Emerging Biomarkers in Kidney Disease

Chronic kidney disease is a progressive condition that affects >10% of the general population worldwide (1). Current clinical biomarkers prove effective at advanced stages of renal impairment, limiting the timely initiation of potentially successful therapeutic interventions. There is an unmet need for more refined biomarkers capable of detecting CKD at earlier stages, thereby enhancing the prospects for patients’ outcomes.

In the last decade, the advancement in the fields of genomics, proteomics, and metabolomics have led to the identification of potential biomarker candidates that may offer important diagnostic and prognostic information in patients suffering from kidney diseases (2).

Among the current established biomarkers such as serum creatinine, albuminuria, and proteinuria, novel biomarkers for kidney diseases could potentially provide additional prognostic information. They could help to predict treatment response in various clinical settings such as acute kidney injury, transplant rejection or glomerulopathies (2).

Emerging Biomarkers in Kidney Disease

Biomedica offers a range of ELISA assay kits to reliably detect biomarkers in blood samples of patients with kidney diseases.

Endostatin, Vanin-1, Periostin, FGF23, IL-6 and more…

 

 

ENDOSTATIN – a potential biomarker of renal fibrosis, chronic kidney disease (CKD), prognostic marker in acute kidney injury (AKI)

Endostatin is an extracellular matrix protein which is expressed in patients during the progression of renal fibrosis. The significant increase of serum Endostatin levels may be due to the enhanced degradation of the extracellular matrix in patients with chronic kidney disease (3, 4). Endostatin has also been studied as a prognostic marker in patients with acute kidney injury (AKI) (5) and is independently associated with incident cardiovascular events in CKD patients (6).

Endostatin can reliably be quantified in serum, plasma and urine samples:

• Endostatin ELISA | BI-20742
• Endostatin ELISA (Mouse/Rat) | BI-20742MR  (7)

 

VANIN-1 – a potential biomarker of acute kidney injury and drug induced renal injury

Vascular non-inflammatory molecule-1 (Vanin-1) is highly expressed in the kidney (8) and has been proposed as a marker in acute kidney injury and drug induced renal injury (9).  Vanin-1 has been identified as a marker of kidney damage as shown n a rat model of type 1 diabetic nephropathy (10).

Urinary Vanin-1  has been investigated in children with renal fibrosis (11) and as a predictor of acute pyelonephritis in young children with urinary tract infection (12). A recent study investigated the role of urinary Vanin-1 in kidney transplant recipients (13).

Vanin-1 can easily be measured with a conventional ELISA assay:

• Vanin-1 (urine) ELISA | BI-VAN1U
• Vanin-1 ELISA (Mouse/Rat) ELISA | BI-VAN1MR        

 

PERIOSTIN – a potential early biomarker of renal tubular injury

Periostin is a matricellular protein that is involved in tissue remodeling and wound healing. Studies have demonstrated that the expression of Periostin in the kidney correlates with the degree of interstitial fibrosis and a decline in kidney function (15). Elevated urine Periostin levels were found in patients with type 2 diabetes which were present before the onset of microaluminuria. The authors proposed that urinary Periostin could be an early biomarker of renal tubular injury (16).

Periostin can reliably be measured in serum, plasma, and urine samples with a fully validated ELISA assay (17).

• Periostin ELISA | BI-20422
• Periostin ELISA (Mouse/Rat) | BI-20433MR

 

FGF23 – a potential early biomarker cardiovascular events in patients with renal-cardiovascular disease

Fibroblast growth factor 23 (FGF23) is an endocrine hormone that regulates phosphate homeostasis by modulating renal phosphate reabsorption in the kidney. Circulating FGF23 increases with declining kidney function and high FGF23 and phosphate levels are related to cardiovascular disease and mortality (18, 19). 

• FGF23  (C-terminal) multimatrix ELISA | BI-20702
• FGF23 Intact ELISA | BI-20700

 

IL-6 – a biomarker of inflammation

 Interleukin-6 (IL-6) is a cytokine that plays a crucial role in inflammation and in the regulation of immune response. It is a signaling molecule that is involved in various physiological processes, including the activation of immune cells and the coordination of responses to infections or injury. IL-6 is implicated in diseases where inflammation is a prominent feature (20).

•  IL-6 ELISA | BI-IL6
• HIGHLY SENSITIVE – measurable values in serum and plasma samples
• EASY – ready to use calibrators and controls

 

 

