS, Pagonas N, Arndt R, Heller F, Dragun D, Persson P, Schmidt-Ott K, Zidek W, Westhoff TH (2013) Calprotectin and neutrophil gelatinase-associated lipocalin in the differentiation of pre-renal and intrinsic acute kidney injury. Acta Physiol (Oxf) 207:700–708CrossRef Seibert FS, Pagonas N, Arndt R, Heller F, Dragun D, Persson P, Schmidt-Ott K, Zidek W, Westhoff TH (2013) Calprotectin and neutrophil gelatinase-associated lipocalin in the differentiation of pre-renal and intrinsic acute kidney injury. Acta Physiol (Oxf) 207:700–708CrossRef
6.
Zurück zum Zitat Chang CH, Yang CH, Yang HY, Chen TH, Lin CY, Chang SW, Chen YT, Hung CC, Fang JT, Yang CW, Chen YC (2015) Urinary biomarkers improve the diagnosis of intrinsic acute kidney injury in coronary care units. Medicine (Baltimore) 94:e1703 Chang CH, Yang CH, Yang HY, Chen TH, Lin CY, Chang SW, Chen YT, Hung CC, Fang JT, Yang CW, Chen YC (2015) Urinary biomarkers improve the diagnosis of intrinsic acute kidney injury in coronary care units. Medicine (Baltimore) 94:e1703
7.
8.
Zurück zum Zitat Han WK, Bailly V, Abichandani R, Thadhani R, Bonventre JV (2002) Kidney injury molecule-1 (KIM-1): a novel biomarker for human renal proximal tubule injury. Kidney Int 62:237–244CrossRefPubMed Han WK, Bailly V, Abichandani R, Thadhani R, Bonventre JV (2002) Kidney injury molecule-1 (KIM-1): a novel biomarker for human renal proximal tubule injury. Kidney Int 62:237–244CrossRefPubMed
9.
Zurück zum Zitat Nejat M, Pickering JW, Devarajan P, Bonventre JV, Edelstein CL, Walker RJ, Endre ZH (2012) Some biomarkers of acute kidney injury are increased in pre-renal acute injury. Kidney Int 81:1254–1262CrossRefPubMedPubMedCentral Nejat M, Pickering JW, Devarajan P, Bonventre JV, Edelstein CL, Walker RJ, Endre ZH (2012) Some biomarkers of acute kidney injury are increased in pre-renal acute injury. Kidney Int 81:1254–1262CrossRefPubMedPubMedCentral
10.
Zurück zum Zitat Westhoff JH, Tonshoff B, Waldherr S, Poschl J, Teufel U, Westhoff TH, Fichtner A (2015) 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 10:e0143628CrossRefPubMedPubMedCentral Westhoff JH, Tonshoff B, Waldherr S, Poschl J, Teufel U, Westhoff TH, Fichtner A (2015) 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 10:e0143628CrossRefPubMedPubMedCentral
11.
Zurück zum Zitat Akcan-Arikan A, Zappitelli M, Loftis LL, Washburn KK, Jefferson LS, Goldstein SL (2007) Modified RIFLE criteria in critically ill children with acute kidney injury. Kidney Int 71:1028–1035CrossRefPubMed Akcan-Arikan A, Zappitelli M, Loftis LL, Washburn KK, Jefferson LS, Goldstein SL (2007) Modified RIFLE criteria in critically ill children with acute kidney injury. Kidney Int 71:1028–1035CrossRefPubMed
12.
Zurück zum Zitat Selewski DT, Charlton JR, Jetton JG, Guillet R, Mhanna MJ, Askenazi DJ, Kent AL (2015) Neonatal acute kidney injury. Pediatrics 136:e463–473CrossRefPubMed Selewski DT, Charlton JR, Jetton JG, Guillet R, Mhanna MJ, Askenazi DJ, Kent AL (2015) Neonatal acute kidney injury. Pediatrics 136:e463–473CrossRefPubMed
13.
Zurück zum Zitat Schwartz GJ, Munoz A, Schneider MF, Mak RH, Kaskel F, Warady BA, Furth SL (2009) New equations to estimate GFR in children with CKD. J Am Soc Nephrol 20:629–637CrossRefPubMedPubMedCentral Schwartz GJ, Munoz A, Schneider MF, Mak RH, Kaskel F, Warady BA, Furth SL (2009) New equations to estimate GFR in children with CKD. J Am Soc Nephrol 20:629–637CrossRefPubMedPubMedCentral
14.
