• home
• C4d Immunostaining and Molecular Tools for Heart Transplant Rejection

C4d Immunostaining and Molecular Tools for Heart Transplant Rejection – Heart transplantation is currently the most effective treatment option for patients with end-stage heart failure unresponsive to optimal medical therapy (1-3). Despite significant advancements in immunosuppressive therapies and transplant management, acute and chronic rejection-related allograft injuries remain among the leading causes of death and morbidity post-transplant, thereby limiting patient longevity. Improving rejection management remains an unmet medical need (5). Currently, the diagnosis of cardiac rejection predominantly depends on the pathological evaluation of endomyocardial biopsies (EMBs), which involves detecting and grading cellular infiltrates and myocardial injury (1, 6, 7).

C4d Immunostaining and Molecular Tools for Heart Transplant Rejection

In a recent study “Heart allograft rejection: molecular diagnosis using intra-graft targeted gene expression profiling” by Giarraputo A and colleagues explore the use of targeted gene expression analysis within cardiac graft tissue to improve the molecular diagnosis of heart transplant rejection. The research aims to identify specific gene expression patterns associated with rejection episodes, providing a potentially more precise and early detection method compared to traditional histopathological assessment. This approach could enhance rejection monitoring and guide more tailored therapeutic interventions in heart transplant recipients.

The study showed that a novel molecular diagnostic system based on formalin-fixed, paraffin-embedded (FFPE) tissue accurately detects cardiac allograft rejection. A tool that could be easily applicable in clinical settings alongside pathology and has the potential to improve the precision of rejection diagnosis.

> C4d antibodies by BIOMEDICA – for the identification of human complement split product C4d in paraffin and frozen sections as well as by flow cytometry. 

Anti-C4dAntibody | BI-RC4D

• widely cited in over 100 publications 

• for immunohistochemistry on paraffin embedded tissue and frozen sections 

• use in kidney, heart, liver and other transplants 

 

Anti-C4d Antibody (FITC) | BI-RC4D-FITC 

• protocol for cell- or solid-phase bound C4 and C4d split product by flow cytometry 

• for kidney, heart, liver and other transplants 

 

 

Literature:

1. 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: The Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC)Developed with the special contribution of the Heart Failure Association (HFA) of the ESC. Ponikowski P, Voors AA, Anker SD, Bueno H, Cleland JGF, Coats AJS, Falk V, González-Juanatey JR, Harjola VP, Jankowska EA, Jessup M, Linde C, Nihoyannopoulos P, Parissis JT, Pieske B, Riley JP, Rosano GMC, Ruilope LM, Ruschitzka F, Rutten FH, van der Meer P; ESC Scientific Document Group. Eur Heart J. 2016 Jul 14;37(27):2129-2200. PMID: 27206819.
2. 2017 ACC/AHA/HFSA Focused Update of the 2013 ACCF/AHA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Failure Society of America. Yancy CW, Jessup M, Bozkurt B, Butler J, Casey DE Jr, Colvin MM, Drazner MH, Filippatos GS, Fonarow GC, Givertz MM, Hollenberg SM, Lindenfeld J, Masoudi FA, McBride PE, Peterson PN, Stevenson LW, Westlake C. Circulation. 2017 Aug 8;136(6):e137-e161. PMID: 28455343.
3. Molecular Diagnosis of Heart Allograft Rejection Using Intra-Graft Targeted Gene Expression Profiling: the heart HistoMX system. Alessia Giarraputo, Guillaume Coutance, JigneshK. Patel, Marny Fedrigo, Olivier Aubert, Jessy Dagobert, Fariza Mezine, Blaise Robin, Philippe Rouvier, Shaida Varnous, Jean Paul Duong Van Huyen, Patrick Bruneval, Annalisa Angelini, Jon Kobashigawa, Alexandre Loupy.
4. Heart allograft rejection: molecular diagnosis using intra-graft targeted gene expression profiling. Giarraputo A, Coutance G, Patel JK, Fedrigo M, Aubert O, Varnous S, Barison I, Castellani C, Duong Van Huyen JP, Dagobert J, Mezine F, Robin B, Zielinski D, Rouvier P, Leprince P, Achouh P, Gerosa G, Verkarre V, Jouven X, Bruneval P, Angelini A, Kobashigawa J, Loupy A. Eur Heart J. 2026 Feb 23;47(8):956-970. PMID: 41342627.
5. The management of antibodies in heart transplantation: An ISHLT consensus document. Kobashigawa J, Colvin M, Potena L, Dragun D, Crespo-Leiro MG, Delgado JF, Olymbios M, Parameshwar J, Patel J, Reed E, Reinsmoen N, Rodriguez ER, Ross H, Starling RC, Tyan D, Urschel S, Zuckermann A. J Heart Lung Transplant. 2018 May;37(5):537-547. doi: 10.1016/j.healun.2018.01.1291. Epub 2018 Jan 31. PMID: 29452978.
6. Heart Transplant Rejection: From the Endomyocardial Biopsy to Gene Expression Profiling. Biomedicines. Farcas AO, Stoica MC, Maier IM, Maier AC, Sin AI.2024 Aug 22;12(8):1926. doi: 10.3390/biomedicines12081926. PMID: 39200392; PMCID: PMC11351478.
7. A Review of Biomarkers of Cardiac Allograft Rejection: Toward an Integrated Diagnosis of Rejection. Coutance G, Desiré E, Duong Van Huyen JP.Biomolecules. 2022 Aug 18;12(8):1135. doi: 10.3390/biom12081135. PMID: 36009029; PMCID: PMC9405997.

