Novel Biomarkers in Nephrology
Chronic kidney disease (CKD) is a major global health concern, affecting roughly 10 percent of the population, totaling more than 850 million people (1, 2).
CKD involves progressive nephron loss, compensatory hyperfiltration in remaining nephrons, and subsequent glomerulosclerosis (3, 4). This process is often driven by etiologies such as diabetic nephropathy (5), glomerulonephritis, and other systemic or intrinsic renal diseases.
Biochemical hallmarks include decreased clearance of nitrogenous waste products such as urea and creatinine, leading to azotemia (6). The disruption of electrolyte homeostasis may result in hyperkalemia, metabolic acidosis, and disturbances in calcium-phosphate balance, contributing to secondary hyperparathyroidism and vascular calcification (7).
CKD progression is associated with increased cardiovascular morbidity and mortality (8).The disease course can be monitored via estimated glomerular filtration rate (eGFR), albuminuria levels, and imaging findings of renal morphology (9).
Role of the Kidneys
Kidneys are vital organs that regulate fluid balance, blood pressure and produce hormones that stimulate the production of red blood cells . Kidney disease is a condition in which kidneys lose their ability to effectively filter waste products and excess fluids from the blood. Kidney disease commonly leads to a decline in kidney function that may lead to kidney failure, characterized by the complete loss of kidney function. At this stage dialysis or kidney transplantation become the only treatment option.
Kidney problems can emerge suddenly (acute) or gradually over time (chronic). Various conditions, diseases and medications can contribute to acute and chronic kidney problems. Chronic kidney disease (CKD) is characterized by a prolonged period of kidney abnormalities that last for more than three months (10), whereas acute kidney disease – acute kidney injury (AKI) is characterized by a sudden loss of excretory kidney function (11).
Other forms of kidney disease include polycystic kidney disease (PKD) a genetic disorder that leads to kidney enlargement and impaired kidney function over time and glomerulonephritis (GN) (12). GN is a group of diseases characterized by inflammation of the glomeruli, the filtration units of the kidney (13).
Novel Biomarkers in Nephrology
FGF23 • SCLEROSTIN • ENDOSTATIN • VANIN-1 • PERIOSTIN
Advancements in nephrology have led to the identification of several emerging biomarkers that enhance early detection, prognosis, and understanding of kidney injury and disease progression. These novel biomarkers could provide more sensitive and specific insights compared to traditional measures like serum creatinine and albuminuria.
FGF23 – in Acute Kidney Injury
Fibroblast growth factor 23 (FGF23) is a hormone produced by bone that plays a key role in regulating phosphate excretion by the kidneys. In the context of kidney disease, declining renal function leads to an increase in serum phosphate levels, which in turn stimulates the secretion of FGF23. Elevated phosphate levels are also frequently observed in patients with acute kidney injury (AKI) (14).
FGF23 as a Marker of Adverse Outcomes in AKI
Levels of FGF23 rise rapidly during AKI and have been associated with the need for renal replacement therapy (14-17). Furthermore, FGF23 levels possess prognostic value, as demonstrated in a large study in over 1500 patients with AKI (16).
FGF23 and Sclerostin – Novel Biomarkers in Diabetic Kidney Disease
Growing evidence indicates that FGF23 may be involved in type 2 diabetes (T2DM), as levels of FGF23 are elevated in these patients—even among those with normal kidney function—when compared to the general population (18). A recent study demonstrated phosphate-independent effects of FGF23 following glucose loading, showing associations between FGF23 and levels of glucose, insulin, and proinsulin, as well as obesity (19). Additionally, FGF23 has been linked to the development of gestational diabetes mellitus (20).
Sclerostin is a protein produced by bone cells that inhibits bone formation. Recent research suggests that sclerostin also influences lipid and glucose metabolism, as serum sclerostin levels are negatively associated with insulin sensitivity in obese women, but not in lean women (21). Elevated sclerostin levels have also been observed in individuals with prediabetes (22).
FGF23 and Sclerostin can reliable by measured with conventional ELISA assays from BIOMEDICA.
