Skip to main content
SpringerLink
Log in

Association of plasma neutrophil gelatinase-associated lipocalin with parameters of CKD–MBD in maintenance hemodialysis patients

  • Original Article
  • Published:
Journal of Bone and Mineral Metabolism Aims and scope Submit manuscript

Abstract

Introduction

Neutrophil gelatinase-associated lipocalin (NGAL) is not only a biomarker of kidney injury but also a bone-derived factor involved in metabolism. We aimed to explore relationships between plasma NGAL and chronic kidney disease-mineral bone disorder (CKD-MBD) parameters in maintenance hemodialysis (MHD) patients.

Materials and methods

First, a cross sectional observational study, including 105 MHD patients, was conducted to explore relationships between plasma NGAL levels and CKD–MBD parameters. Second, impact of parathyroidectomy and auto-transplantation (PTX + AT) on plasma NGAL was investigated in 12 MHD patients with severe secondary hyperparathyroidism (SHPT).

Results

According to Spearman correlation analysis, plasma NGAL levels were positively correlated with female (r = 0.243, P = 0.012), vintage (r = 0.290, P = 0.003), Klotho (r = 0.234, P = 0.016), calcium(Ca) (r = 0.332, P = 0.001), alkaline phosphatase (ALP) (r = 0.401, P < 0.001) and intact parathyroid hormone (iPTH) (r = 0.256, P = 0.008); while inversely correlated with albumin(Alb) (r = − 0.201, P = 0.039). After adjusting for age, sex, vintage, Alb and all parameters of CKD–MBD(Ca, P, lg(ALP), lg(iPTH), Klotho and fibroblast growth factor 23(FGF23)), lg(NGAL) were positively correlated with Ca (r = 0.481, P < 0.001), P (r = 0.336, P = 0.037), lg(ALP) (r = 0.646, P < 0.001) in Partial correlation analysis; further multiple linear regression analysis showed same positive associations between lg(NGAL) and Ca (β = 0.330, P = 0.002), P (β = 0.218, P = 0.037), lg(ALP) (β = 0.671, P < 0.001). During the 4–7 days after PTX + AT, plasma NGAL decreased from 715.84 (578.73, 988.14) to 688.42 (660.00, 760.26) ng/mL (P = 0.071), Klotho increased from 496.45 (341.73, 848.30) to 1138.25 (593.87, 2009.27) pg/mL (P = 0.099).

Conclusion

Plasma NGAL levels were positively associated with ALP in MHD patients; and downtrends were shown after PTX + AT in patients with severe SHPT. These findings suggest that NGAL is a participant in CKD–MBD under MHD condition.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Han Y, You X, Xing W, Zhang Z, Zou W (2018) Paracrine and endocrine actions of bone-the functions of secretory proteins from osteoblasts, osteocytes, and osteoclasts. Bone Res 6:16

    Article  PubMed  PubMed Central  Google Scholar 

  2. Capulli M, Ponzetti M, Maurizi A, Gemini-Piperni S, Berger T, Mak TW, Teti A, Rucci N (2018) A complex role for lipocalin 2 in bone metabolism: global ablation in mice induces osteopenia caused by an altered energy metabolism. J Bone Miner Res 33:1141–1153

    Article  CAS  PubMed  Google Scholar 

  3. Shang W, Wang Z (2017) The update of NGAL in acute kidney injury. Curr Protein Pept Sci 18:1211–1217

    Article  CAS  PubMed  Google Scholar 

  4. Zeng XF, Li JM, Tan Y, Wang ZF, He Y, Chang J, Zhang H, Zhao H, Bai X, Xie F, Sun J, Zhang Y (2014) Performance of urinary NGAL and L-FABP in predicting acute kidney injury and subsequent renal recovery: a cohort study based on major surgeries. Clin Chem Lab Med 52:671–678

    Article  CAS  PubMed  Google Scholar 

  5. Mårtensson J, Bellomo R (2014) The rise and fall of NGAL in acute kidney injury. Blood Purif 37:304–310

    Article  PubMed  Google Scholar 

  6. Bolignano D, Lacquaniti A, Coppolino G, Donato V, Campo S, Fazio MR, Nicocia G, Buemi M (2009) Neutrophil gelatinase-associated lipocalin (NGAL) and progression of chronic kidney disease. Clin J Am Soc Nephrol 4:337–344

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Seibert FS, Sitz M, Passfall J, Haesner M, Laschinski P, Buhl M, Bauer F, Babel N, Pagonas N, Westhoff TH (2018) prognostic value of urinary calprotectin, NGAL and KIM-1 in chronic kidney disease. Kidney Blood Press Res 43:1255–1262