Antibody-mediated rejection (ABMR) is the major cause of renal graft dysfunction and loss (1). Currently, renal biopsy remains the gold standard for diagnosing rejection (2). C4d staining in kidney biopsies is widely used to identify the presence of complement activation in the small blood vessels and its deposition is a strong indicator of ABMR (3). In a new study, researchers have used our C4d antibody to identify ABMR and to investigate the diagnostic capacity of non-invasive biomarkers for detecting ABMR in kidney transplant recipients (2).

Kidney Transplant Recipients with Acute Antibody-Mediated Rejection Show Altered Levels of Matrix Metalloproteinases and Their Inhibitors: Evaluation of Circulating MMP and TIMP Profiles. Vázquez-Toledo MA et al., Int J Mol Sci. 2025.

Abstract

Antibody-mediated rejection (ABMR) remains a major cause of renal graft dysfunction and loss. The histological hallmark of antibody-mediated rejection is progressive tissue damage, in which extracellular matrix turnover plays an important role. This turnover is mainly regulated by matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs). Recent studies suggest that MMP/TIMP imbalance may favor the progression of renal damage, inflammation, and fibrosis, but the utility of these molecules as a biomarker of antibody-mediated turnover has not been fully explored. We measured plasma MMP and TIMP levels by ELISA in 15 patients with antibody-mediated renal transplant rejection and 12 patients without rejection. There was a significant increase in MMP-1, MMP-2, and MMP-3 concentrations in the plasma of patients with rejection, directly correlating with the severity of different renal lesions. In contrast, TIMP-3 levels were elevated in patients without rejection, showing a negative correlation with the severity of histopathological lesions. The concentrations of these molecules demonstrated good diagnostic capacity for patients with rejection. Our results show that MMP-1, MMP-2, MMP-3, and TIMP-3 could be potential biomarkers of rejection.

> C4d antibodies by BIOMEDICA – for the identification of human complement split product C4d in paraffin and frozen sections as well as by flow cytometry. 

 

 

Anti-C4dAntibody | BI-RC4D

• widely cited in over 100 publications 

• for immunohistochemistry on paraffin embedded tissue and frozen sections 

• use in kidney, heart, liver and other transplants 

 

Anti-C4d Antibody (FITC) | BI-RC4D-FITC 

• protocol for cell- or solid-phase bound C4 and C4d split product by flow cytometry 

• for kidney, heart, liver and other transplants 

 

Literature:

