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Biomedica’s FGF23 ELISA kits now available for the US Biotech community at 25% trial discount.

FGF23 is an endocrine hormone regulating phosphate homeostasis by modulating renal phosphate reabsorption, vitamin D metabolism and parathyroid hormone (PTH) secretion. Epidemiological data suggest that higher FGF23 concentrations are associated with all-cause mortality, cardiovascular mortality, a higher risk of myocardial infarction, stroke and heart failure.
➡️ Learn more: FGF23 – An Overview

Biomedica’s FGF23 (intact) and FGF23 (C-terminal) ELISA kits

Biomedica’s FGF23 ELISA kits, widely recognized in Europe and Asia, are now also available in the US.

💡 What makes them a game-changer?

✓ MULTI-MATRIX: for plasma, serum, cell-culture
✓ CONVENIENT: 50 µl sample/well, all buffers included
✓ RELIABLE: validated following quality guidelines
✓ COMPARABLE: good correlation with existing kits
✓ EASY HANDLING: 7 prediluted standards, 2 controls
✓ TRUSTED: cited in more than 80 publications

Biomedica offers world-leading quality products at competitive pricing.

🚨 Don’t miss out and order your trial kit at 25% discount. Promotion valid until April 15, 2025.

➡️ Contact our US partners for your study quote.

Related kits: Sclerostin . OPG . Periostin . Vanin-1 . NT-proBNP . NT-proANP

Fibroblast growth factor 23 (FGF23) is a hormone primarily known for its role in mineral metabolism, particularly in regulating phosphate homeostasis.

FGF23 is primarily produced in the bone by osteocytes and acts on the kidneys to regulate phosphate reabsorption and vitamin D metabolism. FGF23 helps to maintain phosphate levels within the normal range by promoting urinary phosphate excretion and inhibiting the production of vitamin D (1). The dysregulation of FGF23 can lead to conditions such as hypophosphatemic rickets and hyperphosphatemia.

FGF23 and its effects on the heart

Numerous clinical studies have shown that elevated plasma level concentrations of FGF23 are linked to left ventricular hypertrophy (LVH), heart failure, and increased mortality in the general population, particularly among individuals with chronic kidney disease (CKD) (2). The exact mechanisms by which FGF23 affects the heart are still under investigation, but several possible pathways have been suggested. For instance, FGF23 may induce hypertrophy directly through binding to specific FGF23 receptors expressed by cardiomyocytes in the heart. FGF23 may also promote hypertrophy indirectly by altering mineral metabolism, leading to increased circulating levels of phosphorus, which can contribute to cardiovascular damage.

In addition, FGF23 may have effects on the endothelium, the inner lining of blood vessels. It has been suggested that FGF23 may hinder endothelial function and promote vascular calcification, thereby contributing to the development of cardiovascular disease. Further research is needed to fully understand the exact mechanisms through which FGF23 affects the heart and its role in cardiovascular disease (3).

Measurement of FGF23

FGF23 concentrations can be measured with blood tests. The most common way for measuring FGF23 is with a conventional ELISA assay (enzyme-linked immunosorbent assay). The ELISA utilizes specific antibodies that recognize and bind FGF23 molecules present in the sample. The intensity of the antibody-antigen reaction is measured, allowing an easy quantification of FGF23 in the respective sample.

Currently there are two different assays that allow the measurement of FGF23 in blood samples:

Intact FGF23 Assays

intact FGF23 represents the full length, biologically active form of the hormone. It consists of the complete FGF23 protein structure without being enzymatically cleaved.

The BIOMEDICA FGF23 (intact) human ELISA (cat. no. BI-20700)

is a sandwich-based immunoassay with an anti-human FGF23 capture antibody recognizing a structural epitope in the N-terminal part of FGF23 and a detection antibody binding to the C-terminal part of mature FGF23.

FGF23 C-terminal Assays
The c-terminal fragments of FGF23 are the result of the enzymatic cleavage of the intact FGF23 molecule.
Of note: all commercially available FGF23 c-terminal assays detect both c-terminal FGF23 fragments as well as the intact FGF23 molecule!

The BIOMEDICA FGF23 (C-terminal) human multi-matrix ELISA (cat. no. BI-20702)

is a sandwich-based immunoassayw hich recognizes multiple epitopes in the C-terminal part of FGF23.

Features & Benefits

Validated ELISA kits following international quality guidelines
Biomedica´s FGF23 assay have been used in numerous studies

validation reports and citations can be downloaded here

Literature

Biology of Fibroblast Growth Factor 23: From Physiology to Pathology. Courbebaisse M, Lanske B. Cold Spring Harb Perspect Med. 2018 May 1;8(5):a031260. doi: 10.1101/cshperspect.a031260. PMID: 28778965; PMCID: PMC5932574.
Direct and indirect effects of fibroblast growth factor 23 on the heart. Nakano T, Kishimoto H, Tokumoto M Front Endocrinol (Lausanne). 2023 Feb 24;14:1059179. doi: 10.3389/fendo.2023.1059179. PMID: 36909314; PMCID: PMC9999118.
FGF23 directly impairs endothelium-dependent vasorelaxation by increasing superoxide levels and reducing nitric oxide bioavailability. Silswal N, Touchberry CD, Daniel DR, McCarthy DL, Zhang S, Andresen J, Stubbs JR, Wacker MJ. Am J Physiol Endocrinol Metab. 2014 Sep 1;307(5):E426-36. doi: 10.1152/ajpendo.00264.2014. Epub 2014 Jul 22. PMID: 25053401; PMCID: PMC4154070.

Heart failure (HF) is a leading cause of death in individuals with chronic kidney disease (CKD). CKD is also known as a “silent killer” as many people live with the disease without developing symptoms. CKD is a progressive disease and it is estimated that around 10% of the adult general population worldwide is affected (1). A large number of individuals are undiagnosed as demonstrated in a study from the UK in 3200 participants aged over 60 years (2).

FGF23 and Risk of Heart Failure

What is CKD?

Chronic kidney disease is a condition where kidney function gradually declines. The kidneys play a crucial role in filtering waste from the blood with the help of nephrons. A constant increase in damaged and non-functioning nephrons lead to the progression of the disease.

How does CKD cause Heart Failure?

Impaired kidney function places an additional strain on the heart, as it needs to pump harder to get blood to the kidneys. Changes in blood pressure is also a complication in CKD that can ultimately lead to heart disease. One suggested mechanism for the development of HF in CKD patients is linked to highly elevated levels of FGF23 (3).

What is the role of FGF23 in Heart Failure?

Fibroblast growth factor 23 (FGF 23) is a bone-derived hormone that regulates phosphate and vitamin D. In individuals with CKD, circulating FGF23 blood levels gradually increase with declining kidney function. In patients with end-stage renal disease, FGF23 levels are highly elevated up to 1000-fold above the normal range (4).

Numerous studies indicate that high FGF23 concentrations have a direct effect on the heart and the cardiovascular system. Elevated FGF23 levels have been linked to an increased risk of cardiovascular events, including heart failure, cardiovascular mortality, and left ventricular hypertrophy (5, 6). The precise mechanisms by which FGF23 impacts the heart are still being explored. One potential pathway could be linked to the discovery of FGF23 receptors expressed in the heart by cardiomyocytes. Specific binding of FGF23 to these receptors may directly induce hypertrophy. Additional pathways are under investigation.

In a recent large multicenter prospective cohort study in over 3500 participants, researchers investigated the relationship between elevated FGF23 levels and the risk of HF in individuals with varies HF subtypes. The authors concluded that elevated FGF23 levels were associated with increased risks for all HF subtypes highlighting the need for further research on FGF23 as a potential target in HF prevention in individuals with chronic kidney disease (3).

What are the methods for measuring FGF23?

Circulating blood FGF23 levels can be measured with immunoassays. A commonly employed technique is the ELISA assay (enzyme linked immunosorbent assay).

FGF23 ELISA assays employ specific antibodies designed to detect FGF23 present in the sample (serum / plasma). Currently, two commercially available assays are used for the measurement of circulating FGF23 in blood samples (7):

ELISA for measuring Intact FGF23

The full length, biologically active form of the hormone is intact FGF23 (iFGF23), consisting of the complete and full-length FGF23 protein structure without enzymatical cleavage. The ELISA utilizes two antibodies that target the N-terminal part and the C-terminal domain of the FGF23 molecule, respectively.

FGF23 intact ELISA assay – binding region of antibodies utilized in the BIOMEDICA kit

ELISA for measuring FGF23 C-terminal

C-terminal fragments of FGF23 (cFGF23) result from the enzymatic cleavage of the intact FGF23 molecule. The ELISA utilizes two antibodies that bind to epitopes that are located in the c-terminal domain of the FGF23 molecule.

FGF23 (C-terminal) ELISA assay – binding region of antibodies utilized in the BIOMEDICA kit

OF NOTE: all FGF23 c-terminal assays that are commercially available detect both c-terminal FGF23 fragments as well as the intact FGF23 molecule (7).

BIOMEDICA offers two ELISA kits that reliably quantify FGF23 concentrations in human serum and plasma samples:

FGF23 – complete ready to use ELISA kits – User-Friendly and Reliable

FGF23 intact ELISA (cat. no. BI-20700)
FGF23 (C-terminal) ELISA (cat. no. BI-20702)

BIOMEDICA FGF23 intact ELISA assay (#BI-20700)

BIOMEDICA FGF23 multimatrix (C-terminal) ELISA assay (#BI-20702)

Validated FGF23 ELISA kits according to international quality guidelines
Numerous citations /references in top-ranking journals

FGF23 ELISA assays are Developed & Manufactured by Biomedica

Literature

Epidemiology of chronic kidney disease: an update 2022. Kovesdy CP. Kidney Int Suppl (2011). 2022. 12(1):7-11. PMID: 35529086; PMCID: PMC9073222
Prevalence of chronic kidney disease in the community using data from OxRen: a UK population-based cohort study. Hirst JAet al., Br J Gen Pract. 2020. 26;70(693):e285-e293. PMID: 32041766; PMCID: PMC7015167.
Chronic Renal Insufficiency Cohort (CRIC) study investigators. Fibroblast Growth Factor 23 and Risk of Heart Failure Subtype: The CRIC (Chronic Renal Insufficiency Cohort) Study. Leidner Aset al.,Kidney Med. 2023. 5(11):100723. PMID: 37915961; PMCID: PMC10616385.
Fibroblast growth factor-23 mitigates hyperphosphatemia but accentuates calcitriol deficiency in chronic kidney disease. Gutierrez O et al., Journal of the American Society of Nephrology. 2005;16(7):2205–2215.
FGF23 and Cardiovascular Risk. Prié D. Ann Endocrinol (Paris). 2021. 82(3-4):141-143. PMID: 32950228.
Paracrine Effects of FGF23 on the Heart. Front Endocrinol (Lausanne). Leifheit-Nestler M, Haffner D 2018. 28;9:278. PMID: 29892269; PMCID: PMC5985311.
The Measurement and Interpretation of Fibroblast Growth Factor 23 (FGF23) Concentrations. Calcif Tissue Int. Heijboer AC, Cavalier E. 2023 Feb;112(2):258-270. PMID: 35665817; PMCID: PMC9859838.

November is “Diabetes Awareness Month” raising attention to this fast growing and life-threating epidemic. Patients suffering from diabetes have a risk of additional health complications, including heart disease, strokes, and diabetic kidney disease (DKD). People who develop DKD mostly have few symptoms in the early stage of the disease, although the risk of developing severe kidney damage is very high. High blood sugar levels may damage the small blood vessels in the kidney leading to kidney damage, kidney failure, and high blood pressure (1).

