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Clinical and Experimental Nephrology

, Volume 22, Issue 1, pp 28–34 | Cite as

Plasma neutrophil gelatinase-associated lipocalin is associated with iron status in anemic patients with pre-dialysis chronic kidney disease

  • Il Young Kim
  • Joo Hui Kim
  • Dong Won Lee
  • Soo Bong LeeEmail author
  • Harin Rhee
  • Sang Heon Song
  • Eun Young Seong
  • Ihm Soo Kwak
Original article

Abstract

Background

Iron deficiency anemia is common in patients with chronic kidney disease (CKD). Neutrophil gelatinase-associated lipocalin (NGAL), a biomarker of acute kidney injury, is known to be associated with iron metabolism. We investigated whether plasma NGAL level is associated with iron status in pre-dialysis CKD patients with anemia.

Methods

This study included 419 patients who had anemia. The subjects were into categorized into a pre-dialysis group (estimated glomerular filtration rate [eGFR] <60 ml/min/1.73 m2, n = 288) and a non-CKD group (eGFR >60 ml/min/1.73 m2, n = 131). The associations between plasma NGAL and iron status (serum ferritin and transferrin saturation [TSAT]), eGFR, albumin, uric acid, total cholesterol, calcium, phosphate, and C-reactive protein (CRP) were assessed.

Results

In non-CKD group, plasma NGAL was not associated with any baseline variables including iron indices (TSAT and serum ferritin). In pre-dialysis group, univariate analysis showed plasma NGAL correlated with eGFR, CRP, TSAT, and serum ferritin. In multivariate analysis, plasma NGAL was independently associated with TSAT. However, serum ferritin lost its association with plasma NGAL. In ROC analysis for identifying iron deficiency, the plasma NGAL (best cut-off value ≤394 ng/ml) was superior to the serum ferritin (suggested cut-off value ≤500 ng/ml) in both sensitivity and specificity.

Conclusions

Plasma NGAL is associated with iron status in anemic patients with pre-dialysis CKD. Further studies are needed to demonstrate the role of plasma NGAL in assessing the iron deficiency and in guiding the iron therapy for pre-dialysis CKD patients.

Keywords

Anemia Chronic kidney disease Iron deficiency Neutrophil gelatinase-associated lipocalin 

Notes

Compliance with ethical standards

Conflict of interest

The authors have declared that no conflict of interest exists.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee at which the studies were conducted (Pusan National University Yangsan Hospital Review Board IRB No. 05-2016-064) and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was waived by the IRB due to the retrospective nature of the analysis using information contained in medical charts and records which were anonymized.

