Neutrophil Gelatinase-Associated Lipocalin (NGAL) in Chronic Cardiorenal Failure is Correlated with Endogenous Erythropoietin Levels and Decreases in Response to Low-Dose Erythropoietin Treatment

被引:18
作者
Emans, Mireille E. [1 ]
Braam, Branko [2 ]
Diepenbroek, Adry [3 ]
van der Putten, Karien [4 ]
Cramer, Maarten J. [1 ]
Wielders, Jos P. M. [5 ]
Swinkels, Dorine W. [6 ]
Doevendans, Pieter A. [1 ]
Gaillard, Carlo A. [3 ,7 ]
机构
[1] Univ Med Ctr Utrecht, Dept Cardiol, Utrecht, Netherlands
[2] Univ Alberta, Dept Med, Div Nephrol & Immunol, Edmonton, AB, Canada
[3] Meander Med Ctr Amersfoort, Dept Internal Med, Amersfoort, Netherlands
[4] Leiden Univ, Med Ctr, Dept Nephrol, NL-2300 RA Leiden, Netherlands
[5] Meander Med Ctr Amersfoort, Dept Clin Chem, Amersfoort, Netherlands
[6] Radboud Univ Nijmegen, Med Ctr, Dept Lab Med, Lab Genet Endocrine & Metab Dis, NL-6525 ED Nijmegen, Netherlands
[7] Vrije Univ Amsterdam Med Ctr, Dept Nephrol, NL-1007 MB Amsterdam, Netherlands
关键词
Cardiorenal syndrome; NGAL; Erythropoietin; Iron homeostasis; Biomarkers; Chronic kidney disease; Chronic heart failure; CHRONIC HEART-FAILURE; CHRONIC KIDNEY-DISEASE; RANDOMIZED CONTROLLED-TRIAL; BETA-D-GLUCOSAMINIDASE; RENAL-FAILURE; MASS-SPECTROMETRY; EUROPEAN-SOCIETY; HEPCIDIN; INJURY; ANEMIA;
D O I
10.1159/000343392
中图分类号
Q4 [生理学];
学科分类号
071003 ;
摘要
Background: Neutrophil-gelatinase associated lipocalin (NGAL), a tubular injury marker, is associated with iron metabolism in hemodialysis patients. We investigated whether serum NGAL levels reflect iron metabolism in combined chronic heart failure and chronic kidney disease (CHF/CKD) and whether treatment with low-dose erythropoietin stimulating agent (ESA) modulates NGAL levels. Methods: In the EPOCARES trial (ClinTrialsNCT00356733) serum NGAL, hepcidin-25, transferrin saturation (TSAT), reticulocyte hemoglobin content (Ret-He) and endogenous erythropoietin (EPO) levels were measured. Results: Baseline serum NGAL levels correlated with cystatin C (r=0.767, p<0.001) and baseline EPO levels (r=-0.395, p=0.003). There was no correlation with baseline TSAT, Ret-He, and hepcidin-25 levels. After two weeks, NGAL levels decreased in the ESA-group (p=0.02), while there was no change in the no-ESA group (p=0.62). The magnitude in NGAL decrease in the ESA-group correlated with baseline EPO levels (r=0.431, p=0.01). Conclusions: In contrast to in HD patients, in combined CKD/CHF, serum NGAL levels did not correlate with iron metabolism, hence NGAL might reflect tubular damage in these patients. NGAL levels inversely correlated with baseline EPO levels and decreased in response to short-term ESA treatment, which might reflect an effect of ESA on tubular damage. These findings need to be confirmed and alternative explanations should be evaluated. Copyright (C) 2012 S. Karger AG, Basel
引用
收藏
页码:344 / 354
页数:11
相关论文
共 33 条
[1]   Low-dose therapy with the long-acting erythropoietin analogue darbepoetin alpha persistently activates endothelial Akt and attenuates progressive organ failure [J].
Bahlmann, FH ;
Song, R ;
Boehm, SM ;
Mengel, M ;
von Wasielewski, R ;
Lindschau, C ;
Kirsch, T ;
de Groot, K ;
Laudeley, R ;
Niemczyk, E ;
Güler, F ;
Menne, J ;
Haller, H ;
Fliser, D .
CIRCULATION, 2004, 110 (08) :1006-1012
[2]   Neutrophil gelatinase-associated lipocalin reflects the severity of renal impairment in subjects affected by chronic kidney disease [J].