FGF23 and Sclerostin – novel biomarkers in diabetic kidney disease

Traditionally, the bone is regarded as a structural organ that gives the human body support and facilitates physical movement. However, bone is also a source of various hormones including fibroblast growth factor 23 and sclerostin that play an important role in regulating glucose metabolism and DKD (2).

FGF23 and Sclerostin – novel biomarkers in diabetic kidney disease

FGF23 and Sclerostin – bone derived hormones regulate glucose metabolism

Fibroblast growth factor 23 (FGF23) is a bone-derived protein that regulates phosphate metabolism, by inhibiting renal phosphate reabsorption. There is increasing evidence that FGF23 plays a role in type 2 diabetes (T2DM), as FGF23 levels are elevated in these patients, even in individuals with preserved kidney function when compared to the general population (3). Phosphate independent effects on FGF23 following glucose loading were shown in a recent study demonstrating that FGF23 is associated with glucose, insulin and proinsulin levels, as well as obesity (4 ). Furthermore, FGF23 has also been shown to be associated with the development of gestational diabetes mellitus (5).

Sclerostin is a protein that is produced by bone cells that inhibits bone formation. Recent research suggests that Sclerostin also plays a role in lipid and glucose metabolism as serum sclerostin is negatively associated with insulin sensitivity as measured in obese, but not lean women (5). Sclerostin levels have also been shown to be increased in individuals with prediabetes (6).

FGF23 and Sclerostin can reliable by measured with conventional ELISA assays from BIOMEDICA.

FGF23 (C-terminal), #BI-20700 and FGF23 intact ELISA, #BI-20700

RELIABLE – validated following international quality guidelines
CITED in over 60 publications
EASY – 8 standards and 2 controls included
For SERUM & PLASMA samples
HIGH QUALITY guaranteed!

Sclerostin ELISA, #BI-20492

MOST referenced in more than 280 citations
LOW sample volume – 20µl sample /well
For SERUM & PLASMA samples
RELIABLE – full validation package

Bioactive Sclerostin ELISA, BI-20472

CHARACTERIZED ANTIBODIES – targeting the receptor binding region
RIGOROUSLY validated for clinical samples
LOW sample volume – 20µl sample /well

Literature

Renal microvascular disease predicts renal function in diabetes. Futrakul N, Futrakul P. Ren Fail. 2012;34(1):126-9. doi: 10.3109/0886022X.2011.623490. Epub 2011 Oct 20. PMID: 22010784.
The Emerging Role of Bone-Derived Hormones in Diabetes Mellitus and Diabetic Kidney Disease. Li Y, Gu Z, Wang J, Wang Y, Chen X, Dong B. Front Endocrinol (Lausanne). 2022 Jul 11;13:938830. doi: 10.3389/fendo.2022.938830. PMID: 35966090; PMCID: PMC9367194.
Earlier onset and greater severity of disordered mineral metabolism in diabetic patients with chronic kidney disease Wahl P., Xie H., Scialla J., Anderson C.A.M., Bellovich K., Brecklin C.et al.. (2012) Diabetes Care 35, 994–1001 10.2337/dc11-2235
Fibroblast Growth Factor 23, Glucose Homeostasis, and Incident Diabetes: Findings of 2 Cohort Studies, Amarens van der Vaart, Coby Eelderink, André P van Beek, Stephan J L Bakker, Peter R van Dijk, Martin H de Borst, The Journal of Clinical Endocrinology & Metabolism, Volume 108, Issue 10, October 2023, Pages e971–e978, https://doi.org/10.1210/clinem/dgad246.
Fibroblast growth factor 23 is associated with the development of gestational diabetes mellitus. Hocher CF, Chen X, Zuo J, Horvathova K, Hocher B, Krämer BK, Chu C. Diabetes Metab Res Rev. 2023 Aug 8:e3704. doi: 10.1002/dmrr.3704. Epub ahead of print. PMID: 37553983.
Serum sclerostin is negatively associated with insulin sensitivity in obese but not lean women. Aznou A, Meijer R, van Raalte D, den Heijer M, Heijboer A, de Jongh R. Endocr Connect. 2021 Feb;10(2):131-138. doi: 10.1530/EC-20-0535. PMID: 33480863; PMCID: PMC7983521.
Sclerostin and Insulin Resistance in Prediabetes: Evidence of a Cross Talk Between Bone and Glucose Metabolism. Daniele G, Winnier D, Mari A, Bruder J, Fourcaudot M, Pengou Z, Tripathy D, Jenkinson C, Folli F. Diabetes Care. 2015 Aug;38(8):1509-17. doi: 10.2337/dc14-2989. Epub 2015 Jun 17. PMID: 26084344.

Fibroblast growth factor 23 (FGF23) is a protein that is produced by osteocytes, which are specialized cells found in bone tissue (1). FGF23 plays a key role in maintaining the balance of phosphate and vitamin D in the body (2). FGF23 primary function is to regulate blood phosphate levels by stimulating the removal of excess phosphate by the kidneys.

Elevated FGF23 levels in the bloodstream lead to a reduction in blood phosphate levels, a decrease in 1,25(OH)2 vitamin D, and the development of osteomalacia (3).

In addition to its known effects on bone and mineral regulation, it has been suggested that FGF23 may play a significant role in the development of type 2 diabetes mellitus (4). Findings showed that FGF23 is linked to indicators of obesity, metabolic syndrome and insulin levels.

FGF23 associated with the development of gestational diabetes

Gestational diabetes mellitus (GDM) is a type of diabetes that can develop during pregnancy in women who do not have existing diabetes. It is defined as glucose intolerance that is recognized first during pregnancy. GDM and impaired glucose tolerance during pregnancy are associated with persistent metabolic dysfunction three years after delivery, independent of other clinical risk factors (5).

FGF23 associated with the development of gestational diabetes

In the current study by Hocher CF and colleagues (6), the researchers investigated the association of maternal and foetal FGF23 with gestational diabetes mellitus (GDM) in a German birth cohort. Both FGF23 (c-terminal) and FGF23 intact levels were analysed in 826 random mother/child pairs with ELISA assays from BIOMEDICA. Of note: c-terminal FGF23 ELISA kits recognize both full-length intact FGF23 and c-terminal fragments of FGF23, and intact FGF23 assays solely detect full-length intact FGF23. The use of both assays in the current study is based on evidence from head to head comparison studies where clinical associations were reported based on the FGF23 assays used ( 7, 8). In summary, the study of a representative German birth cohort showed that maternal but not foetal iFGF23 is independently associated with GDM (6).

FGF23 can reliably be measured by ELISA assay

FGF23 intact ELISA, cat. no. BI-20700

FGF23 (c-terminal) ELISA, cat. no. BI-20702

BIOMEDICA´s FGF23 ELISA Kits:

Low sample volume: 50µl / well
For plasma (EDTA, citrate, heparın), serum, urine, cell culture supernatant
Kit controls (high and low) included
Full validation following international quality guidelines
Numerous top journal citations

BIOMEDICA FGF23 ELISA assay

Literature:

The osteocyte: A multifunctional cell within the bone. Tresguerres FGF, Torres J, López-Quiles J, Hernández G, Vega JA, Tresguerres IF. Ann Anat. 2020 Jan;227:151422. doi: 10.1016/j.aanat.2019.151422. Epub 2019 Sep 26. Erratum in: Ann Anat. 2020 Jul;230:151510. PMID: 31563568.
Role of phosphate sensing in bone and mineral metabolism. Chande S, Bergwitz C. Nat Rev Endocrinol. 2018 Nov;14(11):637-655. doi: 10.1038/s41574-018-0076-3. PMID: 30218014; PMCID: PMC8607960.
FGF23 and Hypophosphatemic Rickets/Osteomalacia. Takashi Y, Kawanami D, Fukumoto S. Curr Osteoporos Rep. 2021 Dec;19(6):669-675. doi: 10.1007/s11914-021-00709-4. Epub 2021 Nov 10. PMID: 34755323.
The Emerging Role of Bone-Derived Hormones in Diabetes Mellitus and Diabetic Kidney Disease. Li Y, Gu Z, Wang J, Wang Y, Chen X, Dong B. Front Endocrinol (Lausanne). 2022 Jul 11;13:938830. doi: 10.3389/fendo.2022.938830. PMID: 35966090; PMCID: PMC9367194.
Gestational glucose tolerance and maternal metabolic profile at 3 years postpartum. Stuebe AM, Mantzoros C, Kleinman K, Gillman MW, Rifas-Shiman S, Seely EW, Rich-Edwards J. Obstet Gynecol. 2011 Nov;118(5):1065-1073. doi: 10.1097/AOG.0b013e3182325f5a. PMID: 22015874; PMCID: PMC3268071.
Fibroblast growth factor 23 is associated with the development of gestational diabetes mellitus. Hocher CF, Chen X, Zuo J, Horvathova K, Hocher B, Krämer BK, Chu C. Diabetes Metab Res Rev. 2023 Aug 8:e3704. doi: 10.1002/dmrr.3704. Epub ahead of print. PMID: 37553983.
C-terminal and intact FGF23 in kidney transplant recipients and their associations with overall graft survival. Chu C, Elitok S, Zeng S, Xiong Y, Hocher CF, Hasan AA, Krämer BK, Hocher B. BMC Nephrol. 2021 Apr 8;22(1):125. doi: 10.1186/s12882-021-02329-7. PMID: 33832449; PMCID: PMC8033679.
Fibroblast growth factor 23 concentrations and modifying factors in children from age 12 to 24 months. Enlund-Cerullo M, Hauta-Alus H, Valkama S, Rosendahl J, Andersson S, Mäkitie O, Holmlund-Suila E. Bone. 2020 Dec;141:115629. doi: 10.1016/j.bone.2020.115629. Epub 2020 Sep 10. PMID: 32919110.

The development of heart failure is a concerning complication for patients who undergo heart valve and/or coronary bypass grafting surgery. In this context, risk prediction tools for patients undergoing cardiac surgery are of great interest. This article highlights a recent study investigating the predictive power of preoperative FGF23 levels in patients undergoing cardiac surgery.

Fibroblast growth factor 23 (FGF23)

Fibroblast growth factor 23 (FGF23) is a protein that plays a vital role in regulating phosphate and vitamin D levels and is associated with an elevated cardiovascular risk. A recent study by Hofer F et al., aimed to explore how FGF23 affects cardiovascular outcomes in a group of patients who underwent cardiac surgery. The analysis included a cohort of 451 patients who were observed for a median duration of 3.9 years. The results indicated that individuals with higher FGF23 levels showed elevated incidence of cardiovascular death. Therefore, the assessment of FGF23 may be a tool for risk stratification and could allow early identification of patients who have a high risk for adverse cardiovascular outcomes.

“Plasma FGF‐23 concentrations were assessed with a sandwich enzyme immunoassay (Biomedica Medizinprodukte GmbH, Vienna, Austria). The intra‐assay and interassay precision values were ≤12% and ≤10%, respectively. The assay limit of detection (0 pmol/L+3 SDs) was 0.08 pmol/L. For better clinical evaluation, FGF‐23 was converted to units of pg/mL, with a conversion factor of 1 pg/mL=0.133 pmol/L.”

Predictive power of preoperative FGF23 levels in patients undergoing cardiac surgery

Routine measurement of preoperative FGF23 levels may improve the detection of high-risk patients undergoing cardiac surgery.

BIOMEDICA FGF23 ELISA assays for serum & plasma samples

FGF23 (c-terminal) ELISA (cat. no BI-20702) and FGF23 intact ELISA (cat. no. BI-20700)

developed & manufactured by Biomedica , Vienna, Austria
fully validated according to international quality guidelines
numerous citations in top journals

Related Publications

Relationship of Fibroblast Growth Factor 23 With Hospitalization for Heart Failure and Cardiovascular Outcomes in Patients Undergoing Cardiac Surgery. Hofer F, Hammer A, Pailer U, Koller L, Kazem N, Steinacher E, Steinlechner B, Andreas M, Laufer G, Wojta J, Zelniker TA, Hengstenberg C, Niessner A, Sulzgruber P. J Am Heart Assoc. 2023 Mar 7;12(5):e027875. doi: 10.1161/JAHA.122.027875. Epub 2023 Feb 21. PMID: 36802737; PMCID: PMC10111457.

