Hepcidin-A Potential Novel Biomarker for Iron Status in Chronic Kidney Disease

被引:253
作者
Zaritsky, Joshua [1 ]
Young, Brian [2 ]
Wang, He-Jing [3 ]
Westerman, Mark [4 ]
Olbina, Gordana [4 ]
Nemeth, Elizabeta [2 ]
Ganz, Tomas [2 ]
Rivera, Seth [2 ]
Nissenson, Allen R. [2 ]
Salusky, Isidro B. [1 ]
机构
[1] Univ Calif Los Angeles, Dept Pediat, David Geffen Sch Med, Los Angeles, CA 90024 USA
[2] Univ Calif Los Angeles, Dept Med, David Geffen Sch Med, Los Angeles, CA 90024 USA
[3] Univ Calif Los Angeles, Dept Biomath, David Geffen Sch Med, Los Angeles, CA 90024 USA
[4] Intrins Life Sci, La Jolla, CA USA
来源
CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY | 2009年 / 4卷 / 06期
基金
美国国家卫生研究院;
关键词
GLOMERULAR-FILTRATION-RATE; PEPTIDE HEPCIDIN; SERUM FERRITIN; RENAL-FAILURE; INFLAMMATION; ANEMIA; PROHEPCIDIN; ASSOCIATION; ABSORPTION; CREATININE;
D O I
10.2215/CJN.05931108
中图分类号
R5 [内科学]; R69 [泌尿科学(泌尿生殖系疾病)];
学科分类号
1002 ; 100201 ;
摘要
Background and objectives: Hepcidin is a key regulator of iron homeostasis, but its study in the setting of chronic kidney disease (CKD) has been hampered by the lack of validated serum assays. Design, setting, participants, & measurements: This study reports the first measurements of bioactive serum hepcidin using a novel competitive ELISA in 48 pediatric (PCKD2-4) and 32 adult (ACKD2-4) patients with stages 2 to 4 CKD along with 26 pediatric patients with stage 5 CKD (PCKD5D) on peritoneal dialysis. Results: When compared with their respective controls (pediatric median = 25.3 ng/ml, adult = 72.9 ng/ml), hepcidin was significantly increased in PCKD2-4 (127.3 ng/ml), ACKD2-4 (269.9 ng/ml), and PCKD5D (652.4 ng/ml). Multivariate regression analysis was used to assess the relationship between hepcidin and indicators of anemia, iron status, inflammation, and renal function. In PCKD2-4 (R-2 = 0.57), only ferritin correlated with hepcidin. In ACKD2-4 (R-2 = 0.78), ferritin and soluble transferrin receptor were associated with hepcidin, whereas GFR was inversely correlated. In PCKD5D (R-2 = 0.52), percent iron saturation and ferritin were predictors of hepcidin. In a multivariate analysis that incorporated all three groups (R-2 = 0.6), hepcidin was predicted by ferritin, C-reactive protein, and whether the patient had stage 5D versus stages 2 to 4 CKD. Conclusions: These findings suggest that increased hepcidin across the spectrum of CKD may contribute to abnormal iron regulation and erythropoiesis and may be a novel biomarker of iron status and erythropoietin resistance. Clin J Am Soc Nephrol 4: 1051-1056, 2009. doi: 10.2215/CJN.05931108
引用
收藏
页码:1051 / 1056
页数:6
相关论文
共 34 条
  • [1] ASHBY DR, 2009, KIDNEY INT IN PRESS
  • [2] Serum pro-hepcidin: measuring active hepcidin or a non-functional precursor?
    Brookes, MJ
    Sharma, NK
    Tselepis, C
    Iqbal, TH
    [J]. GUT, 2005, 54 (01) : 169 - 170
  • [3] CHONCHOL M, 2008, NEPHROL DIAL TRANSPL, V23, P584
  • [4] K/DOQI clinical practice guidelines for chronic kidney disease: Evaluation, classification, and stratification - Foreword
    Eknoyan, G
    Levin, NW
    [J]. AMERICAN JOURNAL OF KIDNEY DISEASES, 2002, 39 (02) : S14 - S266
  • [5] Immunoassay for human serum hepcidin
    Ganz, Tomas
    Olbina, Gordana
    Girelli, Domenico
    Nemeth, Elizabeta
    Westerman, Mark
    [J]. BLOOD, 2008, 112 (10) : 4292 - 4297
  • [6] Molecular control of iron transport
    Ganz, Tomas
    [J]. JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY, 2007, 18 (02): : 394 - 400
  • [7] Iron absorption by healthy women is not associated with either serum or urinary prohepcidin
    Hadley, Kevin B.
    Johnson, LuAnn K.
    Hunt, Janet R.
    [J]. AMERICAN JOURNAL OF CLINICAL NUTRITION, 2006, 84 (01) : 150 - 155
  • [8] Effect of malnutrition-inflammation complex syndrome on EPO hyporesponsiveness in maintenance hemodialysis patients
    Kalantar-Zadeh, K
    McAllister, CJ
    Lehn, RS
    Lee, GH
    Nissenson, AR
    Kopple, JD
    [J]. AMERICAN JOURNAL OF KIDNEY DISEASES, 2003, 42 (04) : 761 - 773
  • [9] The fascinating but deceptive ferritin: To measure it or not to measure it in chronic kidney disease?
    Kalantar-Zadeh, Kamyar
    Kalantar-Zadeh, Kourosh
    Lee, Grace H.
    [J]. CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY, 2006, 1 : S9 - S18
  • [10] Association of prohepcidin and hepcidin-25 with erythropoietin response and ferritin in hemodialysis patients
    Kato, Akihiko
    Tsuji, Takayuki
    Luo, Jinghui
    Sakao, Yukitoshi
    Yasuda, Hideo
    Hishida, Akira
    [J]. AMERICAN JOURNAL OF NEPHROLOGY, 2008, 28 (01) : 115 - 121