Zurück zum Zitat Abitbol CL, Seeherunvong W, Galarza MG, Katsoufis C, Francoeur D, Defreitas M, Edwards-Richards A, Master Sankar Raj V, Chandar J, Duara S, Yasin S, Zilleruelo G (2014) Neonatal kidney size and function in preterm infants: what is a true estimate of glomerular filtration rate? J Pediatr 164(1026–1031):e1022 Abitbol CL, Seeherunvong W, Galarza MG, Katsoufis C, Francoeur D, Defreitas M, Edwards-Richards A, Master Sankar Raj V, Chandar J, Duara S, Yasin S, Zilleruelo G (2014) Neonatal kidney size and function in preterm infants: what is a true estimate of glomerular filtration rate? J Pediatr 164(1026–1031):e1022
15.
16.
Zurück zum Zitat Treiber M, Pecovnik Balon B, Gorenjak M (2015) A new serum cystatin C formula for estimating glomerular filtration rate in newborns. Pediatr Nephrol 30:1297–1305CrossRefPubMed Treiber M, Pecovnik Balon B, Gorenjak M (2015) A new serum cystatin C formula for estimating glomerular filtration rate in newborns. Pediatr Nephrol 30:1297–1305CrossRefPubMed
17.
Zurück zum Zitat Zappitelli M, Parikh CR, Akcan-Arikan A, Washburn KK, Moffett BS, Goldstein SL (2008) Ascertainment and epidemiology of acute kidney injury varies with definition interpretation. Clin J Am Soc Nephrol 3:948–954CrossRefPubMedPubMedCentral Zappitelli M, Parikh CR, Akcan-Arikan A, Washburn KK, Moffett BS, Goldstein SL (2008) Ascertainment and epidemiology of acute kidney injury varies with definition interpretation. Clin J Am Soc Nephrol 3:948–954CrossRefPubMedPubMedCentral
18.
Zurück zum Zitat Palmieri T, Lavrentieva A, Greenhalgh D (2009) An assessment of acute kidney injury with modified RIFLE criteria in pediatric patients with severe burns. Intensive Care Med 35:2125–2129CrossRefPubMedPubMedCentral Palmieri T, Lavrentieva A, Greenhalgh D (2009) An assessment of acute kidney injury with modified RIFLE criteria in pediatric patients with severe burns. Intensive Care Med 35:2125–2129CrossRefPubMedPubMedCentral
19.
Zurück zum Zitat Pedersen KR, Ravn HB, Hjortdal VE, Norregaard R, Povlsen JV (2010) Neutrophil gelatinase-associated lipocalin (NGAL): validation of commercially available ELISA. Scand J Clin Lab Invest 70:374–382CrossRefPubMed Pedersen KR, Ravn HB, Hjortdal VE, Norregaard R, Povlsen JV (2010) Neutrophil gelatinase-associated lipocalin (NGAL): validation of commercially available ELISA. Scand J Clin Lab Invest 70:374–382CrossRefPubMed
20.
Zurück zum Zitat Vogl T, Tenbrock K, Ludwig S, Leukert N, Ehrhardt C, van Zoelen MA, Nacken W, Foell D, van der Poll T, Sorg C, Roth J (2007) Mrp8 and Mrp14 are endogenous activators of toll-like receptor 4, promoting lethal, endotoxin-induced shock. Nat Med 13:1042–1049CrossRefPubMed Vogl T, Tenbrock K, Ludwig S, Leukert N, Ehrhardt C, van Zoelen MA, Nacken W, Foell D, van der Poll T, Sorg C, Roth J (2007) Mrp8 and Mrp14 are endogenous activators of toll-like receptor 4, promoting lethal, endotoxin-induced shock. Nat Med 13:1042–1049CrossRefPubMed
21.