Abstract

Background Fibroblast growth factor 23 (FGF-23) is crucial in regulating phosphate and vitamin D metabolism and is moreover associated with an increased cardiovascular risk. The specific objective of this study was to investigate the influence of FGF-23 on cardiovascular outcomes, including hospitalization for heart failure (HHF), postoperative atrial fibrillation, and cardiovascular death, in an unselected patient population after cardiac surgery. Methods and Results Patients undergoing elective coronary artery bypass graft and/or cardiac valve surgery were prospectively enrolled. FGF-23 blood plasma concentrations were assessed before surgery. A composite of cardiovascular death/HHF was chosen as primary end point. A total of 451 patients (median age 70 years; 28.8% female) were included in the present analysis and followed over a median of 3.9 years. Individuals with higher FGF-23 quartiles showed elevated incidence rates of the composite of cardiovascular death/HHF (quartile 1, 7.1%; quartile 2, 8.6%; quartile 3, 15.1%; and quartile 4, 34.3%). After multivariable adjustment, FGF-23 modeled as a continuous variable (adjusted hazard ratio for a 1-unit increase in standardized log-transformed biomarker, 1.82 [95% CI, 1.34-2.46]) as well as using predefined risk groups and quartiles remained independently associated with the risk of cardiovascular death/HHF and the secondary outcomes, including postoperative atrial fibrillation. Reclassification analysis indicated that the addition of FGF-23 to N-terminal pro-B-type natriuretic peptide provides a significant improvement in risk discrimination (net reclassification improvement at the event rate, 0.58 [95% CI, 0.34-0.81]; P<0.001; integrated discrimination increment, 0.03 [95% CI, 0.01-0.05]; P<0.001). Conclusions FGF-23 is an independent predictor of cardiovascular death/HHF and postoperative atrial fibrillation in individuals undergoing cardiac surgery. Considering an individualized risk assessment, routine preoperative FGF-23 evaluation may improve detection of high-risk patients.

A single preoperative FGF23 measurement is a strong predictor of outcome in patients undergoing elective cardiac surgery: a prospective observational study. Speer T, Groesdonk HV, Zapf B, Buescher V, Beyse M, Duerr L, Gewert S, Krauss P, Poppleton A, Wagenpfeil S, Fliser D, Schaefers HJ, Klingele M.Crit Care. 2015 Apr 23;19(1):190. doi: 10.1186/s13054-015-0925-6. PMID: 25902817; PMCID: PMC4424828.

The BIOMEDICA FGF23 ELISA assays were recently used in a study investigating hepcidin and iron status in patients with inflammatory bowel disease undergoing therapy (1). Hepcidin, a peptide produced by liver cells, plays a vital role in regulating the body´s iron levels. In instances of inflammation, circulating hepcidin levels rise. Inflammation and iron deficiency have also been shown to stimulate FGF23 production (2). Iron deficiency enhances both the transcription and post-translational cleavage of FGF23 (3). Typically, this results in increased serum FGF23 C-terminal levels, with little to no effect on the biologically active intact FGF23 concentrations (4).

About FGF23

Fibroblast growth factor 23 (FGF23) is a protein that plays a crucial role in regulating phosphate and vitamin D metabolism in the body.

It is primarily produced by bone cells in the tissue called osteocytes. FGF 23 acts on the kidneys and decreases phosphate reabsorption thereby preventing the excessive accumulation of phosphate in the body.

Inflammatory bowel disease and FGF23

Patients with inflammatory bowel disease (IBD) face a greater risk to develop osteopenia and osteoporosis compared to the general population (5). In a study investigating the role of FGF23 in childhood inflammatory bowel disease, serum FGF23 was significantly higher in patients with IBD compared to controls (6)

How can you quantify circulating FGF23 levels?

FGF23 can easily be measured in blood samples (serum or plasma) with a conventional ELISA assay. The levels of FGF23 in the bloodstream consist of both the active intact hormone (iFGF23) and the inactive c-terminal fragments (cFGF23).

The C-terminal FGF23 assay captures both the intact FGF23 hormone and the fragments that form after FGF23 has been cleaved. The intact FGF23 assays utilize antibodies that are positioned in the N-terminal and C-terminal regions of the hormone, specifically targeting the biologically active intact FGF23.

Effects of FGF23 on the heart

High FGF23 concentrations have been found to be associated with multiple cardiac diseases, including left ventricular hypertrophy, heart attacks, heart failure, and cardiovascular related deaths (3-5).

Present findings exploring the relationship of FGF23 and cardiac events are presented in a recent review. The authors further discuss the potential mechanisms by which FGF23 directly or indirectly triggers left ventricular hypertrophy (6).

Learn more: Direct and indirect effects of fibroblast growth factor 23 on the heart. Nakano T et al., 2023.

Download our leaflet “FGF23 – an overview” here

How can FGF23 be measured?

Circulating FGF23 concentrations can be measured through blood tests by immunoassays. A widely used method for measuring FGF23 is with an ELISA assay (enzyme-linked immunosorbent assays). FGF23 ELISA assays utilize specific antibodies that recognize and bind FGF23 present in the sample.

Currently, there are two different assays commercially available for measuring circulating FGF23 in blood samples (7).

Intact FGF23 Assays

intact FGF23 (iFGF23) represents the full length, biologically active form of the hormone. It consists of the complete FGF23 protein structure without being enzymatically cleaved. The two antibodies in these assays target the N-terminal part and the C-terminal domain of the FGF23 molecule, respectively.

FGF23 C-terminal Assays

The c-terminal fragments of FGF23 (cFGF23) are the result of the enzymatic cleavage of the intact FGF23 molecule. The antibodies utilized in the cFGF23 assays bind to specific epitopes that are located in the c-terminal domain of the FGF23 molecule.

Noteworthy, all commercially available FGF23 c-terminal assays detect both c-terminal FGF23 fragments as well as the intact FGF23 molecule (7).

BIOMEDICA has developed two distinct ELISA assays to reliably quantify FGF23 concentrations in human serum and plasma.

· FGF23 intact ELISA (cat. no. BI-20700)

· FGF23 (C-terminal) ELISA (cat. no. BI-20702)

Validated FGF23 ELISA kits according to international quality guidelines
Numerous references in top-ranking journals

All Assays are Developed & Manufactured by Biomedica

Literature

The regulation of FGF23 under physiological and pathophysiological conditions. Rausch S, Föller M. Pflugers Arch. 2022 Mar;474(3):281-292. doi: 10.1007/s00424-022-02668-w. Epub 2022 Jan 27. PMID: 35084563; PMCID: PMC8837506.
Regulation and Effects of FGF23 in Chronic Kidney Disease. Musgrove J, Wolf M. Annu Rev Physiol. 2020 Feb 10;82:365-390. doi: 10.1146/annurev-physiol-021119-034650. Epub 2019 Nov 19. PMID: 31743079.
FGF23 and Cardiovascular Risk. Prié D. Ann Endocrinol (Paris). 2021 Jun;82(3-4):141-143. doi: 10.1016/j.ando.2020.03.007. Epub 2020 Mar 10. PMID: 32950228.
FGF23 predicts outcomes in heart failure but questions remain unanswered. Duran A, daSilva-deAbreu A, Joury A, Ventura HO. Int J Cardiol. 2021 Sep 1;338:145-146. doi: 10.1016/j.ijcard.2021.06.036. Epub 2021 Jun 19. PMID: 34157358.
Paracrine Effects of FGF23 on the Heart. Front Endocrinol (Lausanne). Leifheit-Nestler M, Haffner D 2018 May 28;9:278. doi: 10.3389/fendo.2018.00278. PMID: 29892269; PMCID: PMC5985311.
Direct and indirect effects of fibroblast growth factor 23 on the heart. Nakano T, Kishimoto H, Tokumoto M Front Endocrinol (Lausanne). 2023 Feb 24;14:1059179. doi: 10.3389/fendo.2023.1059179. PMID: 36909314; PMCID: PMC9999118.
The Measurement and Interpretation of Fibroblast Growth Factor 23 (FGF23) Concentrations. Calcif Tissue Int. Heijboer AC, Cavalier E. 2023 Feb;112(2):258-270. doi: 10.1007/s00223-022-00987-9. Epub 2022 Jun 4. PMID: 35665817; PMCID: PMC9859838.

Acute kidney injury (AKI) – also called acute renal failure – occurs when the kidneys suddenly fail to function due to an injury medication, or an infection. It happens within a few hours or days and is usually accompanied with other medical conditions e.g. blood vessel blockage, diabetes, heart failure, kidney and liver disease, hospitalization (ICU) and other.

FGF23 in Acute Kidney Injury

Fibroblast growth factor 23 (FGF23) is a bone derived hormone that regulates renal phosphate excretion in the kidney. In kidney disease, when the function of the kidney declines, serum phosphate levels rise which subsequently leads to the secretion of FGF-23. High phosphate levels are also common in patients with acute kidney injury (AKI) (1).

FGF23 marker of adverse outcomes in acute kidney injury

Fibroblast growth factor 23 (FGF23) levels rise rapidly with acute kidney injury and are associated with the requirement for renal replacement therapy (1-4). FGF-23 levels also have prognostic utility as shown in a large study in over 1500 patients with AKI (3).

Most studies measuring elevated FGF23 levels in AKI patients are performed using FGF23 (C-terminal) assays, which detect intact and C-terminal FGF23. Although the results mirror an increase of FGF23 production they may not necessarily reflect the bioactivity of FGF23 (5).

Quantifying circulating FGF23 levels

Circulating FGF23 levels include the bioactive intact hormone (iFGF23) and the inactive N-terminal and C-terminal fragments. FGF23 can be measured with two commercially available assay types (6). The C-terminal FGF23 assay captures both intact and the c-terminal fragments of FGF23, which result after cleavage. The intact FGF23 assay utilizes antibodies that are located in the N-terminal and in the C-terminal region of the FGF23 hormone, thus capturing only biologically active intact FGF23.

Learn more: FGF23 – an Overview

BIOMEDICA offers quality FGF23 assays for serum & plasma samples

FGF23 (c-terminal) ELISA, cat. no. BI-20702

FGF23 intact ELISA, cat no. BI-20700

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Literature

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, Simic P, Rhee EP. Nephron. 2022;146(3):239-242. doi: 10.1159/000517734. Epub 2021 Jul 20. PMID: 34284404; PMCID: PMC8770696.
Fibroblast growth factor 23 associates with death in critically ill patients. Leaf DE, Siew ED, Eisenga MF, Singh K, Mc Causland FR, Srivastava A, Ikizler TA, Ware LB, Ginde AA, Kellum JA, Palevsky PM, Wolf M, Waikar SS, 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, Wolf M, Waikar SS, Chase H, Christov M, Cremers S, Stern L. Clin J Am Soc Nephrol. 2012. 7(8):1217-23.
Fibroblast Growth Factor 23 and αKlotho in Acute Kidney Injury: Current Status in Diagnostic and Therapeutic Applications. Neyra JA, Hu MC, Moe OW. Nephron. 2020;144(12):665-672. doi: 10.1159/000509856. Epub 2020 Aug 25. PMID: 32841947; PMCID: PMC7708396.
The Measurement and Interpretation of Fibroblast Growth Factor 23 (FGF23) Concentrations. Heijboer AC, Cavalier E. Calcif Tissue Int. 2023. 112(2):258-270.