Literature

1.  Epidemiology of chronic kidney disease: an update 2022. Kovesdy CP. Kidney Int Suppl (2011). 2022. 12(1):7-11. doi: 10.1016/j.kisu.2021.11.003. PMID: 35529086; PMCID: PMC9073222.
2. Emerging Biomarkers for Early Detection of Chronic Kidney Disease. Mizdrak M, Kumrić M, Kurir TT, Božić J. J Pers Med. 2022. 12(4):548. doi: 10.3390/jpm12040548. PMID: 35455664.
3. A defective angiogenesis in chronic kidney disease. Futrakul N, Butthep P, Laohareungpanya N, Chaisuriya P, Ratanabanangkoon K. Ren Fail. 2008. 30(2):215-7. doi: 0.1080/08860220701813335. PMID: 18300124.
4. Endostatin in Renal and Cardiovascular Diseases. Li M, Popovic Z, Chu C, Krämer BK, Hocher B., Kidney Dis (Basel). 2021.9;7(6):468-481. doi: 10.1159/000518221. PMID: 34901193.
5. Prognostic value of dynamic plasma endostatin for the prediction of mortality in acute kidney injury: A prospective cohort study. Jia HM, Zheng Y, Han Y, Ma WL, Jiang YJ, Zheng X, Guo SY, Zhang TE, Li WX., J Int Med Res. 2020.  48(7):300060520940856. PMID: 32691651.
6. Endostatin in chronic kidney disease: Associations with inflammation, vascular abnormalities, cardiovascular events and survival. Kanbay M, Afsar B, Siriopol D, Unal HU, Karaman M, Saglam M, Gezer M, Taş A, Eyileten T, Guler AK, Aydin İ, Oguz Y, Tarim K, Covic A, Yilmaz MI. Eur J Intern Med. 2016. 33:81-7. doi: 10.1016/j.ejim.2016.06.033. PMID: 27394925.
7. Validation of an enzyme-linked immunosorbent assay (ELISA) for quantification of endostatin levels in mice as a biomarker of developing glomerulonephritis. Wallwitz J, Aigner P, Gadermaier E, Bauer E, Casanova E, Bauer A, Stoiber D. PLoS One. 2019. 14(8):e0220935. doi: 10.1371/journal.pone.0220935. PMID: 31404120.
8. Chemical biology tools to study pantetheinases of the vanin family. Schalkwijk, J, Jansen, P. Biochem Soc Trans. 2014. 42, 1052–1055.
9. Urinary Vanin-1 As a Novel Biomarker for Early Detection of Drug-Induced Acute Kidney Injury. Hosohata K et al.J  Pharm  Exp Ther. 2012. 341, 656–662.
10. Proteomic identification of vanin-1 as a marker of kidney damage in a rat model of type 1 diabetic nephropathy. Fugmann T et al., Kidney Int. 2011. 80, 272–281.
11. The Usefulness of Vanin-1 and Periostin as Markers of an Active Autoimmune Process or Renal Fibrosis in Children with IgA Nephropathy and IgA Vasculitis with Nephritis-A Pilot Study. Mizerska-Wasiak M, Płatos E, Cichoń-Kawa K, Demkow U, Pańczyk-Tomaszewska M. J Clin Med. 2022. 11(5):1265. doi: 10.3390/jcm11051265. PMID: 35268356. 
12. Urinary vanin-1 for predicting acute pyelonephritis in young children with urinary tract infection: a pilot study. Krzemień G, Pańczyk-Tomaszewska M, Górska E, Szmigielska A. Biomarkers. 2021. 26(4):318-324.
13. Urinary vanin-1, tubular injury, and graft failure in kidney transplant recipients. Alkaff FF, Kremer D, Niekolaas TM, van den Born J, Rimbach G, Tseng TL, Berger SP, Bakker SJL, de Borst MH. Sci Rep. 2024. 4(1):2283. doi: 10.1038/s41598-024-52635-x. PMID: 38280883.
14. Development of an immunoassay that reveals altered uninary Vanin-1 in human with kidney disease. Wallwitz, J., Eichinger, B., Berg, G., Gadermaier, E., Himmler, G. 2018. Nephrology Dialysis Transplantation, Volume 33, Issue suppl_1, Page i126. 
15. Periostin in the Kidney. Wallace DP et al., Adv Exp Med Biol. 2019, 1132:99-112.
16. Periostin as a tissue and urinary biomarker of renal injury in type 2 diabetes mellitus. Satirapoj B et al., PLoS One. 2015, 17;10(4):e0124055.
17. Characterization of a sandwich ELISA for the quantification of all human periostin isoforms. Gadermaier E et al., J Clin Lab Anal. 2018, 32(2):e22252.
18. Higher fibroblast growth factor-23 increases the risk of all-cause and cardiovascular mortality in the community. Ärnlöv J, Carlsson AC, Sundström J, Ingelsson E, Larsson A, Lind L, Larsson TE.  Kidney Int. 2013. 83(1):160-6. doi: 10.1038/ki.2012.327. PMID: 22951890. 
19. Fibroblast growth factor-23, cardiovascular prognosis, and benefit of angiotensin-converting enzyme inhibition in stable ischemic heart disease. Udell JA, Morrow DA, Jarolim P, Sloan S, Hoffman EB, O’Donnell TF, Vora AN, Omland T, Solomon SD, Pfeffer MA, Braunwald E, Sabatine MS. J Am Coll Cardiol. 2014. 10;63(22):2421-8, doi: 10.1016/j.jacc.2014.03.026. PMID: 24727254; PMCID: PMC4213068.
20. Interleukin 6 and Cardiovascular Outcomes in Patients With Chronic Kidney Disease and Chronic Coronary Syndrome. Batra G, Ghukasyan Lakic T, Lindbäck J, Held C, White HD, Stewart RAH, Koenig W, Cannon CP, Budaj A, Hagström E, Siegbahn A, Wallentin L; STABILITY Investigators. JAMA Cardiol. 2021. 6(12):1440-1445. doi: 10.1001/jamacardio.2021.3079. PMID: 34431970; PMCID: PMC8387946.
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