Zurück zum Zitat Sampson B, Fagerhol MK, Sunderkotter C, Golden BE, Richmond P, Klein N, Kovar IZ, Beattie JH, Wolska-Kusnierz B, Saito Y, Roth J (2002) Hyperzincaemia and hypercalprotectinaemia: a new disorder of zinc metabolism. Lancet 360:1742–1745CrossRefPubMed Sampson B, Fagerhol MK, Sunderkotter C, Golden BE, Richmond P, Klein N, Kovar IZ, Beattie JH, Wolska-Kusnierz B, Saito Y, Roth J (2002) Hyperzincaemia and hypercalprotectinaemia: a new disorder of zinc metabolism. Lancet 360:1742–1745CrossRefPubMed
22.
Zurück zum Zitat Pillay SN, Asplin JR, Coe FL (1998) Evidence that calgranulin is produced by kidney cells and is an inhibitor of calcium oxalate crystallization. Am J Physiol 275:F255–261PubMed Pillay SN, Asplin JR, Coe FL (1998) Evidence that calgranulin is produced by kidney cells and is an inhibitor of calcium oxalate crystallization. Am J Physiol 275:F255–261PubMed
23.
Zurück zum Zitat Thurgood LA, Ryall RL (2010) Proteomic analysis of proteins selectively associated with hydroxyapatite, brushite, and uric acid crystals precipitated from human urine. J Proteome Res 9:5402–5412CrossRefPubMed Thurgood LA, Ryall RL (2010) Proteomic analysis of proteins selectively associated with hydroxyapatite, brushite, and uric acid crystals precipitated from human urine. J Proteome Res 9:5402–5412CrossRefPubMed
24.
Zurück zum Zitat Giorgini A, Brown HJ, Sacks SH, Robson MG (2010) Toll-like receptor 4 stimulation triggers crescentic glomerulonephritis by multiple mechanisms including a direct effect on renal cells. Am J Pathol 177:644–653CrossRefPubMedPubMedCentral Giorgini A, Brown HJ, Sacks SH, Robson MG (2010) Toll-like receptor 4 stimulation triggers crescentic glomerulonephritis by multiple mechanisms including a direct effect on renal cells. Am J Pathol 177:644–653CrossRefPubMedPubMedCentral
25.
Zurück zum Zitat Gluba A, Banach M, Hannam S, Mikhailidis DP, Sakowicz A, Rysz J (2010) The role of toll-like receptors in renal diseases. Nat Rev Nephrol 6:224–235CrossRefPubMed Gluba A, Banach M, Hannam S, Mikhailidis DP, Sakowicz A, Rysz J (2010) The role of toll-like receptors in renal diseases. Nat Rev Nephrol 6:224–235CrossRefPubMed
26.
Zurück zum Zitat Soylu A, Kizildag S, Kavukcu S, Cingoz S, Turkmen M, Demir BK, Sakizli M (2010) TLR-2 Arg753Gln, TLR-4 Asp299Gly, and TLR-4 Thr399Ile polymorphisms in henoch schonlein purpura with and without renal involvement. Rheumatol Int 30:667–670CrossRefPubMed Soylu A, Kizildag S, Kavukcu S, Cingoz S, Turkmen M, Demir BK, Sakizli M (2010) TLR-2 Arg753Gln, TLR-4 Asp299Gly, and TLR-4 Thr399Ile polymorphisms in henoch schonlein purpura with and without renal involvement. Rheumatol Int 30:667–670CrossRefPubMed
27.
Zurück zum Zitat Wolfs TG, Buurman WA, van Schadewijk A, de Vries B, Daemen MA, Hiemstra PS, van’t Veer C (2002) In vivo expression of toll-like receptor 2 and 4 by renal epithelial cells: IFN-gamma and TNF-alpha mediated up-regulation during inflammation. J Immunol 168:1286–1293CrossRefPubMed Wolfs TG, Buurman WA, van Schadewijk A, de Vries B, Daemen MA, Hiemstra PS, van’t Veer C (2002) In vivo expression of toll-like receptor 2 and 4 by renal epithelial cells: IFN-gamma and TNF-alpha mediated up-regulation during inflammation. J Immunol 168:1286–1293CrossRefPubMed
28.