Valvular heart disease is a leading cause of cardiovascular morbidity. Transcatheter aortic valve replacement (TAVR) is a minimally invasive procedure that replaces the aortic valve in patients with aortic stenosis. Mineral homeostasis, the process that regulates the body’s levels of calcium and phosphorus, plays an important role in the progression of cardiovascular diseases, including calcific aortic valve stenosis. FGF23 is a bone-derived phosphotropic hormone that regulates phosphate and vitamin D metabolism. FGF23 has been shown to be an independent risk factor for CV morbidity and mortality.

FGF23 is a novel risk factor for patients undergoing TAVR

A study by Mirna et al. evaluated the predictive potential of both C-terminal FGF23 (cFGF23) and intact FGF23 (iFGF23) for adverse outcomes in patients undergoing transcatheter aortic valve replacement (TAVR) with regard to renal function. Patients were followed up at 12 months.

The authors demonstrated:

significant association of high cFGF23 levels with mortality in patients with an estimated glomerular filtration rate (eGFR) ≥45 ml/min/1.73m².
patients with cFGF23 levels above the cut-off of 6.82 pmol/l had a worse 1-year-mortality
cFGF23 could be a novel risk factor for patients undergoing TAVR with eGFR ≥45ml/min/1.73m².

FGF23 (C-terminal) and FGF23 intact were both measured with an ELISA assay from BIOMEDICA.

Assay Highlights

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LITERATURE

Serum levels of C-terminal FGF23 (cFGF23) are associated with 1-year-mortality in patients undergoing transcatheter aortic valve replacement (TAVR).

Mirna M, Lauten A, Jirak P, Rezar R, Wernly B, Paar V, Felder TK, Hoppe UC, Motloch LJ, Jung C, Alushi B, Lichtenauer M, Salmhofer H. Eur J Intern Med. 2021. 85:98-107. doi: 10.1016/j.ejim.2020.09.022. Epub 2020 Nov 13. PMID: 33191056.

Abstract

Introduction: Serum levels of FGF23 have been associated with adverse outcomes in cardiovascular diseases in patients with and without impaired renal function. Hence, this study aimed to explore the prognostic relevance of intact FGF23 (iFGF23) and its derivate C-terminal FGF23 (cFGF23) in patients undergoing transcatheter aortic valve replacement (TAVR) with regard to renal function.

Methods: A total of 274 patients undergoing transfemoral TAVR were enrolled in this study. Blood samples were obtained preinterventionally and analyzed for iFGF23 and cFGF23 by means of enzyme linked immunosorbent assay (ELISA). Follow-up was obtained for 12 months.

Results: Serum levels of cFGF23 and iFGF23 both correlated positively with serum creatinine and inversely with estimated glomerular filtration rate (eGFR). Cox regression analysis revealed a significant association of cFGF23 with 1-year-mortality in patients with eGFR ≥45ml/min/1.73m², but not in patients with an eGFR <45ml/min/1.73m². A cut-off was calculated for cFGF23 (6.82 pmol/l) and patients with eGFR ≥45ml/min/1.73m² were retrospectively divided into two groups (above/below cut-off). Patients above the cut-off had a significantly worse 1-year-mortality than patients below the cut-off (33.3% vs. 19.6%; OR 2.05 (95%CI 1.03-4.07), p= 0.038). The association of cFGF23 with 1-year-mortality in patients with eGFR ≥45ml/min/1.73m² remained statistically significant even after correction for possible confounders in a multivariate Cox regression analysis.

Conclusion: cFGF23 could be an individual risk factor for mortality in patients undergoing TAVR with an eGFR ≥45ml/min/1.73m².

FGF23 is a cardiovascular toxin in CKD

Chronic kidney disease (CKD) is a serious health problem that involves gradual loss of kidney function. The major cause of death in CKD patients is cardiovascular disease is triggered by the cardiovascular toxins fibroblast growth factor (FGF23) and phosphate.

Declining kidney function leads to elevated serum phosphate levels which are regulated by the phophaturic hormone FGF23 in CKD patients. In later stages of chronic kidney disease, access FGF23 and phosphate levels lead to increased cardiovascular disease and mortality. Ongoing experimental studies are identifying novel therapeutic strategies in order to prevent toxicity of FGF23 and hyperphosphatemia in CKD patients.

FGF23 is a cardiovascular toxin in chronic kidney disease

FGF23 and Phosphate-Cardiovascular Toxins in CKD.

Vogt I, Haffner D, Leifheit-Nestler M. Toxins (Basel). 2019 Nov 6;11(11):647. doi: 10.3390/toxins11110647. PMID: 31698866; PMCID: PMC6891626.

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FGF23 and Phosphate-Cardiovascular Toxins in CKD full text link

Abstract

Elevated levels of fibroblast growth factor 23 (FGF23) and phosphate are highly associated with increased cardiovascular disease and mortality in patients suffering from chronic kidney disease (CKD). As the kidney function declines, serum phosphate levels rise and subsequently induce the secretion of the phosphaturic hormone FGF23. In early stages of CKD, FGF23 prevents the increase of serum phosphate levels and thereby attenuates phosphate-induced vascular calcification, whereas in end-stage kidney disease, FGF23 fails to maintain phosphate homeostasis. Both hyperphosphatemia and elevated FGF23 levels promote the development of hypertension, vascular calcification, and left ventricular hypertrophy by distinct mechanisms. Therefore, FGF23 and phosphate are considered promising therapeutic targets to improve the cardiovascular outcome in CKD patients. Previous therapeutic strategies are based on dietary and pharmacological reduction of serum phosphate, and consequently FGF23 levels. However, clinical trials proving the effects on the cardiovascular outcome are lacking. Recent publications provide evidence for new promising therapeutic interventions, such as magnesium supplementation and direct targeting of phosphate and FGF receptors to prevent toxicity of FGF23 and hyperphosphatemia in CKD patients.

RELATED PUBLICATIONS

Fibroblast Growth Factor-23-A Potential Uremic Toxin.

Kuczera P, Adamczak M, Wiecek A Toxins (Basel). 2016 Dec 8;8(12):369. doi: 10.3390/toxins8120369. PMID: 27941640; PMCID: PMC5198563.

Abstract

Fibroblast growth factor-23 (FGF23) is a circulating member of the FGF family produced mainly by the osteocytes and osteoblasts that can act as a hormone. The main action of FGF23 is to lower phosphatemia via the reduction of urinary phosphate reabsorption and the decrease of 1,25(OH)₂-D generation in the kidney. In the course of chronic kidney disease (CKD), plasma FGF23 concentration rises early, most probably to compensate the inability of the deteriorating kidneys to excrete an adequate amount of phosphate. However, this comes at the cost of FGF23-related target organ toxicity. Results of clinical studies suggest that elevated plasma FGF23 concentration is independently associated with the increased risk of CKD progression, occurrence of cardio-vascular complications, and mortality in different stages of CKD. FGF23 also contributes to cardiomyocyte hypertrophy, vascular calcification, and endothelial dysfunction. The impact of FGF23 on heart muscle is not dependent on Klotho, but rather on the PLCγ-calcineurin-NFAT (nuclear factor of activated T-cells) pathway. Among the factors increasing plasma FGF23 concentration, active vitamin D analogues play a significant role. Additionally, inflammation and iron deficiency can contribute to the increase of plasma FGF23. Among the factors decreasing plasma FGF23, dietary phosphate restriction, some intestinal phosphate binders, cinacalcet (and other calcimimetics), and nicotinamide can be enumerated. Anti-FGF23 antibodies have also recently been developed to inhibit the action of FGF23 in target organs. Still, the best way to normalize plasma FGF23 in maintenance hemodialysis patients is restoring kidney function by successful kidney transplantation.

Effect of different phosphate binders on fibroblast growth factor 23 levels in patients with chronic kidney disease: a systematic review and meta-analysis of randomized controlled trials.

Zhao SJ, Wang ZX, Chen L, Wang FX, Kong LD. Ann Palliat Med. 2022 Apr;11(4):1264-1277. doi: 10.21037/apm-21-1943. Epub 2021 Nov 2. PMID: 34775773.

Simultaneous management of disordered phosphate and iron homeostasis to correct fibroblast growth factor 23 and associated outcomes in chronic kidney disease.

Courbon G, Martinez-Calle M, David V. Curr Opin Nephrol Hypertens. 2020 Jul;29(4):359-366. doi: 10.1097/MNH.0000000000000614. PMID: 32452919; PMCID: PMC7769207.

Intracerebral hemorrhage (ICH) is caused by bleeding within the brain. Very few circulating biomarkers are known to be associated with the risk of ICH. Fibroblast growth factor 23 (FGF23) is a bone-derived protein hormone associated with mortality in patients with heart failure. A recent nested case–control study showed that FGF23 is associated with risk of intracerebral hemorrhage: Fibroblast growth factor 23 is associated with risk of intracerebral hemorrhage. Svensson EH, Söderholm M. Eur J Neurol. 2022 Jan;29(1):114-120. doi: 10.1111/ene.15060. PMID: 34379844.

Abstract

Background and purpose: Fibroblast growth factor 23 (FGF23) is an osteogenic hormone associated with chronic kidney disease and is an emerging risk factor for several cardiovascular diseases. The association of FGF23 with stroke is unclear. The aim of this study was to investigate the association of FGF23 with incident intracerebral hemorrhage (ICH).

Methods: This was a nested case-control study of 220 ICH cases and 244 age- and sex-matched controls from the population-based Malmö Diet and Cancer Study (n = 28,449). Incident ICH cases were ascertained using national registers and classified by bleeding location. Logistic regression was used to study the association of plasma levels of FGF23 with incident ICH, adjusting for potential ICH risk factors. Subgroup analyses were performed for lobar and non-lobar ICH, fatal ICH, ICH with large volume and ICH with poor functional outcome, respectively.

Results: Higher FGF23 levels at baseline were significantly associated with incident ICH. After multivariable adjustment, the odds ratio for the association with all ICH was 1.84 (95% confidence interval [CI] 1.25-2.71, p = 0.002) per doubling of FGF23 concentration. For lobar and non-lobar ICH, odds ratios were 1.73 (95% CI 1.04-2.87, p = 0.035) and 2.13 (95% CI 1.32-3.45, p = 0.002), respectively. FGF23 was also significantly associated with fatal ICH, ICH with large volume and ICH with poor functional outcome.

Conclusions: Higher FGF23 was associated with incident ICH in this nested case-control study. Further studies are required to explore whether the association is causal.

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Related publications

Plasma FGF23 and the risk of stroke: the Northern Manhattan Study (NOMAS).

Wright CB, Dong C, Stark M, Silverberg S, Rundek T, Elkind MS, Sacco RL, Mendez A, Wolf M. Neurology 2014. 13;82(19):1700-6. PMID: 24706015.

Abstract

Objective: To examine fibroblast growth factor 23 (FGF23) as a risk factor for incident stroke in a racially/ethnically diverse population-based urban cohort.

Methods: Stroke-free Northern Manhattan Study participants with FGF23 measurements (n = 2,525) were followed for a mean of 12 (±5) years to detect incident strokes. We used Cox proportional hazards models to estimate the association of baseline FGF23 with incident total, ischemic, and hemorrhagic stroke.

Results: Median FGF23 was 57 relative units (RU)/mL (interquartile range = 44-81 RU/mL). Each unit increase of natural log-transformed FGF23 conferred a 40% greater overall stroke risk after adjusting for estimated glomerular filtration rate and sociodemographic and vascular risk factors (hazard ratio = 1.4, 95% confidence interval 1.1-1.6, p = 0.004). Penalized spline analysis revealed a linear association with overall stroke risk at ≥90 RU/mL FGF23, compared with <90 RU/mL (hazard ratio = 1.5, 95% confidence interval = 1.2-2.1, p = 0.004). Greater FGF23 conferred a doubling of intracerebral hemorrhage (ICH) risk but no significant increased risk of ischemic stroke. The associations of elevated FGF23 levels with greater risks of overall stroke and ICH events were independent of phosphate and parathyroid hormone levels and were similar among participants without chronic kidney disease.