    Article  CAS  PubMed  Google Scholar 

  8. Alderson HV, Ritchie JP, Pagano S, Middleton RJ, Pruijm M, Vuilleumier N, Kalra PA (2016) The associations of blood kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin with progression from CKD to ESRD. Clin J Am Soc Nephrol 11:2141–2149

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Capulli M, Rufo A, Teti A, Rucci N (2009) Global transcriptome analysis in mouse calvarial osteoblasts highlights sets of genes regulated by modeled microgravity and identifies a “mechanoresponsive osteoblast gene signature.” Cell Biochem 107:240–252

    Article  CAS  Google Scholar 

  10. Rucci N, Capulli M, Piperni SG, Cappariello A, Lau P, Frings-Meuthen P, Heer M, Teti A (2015) J Bone Miner Res 30:357–368

    Article  CAS  PubMed  Google Scholar 

  11. Veeriah V, Zanniti A, Paone R, Chatterjee S, Rucci N, Teti A, Capulli M (2016) Interleukin-1beta, lipocalin 2 and nitric oxide synthase 2 are mechano-responsive mediators of mouse and human endothelial cell-osteoblast crosstalk. Sci Rep 6:29880

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Lu M, Xia L, Liu YC, Hochman T, Bizzari L, Aruch D, Lew J, Weinberg R, Goldberg JD, Hoffman R (2015) Lipocalin produced by myelofibrosis cells affects the fate of both hematopoietic and marrow microenvironmental cells. Blood 126:972–982

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Lim WH, Wong G, Lim EM, Byrnes E, Zhu K, Devine A, Pavlos NJ, Prince RL, Lewis JR (2015) Circulating lipocalin 2 levels predict fracture-related hospitalizations in elderly women: a prospective cohort study. J Bone Miner Res 30:2078–2085

    Article  CAS  PubMed  Google Scholar 

  14. Asimakopoulou A, Borkham-Kamphorst E, Tacke F, Weiskirchen R (2016) Lipocalin-2 (NGAL/LCN2), a “help-me” signal in organ inflammation. Hepatology 63:669–671

    Article  PubMed  Google Scholar 

  15. Buonafine M, Martinez-Martinez E, Jaisser F (2018) More than a simple biomarker: the role of NGAL in cardiovascular and renal diseases. Clin Sci (Lond) 132:909–923

    Article  CAS  Google Scholar 

  16. Abella V, Scotece M, Conde J, Gómez R, Lois A, Pino J, Gómez-Reino JJ, Lago F, Mobasheri A, Gualillo O (2015) The potential of lipocalin-2/NGAL as biomarker for inflammatory and metabolic diseases. Biomarkers 20:565–571

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Gouweleeuw L, Naudé PJ, Rots M, DeJongste MJ, Eisel UL, Schoemaker RG (2015) The role of neutrophil gelatinase associated lipocalin (NGAL) as biological constituent linking depression and cardiovascular disease. Brain Behav Immun 46:23–32

    Article  CAS  PubMed  Google Scholar 

  18. Ketteler M, Block GA, Evenepoel P, Fukagawa M, Herzog CA, McCann L, Moe SM, Shroff R, Tonelli MA, Toussaint ND, Vervloet MG, Leonard MB (2017) Executive summary of the 2017 KDIGO chronic kidney disease-mineral and bone disorder (CKD-MBD) Guideline Update: what’s changed and why it matters. Kidney Int 92:26–36

    Article  Google Scholar 

  19. Yamada S, Giachelli CM (2017) Vascular calcification in CKD-MBD: roles for phosphate, FGF23, and Klotho. Bone 100:87–93

    Article  CAS  PubMed  Google Scholar 

  20. Waziri B, Duarte R, Naicker S (2019) Chronic kidney disease-mineral and bone disorder (CKD-MBD): current perspectives. Int J Nephrol Renovasc Dis 12:263–276

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Yazdani M, Merrikhi A, Beni ZN, Baradaran A, Soleimani N, Musazade H (2014) Association between neutrophil geletinase-associated lipocalin and iron deficiency anemia in children on chronic dialysis. J Res Med Sci 19:624–628

    CAS  PubMed  PubMed Central  Google Scholar 

  22. Imamaki H, Ishii A, Yokoi H, Kasahara M, Kuwabara T, Mori KP, Kato Y, Kuwahara T, Satoh M, Nakatani K, Saito Y, Tomosugi N, Sugawara A, Nakao K, Mukoyama M, Yanagita M, Mori K (2015) Low serum neutrophil gelatinase-associated lipocalin level as a marker of malnutrition in maintenance hemodialysis patients. PLoS One 10:e0132539

