Association of serum lncRNA H19 expression with inflammatory and oxidative stress markers and routine biochemical parameters in chronic kidney disease



Chronic kidney disease (CKD) is a disorder that affects millions worldwide, and current treatment options aiming at inhibiting the progression of kidney damage are limited. Long noncoding RNA (lncRNA) H19 is one of the first explored lncRNAs and its deregulation is associated with renal pathologies, such as renal cell injury and nephrotic syndrome. However, there is still no research investigating the connection between serum lncRNA H19 expressions and clinical outcomes in CKD patients. Therefore, we investigated the relation of serum lncRNA H19 expressions with routine biochemical parameters, inflammatory cytokines, oxidative stress and mineralization markers in advanced CKD patients.


lncRNA H19 serum levels from 56 CKD patients and 20 healthy controls were analyzed with reverse-transcription quantitative polymerase chain reaction method. Serum tumor necrosis factor-alpha (TNF-α), interleukin 6 (IL-6), and osteocalcin (OC) levels were measured with enzyme linked-immunosorbent assay. Total antioxidant status (TAS) and total oxidative status (TOS) levels were evaluated by the routine measurement method.


We found that lncRNA H19 expressions were upregulated in patients with CKD compared to the controls. Furthermore, lncRNA H19 relative expression levels showed a negative relationship with glomerular filtration rate (GFR) while it was positively correlated with ferritin, phosphorus, parathyroid hormone, TNF-α, IL-6, OC, TAS and TOS levels.


lncRNA H19 expressions were increased in CKD stage 3–5 and HD patients, and elevated lncRNA H19 expressions were associated with decreased glomerular filtration rate, inflammation, and mineralization markers in these patients.

This is a preview of subscription content, access via your institution.

Fig. 1
Fig. 2
Fig. 3


  1. 1.

    Webster AC, Nagler EV, Morton RL, Masson P. Chronic kidney disease. Lancet. 2017;389(10075):1238–52.

    Article  Google Scholar 

  2. 2.

    Glassock RJ, Warnock DG, Delanaye P. The global burden of chronic kidney disease: estimates, variability and pitfalls. Nat Rev Nephrol. 2017;13(2):104–14.

    CAS  Article  Google Scholar 

  3. 3.

    Honeycutt AA, Segel JE, Zhuo X, Hoerger TJ, Imai K, Williams D. Medical costs of CKD in the medicare population. J Am Soc Nephrol. 2013;24(9):1478–83.

    Article  Google Scholar 

  4. 4.

    Zhou Q, Chen W, Yu XQ. Long non-coding RNAs as novel diagnostic and therapeutic targets in kidney disease. Chronic Dis Transl Med. 2019;5(4):252–7.

    PubMed  Google Scholar 

  5. 5.

    Maass PG, Luft FC, Bahring S. Long non-coding RNA in health and disease. J Mol Med (Berl). 2014;92(4):337–46.

    CAS  Article  Google Scholar 

  6. 6.

    Xie H, Xue JD, Chao F, Jin YF, Fu Q. Long non-coding RNA-H19 antagonism protects against renal fibrosis. Oncotarget. 2016;7(32):51473–81.

    Article  Google Scholar 

  7. 7.

    Xu J, Ge T, Zhou H, Zhang L, Zhao L. Absence of long noncoding RNA H19 promotes childhood nephrotic syndrome through Inhibiting ADCK4 signal. Med Sci Monit. 2020;26:e922090.

    CAS  PubMed  PubMed Central  Google Scholar 

  8. 8.

    Liu H, Ye T, Yang X, Liu J, Jiang K, Lu H, et al. H19 promote calcium oxalate nephrocalcinosis-induced renal tubular epithelial cell injury via a ceRNA pathway. EBioMedicine. 2019;50:366–78.

    Article  Google Scholar 

  9. 9.

    Fan W, Peng Y, Liang Z, Yang Y, Zhang J. A negative feedback loop of H19/miR-675/EGR1 is involved in diabetic nephropathy by downregulating the expression of the vitamin D receptor. J Cell Physiol. 2019;234(10):17505–13.

    CAS  Article  Google Scholar 

  10. 10.

    Erel O. A new automated colorimetric method for measuring total oxidant status. Clin Biochem. 2005;38(12):1103–11.

    CAS  Article  Google Scholar 

  11. 11.

    Erel O. A novel automated method to measure total antioxidant response against potent free radical reactions. Clin Biochem. 2004;37(2):112–9.

    CAS  Article  Google Scholar 

  12. 12.

    Wang L, Su N, Zhang Y, Wang G. Clinical significance of serum lncrna cancer susceptibility candidate 2 (CASC2) for chronic renal failure in patients with type 2 diabetes. Med Sci Monit. 2018;24:6079–84.

    CAS  Article  Google Scholar 

  13. 13.

    Hajian-Tilaki K. Receiver operating characteristic (ROC) Curve analysis for medical diagnostic test evaluation. Caspian J Intern Med. 2013;4(2):627–35.

    PubMed  PubMed Central  Google Scholar 

  14. 14.

    Lorenzen JM, Schauerte C, Kielstein JT, Hubner A, Martino F, Fiedler J, et al. Circulating long noncoding RNATapSaki is a predictor of mortality in critically ill patients with acute kidney injury. Clin Chem. 2015;61(1):191–201.

    CAS  Article  Google Scholar 

  15. 15.

    Wang L, Cai Y, Zhao X, Jia X, Zhang J, Liu J, et al. Down-regulated long non-coding RNA H19 inhibits carcinogenesis of renal cell carcinoma. Neoplasma. 2015;62(3):412–8.

    CAS  Article  Google Scholar 

  16. 16.

    Gabory A, Ripoche MA, Yoshimizu T, Dandolo L. The H19 gene: regulation and function of a non-coding RNA. Cytogenet Genome Res. 2006;113(1–4):188–93.

    CAS  Article  Google Scholar 

Download references


This work is supported by the Scientific Research Project Fund of Hatay Mustafa Kemal University under project number: 19.M.013.

Author information




HMO, SD and FHT designed the study. HMO, SD, and MYT performed genetic and biochemistry laboratory analyses. HMO, SD, MYT, MAB, and FHT wrote/drafted/edited the manuscript and interpreted the results. HMO, SD, MYT, MAB, and FHT conducted analyses, prepared graphs/figures and revised the manuscript.

Corresponding author

Correspondence to Hamza Malik Okuyan.

Ethics declarations

Conflict of interest

We all declare that we do not have any conflicts of interest.

Ethical approval

All procedures performed in the present study were approved by the institutional review board and were in compliance with the 1964 Helsinki Declaration (Approval number: 2019/26).

Informed consent

Informed consent was obtained from all individual participants included in the study.

Additional information

Publisher's Note

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

About this article

Verify currency and authenticity via CrossMark

Cite this article

Okuyan, H.M., Dogan, S., Terzi, M.Y. et al. Association of serum lncRNA H19 expression with inflammatory and oxidative stress markers and routine biochemical parameters in chronic kidney disease. Clin Exp Nephrol 25, 522–530 (2021).

Download citation


  • Chronic kidney disease
  • lncRNA H19
  • TNF-α
  • IL-6
  • Oxidative stress