Conclusions: Elevated FGF23 was a risk factor for overall stroke and ICH events, in particular in a racially and ethnically diverse urban community, independent of chronic kidney disease.

Fibroblast growth factor 23 and risk of incident stroke in community-living adults.

Panwar B, Jenny NS, Howard VJ, Wadley VG, Muntner P, Kissela BM, Judd SE, Gutiérrez OM. Stroke. 2015. 46(2):322-8. doi: 10.1161/STROKEAHA.114.007489. PMID: 25563643.

Abstract

Background and purpose: Fibroblast growth factor 23 (FGF23) is a hormone that regulates phosphorus and vitamin D metabolism. Elevated FGF23 concentrations are associated with excess risk of cardiovascular disease. Associations of FGF23 with stroke outcomes are less clear.

Methods: Using a case-cohort study design, we examined the association of baseline plasma FGF23 concentrations with incident stroke in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study, a cohort of black and white adults aged ≥45 years. FGF23 was measured in 615 participants who developed incident stroke (cases) and in 936 participants randomly selected from the REGARDS cohort (comparison subcohort).

Results: In multivariable-adjusted models, higher calcium and phosphorus concentrations, lower estimated glomerular filtration rate and higher urine albumin excretion were independently associated with higher FGF23. There was no statistically significant association of FGF23 with risk of all-cause stroke in Cox models adjusted for demographic factors and established stroke risk factors (hazard ratio comparing fourth with first quartile 1.19; 95% confidence interval, 0.78-1.82). In prespecified models stratified by stroke subtypes, there was a graded association of FGF23 with risk of cardioembolic stroke in fully adjusted models (quartile 1, reference; quartile 2 hazard ratio, 1.48; 95% confidence interval, 0.63-3.47; quartile 3 hazard ratio, 1.99; 95% confidence interval, 0.89-4.44; quartile 4 hazard ratio, 2.52; 95% confidence interval, 1.08-5.91). There were no statistically significant associations of FGF23 with other ischemic stroke subtypes or with hemorrhagic strokes.

Conclusions: Higher FGF23 concentrations were associated with higher risk of cardioembolic but not with other stroke subtypes in community-dwelling adults. Additional studies should delineate reasons for these findings.

Blood and urine biomarkers are tools to detect diseases, discover drugs and monitor patients. Biomarker research has identified Endostatin and Vanin-1 as promising novel markers to detect microvascular tissue injuries and renal tubular damage in drug-induced acute kidney injury, respectively. These and other proteins e.g. FGF23 and Periostin can easily be detected by ELISA. Check out our assay portfolio for clinical and preclinical research – novel biomarkers in clinical nephrology: www.bmgrp.com.

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Biomarkers in Clinical Nephrology – FGF23 ∙ Endostatin ∙ Periostin ∙ Vanin-1

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Related Publications:

ENDOSTATIN FOR THE DETECTION OF ADVANCED MICROVASCULAR KIDNEY DAMAGE AND THE PROGRESSION OF KIDNEY DISEASE

Plasma endostatin predicts kidney outcomes in patients with type 2 diabetes. Chauhan K et al., Kidney Int, 2019; 95(2):439-446. Link. “Plasma endostatin was strongly associated with kidney outcomes in type 2 diabetics with preserved eGFR and improved risk discrimination over traditional predictors.”

The association between endostatin and kidney disease and mortality in patients with type 2 diabetes. Carlsson et al., Diabetes Metab, 2016; 42(5):351-357. Link. “In patients with T2D, circulating endostatin levels can predict the progression of kidney disease and mortality independently of established kidney disease markers.”

Endostatin in chronic kidney disease: Associations with inflammation, vascular abnormalities, cardiovascular events and survival. Kanbay et al., Eur J Intern Med, 2016; 33:81-87. Link. “Endostatin levels are independently associated with incident CVE in CKD patients.”

Elevated plasma levels of endostatin are associated with chronic kidney disease. Chen et al., Am J Nephrol, 2012; 35(4):335-340. Link. “These data indicate that elevated plasma endostatin is strongly and independently associated with CKD.”

VANIN-1 A MARKER FOR DRUG-INDUCED & SPONTANEOUS ACUTE KIDNEY INJURY AND OBSTRUCTIVE & DIABETIC NEPHROPATHY

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. Link. “ .. urinary vanin-1 is associated with lower eGFR and higher UPCR and UACR, and might be a potential marker of decreased kidney function in hypertensive patients.”

A Novel Biomarker for Acute Kidney Injury, Vanin-1, for Obstructive Nephropathy: A Prospective Cohort Pilot Study. Washino et al., Int J Mol Sci, 2019; 20(4). Link. “Urinary Vanin-1 is a useful biomarker to detect and monitor the clinical course of obstructive nephropathy.”

Urinary Vanin-1 as a Novel Biomarker for Early Detection of Drug-Induced Acute Kidney Injury. Hosohata et al., J Pharm Exp Ther, 2002; 341(3):656–662. Link. “… compared with urinary Kim-1 and NGAL, urinary vanin-1 is an earlier and equally sensitive biomarker for drug-induced AKI.”

Vanin-1: A Potential Biomarker for Nephrotoxicant-Induced Renal Injury. Hosohata et al., Toxicology, 2011; 290(1):82–88. Link. “These results suggest that vanin-1 is a useful and rapid biomarker for renal tubular injury induced by organic solvents.”

Early Detection of Renal Injury Using Urinary Vanin-1 in Rats with Experimental Colitis. Hosohata et al., J App Tox, 2014; 34(2):184–190. Link. “Compared with Kim-1 and MCP-1, vanin-1 might be an earlier biomarker for the detection of renal injury in rats with experimental colitis.”

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(3):272-81. Link

FGF23 FOR RISK PREDICTION IN CHRONIC RENAL INSUFFICIENCY AND TO DETERMINE CARDIOVASCULAR RISK IN CKD

Association of Fibroblast Growth Factor 23 with Atrial Fibrillation in Chronic Kidney Disease, From the Chronic Renal Insufficiency Cohort Study. Mehta et al., JAMA Cardiology, 2016; 1(5):548-556. Link . “Elevated FGF23 is independently associated with prevalent and incident atrial fibrillation in patients with mild to severe CKD.”

Fibroblast growth factor 23 in patients with acute dyspnea: Data from the Akershus Cardiac Examination (ACE) 2 Study. Lyngbakkena et al., Clin Biochem, 2018; 52:41-47 . Link. “Circulating FGF23 concentrations provide incremental prognostic information to established risk indices in patients with acute dyspnea.”

FGF23 and vitamin D metabolism in chronic kidney disease – mineral bone disorder. Piec et al., Bone Abstracts, 2016; 5:P469. Link. “cFGF23 is raised in patients with CKD as a compensatory response to hyperphosphatemia or phosphate overload.”

Renal and Extrarenal Effects of Fibroblast Growth Factor 23. Vervloet, Nature Reviews, 2019; Nephrology 1(2):109–120. Link. “.. FGF23 is also a valuable biomarker as it predicts risk of a wide variety of clinical events, in particular heart failure.”

PERIOSTIN A BIOMARKER FOR SEVERITY, PROGRESSION AND RESPONSE TO THERAPY IN HUMAN KIDNEY DISEASE ASSOCIATED TO HYPERTENSION

Identification of periostin as a critical marker of progression/reversal of hypertensive nephropathy. Guerrot et al., PLoS One, 2012; 7(3):e31974. Link. “… the results identify Periostin as a previously unrecognized marker associated with hypertensive nephropathy.”

Periostin Induces Kidney Fibrosis after Acute Kidney Injury via the p38 MAPK Pathway. An et al., Am J Physiol Renal Physiol, 2019; 316(3):F426-F437. Link. “Periostin promotes kidney fibrosis via the p38 MAPK pathway following acute kidney injury triggered by a hypoxic or ischemic insult. Periostin ablation may protect against chronic kidney disease progression”.

Periostin as a tissue and urinary biomarker of renal injury in type 2 diabetes mellitus. Satirapoj et al., PLoS One, 2015; 17; 10(4):e0124055. Link. “Urinary periostin is an associated renal derangement in patients with established diabetic nephropathy and it may be used as an early marker of diabetic renal injury.”

Urinary Periostin Excretion Predicts Renal Outcome in IgA Nephropathy. Hwang et al., Am J Nephrol, 2016; 44(6):481-492. Link. “POSTN/Cr value at initial diagnosis correlated with renal fibrosis and predicted the renal outcomes in patients with IgAN. It could be a promising urinary biomarker for renal fibrosis.”

Effects of periostin deficiency on kidney aging and lipid metabolism. An JN Aging (Albany NY). 2021. 13(19):22649-22665. Link.

Periostin in the Kidney. Wallace DP. Adv Exp Med Biol. 2019;1132:99-112. Link.

The research status and prospect of Periostin in chronic kidney disease. Jia YY, Yu Y, Li HJ. Ren Fail. 2020 Nov;42(1):1166-1172. Link.

Polycystic Kidney Disease and Renal Fibrosis. Xue C, Mei CL. Adv Exp Med Biol. 2019;1165:81-100. Link.

Periostin Promotes Cell Proliferation and Macrophage Polarization to Drive Repair after AKI. Kormann R J Am Soc Nephrol. 2020; 31(1):85-100. Link.

Kidney Injury Molecule-1 and Periostin Urinary Excretion and Tissue Expression Levels and Association with Glomerular Disease Outcomes. Wu Q Glomerular Dis. 2021 Jun;1(2):45-59. doi: 10.1159/000513166. Epub 2021. Link.

SCLEROSTIN FOR THE DIAGNOSIS OF HIGH BONE TURNOVER IN CKD AND THE PREDICTION OF CORONARY ARTERY CALCIFICATION

Circulating levels of sclerostin but not DKK1 associate with laboratory parameters of CKD-MBD. Behets et al., PLOS ONE, 2017; 12(5). Link. “Sclerostin, as opposed to DKK1, may qualify as a biomarker of CKD-MBD, particularly in dialysis patients.”

Sclerostin serum levels correlate positively with bone mineral density and microarchitecture in haemodialysis patients. Cejka et al., Nephrol Dial Transplant, 2012; 27:226-230. Link. “Dialysis patients had significantly higher Sclerostin levels than controls.”

Serum Sclerostin and adverse outcomes in nondialyzed chronic kidney disease patients. Kanbay et al., J Clin Endocrinol, 2014; 99(10):E1854–E1861. Link. “Serum sclerostin values are associated, even after multiple adjustments, with fatal and nonfatal cardiovascular events in a nondialyzed CKD population.”

Relationship between plasma levels of sclerostin, calcium–phosphate disturbances, established markers of bone turnover, and inflammation in haemodialysis patients. Pietrzyk et al., Int Urol Nephrol, 2019; 51(3):519-526. Link. “Increased circulating sclerostin levels seem to reflect slower bone turnover in HD patients. Low levels of sclerostin are associated with vitamin D deficiency and good phosphates alignment.”

Sclerostin in chronic kidney disease-mineral bone disorder think first before you block it! Brandenburg VM et al., Nephrol Dial Transplant, 2019; ;34(3):408-414. Link

FGF23, a novel muscle biomarker detected in the early stages of ALS: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive muscle weakness. Currently, there are no biomarkers that can predict prognosis or disease progression. FGF23 is a protein secreted in the plasma by bone cells. A recent report identifies skeletal muscle as a potential target of FGF23. In a large collection of human ALS muscle samples the researchers observed that FGF23 protein is increased up to 50-fold in ALS muscle tissues .This report raises important questions of the role of FGF23 in ALS disease pathology.