    Article  PubMed  PubMed Central  Google Scholar 

  23. Kim IY, Kim JH, Kim MJ, Lee DW, Hwang CG, Han M, Rhee H, Song SH, Seong EY, Lee SB (2018) Plasma neutrophil gelatinase-associated lipocalin is independently associated with left ventricular hypertrophy and diastolic dysfunction in patients with chronic kidney disease. PLoS One 13:e0205848

    Article  PubMed  PubMed Central  Google Scholar 

  24. Bolignano D, Coppolino G, Romeo A, Lacquaniti A, Buemi M (2010) Neutrophil gelatinase-associated lipocalin levels in chronic haemodialysis patients. Nephrology (Carlton) 15:23–26

    Article  CAS  Google Scholar 

  25. Nevo A, Armaly Z, Abd El Kadir A, Douvdevani A, Tovbin D (2018) Elevated neutrophil gelatinase lipocalin levels are associated with increased oxidative stress in hemodialysis patients. J Clin Med Res 10:461–465

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Malyszko J, Malyszko JS, Koc-Zorawska E, Kozminski P, Mysliwiec M (2009) Neutrophil gelatinase-associated lipocalin in dialyzed patients is related to residual renal function, type of renal replacement therapy and inflammation. Kidney Blood Press Res 32:464–469

    Article  CAS  PubMed  Google Scholar 

  27. Bauvois B, Susin SA (2018) Revisiting neutrophil gelatinase-associated lipocalin (NGAL) in cancer: saint or sinner? Cancers (Basel) 10:336

    Article  Google Scholar 

  28. Liu DM, Zhao HY, Zhao L, Zhang MJ, Liu TT, Tao B, Sun LH, Liu JM (2018) The relationship among serum lipocalin 2, bone turnover markers, and bone mineral density in outpatient women. Endocrine 59:304–310

    Article  CAS  PubMed  Google Scholar 

  29. Luo Y, Ma X, Pan X, Xu Y, Xiong Q, Xiao Y, Bao Y, Jia W (2016) Serum lipocalin-2 levels are positively associated with not only total body fat but also visceral fat area in Chinese men. Medicine (Baltimore) 95:e4039

    Article  CAS  Google Scholar 

  30. Park JC, Kovesdy CP, Duong U, Streja E, Rambod M, Nissenson AR, Sprague SM, Kalantar-Zadeh K (2010) Association of serum alkaline phosphatase and bone mineral density in maintenance hemodialysis patients. Hemodial Int 14:182–192

    Article  PubMed  PubMed Central  Google Scholar 

  31. Bergman A, Qureshi AR, Haarhaus M, Lindholm B, Barany P, Heimburger O, Stenvinkel P, Anderstam B (2017) Total and bone-specific alkaline phosphatase are associated with bone mineral density over time in end-stage renal disease patients starting dialysis. J Nephrol 30:255–262

    Article  CAS  PubMed  Google Scholar 

  32. Maruyama Y, Taniguchi M, Kazama JJ, Yokoyama K, Hosoya T, Yokoo T, Shigematsu T, Iseki K, Tsubakihara Y (2014) A higher serum alkaline phosphatase is associated with the incidence of hip fracture and mortality among patients receiving hemodialysis in Japan. Nephrol Dial Transpl 29:1532–1538

    Article  CAS  Google Scholar 

  33. Shantouf R, Kovesdy CP, Kim Y, Ahmadi N, Luna A, Luna C, Rambod M, Nissenson AR, Budoff MJ, Kalantar-Zadeh K (2009) Association of serum alkaline phosphatase with coronary artery calcification in maintenance hemodialysis patients. Clin J Am Soc Nephrol 4:1106–1114

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Chen J, Mohler ER, Xie D, Shlipak M, Townsend RR, Appel LJ, Ojo A, Schreiber M, Nessel L, Zhang X, Raj D, Strauss L, Lora CM, Rahman M, Hamm LL, He J, CRIC Study Investigators (2016) Traditional and non-traditional risk factors for incident peripheral arterial disease among patients with chronic kidney disease. Nephrol Dial Transplant 31:1145–1151

    Article  PubMed  Google Scholar 

  35. Haarhaus M, Brandenburg V, Kalantar-Zadeh K, Stenvinkel P, Magnusson P (2017) Alkaline phosphatase: a novel treatment target for cardiovascular disease in CKD. Nat Rev Nephrol 13:429–442

    Article  CAS  PubMed  Google Scholar 

  36. Azpiazu D, Gonzalo S, Villa-Bellosta R (2019) Tissue non-specific alkaline phosphatase and vascular calcification: a potential therapeutic target. Curr Cardiol Rev 15:91–95