Bolignano, Davide ;
Lacquaniti, Antonio ;
Coppolino, Giuseppe ;
Campo, Susanna ;
Arena, Adriana ;
Buemi, Michele .
KIDNEY & BLOOD PRESSURE RESEARCH, 2008, 31 (04) :255-258
[3]   Neutrophil gelatinase-associated lipocalin (NGAL) as a marker of kidney damage [J].
Bolignano, Davide ;
Donato, Valentina ;
Coppolino, Giuseppe ;
Campo, Susanna ;
Buemi, Antoine ;
Lacquaniti, Antonio ;
Buemi, Michele .
AMERICAN JOURNAL OF KIDNEY DISEASES, 2008, 52 (03) :595-605
[4]   Neutrophil gelatinase-associated lipocalin (NGAL) reflects iron status in haemodialysis patients [J].
Bolignano, Davide ;
Coppolino, Giuseppe ;
Romeo, Adolfo ;
De Paola, Luciano ;
Buemi, Antoine ;
Lacquaniti, Antonio ;
Nicocia, Giacomo ;
Lombardi, Luigi ;
Buemi, Michele .
NEPHROLOGY DIALYSIS TRANSPLANTATION, 2009, 24 (11) :3398-3403
[5]   Clinical outcome of renal tubular damage in chronic heart failure [J].
Damman, Kevin ;
Masson, Serge ;
Hillege, Hans L. ;
Maggioni, Aldo P. ;
Voors, Adriaan A. ;
Opasich, Cristina ;
van Veldhuisen, Dirk J. ;
Montagna, Laura ;
Cosmi, Franco ;
Tognoni, Gianni ;
Tavazzi, Luigi ;
Latini, Roberto .
EUROPEAN HEART JOURNAL, 2011, 32 (21) :2705-2712
[6]   Plasma neutrophil gelatinase-associated lipocalin predicts acute kidney injury, morbidity and mortality after pediatric cardiac surgery: a prospective uncontrolled cohort study [J].
Dent, Catherine L. ;
Ma, Qing ;
Dastrala, Sudha ;
Bennett, Michael ;
Mitsnefes, Mark M. ;
Barasch, Jonathan ;
Devarajan, Prasad .
CRITICAL CARE, 2007, 11 (06)
[7]   ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure 2008 The Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2008 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association of the ESC (HFA) and endorsed by the European Society of Intensive Care Medicine (ESICM) [J].
Dickstein, Kenneth ;
Cohen-Solal, Alain ;
Filippatos, Gerasimos ;
McMurray, John J. V. ;
Ponikowski, Piotr ;
Poole-Wilson, Philip Alexander ;
Stromberg, Anna ;
van Veldhuisen, Dirk J. ;
Atar, Dan ;
Hoes, Amo W. ;
Keren, Andre ;
Mebazaa, Alexandre ;
Nieminen, Markku ;
Priori, Silvia Gluliana ;
Swedberg, Karl .
EUROPEAN JOURNAL OF HEART FAILURE, 2008, 10 (10) :933-989
[8]   Normalization of hemoglobin level in patients with chronic kidney disease and anemia [J].
Drueke, Tilman B. ;
Locatelli, Francesco ;
Clyne, Naomi ;
Eckardt, Kai-Uwe ;
Macdougall, Iain C. ;
Tsakiris, Dimitrios ;
Burger, Hans-Ulrich ;
Scherhag, Armin .
NEW ENGLAND JOURNAL OF MEDICINE, 2006, 355 (20) :2071-2084
[9]   Assessing the clinical benefits of erythropoietic agents using area under the hemoglobin change curve [J].
Duh, MS ;
Lefebvre, P ;
Fastenau, J ;
Piech, CT ;
Waltzman, RJ .
ONCOLOGIST, 2005, 10 (06) :438-448
[10]   Serum hepcidin: reference ranges and biochemical correlates in the general population [J].
Galesloot, Tessel E. ;
Vermeulen, Sita H. ;
Geurts-Moespot, Anneke J. ;
Klaver, Siem M. ;
Kroot, Joyce J. ;
van Tienoven, Dorlene ;
Wetzels, Jack F. M. ;
Kiemeney, Lambertus A. L. M. ;
Sweep, Fred C. ;
den Heijer, Martin ;
Swinkels, Dorine W. .
BLOOD, 2011, 117 (25) :E218-E225