Learn more: FGF23, a novel muscle biomarker detected in the early stages of ALS. Si Y, Kazamel M, Benatar M, Wuu J, Kwon Y, Kwan T, Jiang N, Kentrup D, Faul C, Alesce L, King PH. Sci Rep. 2021 Jun 8;11(1):12062. doi: 10.1038/s41598-021-91496-6. PMID: 34103575; PMCID: PMC8187665.

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FGF23, a novel muscle biomarker detected in the early stages of ALS.

Abstract:

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive muscle weakness. Skeletal muscle is a prime source for biomarker discovery since it is one of the earliest sites to manifest disease pathology. From a prior RNA sequencing project, we identified FGF23 as a potential muscle biomarker in ALS. Here, we validate this finding with a large collection of ALS muscle samples and found a 13-fold increase over normal controls. FGF23 was also increased in the SOD1^G93A mouse, beginning at a very early stage and well before the onset of clinical symptoms. FGF23 levels progressively increased through end-stage in the mouse. Immunohistochemistry of ALS muscle showed prominent FGF23 immunoreactivity in the endomysial connective tissue and along the muscle membrane and was significantly higher around grouped atrophic fibers compared to non-atrophic fibers. ELISA of plasma samples from the SOD1^G93A mouse showed an increase in FGF23 at end-stage whereas no increase was detected in a large cohort of ALS patients. In conclusion, FGF23 is a novel muscle biomarker in ALS and joins a molecular signature that emerges in very early preclinical stages. The early appearance of FGF23 and its progressive increase with disease progression offers a new direction for exploring the molecular basis and response to the underlying pathology of ALS.

Related publications:

Improving clinical trial outcomes in amyotrophic lateral sclerosis. Kiernan MC, Vucic S, Talbot K, McDermott CJ, Hardiman O, Shefner JM, Al-Chalabi A, Huynh W, Cudkowicz M, Talman P, Van den Berg LH, Dharmadasa T, Wicks P, Reilly C, Turner MR. Nat Rev Neurol. 2021 Feb;17(2):104-118. doi: 10.1038/s41582-020-00434-z. Epub 2020 Dec 18. PMID: 33340024; PMCID: PMC7747476. Full text link

The gut microbiome: a key player in the complexity of amyotrophic lateral sclerosis (ALS). Boddy SL, Giovannelli I, Sassani M, Cooper-Knock J, Snyder MP, Segal E, Elinav E, Barker LA, Shaw PJ, McDermott CJ. BMC Med. 2021 Jan 20;19(1):13. doi: 10.1186/s12916-020-01885-3. PMID: 33468103; PMCID: PMC7816375. Full text link

Gene therapy for ALS: A review. Amado DA, Davidson BL. Mol Ther. 2021 Apr 9:S1525-0016(21)00195-7. doi: 10.1016/j.ymthe.2021.04.008. Epub ahead of print. PMID: 33839324. Full text link

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Total Neuropilin-1 ELISA (cat.no. BI-20409)

Expression of the axon-guidance protein receptor Neuropilin 1 is increased in the spinal cord and decreased in muscle of a mouse model of amyotrophic lateral sclerosis. Körner S et al., Eur J Neurosci. 2019.

Background:

Fibroblast growth factor 23 (FGF23) is a key regulator of Vitamin D and phosphate metabolism. Preclinical studies have linked FGF23 with left ventricular hypertrophy. In a recent large prospective study, researchers identified that biologically active intact FGF23 is independently associated with all-cause and cardiovascular mortality. This finding opens the possibility for consideration of trials targeting FGF23 lowering in community-living individuals, as are being evaluated in other study populations. Read more

Fibroblast growth factor 23 (FGF23) is a 251 amino acid (AA) protein mainly produced by bone cells and functions as a central endocrine hormone regulating phosphate balance. The full-length protein comprises 251 AA including a 24 AA signal peptide. A proportion of FG23 is proteolytically processed between arginine179 and serine180 to generate N-terminal and C-terminal fragments. Therefore, the major forms of FGF23 present in human circulation are hormonally intact FGF23 and inactive N-terminal and C-terminal fragments. Depending on the epitope specificity of the antibodies utilized in commercial FGF23 assays, quantification of circulating FGF23 is based on two distinct approaches: Intact FGF23 (iFGF23) assays utilize a capture antibody that flanks the proteolytic cleavage site of FGF23, thus measuring exclusively biologically active intact FGF23 (AA 25 –251). By contrast, C-terminal FGF23 (cFGF23) assays detect both c-terminal inactive fragments of FGF23 (AA 180-251) as well as the biologically active intact FGF23. The epitopes of the antibodies utilized in these assays lie within the c-terminal region of FGF23.

Most of the existing epidemiological studies on the association of FGF23 with clinical events related to mortality, cardiovascular disease and inflammation, measured FGF23 with a C-terminal FGF23 assay that detects both the biologically active intact hormone (iFGF23) as well as the inactive C-terminal fragments (cFGF23). These studies were performed both in the general population and in patients with kidney disease. Newer research however demonstrates that iron deficiency and inflammation induce FGF23 cleavage, increasing mainly cFGF23 degradation fragment levels whereas iFGF23 levels remain mostly unchanged. Thus, it remains uncertain if the observed clinical associations are related to the biologically intact FGF23 hormone or if the effects of iron and inflammation on cFGF23 levels, influence the findings.

To closer evaluate the relationship of active FGF23 and its biological functions, a group of researchers recently investigated its association with mortality in a large prospective cohort of community-dwelling well-functioning older adults. The study published by Sharma et al. included 2,763 individuals between 70-79 years who were followed up for more than 8 years. The results of the study indicate that intact FGF23 is independently associated with all-cause and cardiovascular mortality in community-living older individuals. The authors concluded that the association seems to be restricted to certain death sub-types, in particular cardiovascular disease. In summary, the findings suggest that the associations of FGF23 with the clinical outcomes are specific and provide insights into the biological mechanisms of FGF23.

Click here to read full text: FGF23 and Cause-Specific Mortality in Community-Living Individuals-The Health, Aging, and Body Composition Study. Sharma S et al., 2021. Am Geriatr Soc, 69(3):711-717.

Abstract

Objectives: Fibroblast growth factor (FGF)-23 is a key regulator of mineral metabolism and has been linked with left ventricular hypertrophy in animal models. Most existing epidemiologic studies evaluated a C-terminal FGF23 assay which measures both the intact (active) hormone and inactive fragments. The relationship of intact FGF23 with cause-specific mortality is unknown.

Design: Prospective analyses of data from Health, Aging, & Body Composition (HABC) study

Setting: Community-living adults aged 70–79 years with longitudinal follow up.

Participants: 2763 older adults who participated in the HABC study

Measurements: Plasma intact FGF23 levels were measured from samples drawn in 2000 and 2001, and participants were followed through 2012. Mortality and its causes were determined by an adjudication committee. Associations of FGF23 with all-cause and cause-specific mortality were evaluated using Cox proportional hazards models adjusted for demographics, prevalent cardiovascular disease (CVD) and its risk factors, and kidney function.

Results: Median baseline intact FGF23 was 47 (IQR 37, 60) pg/ml and mean estimated glomerular filtration rate (eGFR) was 72 ± 18 ml/min/1.73m². During 8.3 years (median) follow-up, there were 821 deaths. In adjusted analysis, each two-fold higher FGF23 was associated with risk for all-cause mortality (HR 1.24 [95% CI 1.12, 1.37]). When evaluating cause-specific mortality, higher FGF23 was associated with cardiovascular mortality (HR 1.31 [95% CI 1.11, 1.54]), but not significantly with cancer (HR 1.01 [95% CI 0.83, 1.23]), gastrointestinal bleed (HR 2.49 [95% CI 0.86, 7.21]), and kidney failure (HR 1.25 [95% CI 0.77, 2.03]), dementia (HR 0.84 [95% CI 0.56, 1.26]), sepsis (HR 0.73 [95% CI 0.31, 1.73]) or pulmonary disease related mortality (HR 1.40 [95% CI 0.87, 2.27]).

Conclusion: Although higher intact FGF23 concentrations are associated with all-cause mortality in community-living individuals, the association appears limited to certain death sub-types, particularly CVD. Future studies are needed to evaluate potential mechanisms linking FGF23 concentrations with specific causes of death.

Did you know?

Intact and c-terminal FGF23 can reliably be measured by ELISA in human serum and plasma with Biomedica’s fully validated kits. Only 50 µl of sample volume is required. The kits incorporate characterized epitope mapped antibodies and ready to use standards and controls. The assay range is optimized for clinical samples.

Biomedica´s Intact FGF23 and C-terminal FGF23 ELISA kits

Is your lab measuring FGF23?

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The FGF23 ELISA kits are developed and manufactured by

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Literature:

C-terminal and intact FGF23 in kidney transplant recipients and their associations with overall graft survival. Chu C, Elitok S, Zeng S, Xiong Y, Hocher CF, Hasan AA, Krämer BK, Hocher B. BMC Nephrol. 2021 Apr 8;22(1):125. doi: 10.1186/s12882-021-02329-7. PMID: 33832449; PMCID: PMC8033679.

FGF23 and Cause-Specific Mortality in Community-Living Individuals-The Health, Aging, and Body Composition Study. Sharma S, Katz R, Dubin RF, Drew DA, Gutierrez OM, Shlipak MG, Sarnak MJ, Ix JH. J Am Geriatr Soc. 2021 Mar;69(3):711-717. doi: 10.1111/jgs.16910. Epub 2020 Nov 10. PMID: 33170519; PMCID: PMC8175094.

Intact and C-Terminal FGF23 Assays-Do Kidney Function, Inflammation, and Low Iron Influence Relationships With Outcomes? Sharma S, Katz R, Bullen AL, Chaves PHM, de Leeuw PW, Kroon AA, Houben AJHM, Shlipak MG, Ix JH. J Clin Endocrinol Metab. 2020 Dec 1;105(12):e4875–85. doi: 10.1210/clinem/dgaa665. PMID: 32951052; PMCID: PMC7571450.

FGF23 at the crossroads of phosphate, iron economy and erythropoiesis. Edmonston D, Wolf M. Nat Rev Nephrol. 2020 Jan;16(1):7-19. doi: 10.1038/s41581-019-0189-5. Epub 2019 Sep 13. PMID: 31519999.

Renal and extrarenal effects of fibroblast growth factor 23. Vervloet M. Nat Rev Nephrol. 2019 Feb;15(2):109-120. doi: 10.1038/s41581-018-0087-2. PMID: 30514976.

FGF23 in Cardiovascular Disease: Innocent Bystander or Active Mediator? Stöhr R, Schuh A, Heine GH, Brandenburg V. Front Endocrinol (Lausanne). 2018 Jun 27;9:351. doi: 10.3389/fendo.2018.00351. Erratum in: Front Endocrinol (Lausanne). 2018 Jul 18;9:422. PMID: 30013515; PMCID: PMC6036253.

Physiological Actions of Fibroblast Growth Factor-23. Front Endocrinol (Lausanne). Erben RG. 2018 May 28;9:267. doi: 10.3389/fendo.2018.00267. PMID: 29892265; PMCID: PMC5985418.

Coupling fibroblast growth factor 23 production and cleavage: iron deficiency, rickets, and kidney disease. Wolf M, White KE. Curr Opin Nephrol Hypertens. 2014 Jul;23(4):411-9. doi: 10.1097/01.mnh.0000447020.74593.6f. PMID: 24867675; PMCID: PMC4322859.