References

  1. 1.
    Kazmi WH, Kausz AT, Khan S, Abichandani R, Ruthazer R, Obrador GT, et al. Anemia: an early complication of chronic renal insufficiency. Am J Kidney Dis. 2001;38:803–12.CrossRefPubMedGoogle Scholar
  2. 2.
    Vlagopoulos PT, Tighiouart H, Weiner DE, Griffith J, Pettitt D, Salem DN, et al. Anemia as a risk factor for cardiovascular disease and all-cause mortality in diabetes: the impact of chronic kidney disease. J Am Soc Nephrol. 2005;16:3403–10.CrossRefPubMedGoogle Scholar
  3. 3.
    Weiss G, Goodnough LT. Anemia of chronic disease. N Engl J Med. 2005;352:1011–23.CrossRefPubMedGoogle Scholar
  4. 4.
    Disease Kidney. Improving global outcomes (KDIGO) Anemia Work Group: KDIGO clinical practice guideline for anemia in chronic kidney disease. Kidney Int Suppl. 2012;2:3.CrossRefGoogle Scholar
  5. 5.
    Wish JB. Assessing iron status: beyond serum ferritin and transferrin saturation. Clin J Am Soc Nephrol. 2006;1(Suppl 1):S4–8.CrossRefPubMedGoogle Scholar
  6. 6.
    Mishra J, Ma Q, Prada A, Mitsnefes M, Zahedi K, Yang J, et al. Identification of neutrophil gelatinase-associated lipocalin as a novel early urinary biomarker for ischemic renal injury. J Am Soc Nephrol. 2003;14:2534–43.CrossRefPubMedGoogle Scholar
  7. 7.
    Bolignano D, Lacquaniti A, Coppolino G, Donato V, Campo S, Fazio MR, et al. Neutrophil gelatinase-associated lipocalin (NGAL) and progression of chronic kidney disease. Clin J Am Soc Nephrol. 2009;4:337–44.CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Bolignano D, Coppolino G, Romeo A, De Paola L, Buemi A, Lacquaniti A, et al. Neutrophil gelatinase-associated lipocalin (NGAL) reflects iron status in haemodialysis patients. Nephrol Dial Transplant. 2009;24:3398–403.CrossRefPubMedGoogle Scholar
  9. 9.
    Levey AS, Bosch JP, Lewis JB, Greene T, Rogers N, Roth D. A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation Modification of Diet in Renal Disease Study Group. Ann Intern Med. 1999;130:461–70.CrossRefPubMedGoogle Scholar
  10. 10.
    DeLong ER, DeLong DM, Clarke-Pearson DL. Comparing the areas under two or more correlated receiver operating characteristic curves: a nonparametric approach. Biometrics. 1988;44:837–45.CrossRefPubMedGoogle Scholar
  11. 11.
    Fishbane S, Maesaka JK. Iron management in end-stage renal disease. Am J Kidney Dis. 1997;29:319–33.CrossRefPubMedGoogle Scholar
  12. 12.
    Besarab A, Szczech L. Uses and interpretation of iron studies in patients on chronic dialysis. Semin Dial. 2014;27:579–81.CrossRefPubMedGoogle Scholar
  13. 13.
    Tarng DC. The conundrum of serum ferritin measurement in patients with chronic kidney disease. Nat Clin Pract Nephrol. 2009;5:66–7.CrossRefPubMedGoogle Scholar
  14. 14.
    Xu S, Venge P. Lipocalins as biochemical markers of disease. Biochim Biophys Acta. 2000;1482:298–307.CrossRefPubMedGoogle Scholar
  15. 15.
    Bolignano D, Lacquaniti A, Coppolino G, Campo S, Arena A, Buemi M. Neutrophil gelatinase-associated lipocalin reflects the severity of renal impairment in subjects affected by chronic kidney disease. Kidney Blood Press Res. 2008;31:255–8.CrossRefPubMedGoogle Scholar
  16. 16.
    Avci Cicek E, Rota S, Dursun B, Kavalci E. Evaluation of serum NGAL and hepcidin levels in chronic kidney disease patients. Ren Fail. 2016;38:35–9.CrossRefPubMedGoogle Scholar
  17. 17.
    Emans ME, Braam B, Diepenbroek A, van der Putten K, Cramer MJ, Wielders JP, et al. Neutrophil gelatinase-associated lipocalin (NGAL) in chronic cardiorenal failure is correlated with endogenous erythropoietin levels and decreases in response to low-dose erythropoietin treatment. Kidney Blood Press Res. 2012;36:344–54.CrossRefPubMedGoogle Scholar
  18. 18.
    Goetz DH, Holmes MA, Borregaard N, Bluhm ME, Raymond KN, Strong RK. The neutrophil lipocalin NGAL is a bacteriostatic agent that interferes with siderophore-mediated iron acquisition. Mol Cell. 2002;10:1033–43.CrossRefPubMedGoogle Scholar
  19. 19.
    Bao G, Clifton M, Hoette TM, Mori K, Deng SX, Qiu A, et al. Iron traffics in circulation bound to a siderocalin (Ngal)-catechol complex. Nat Chem Biol. 2010;6:602–9.CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Imamaki H, Ishii A, Yokoi H, Kasahara M, Kuwabara T, Mori KP, et al. Low serum neutrophil gelatinase-associated lipocalin level as a marker of malnutrition in maintenance hemodialysis patients. PLoS One. 2015;10:e0132539.CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Weizer-Stern O, Adamsky K, Amariglio N, Rachmilewitz E, Breda L, Rivella S, et al. mRNA expression of iron regulatory genes in beta-thalassemia intermedia and beta-thalassemia major mouse models. Am J Hematol. 2006;81:479–83.CrossRefPubMedGoogle Scholar
  22. 22.
    Jiang W, Constante M, Santos MM. Anemia upregulates lipocalin 2 in the liver and serum. Blood Cells Mol Dis. 2008;41:169–74.CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Malyszko J, Malyszko JS, Kozminski P, Koc-Zorawska E, Mysliwiec M, Macdougall I. Possible relationship between neutrophil gelatinase-associated lipocalin, hepcidin, and inflammation in haemodialysed patients. Nephron Clin Pract. 2010;115:c268–75.CrossRefPubMedGoogle Scholar
  24. 24.
    Malyszko J, Tesar V, Macdougall IC. Neutrophil gelatinase-associated lipocalin and hepcidin: what do they have in common and is there a potential interaction? Kidney Blood Press Res. 2010;33:157–65.CrossRefPubMedGoogle Scholar
  25. 25.
    Mori K, Nakao K. Neutrophil gelatinase-associated lipocalin as the real-time indicator of active kidney damage. Kidney Int. 2007;71:967–70.CrossRefPubMedGoogle Scholar

Copyright information

© Japanese Society of Nephrology 2017

Authors and Affiliations

  • Il Young Kim
    • 1
    • 2
  • Joo Hui Kim
    • 1
    • 2
  • Dong Won Lee
    • 1
    • 2
  • Soo Bong Lee
    • 1
    • 2
    Email author
  • Harin Rhee
    • 1
    • 3
  • Sang Heon Song
    • 1
    • 3
  • Eun Young Seong
    • 1
    • 3
  • Ihm Soo Kwak
    • 1
    • 3
  1. 1.Division of Nephrology, Department of Internal MedicinePusan National University School of MedicineYangsanSouth Korea
  2. 2.Research Institute for Convergence of Biomedical Science and TechnologyPusan National University Yangsan HospitalYangsanSouth Korea
  3. 3.Medical Research InstitutePusan National University HospitalBusanSouth Korea

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