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Bover J, Ureña P, Aguilar A, Mazzaferro S, Benito S, López-Báez V, Ramos A, daSilva I, Cozzolino M (2018) Alkaline phosphatases in the complex chronic kidney disease-mineral and bone disorders. Calcif Tissue Int 103:111–124

    Article  CAS  PubMed  Google Scholar 

  38. Mosialou I, Shikhel S, Liu JM, Maurizi A, Luo N, He Z, Huang Y, Zong H, Friedman RA, Barasch J, Lanzano P, Deng L, Leibel RL, Rubin M, Nickolas T, Chung W, Zeltser LM, Williams KW, Pessin JE, Kousteni S (2017) MC4R-dependent suppression of appetite by bone-derived lipocalin 2. Nature 543:385–390

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Rau S, Habicht A, Kauke T, Hillmer A, Wessely M, Stangl M, Guba M, Fischereder M, Schönermarck U (2013) Neutrophil gelatinase-associated lipocalin and end-stage renal disease: it is not all about the kidneys! Eur J Clin Invest 43:816–820

    Article  CAS  PubMed  Google Scholar 

  40. Bolignano D, Coppolino G, Donato V, Lacquaniti A, Bono C, Buemi M (2010) Neutrophil gelatinase-associated lipocalin (NGAL): a new piece of the anemia puzzle. Med Sci Monit 16:RA131–135

    CAS  PubMed  Google Scholar 

  41. Takahashi H, Komaba H, Takahashi Y, Sawada K, Tatsumi R, Kanai G, Suzuki H, Kakuta T, Fukagawa M (2014) Impact of parathyroidectomy on serum FGF23 and soluble Klotho in hemodialysis patients with severe secondary hyperparathyroidism. J Clin Endocrinol Metab 99:E652–E658

    Article  CAS  PubMed  Google Scholar 

  42. Lau WL, Leaf EM, Hu MC, Takeno MM, Kuro-o M, Moe OW, Giachelli CM (2012) Vitamin D receptor agonists increase klotho and osteopontin while decreasing aortic calcification in mice with chronic kidney disease fed a high phosphate diet. Kidney Int 82:1261–1270

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

We would like to thank Dr Fang Tang, at center for data science in health and medicine, the First Affiliated Hospital of Shandong First Medical University, Jinan, China, for their valuable inputs in data analysis. The authors’ responsibilities were as follows- XJ and DX: designed research; XJ, KW, JC, YW, ZW, YL, LL and LW: conducted research; XJ, XK and YL: analyzed data; XJ, DX, KW, LX and YW: wrote the paper; DX: had primary responsibility for final content; and all authors: read and approved the final manuscript.

Funding

This work was supported by the National Natural Science Foundation of China (81970615 to Dongmei Xu); the National Natural Science Foundation of China (82004088 to Kai Wei); the National Natural Science Foundation of China (82000728 to Xianglei Kong).

Author information

Authors and Affiliations

  1. Department of Nephrology, The First Affiliated Hospital of Shandong First Medical University, No.16766, Jingshi Road, Jinan, 250014, China

    Xiao-yan Jia, Kai Wei, Juan Chen, Xiang-lei Kong, Yong Wei, Li Wang, Zun-song Wang, Yi-peng Liu, Li-ming Liang & Dong-mei Xu

  2. Department of Nephrology, Shandong Provincial Qianfoshan Hospital, Jinan, China

    Xiao-yan Jia, Kai Wei, Juan Chen, Xiang-lei Kong, Yong Wei, Li Wang, Zun-song Wang, Yi-peng Liu, Li-ming Liang & Dong-mei Xu

  3. Shandong Provincial Insititute of Nephrology, Jinan, China

    Xiao-yan Jia, Kai Wei, Juan Chen, Xiang-lei Kong, Yong Wei, Li Wang, Zun-song Wang, Yi-peng Liu, Li-ming Liang & Dong-mei Xu

  4. Department of Plastic and Reconstructive Surgery, Shandong Provincial Qianfoshan Hospital, Jinan, China

    Lin-he Xi

Authors
  1. Xiao-yan Jia
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kai Wei
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Juan Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Lin-he Xi
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Xiang-lei Kong
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Yong Wei
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Li Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Zun-song Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Yi-peng Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Li-ming Liang
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Dong-mei Xu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Dong-mei Xu.

Ethics declarations

Conflict of interest

The authors have no conflicts of interest to declare.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Jia, Xy., Wei, K., Chen, J. et al. Association of plasma neutrophil gelatinase-associated lipocalin with parameters of CKD–MBD in maintenance hemodialysis patients. J Bone Miner Metab 39, 1058–1065 (2021). https://doi.org/10.1007/s00774-021-01248-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00774-021-01248-9

Keywords

Search

Navigation