Fibroblast Growth Factor-23 and Frailty in Elderly Community-Dwelling Individuals: The Cardiovascular Health Study. Beben T, Ix JH, Shlipak MG, Sarnak MJ, Fried LF, Hoofnagle AN, Chonchol M, Kestenbaum BR, de Boer IH, Rifkin DE. J Am Geriatr Soc. 2016 Feb;64(2):270-6. doi: 10.1111/jgs.13951. PMID: 26889836; PMCID: PMC5510331.

Inflammation and functional iron deficiency regulate fibroblast growth factor 23 production. David V, Martin A, Isakova T, Spaulding C, Qi L, Ramirez V, Zumbrennen-Bullough KB, Sun CC, Lin HY, Babitt JL, Wolf M. Kidney Int. 2016 Jan;89(1):135-46. doi: 10.1038/ki.2015.290. Epub 2016 Jan 4. PMID: 26535997; PMCID: PMC4854810.

Fibroblast growth factor 23 and risk of all-cause mortality and cardiovascular events: a meta-analysis of prospective cohort studies. Xiao Y, Luo X, Huang W, Zhang J, Peng C. Int J Cardiol. 2014 Jul 1;174(3):824-8. doi: 10.1016/j.ijcard.2014.04.138. Epub 2014 Apr 22. PMID: 24820751.

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 Jan;83(1):160-6. doi: 10.1038/ki.2012.327. Epub 2012 Sep 5. PMID: 22951890.

Fibroblast growth factor 23 (FGF23) is a bone derived hormone involved in the regulation of phosphate and vitamin D metabolism. FGF23 is increased in patients with renal failure and has been shown to be a risk factor in cardiovascular mortality not only in kidney disease but also in the general population. FGF23 levels are elevated in obese people and increased energy intake is a potential predictor of plasma FGF23 concentrations. In a recent study, three groups of rats were fed diets with high, normal and low caloric content that resulted in different energy intake. The authors could demonstrate that FGF23 production is directly regulated by energy availability.
Read more: https://lnkd.in/eVZMvvF

Check out the Biomedica FGF23 ELISA assays: https://lnkd.in/ezCdsyN

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Researchers have identified the c-terminal fragment of the phosphate regulating hormone FGF23 (cFGF23) to better predict the risk of graft loss in kidney transplant recipients (KTRs) than its biologically active form (intact FGF23). The prospective observational cohort study included 562 maintenance KTRs with a median follow-up of 4 years.

C-terminal and intact FGF23 in kidney transplant recipients and their associations with overall graft survival. Chu C et al.,BMC Nephrology (2021) 22:125.

FGF23 (intact) and FGF23 (C-terminal) can reliably be measured by ELISA
√ CE-marked – for IVD use in the EU
√ CORRELATE with existing ELISA methods
√ Excellent stability in all matrices
√ For plasma & serum
√ HIGH QUALITY – fully validated according to international guidelines (ICH/FDA/EMEA)

Today’s bulletin highlights a recent study investigating the association between bone quality, bone turnover, and anemia in a population-based study cohort. As FGF23 could be a link between the pathogenesis of anemia and osteoporosis, the researchers tested the hypothesis that FGF23 levels associate with hemoglobin levels and with bone quality.

Read more:

Interactions of Anemia, FGF-23, and Bone in Healthy Adults-Results From the Study of Health in Pomerania (SHIP). Hannemann A et al., J Clin Endocrinol Metab, 2021, Jan 1;106(1):e288-e299.

FGF23 (intact) and FGF23 (C-terminal) can reliably be measured by ELISA

√ CE-marked – for IVD use in the EU
√ CORRELATE with existing ELISA methods
√ Excellent stability in all matrices
√ For plasma & serum
√ HIGH QUALITY – fully validated according to international guidelines (ICH/FDA/EMEA)

Fibroblast growth factor 23 (FGF23) is a protein produced by bone and is an important regulator of phosphate homeostasis. Bone impairment seen in disorders of FGF23 expression include hypophosphatemic rickets, tumoral-induced osteomalacia, and chronic kidney disease. In a study by Bilha SC et al., the researchers investigated the relationship between FGF23 and bone mass parameters in the general population, according to age, sex, menopausal, and nutritional status. FGF23 was found to be an independent predictor for bone mineral density in postmenopausal women, but was not a fine discriminator between normal bone mass and osteopenia/osteoporosis. The mechanism through which FGF23 acts upon the bone seems independent of the nutritional status, requiring further investigation. https://buff.ly/2NMb2eP

FGF23 can reliably measured by ELISA. Check out the Biomedica human FGF23 (C-terminal) and human FGF23 (intact) kits: https://buff.ly/37sunK0

• For serum and plasma samples

• Extensively validated according to international quality guidelines (FDA/ICH/EMEA)

• CE marked – for IVD use in the EU

• Plasma based standards and controls included

• Excellent correlation with existing methods

Rafiou Agoro, Pu Ni, Megan L. Noonan, and Kenneth E. White. Front Endocrinol (Lausanne). 2020; 11: 592.

Full publication https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7485387/

FGF23 is a phosphaturic hormone derived and secreted primarily by bone osteocytes. Mature, bioactive FGF23 is physiologically designed to target the kidney to regulate phosphate and vitamin D homeostasis; and, in a feedback mechanism to control bone mineralization and FGF23 production.

This review explores the signals involved in the positive and negative regulation of FGF23 in osteocytes, and bridges bone responses with the review of current knowledge on FGF23 endocrine functions in the kidneys.

Check out the Biomedica human FGF23 (C-terminal) and human FGF23 (intact) ELISA kits: https://www.bmgrp.com/shop?category=&type=&reactivity=&s=fgf

For serum and plasma samples
Extensively validated according to FDA/ICH/EMEA guidelines
CE marked – for IVD use in the EU
Excellent correlation with existing methods

Fibroblast growth factor 23 (FGF23) and parathyroid hormone (PTH) are regulators of renal phosphate excretion and vitamin D metabolism.

In chronic kidney disease, circulating FGF23 and PTH concentrations progressively increase as renal function declines. Oxidation of PTH at two methionine residues (positions 8 and 18) causes a loss of PTH function. However, the impact of non-oxidized PTH and oxidized PTH on FGF23 synthesis and how n‐oxPTH and oxPTH concentrations are affected by CKD, is yet unknown.

Research by Zeng et al. now shows that only non-oxidized PTH correlates with increased FGF23 synthesis in CKD. Simultaneously, ox-PTH and intact PTH concentrations increase more substantially than n-ox-PTH. This highlights the importance of different PTH derivatives.

Learn more about Biomedica’s C-terminal & intact FGF23 Assays

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Recent advancements in genetic #research have uncovered new forms of monogenic #osteoporosis. Mutations in WNT1, encoding a WNT/β-catenin pathway ligand WNT1, and PLS3, encoding X chromosomally inherited plastin 3 (PLS3), both result in early-onset osteoporosis with prevalent fractures and disrupted bone metabolism.

Data from a study by Mäkitie RE et al. indicate a link between PLS3 and DKK1 and WNT1 and FGF23 in bone metabolism (measured with biomedica kits). Therefore, DKK1 and FGF23 may be clinically useful biomarkers for PLS3 and WNT1 osteoporosis, respectively.

Check out the Biomedica DKK-1 and FGF23 ELISA kits:

– Reliable – validated according to international guidelines
– Specific – epitope mapped antibodies
– CE marked – widely cited in clinical studies

Biomarkers in WNT1 and PLS3 Osteoporosis: Altered Concentrations of DKK1 and FGF23 . Mäkitie RE et al., J Bone Miner Res, 2020 May;35(5):901-912.

Why is it important to measure the ratio of active intact and inactive C-terminal FGF23 fragments?

FGF23 is an endocrine hormone regulating phosphate homeostasis by modulating renal phosphate reabsorption, vitamin D metabolism and parathyroid hormone (PTH) secretion. Epidemiological data suggests that higher FGF23 concentrations are associated with all-cause mortality, cardiovascular mortality, a higher risk of myocardial infarction, stroke and heart failure.

Levels of FGF23 and intact: C-terminal fragment FGF23 ratios can be altered in both genetic and acquired diseases. A primary excess in circulating intact FGF23 is the underlying cause of diseases like XLH, ADHR/ARHR or tumor-induced osteomalacia. The excessive FGF23 levels in these diseases cause renal phosphate wasting, low active vitamin D concentrations and defective mineralization of bones. By contrast, during iron deficiency FGF23 synthesis and cleavage are upregulated in a coupled manner, resulting in normal levels of intact FGF23 and high levels of cFGF23.

Therefore, different conditions result in varying characteristic iFGF23:cFGF23 ratios.

For more information on why iFGF23:cFGF23 ratios differ between diseases check out “Coupling Fibroblast Growth Factor 23 Production and Cleavage: Iron Deficiency, Rickets, and Kidney Disease” or check out out iFGF23 and cFGF12 ELISA.

FGF23 (Fibroblast Growth Factor 23), a well-known marker for phosphate metabolism, has achieved independent significance in the cardiovascular system [1]. Several large-scale prospective studies have established FGF23 as an independent risk marker for heart failure and mortality [2,3]. There is also growing evidence that FGF-23 levels can predict the response to therapies aimed to reduce heart failure risk [4].

FGF23 is expressed in the heart and is significantly elevated in heart failure

Recent studies indicate that FGF23 is also expressed in the heart [5]. It is significantly enhanced in clinical and experimental settings of cardiac remodeling and heart failure independent of renal function [6, 10]. Secreted by cardiac myocytes, FGF23 can stimulate pro-fibrotic factors in myocytes to induce fibrosis-related pathways in fibroblasts and consequently cardiac fibrosis. While acting on cardiac myocytes, FGF23 directly induces pro-hypertrophic genes and promotes the progression of LVH (left ventricular hypertrophy) in an autocrine and paracrine fashion. Thus, enhanced FGF23 may promote cardiac injury in various clinical settings by endocrine and paracrine/autocrine mechanisms [7].

FGF23 measurement for prognosis and risk assessment in heart failure

Several large-scale prospective studies show a linear correlation between FGF23 levels and mortality risk, particularly because of LVH and systolic heart insufficiency (heart failure with reduced ejection fraction, HFREF) [2,8]. This clinically evident association between HFREF and FGF23, is likely explained by FGF23 ‘s direct cardiotoxic effects on cardiomyocytes.

Besides the known risk markers in HFREF patients such as serum sodium and BNP, the measurement of FGF23 can thus be of considerable use for risk stratification of individual patients. Of special relevance is the growing evidence that FGF23 levels can predict the response to a therapy with a blocker of the renin-angiotensin-aldosterone system [9].

Cardiovascular risk assessment under ACE therapy

In the PEACE Study (Prevention of Events With Angiotensin-Converting Enzyme) FGF23 was determined in 3,627 patients with stable ischemic heart disease (SIHD) [4]. Increased FGF23 levels correlated, with mortality rate and heart failure, but also identified those patients who benefitted significantly from treatment with ACE inhibitor. This effect was independent of renal function. These results indicate that FGF23 may become an attractive tool for individualized HFREF therapy. Patients with cardiorenal syndrome (combined heart and kidney failure) may benefit from FGF23 determination for estimation of individual risk and initiation of individualized treatment.

FGF23 and therapy monitoring

Patients with kidney disease show elevated serum concentrations of FGF23, associated with cardiovascular and all-cause mortality. A therapeutic approach to reduce increased FGF23 levels is the administration of (calcium-free) phosphatebinders (calcimimetics). The „EVOLVE“ study (2,985 patients receiving hemodialysis with secondary Hyperparathyroidism), demonstrated that treatment-induced reductions in serum FGF23 were associated with lower rates of cardiovascular death and major cardiovascular events. Among patients randomized to cinacalcet, a ≥30% reduction in serum FGF23 between baseline and week 20 was associated with a reduction in the relative hazard of the clinically relevant end point, cardiovascular mortality, sudden cardiac death, and heart failure [9].