- FGF23 (C-terminal) |BI-20700 and FGF23 intact ELISA |BI-20700
- Sclerostin ELISA |BI-20492 and Bioactive Sclerostin ELISA |BI-20472
Endostatin – A Potential Biomarker for Renal Fibrosis, CKD, and Prognosis in AKI
Endostatin is a protein found in the extracellular matrix that is expressed during the progression of renal fibrosis. Elevated serum levels of endostatin may result from increased degradation of the extracellular matrix in patients with chronic kidney disease (CKD) (23, 24). Additionally, endostatin has been explored as a prognostic marker in individuals with acute kidney injury (AKI) (25) and has been independently linked to the occurrence of cardiovascular events in CKD patients (26).
Endostatin can reliably be quantified in serum, plasma and urine samples:
- Endostatin ELISA | BI-20742
VANIN-1 – A Potential Biomarker for Acute Kidney Injury and Drug-Induced Renal Injury
Vascular non-inflammatory molecule-1 (Vanin-1) is highly expressed in the kidney (27) and has been proposed as a biomarker for acute kidney injury (AKI) and drug-induced renal damage (28). It has also been identified as an indicator of kidney injury in a rat model of type 1 diabetic nephropathy (29).
Urinary Vanin-1 has been studied in children with renal fibrosis (30) and as a potential predictor of acute pyelonephritis in young children with urinary tract infections (31). More recently, research has explored the role of urinary Vanin-1 in kidney transplant recipients (32).
Vanin-1 can easily be measured with a conventional ELISA assay:
PERIOSTIN – A Potential Early Biomarker of Renal Tubular Injury
Periostin is a matricellular protein involved in tissue remodeling and wound healing processes. Research has shown that Periostin expression in the kidney correlates with the extent of interstitial fibrosis and a decline in renal function (34). Elevated levels of urinary Periostin have been observed in patients with type 2 diabetes, even before the appearance of microalbuminuria. These findings suggest that urinary Periostin may serve as an early marker of renal tubular injury (35).
Periostin can be accurately measured in serum, plasma, and urine through a fully validated ELISA assay (36).
- Periostin ELISA | BI-20422
BIOMEDICA – HIGH QUALITY ASSAYS – Fully validated according to international quality guidelines
- TRUSTED – Widely cited in over 1800 publications
Biomedica´s Complete ready-to-use ELISA kits
See our brochure on Biomarkers in Clinical Nephrology
Literature
- ISN- International Society of Nephrology
- Global Facts: About Kidney Disease
- Remnant nephron physiology and the progression of chronic kidney disease. Schnaper HW. Pediatr Nephrol. 2014; 29(2):193-202. PMID: 23715783.
- Mechanisms of progression of chronic kidney disease. Fogo AB. Pediatr Nephrol. 2007; 22(12):2011-22. PMID: 17647026.
- Classification and Differential Diagnosis of Diabetic Nephropathy. Qi C et al., J Diabetes Res. 2017; 2017:8637138. PMID: 28316995.
- Azotemia. Tyagi A, Aeddula NR. 2023; In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan–. PMID: 30844172.
- Understanding Vascular Calcification in Chronic Kidney Disease: Pathogenesis and Therapeutic Implications. Siracusa C et al., Int J Mol Sci. 2024; 25(23):13096. PMID: 39684805.
- The Dual Burden: Exploring Cardiovascular Complications in Chronic Kidney Disease. Biomolecules. Caturano A et al., 2024: 14(11):1393. PMID: 39595570.
- The KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease (CKD), 2024. Chronic Kidney Disease Diagnosis and Management: A Review. Chen TK, Knicely DH, Grams ME. JAMA. 2019 Oct 1;322(13):1294-1304. doi: 10.1001/jama.2019.14745. PMID: 31573641; PMCID: PMC7015670.
- Chronic Kidney Disease Diagnosis and Management: A Review. Chen TK et al., JAMA. 2019; 322(13):1294-1304. PMID: 31573641.