Zurück zum Zitat Polat M, Fidan K, Derinoz O, Gonen S, Soylemezoglu O (2013) Neutrophil gelatinase-associated lipocalin as a follow-up marker in critically ill pediatric patients with established acute kidney injury. Ren Fail 35:352–356CrossRefPubMed Polat M, Fidan K, Derinoz O, Gonen S, Soylemezoglu O (2013) Neutrophil gelatinase-associated lipocalin as a follow-up marker in critically ill pediatric patients with established acute kidney injury. Ren Fail 35:352–356CrossRefPubMed
29.
Zurück zum Zitat Tchkonia T, Zhu Y, van Deursen J, Campisi J, Kirkland JL (2013) Cellular senescence and the senescent secretory phenotype: therapeutic opportunities. J Clin Invest 123:966–972CrossRefPubMedPubMedCentral Tchkonia T, Zhu Y, van Deursen J, Campisi J, Kirkland JL (2013) Cellular senescence and the senescent secretory phenotype: therapeutic opportunities. J Clin Invest 123:966–972CrossRefPubMedPubMedCentral
30.
Zurück zum Zitat Doi K, Katagiri D, Negishi K, Hasegawa S, Hamasaki Y, Fujita T, Matsubara T, Ishii T, Yahagi N, Sugaya T, Noiri E (2012) Mild elevation of urinary biomarkers in prerenal acute kidney injury. Kidney Int 82:1114–1120CrossRefPubMed Doi K, Katagiri D, Negishi K, Hasegawa S, Hamasaki Y, Fujita T, Matsubara T, Ishii T, Yahagi N, Sugaya T, Noiri E (2012) Mild elevation of urinary biomarkers in prerenal acute kidney injury. Kidney Int 82:1114–1120CrossRefPubMed
31.
Zurück zum Zitat Ostermann M (2014) Diagnosis of acute kidney injury: kidney disease improving global outcomes criteria and beyond. Curr Opin Crit Care 20:581–587CrossRefPubMed Ostermann M (2014) Diagnosis of acute kidney injury: kidney disease improving global outcomes criteria and beyond. Curr Opin Crit Care 20:581–587CrossRefPubMed
32.
33.
Zurück zum Zitat Nickolas TL, Schmidt-Ott KM, Canetta P, Forster C, Singer E, Sise M, Elger A, Maarouf O, Sola-Del Valle DA, O’Rourke M, Sherman E, Lee P, Geara A, Imus P, Guddati A, Polland A, Rahman W, Elitok S, Malik N, Giglio J, El-Sayegh S, Devarajan P, Hebbar S, Saggi SJ, Hahn B, Kettritz R, Luft FC, Barasch J (2012) Diagnostic and prognostic stratification in the emergency department using urinary biomarkers of nephron damage: a multicenter prospective cohort study. J Am Coll Cardiol 59:246–255CrossRefPubMedPubMedCentral Nickolas TL, Schmidt-Ott KM, Canetta P, Forster C, Singer E, Sise M, Elger A, Maarouf O, Sola-Del Valle DA, O’Rourke M, Sherman E, Lee P, Geara A, Imus P, Guddati A, Polland A, Rahman W, Elitok S, Malik N, Giglio J, El-Sayegh S, Devarajan P, Hebbar S, Saggi SJ, Hahn B, Kettritz R, Luft FC, Barasch J (2012) Diagnostic and prognostic stratification in the emergency department using urinary biomarkers of nephron damage: a multicenter prospective cohort study. J Am Coll Cardiol 59:246–255CrossRefPubMedPubMedCentral
Metadaten
Titel
Urinary biomarkers for the differentiation of prerenal and intrinsic pediatric acute kidney injury
verfasst von
Jens H. Westhoff
Alexander Fichtner
Sina Waldherr
Nikolaos Pagonas
Felix S. Seibert
Nina Babel
Burkhard Tönshoff
Frederic Bauer
Timm H. Westhoff
Publikationsdatum
11.06.2016
Verlag
Springer Berlin Heidelberg
Erschienen in
Pediatric Nephrology / Ausgabe 12/2016
Print ISSN: 0931-041X
Elektronische ISSN: 1432-198X
DOI
https://doi.org/10.1007/s00467-016-3418-1

Weitere Artikel der Ausgabe 12/2016

Pediatric Nephrology 12/2016 Zur Ausgabe

Update Pädiatrie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.