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Neutrophil Gelatinase-Associated Lipocalin (NGAL) in Chronic Cardiorenal Failure is Correlated with Endogenous Erythropoietin Levels and Decreases in Response to Low-Dose Erythropoietin TreatmentEmans M.E.a · Braam B.b · Diepenbroek A.c · van der Putten K.d · Cramer M.J.a · Wielders J.P.M.e · Swinkels D.W.f · Doevendans P.A.a,g · Gaillard C.A.c,h
aDept. of Cardiology, University Medical Centre Utrecht, the Netherlands, bDivision of Nephrology and Immunology, Dept. Medicine, University of Alberta, Edmonton, Canada, cDept. of Internal Medicine, Meander Medical Centre Amersfoort, the Netherlands, dDept. of Nephrology, Leiden University Medical Center, the Netherlands, eDept. of Clinical Chemistry, Meander Medical Centre Amersfoort, the Netherlands, fLaboratory of Genetic, Endocrine and Metabolic Diseases, Dept. of Laboratory Medicine, Radboud University Medical Centre, Nijmegen, the Netherlands, gInteruniversitary Cardiological Institute (ICIN), the Netherlands, hDepartment of Nephrology, VU University Medical Centre, Amsterdam, the Netherlands Corresponding Author
Carlo A.J.M. Gaillard, MD, PhD
Department of Nephrology, VU University Medical Center, PO Box7057
1007 MB Amsterdam (The Netherlands)
Tel. +31 204444312, Fax +31 204444960, E-Mail firstname.lastname@example.org
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.
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