- Acute kidney injury. Kellum JA et al.,. Nat Rev Dis Primers. 2021; 15;7(1):52. PMID: 34267223.
- Treatment of Autosomal-Dominant Polycystic Kidney Disease. Jdiaa SS et al.,. Am J Kidney Dis. 2025; 85(4):491-500. PMID: 39424253.
- Advances in primary glomerulonephritis. Ellison B et al., J Hosp Med (Lond). 2024; 30;85(7):1-11. PMID: 39078905.
- Fibroblast Growth Factor 23 and Klotho in AKI. Christov M, Neyra JA, Gupta S, Leaf DE. Semin Nephrol. 2019 Jan;39(1):57-75. doi: 10.1016/j.semnephrol.2018.10.005. PMID: 30606408.
- Fibroblast Growth Factor 23 Regulation and Acute Kidney Injury. Zhou W et al., Nephron. 2022;146(3):239-242. PMID: 34284404.
- Fibroblast growth factor 23 associates with death in critically ill patients. Leaf DE et al., Am Clin J Am Soc Nephrol. 2018. 13(4):531–41.
- FGF-23 levels in patients with AKI and risk of adverse outcomes. Leaf DE et al., Clin J Am Soc Nephrol. 2012. 7(8):1217-23.
- Earlier onset and greater severity of disordered mineral metabolism in diabetic patients with chronic kidney disease Wahl P et al. 2012. Diabetes Care 35, 994–1001.
- Fibroblast Growth Factor 23, Glucose Homeostasis, and Incident Diabetes: Findings of 2 Cohort Studies, Amarens van der Vaart et al., 2023. The Journal of Clinical Endocrinology & Metabolism, 108, 10, e971–e978.
- Fibroblast growth factor 23 is associated with the development of gestational diabetes mellitus. Hocher CF et al., Diabetes Metab Res Rev. 2023. 8:e3704. PMID: 37553983.
- Serum sclerostin is negatively associated with insulin sensitivity in obese but not lean women. Aznou A et al., Endocr Connect. 2021. 10(2):131-138. PMID: 33480863.
- Sclerostin and Insulin Resistance in Prediabetes: Evidence of a Cross Talk Between Bone and Glucose Metabolism. Daniele G et al., Diabetes Care. 2015. 38(8):1509-17. PMID: 26084344.
- A defective angiogenesis in chronic kidney disease. Futrakul N et al., Ren Fail. 2008. 30(2):215-7. PMID: 18300124.
- Endostatin in Renal and Cardiovascular Diseases. Li M et al., Kidney Dis (Basel). 2021.9;7(6):468-481. PMID: 34901193.
- Prognostic value of dynamic plasma endostatin for the prediction of mortality in acute kidney injury: A prospective cohort study. Jia HM et al., J Int Med Res. 2020. 48(7):300060520940856. PMID: 32691651.
- Endostatin in chronic kidney disease: Associations with inflammation, vascular abnormalities, cardiovascular events and survival. Kanbay M et al., Eur J Intern Med. 2016. 33:81-7. PMID: 27394925.
- Chemical biology tools to study pantetheinases of the vanin family. Schalkwijk, J, Jansen, P. Biochem Soc Trans. 2014. 42, 1052–1055.
- 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.
- 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.
- 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 et al., J Clin Med. 2022. 11(5):1265. PMID: 35268356.
- Urinary vanin-1 for predicting acute pyelonephritis in young children with urinary tract infection: a pilot study. Krzemień G et al., Biomarkers. 2021. 26(4):318-324.
- Urinary vanin-1, tubular injury, and graft failure in kidney transplant recipients. Alkaff FF et al., Sci Rep. 2024. 4(1):2283. PMID: 38280883.
- Development of an immunoassay that reveals altered uninary Vanin-1 in human with kidney disease. Wallwitz, J., et al.,. 2018. Nephrology Dialysis Transplantation, Volume 33, Issue suppl_1, Page i126.
- Periostin in the Kidney. Wallace DP et al., Adv Exp Med Biol. 2019, 1132:99-112.
- 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.
- 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.