Low preoperative hepcidin concentration as a risk factor for mortality after cardiac surgery: a pilot study.
OBJECTIVE
Hepcidin regulates iron absorption and recycling and is central to host defense, protection from reactive iron species, and a biomarker of iron-related pathophysiology. We assessed the value of hepcidin measured preoperatively for the prediction of in-hospital mortality and renal outcomes.


METHODS
We studied 100 adult patients undergoing cardiac surgery in the control arm of a randomized, controlled trial. Plasma and urine were sampled before induction of anesthesia, and hepcidin-25 was quantified by competitive enzyme-linked immunoassay. Renal outcomes were acute kidney injury defined by risk, injury, failure, loss of function, end-stage renal disease (RIFLE) classification and need for renal replacement therapy. Variables with the potential to influence hepcidin expression were investigated.


RESULTS
Low preoperative hepcidin concentration in urine (median, 15.3 ng/mL; 25-75 percentiles, 0-129.1) and plasma (median, 49.2 ng/mL; 25th-75th percentile, 0-52.2) predicted mortality (area under the curve-receiver operating characteristic [AUC-ROC] for urine hepcidin, 0.89; 95% confidence interval, 0.73-0.99; cutoff, 130 ng/mL; sensitivity, 73%; specificity, 100%; and AUC-ROC for plasma hepcidin, 0.90; 95% confidence interval, 0.80-0.99; cutoff, 55 ng/mL; sensitivity, 83%; specificity, 100%). Survivors had median preoperative hepcidin concentrations of 325.3 ng/mL (25th-75th percentile, 120-770.1 ng/mL) in urine and 113.1 ng/mL (25th-75th percentile, 77.7-203.1 ng/mL) in plasma. Preoperative serum creatinine did not predict mortality (AUC-ROC, 0.50; 95% confidence interval, 0.10-0.94). Furthermore, preoperative urine, plasma hepcidin, and serum creatinine did not distinguish patients requiring postoperative renal replacement therapy from those without (urine: AUC-ROC, 0.62; 95% confidence interval, 0.38-0.86; plasma: AUC-ROC, 0.63; 95% confidence interval, 0.34-0.91; serum creatinine: AUC-ROC, 0.61; 95% confidence interval, 0.22-0.99). Preoperative renal function and hemoglobin did not correlate with hepcidin indices whereas plasma markers of inflammation did.


CONCLUSIONS
Low preoperative hepcidin concentration might be a risk factor for in-hospital mortality. Findings should be validated in larger patient cohorts with a greater number of events.
Department of Nephrology and Hypertension, Diabetes & Endocrinology, Otto-von-Guericke-University Magdeburg, Germany. anja.haase-fielitz@med.ovgu.de
Anja
A
Haase-Fielitz
Michael
M
Plaß
Hermann
H
Kuppe
Roland
R
Hetzer
Vaughn
V
Ostland
Sabine
S
Westphal
Juliane
J
Hoffmann
John
J
Prowle
Peter Rene
PR
Mertens
Mark
M
Westerman
Rinaldo
R
Bellomo
Michael
M
Haase
D058186:Acute Kidney Injury / Q000209:etiology / Q000401:mortality / Q000628:therapy; D000368:Aged; D023181:Antimicrobial Cationic Peptides / Q000097:blood* / Q000652:urine*; D019540:Area Under Curve; D015415:Biomarkers / Q000097:blood / Q000652:urine; D006348:Cardiac Surgical Procedures / Q000009:adverse effects / Q000401:mortality*; D003404:Creatinine / Q000097:blood; D015536:Down-Regulation; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005858:Germany; D006454:Hemoglobins / Q000378:metabolism; D064451:Hepcidins; D017052:Hospital Mortality; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011237:Predictive Value of Tests; D057234:Preoperative Period; D012372:ROC Curve; D017582:Renal Replacement Therapy; D012307:Risk Factors; D012680:Sensitivity and Specificity; D016896:Treatment Outcome
D023181:Antimicrobial Cationic Peptides; D015415:Biomarkers; D006454:Hemoglobins; D064451:Hepcidins; D018836:Inflammation Mediators; C545475:hepcidin 25, human; D003404:Creatinine