Emerging Biomarkers in Kidney Disease

Chronic kidney disease (CKD) is a progressive condition affecting over 800 million individuals, accounting for roughly 13% of the global population (1). Over the past two decades, CKD has remained one of the leading causes of mortality. Due to its asymptomatic early stages, CKD is frequently diagnosed at advanced stages when severe complications have already developed. Recent research has identified new biomarkers linked to the underlying mechanisms of CKD, including chronic inflammation, tubular injury, and outcomes such as bone and mineral metabolism disorders, cardiovascular events, and overall mortality (2). The discovery and application of these emerging biomarkers, such as FGF23, Endostatin ,  Vanin-1 , and Periostin are  promising avenues for the early detection of e.g.  microvascular tissue injuries and renal tubular damage in drug-induced acute kidney injury and for the detection and improved management of CKD

Biomarker ELISA assay kits in Clinical Nephrology – FGF23 ∙ Endostatin ∙ Periostin ∙ Vanin-1

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Emerging Biomarkers in Kidney Disease

FGF23 ∙ Endostatin ∙ Periostin ∙ Vanin-1

 

Fibroblast Growth Factor 23 (FGF23) is a hormone primarily produced by osteocytes and osteoblasts in the bone. It plays a crucial role in regulating phosphate and vitamin D metabolism (3). FGF23 helps maintain phosphate balance by reducing phosphate reabsorption in the kidneys and decreasing the production of active vitamin D (calcitriol). Elevated levels of circulating FGF23 are associated with a higher risk of adverse outcomes, notably cardiovascular disease, in individuals with CKD as well as in the general population (4).

Vanin-1 is an enzyme belonging to the pantetheinase family, involved in the metabolism of pantothenic acid (vitamin B5). In recent years, Vanin-1 has emerged as a crucial factor in the development and progression of certain diseases, owing to its enzymatic activity. Additionally, Vanin-1 has been suggested to function as an oxidative stress sensor, as its expression increases in response to oxidative injury and it plays a role in maintaining redox homeostasis (5, 6). Vanin-1’s enzymatic activity influences oxidative stress regulation through cysteamine production, which can impact inflammation and tissue repair processes in the renal system.

Vanin-1 plays a significant role in kidney disease, particularly as a biomarker for the early detection of drug-induced acute kidney injury (7): elevated Vanin-1 levels in urine reflect ongoing oxidative stress and tissue damage in the kidneys. Due to its rapid release during kidney injury, Vanin-1 is viewed as a promising early biomarker for detecting renal damage, which could allow for earlier intervention and improved disease management. Continued research is actively investigating its complete diagnostic and therapeutic potential in kidney-related conditions.

Endostatin is an endogenous protein that functions as an inhibitor of angiogenesis, the formation of new blood vessels. It originates from collagen XVIII, a constituent of the extracellular matrix. Endostatin is crucial in controlling blood vessel growth, which is vital in processes such as cancer development, wound repair, and vascular disorders (8). Additionally, it is being studied as a biomarker for several diseases characterized by abnormal blood vessel formation (9).

In kidney disease, Endostatin was strongly associated with kidney outcomes in patients with type 2 diabetes: participants in the highest quartile of plasma Endostatin, had approximately four times the risk of the kidney outcome compared to those in the lowest quartile (10). In addition, elevated levels of plasma Endostatin have been shown to be linked to chronic kidney disease: the findings suggest that higher plasma Endostatin levels are significantly and independently linked to CKD (11).

Periostin is a matricellular protein that plays a crucial role in tissue repair, remodeling, and cell adhesion. Analysis of kidney biopsies from healthy donors revealed a consistent presence of Periostin at the vascular pole of the glomerulus and surrounding Bowman’s capsule, while it was absent in the tubules. Interestingly, some other studies found no periostin expression in kidney samples from individuals without renal pathology (12). However, recent studies have shown that Periostin is abnormally expressed in various types of chronic kidney disease (CKD), with its levels correlating to the extent of interstitial fibrosis and the deterioration of kidney function (13).