1. Antibody-mediated rejection of renal allografts: diagnostic pitfalls and challenges. Novotný M, Kment M, Viklický O. Physiol Res. 2021 Dec 30;70(Suppl4):S551-S565. doi: 10.33549/physiolres.934801. PMID: 35199543; PMCID: PMC9054191.
2. Kidney Transplant Recipients with Acute Antibody-Mediated Rejection Show Altered Levels of Matrix Metalloproteinases and Their Inhibitors: Evaluation of Circulating MMP and TIMP Profiles. Vázquez-Toledo MA, Sánchez-Muñoz F, Zepeda-Quiroz I, Guzmán-Martín CA, Osorio-Alonso H, Daniel JV, Soto-Abraham MV, Moguel-González B, Chacón-Salinas R, Flores-Gama C, Springall R.Int J Mol Sci. 2025 Jun 23;26(13):6011. doi: 10.3390/ijms26136011. PMID: 40649789; PMCID: PMC12250063.
3. The importance of C4d in biopsies of kidney transplant recipients. Corrêa RR, Machado JR, da Silva MV, Helmo FR, Guimarães CS, Rocha LP, Faleiros AC, dos Reis MA. Clin Dev Immunol. 2013;2013:678180. doi: 10.1155/2013/678180. Epub 2013 Jul 9. PMID: 23935649; PMCID: PMC3722852.

C4d and graft loss in KTR with IgAN (abbrev. KTR: kidney transplant recipients, IgAN: IgA nephropathy)

C4d analysis has become an important diagnostic tool used in the evaluation of kidney transplant recipients (1). C4d is a fragment of the complement component C4 that is produced during the activation of the complement system. In the context of kidney transplantation, the presence of C4d in peritubular capillaries can indicate antibody-mediated injury and help assess the immune status of the transplanted kidney (2).

Our Anti-C4d Antibody (FITC)  has recently been used in a study evaluating whether recurrent IgA deposition, which is common after kidney transplantation, is associated with an increased risk of graft failure (1).

IgA nephropathy (IgAN) is the most prevalent type of kidney disorder. It can occur at any age but is more frequently diagnosed in young adults and adolescents (3). IgAN is marked by the deposition of immunoglobulin A (IgA) in the glomeruli, the filtering units of the kidney. The deposition of IgA, particularly in the mesangial cells of the glomeruli, leads to inflammation and kidney damage (4). The exact cause of IgAN is not fully understood, but it is believed to involve abnormal IgA production and a dysregulation of the immune system. IgA nephropathy (IgAN) has been shown to be associated with a risk for posttransplant recurrence (5, 6).

 C4d and graft loss in KTR with IgAN

The study involved sixty-seven kidney transplant recipients (KTR) of which 37% had recurrent IgA deposition (1). The results showed that “there were no clinical differences between KTR with and without recurrent IgA deposition. C4d was present in 48% of the biopsies. During a median follow-up of 9.6 [4.8-14] years, 18 (27%) KTR developed death-censored graft failure. Recurrent IgA deposition was not associated with graft failure. Of the evaluated complement factors, only C4d staining was associated with graft failure in KTR with recurrent IgA deposition” .  

The authors concluded that “ recurrent IgA deposition was not associated with graft failure in itself. C4d, when present, is strongly associated with graft loss in KTR with recurrent IgA deposition, suggesting a pathogenic role for the lectin pathway in recurrent IgAN.” (1).

Our C4d antibodies are used to identify the human complement split product C4d in paraffin and frozen sections as well as by flow cytometry.

 Anti-C4d Antibody | BI-RC4D

• widely cited in 100 publications
• for immunohistochemistry on paraffin embedded tissue and frozen sections
• use in kidney, heart, liver and other transplants

Anti-C4d Antibody (FITC) | BI-RC4D-FITC

• detection of cell- or solid-phase bound C4d and C4d split product by flow cytometry using FlowPRA® Class I and II screening test beads from One Lambda.

 