Further studies on FGF23

Clearly more experimental and clinical studies are required to justify integrating routine measurement of FGF23 as risk marker for heart failure or to guide treatment. However, it is one of the few promising biomarkers that has high potential to ascertain the effect of FGF23 specific therapeutic interventions on clinically relevant endpoints [10].

Literature

[1] Hu MG, Shiizaki K, Kuro-o M, Moe OW. Fibroblast Growth Factor 23 and Klotho: Physiology and Pathophysiology of an Endocrine Network of Mineral Metabolism. Annu Rev Physiol. 2013;75:503-33.
[2] Brandenburg VM, Kleber ME, Vervloet MG, Tomaschitz A, Pilz S, Stojakovic T, Delgado G, Grammer TB, Marx N, März W, Scharnagl H. Fibroblast growth factor 23(FGF23) and mortality: the Ludwigshafen Risk and Cardiovascular Health Study. Atherosclerosis. 2014 Nov;237(1):53-9.
[3] Olauson H, Vervloet MG, Cozzolino M, Massy ZA, Ureña Torres P, Larsson TE. New insights into the FGF23-Klotho axis. Semin Nephrol. 2014 Nov;34(6):586-97.
[4] 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. Fibroblast growth factor-23, cardiovascular prognosis, and benefit of angiotensin-converting enzyme inhibition in stable ischemic heart disease. J Am Coll Cardiol. 2014 Jun 10;63(22):2421-8
[5] Itoh N, Ohta H, Nakayama Y, Konishi M. Roles of FGF signals in heart development, health, and disease. Front Cell Dev Biol (2016) 4:110. doi:10.3389/fcell.2016.00110.
[6] Andrukhova O, Slavic S, Odorfer KI, Erben RG. Experimental myocardial infarction upregulates circulating fibroblast growth factor-23. J Bone Miner Res (2015) 30:1831–9. doi:10.1002/jbmr.2527.
[7] Leifheit-Nestler M and Haffner D. Paracrine effects of FGF23 on the Heart. Frontiers in Endocrinology | www.frontiersin.org May 2018 | Volume 9 | Article 278.
[8] Almahmoud MF, Soliman EZ, Bertoni AG, Kestenbaum B, Katz R, Lima JAC, Ouyang P, Miller PE, Michos ED, Herrington DM; Fibroblast Growth Factor-23 and Heart Failure With Reduced Versus Preserved Ejection Fraction: MESA. J Am Heart Assoc. 2018 Sep 18;7(18):e008334.
[9] Moe SM, Chertow GM, Parfrey PS, Kubo Y, Block GA, Correa-Rotter R, Drüeke TB, Herzog CA, London GM, Mahaffey KW, Wheeler DC, Stolina M, Dehmel B, Goodman WG, Floege J; For the Evaluation of Cinacalcet HCl Therapy to Lower Cardiovascular Events (EVOLVE) Trial Investigators. Cinacalcet, Fibroblast Growth Factor-23, and Cardiovascular Disease in Hemodialysis: The Evaluation of Cinacalcet HCl Therapy to Lower Cardiovascular Events (EVOLVE) Trial. Circulation. 2015 July;132(1):27-39
[10] Vervloet M; Renal and Extrarenal Effects of Fibroblast Growth Factor 23. Nature Reviews. Nephrology 15, Nr. 2 (Februar 2019): 109–20.

Read more on our fully validated and CE marked FGF-23 (intact) ELISA and FGF-23 (C-terminal) multi-matrix ELISA for IVD use.

Features and Benefits

RELIABLE and FULLY VALIDATED for plasma samples – according to ICH Q2
FAST ONE-STEP ELISA – only 3.5 h total incubation time
PLASMA-BASED STANDARDS and CONTROLS INCLUDED – for biologically reliable data
CHARACTERIZED MONOCLONAL ANTIBODIES – high specificity and sensitivity guaranteed
COMPARABLE RESULTS – correlates with existing methods

Biomedica is proud to announce the launch of its CE-marked FGF23 (intact) human ELISA, cat# BI-20700

Features and Benefits

RELIABLE & FULLY VALIDATED for plasma samples – according to ICH Q2
SERUM, URINE and CC SUPERNATANT are compatible with this ELISA
FAST ONE-STEP ELISA – only 3.5 h total incubation time
PLASMA BASED STANDARDS and CONTROLS INCLUDED – for biologically reliable data
CHARACTERIZED MONOCLONAL RECOMBINANT ANTIBODIES – high specificity guaranteed

The new intact FGF23 ELISA was mentioned in the most recent Biocompare newsletter as a featured product. Check out the drug discovery and development newsletter to learn more.

FGF23 (intact) human ELISA

Features and Benefits

• RELIABLE and FULLY VALIDATED for plasma samples – according to ICH Q2

• SERUM, URINE and CC SUPERNATANT are compatible with this ELISA

• FAST ONE-STEP ELISA – only 3.5 h total incubation time

• PLASMA BASED STANDARDS and CONTROLS INCLUDED – for biologically reliable data

• CHARACTERIZED MONOCLONAL ANTIBODIES – high specificity and sensitivity guaranteed
• GOOD CORRELATION with existing ELISA methods

Why FGF23 ELISA from Biomedica?

√ Proprietary products – developed and manufactured in our European facilities

√ Excellent stability in all matrices after sample collection

√ CE registration in progress

Please click below for:

– Assay Validation Data
– Instruction For Use
– Biomedica FGF23 Info Leaflet
– Product Website

Related Product:
FGF23 (C-terminal) ELISA

BIOMEDICA is happy to announce the launch of its:

FGF23 (intact) human ELISA

Features and Benefits

• RELIABLE and FULLY VALIDATED for plasma samples – according to ICH Q2

• SERUM, URINE and CC SUPERNATANT are compatible with this ELISA

• FAST ONE-STEP ELISA – only 3.5 h total incubation time

• PLASMA BASED STANDARDS and CONTROLS INCLUDED – for biologically reliable data

• CHARACTERIZED MONOCLONAL ANTIBODIES – high specificity and sensitivity guaranteed
• GOOD CORRELATION with existing ELISA methods

Why FGF23 ELISA from Biomedica?

√ Proprietary products – developed and manufactured in our European facilities

√ Excellent stability in all matrices after sample collection

√ CE registration in progress

Please click below for:

– Assay Validation Data
– Instruction For Use
– Biomedica FGF23 Info Leaflet
– Product Website

Related Product:
FGF23 (C-terminal) ELISA

Human intact FGF23 ELISA:

Extensively validated according to FDA/ICH/EMEA guidelines
Correlates with existing methods
One-step ELISA

C-terminal FGF23 ELISA kit highlights:

Only ELISA that can detect human FGF23 (C-terminal) in both serum and plasma samples
Extensively validated according to FDA/ICH/EMEA guidelines

VANIN-1 a biomarker for survival in PAD – Peripheral artery disease (PAD) is a condition characterized by the narrowing of the peripheral arteries, often due to atherosclerosis, which reduces blood flow to the limbs, particularly the legs (1). This can lead to symptoms such as leg pain, cramping, and weakness during physical activity. In more severe cases, PAD can result in critical limb ischemia, ulcers, or even gangrene. It is closely associated with cardiovascular conditions and risk factors, including high blood pressure, diabetes, and chronic kidney disease.

Chronic kidney disease (CKD) significantly increases the risk of developing peripheral artery disease (PAD) and is also a common co-morbidity factor that is associated with PAD (2). Despite its clinical significance, there is currently no specific marker available for conducting a functional risk assessment of kidney disease patients suffering from peripheral artery disease (PAD), particularly in the early stages.

VANIN-1 a biomarker for survival in PAD

In search of novel biomarkers that may serve as tools of risk assessment, Zierfuss B. and colleagues investigated the relationship between urinany Vanin-1 (uVNN-1) as a marker of kidney disease and PAD severity (3). The study included patients with stable PAD (n = 304) who were followed up for up to 10 years. Urinary Vanin-1 (uVNN1) was measured by an enzyme-linked immunosorbent assay (ELISA) from Biomedica. Urinary Vanin-1 (uVNN1) concentration were normalized to urine creatinine levels (uVNN1/Cr).

The results of the study demonstrate that uVNN-1 is an independent link to both all-cause and cardiovascular mortality in patients with peripheral artery disease (PAD). As a result, uVNN1/Cr may serve as a practical and accessible marker for risk stratification in early kidney disease patients with PAD, aiding in the identification of those patients who are at high risk for fatal events.

Human VANIN -1 (urine) ELISA Assay Kit (cat. no. BI-VNN1)

The assay is optimized for human urine samples
Characterized antibodies enable high SPECIFICITY
Rigorously validated assay following international quality guidelines
Easy and quick one-step ELISA

Related products

-Mouse/rat Vanin-1 ELISA

-Nephrology and Transplant: FGF23, Endostatin, Anti C4d

-Cardiovascular: NT-proBNP, Endothelins, proANP, NT-proCNP

About Vanin-1 (VNN1)

Vascular non-inflammatory molecule-1 or VANIN-1 (VNN1) is a protein that is part of the Vanin family of enzymes that possesses pantetheinase activity and primarily carries out its physiological functions through the products of its enzyme catalysis, such as pantothenic acid and cysteamine. VNN1 is involved in various biological processes, including inflammation, oxidative stress, and tissue repair (4). Vanin-1 is primarily expressed in certain tissues, such as the liver, kidneys, and immune cells. The capacity of VNN1 to influence various metabolic pathways and its role in oxidative stress in either worsening or alleviating pathological processes, has led to the hypothesis that it is a crucial factor in disease progression (5).

The potential of Vanin-1 as a marker of acute kidney injury and as a predictor of acute pyelonephritis in young children with urinary tract infection has been investigated, particularly as urinary VNN1 concentrations are higher in these patients (6, 7).

Literature

Peripheral Artery Disease: A Comprehensive Updated Review. Shamaki GR, Markson F, Soji-Ayoade D, Agwuegbo CC, Bamgbose MO, Tamunoinemi BM. Curr Probl Cardiol. 2022; 47(11):101082. doi: 10.1016/j.cpcardiol.2021.101082. PMID: 34906615.
The Impact of Chronic Kidney Disease on Peripheral Artery Disease and Peripheral Revascularization. Serra R, Bracale UM, Ielapi N, Del Guercio L, Di Taranto MD, Sodo M, Michael A, Faga T, Bevacqua E, Jiritano F, Serraino GF, Mastroroberto P, Provenzano M, Andreucci M.Int J Gen Med. 2021; 14:3749-3759. doi: 10.2147/IJGM.S322417. PMID: 34326661.
Urinary vanin-1 as a novel biomarker for survival in peripheral artery disease. Zierfuss B, Karlinger A, Bojic M, Koppensteiner R, Schernthaner GH, Höbaus C. Vasc Med. 2024; 29(4):390-397. doi: 10.1177/1358863X241240428. PMID: 38607943.
Vanin 1: Its Physiological Function and Role in Diseases. Bartucci R, Salvati A, Olinga P, Boersma YL. Int J Mol Sci. 2019; 20(16):3891. doi: 10.3390/ijms20163891. PMID: 31404995.
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FGF23 and its effects on the heart

The BIOMEDICA FGF23 (intact) human ELISA (cat. no. BI-20700)

The BIOMEDICA FGF23 (C-terminal) human multi-matrix ELISA (cat. no. BI-20702)

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About FGF23

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Quantifying circulating FGF23 levels

BIOMEDICA offers quality FGF23 assays for serum & plasma samples

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FGF23 (C-terminal) and FGF23 intact were both measured with an ELISA assay from BIOMEDICA.

Biomarkers in Clinical Nephrology – FGF23 ∙ Endostatin ∙ Periostin ∙ Vanin-1

Abstract

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Tel. +43/1/291 07 45