Literature

1. New and Emerging Biomarkers in Chronic Kidney Disease. Dopierała M, Nitz N, Król O, Wasicka-Przewoźna K, Schwermer K, Pawlaczyk K. Biomedicines. 2025; 13(6):1423. https://doi.org/10.3390/biomedicines13061423
2. Biomarkers of Acute and Chronic Kidney Disease. Zhang WR, Parikh CR. Annu Rev Physiol. 2019 Feb 10;81:309-333. doi: 10.1146/annurev-physiol-020518-114605. PMID: 30742783; PMCID: PMC7879424.
3. Regulation of FGF23 production and phosphate metabolism by bone-kidney interactions. Agoro R, White KE.Nat Rev Nephrol. 2023 Mar;19(3):185-193. doi: 10.1038/s41581-022-00665-x. Epub 2023 Jan 9. PMID: 36624273.
4. FGF23 and Klotho in chronic kidney disease. Olauson H, Larsson TE.Curr Opin Nephrol Hypertens. 2013 Jul;22(4):397-404. doi: 10.1097/MNH.0b013e32836213ee. PMID: 23666415.
5. Role of the Vnn1 pantetheinase in tissue tolerance to stress. Biochem Soc Trans. Naquet P, Pitari G, Duprè S, Galland F. 2014 Aug;42(4):1094-100. doi: 10.1042/BST20140092. PMID: 25110008.
6. Oxidative Stress in the Pathophysiology of Kidney Disease: Implications for Noninvasive Monitoring and Identification of Biomarkers. Gyurászová M, Gurecká R, Bábíčková J, Tóthová Ľ.Oxid Med Cell Longev. 2020 Jan 23;2020:5478708. doi: 10.1155/2020/5478708. PMID: 32082479; PMCID: PMC7007944.
7. Urinary vanin-1 associated with chronic kidney disease in hypertensive patients: A pilot study. Hosohata K et al.,  J Clin Hypertens (Greenwich). 2020 Aug;22(8):1458-1465
8. Endostatin in Renal and Cardiovascular Diseases. Li M, Popovic Z, Chu C, Krämer BK, Hocher B.Kidney Dis (Basel). 2021 Sep 9;7(6):468-481. doi: 10.1159/000518221. PMID: 34901193; PMCID: PMC8613550.
9. Endostatin in fibrosis and as a potential candidate of anti-fibrotic therapy. Zhang Z, Liu X, Shen Z, Quan J, Lin C, Li X, Hu G. Drug Deliv. 2021 Dec;28(1):2051-2061. doi: 10.1080/10717544.2021.1983071. PMID: 34595978; PMCID: PMC8491667.
10. Plasma endostatin predicts kidney outcomes in patients with type 2 diabetes. Chauhan K, Verghese DA, Rao V, Chan L, Parikh CR, Coca SG, Nadkarni GN. Kidney Int. 2019 Feb;95(2):439-446. doi: 10.1016/j.kint.2018.09.019. Epub 2018 Dec 24. PMID: 30591223; PMCID: PMC6342645.
11. Elevated plasma levels of endostatin are associated with chronic kidney disease. Chen J, Hamm LL, Kleinpeter MA, Husserl F, Khan IE, Chen CS, Liu Y, Mills KT, He C, Rifai N, Simon EE, He J.Am J Nephrol. 2012;35(4):335-40. doi: 10.1159/000336109. Epub 2012 Mar 27. PMID: 22456114; PMCID: PMC3362190.
12. The role of periostin in kidney diseases. Turczyn A, Pańczyk-Tomaszewska M. Cent Eur J Immunol. 2021;46(4):494-501. doi: 10.5114/ceji.2021.110317. Epub 2021 Nov 1. PMID: 35125949; PMCID: PMC8808300.
13. Periostin in the Kidney. Wallace DP. Adv Exp Med Biol. 2019;1132:99-112. doi: 10.1007/978-981-13-6657-4_11. PMID: 31037629.