Literature

1. C4d, rather than C3d and C5b-9, is associated with graft loss in recurrent IgA deposition after kidney transplantation. Alkaff FF, Uffing A, Tiller G, Lammerts RGM, van den Heuvel MC, Bajema IM, Daha MR, van den Born J, Berger SP. Am J Nephrol. 2024 Aug 17. doi: 10.1159/000540986. Epub ahead of print. PMID: 39154645.
2. The diagnostic significance of C4d deposits, as an immunohistochemical proof of complement activation, in kidney glomerular pathologies and kidney transplantation. Hresko S, Madarova M, Dobosova M, Palusekova N, Niznerova P, Ziaran S, Varga I. Bratisl Lek Listy. 2024;125(5):275-280. doi: 10.4149/BLL_2024_41. PMID: 38624051.
3. Significance of C4d expression in peritubular capillaries concurrent with microvascular inflammation in for-cause biopsies of ABO-incompatible renal allografts. Cho H, Baek CH, Park SK, Kim H, Go H. Kidney Res Clin Pract. 2024 Jan;43(1):82-92. doi: 10.23876/j.krcp.22.221. Epub 2023 May 12. PMID: 37448281; PMCID: PMC10846988.
4. Complement Activation Is Associated With Crescents in IgA Nephropathy. Wang Z, Xie X, Li J, Zhang X, He J, Wang M, Lv J, Zhang H. Front Immunol. 2021 Sep 14;12:676919. doi: 10.3389/fimmu.2021.676919. PMID: 34594322; PMCID: PMC8477028.
5. Risk for graft loss in pediatric and young adult kidney transplant recipients due to recurrent IgA nephropathy. Engen RM, Bartosh SM, Smith JM, Perkins JD, Harshman LA.Am J Transplant. 2024 Jan;24(1):37-45. doi: 10.1016/j.ajt.2023.08.007. Epub 2023 Aug 16. PMID: 37595842.
6. Recurrence of IgA Nephropathy after Kidney Transplantation in Adults. Uffing A, Pérez-Saéz MJ, Jouve Tet al.,. Clin J Am Soc Nephrol. 2021 Aug;16(8):1247-1255. doi: 10.2215/CJN.00910121. PMID: 34362788; PMCID: PMC8455056.

In kidney transplantation recipients antibody mediated rejection (AMR) is a common complication that contributes to graft loss. C4d staining in kidney biopsies is widely used to identify the presence of complement activation in the small blood vessels of the kidney. Therefore C4d has been recognized as a marker for identifying AMR in kidney transplants (1).

C4d a biomarker of transplant rejection

 

C4d antibodies by Biomedica – for the identification of human complement split product C4d in paraffin and frozen sections as well as by flow cytometry.

Anti-C4d Antibody | BI-RC4D

• widely cited in over 90 citations
• for immunohistochemistry on paraffin embedded tissue and frozen sections
• use in kidney, heart, liver and other transplants

 

Anti-C4d Antibody (FITC) | BI-RC4D-FITC

• protocol for cell- or solid-phase bound C4 and C4d split product by flow cytometry
• for kidney, heart, liver and other transplants

 

The Biomedica C4d antibody was highlighted in the following publication: Response to treatment and long-term outcomes in kidney transplant recipients with acute T cell-mediated rejection. “Complement split product C4d staining was performed by immunochemical analysis of paraffin sections using polyclonal human anti‐C4d antibodies (Biomedica Gruppe, Vienna, Austria)”.

 

Literature

1. The Banff 2019 Kidney Meeting Report (I): Updates on and clarification of criteria for T cell- and antibody-mediated rejection. Loupy A, Haas M, Roufosse C, Naesens M, Adam B, Afrouzian M, Akalin E, Alachkar N, Bagnasco S, Becker JU, Cornell LD, Clahsen-van Groningen MC, Demetris AJ, Dragun D, Duong van Huyen JP, Farris AB, Fogo AB, Gibson IW, Glotz D, Gueguen J, Kikic Z, Kozakowski N, Kraus E, Lefaucheur C, Liapis H, Mannon RB, Montgomery RA, Nankivell BJ, Nickeleit V, Nickerson P, Rabant M, Racusen L, Randhawa P, Robin B, Rosales IA, Sapir-Pichhadze R, Schinstock CA, Seron D, Singh HK, Smith RN, Stegall MD, Zeevi A, Solez K, Colvin RB, Mengel M. Am J Transplant. 2020 Sep;20(9):2318-2331. doi: 10.1111/ajt.15898. Epub 2020 May 28. PMID: 32463180; PMCID: PMC7496245.

 

Liver transplantation has become a routine treatment for children with end stage liver failure. Antibody-mediated rejection of the transplant can be monitored by C4d.  This recent study utilized the Biomedica “anti-C4d antibody”:

Liver Histopathology in Late Protocol Biopsies after Pediatric Liver Transplantation.

Markiewicz-Kijewska M, Szymańska S, Pyzlak M, Kaliciński P, Teisseyre J, Kowalski A, Jankowska I, Czubkowski P, Ismail H. Children (Basel). 2021 Aug 1;8(8):671. doi: 10.3390/children8080671. PMID: 34438562; PMCID: PMC8392008.

Liver Transplant: antibody-mediated rejection monitored by C4d

Anti-C4d Antibody Features

√  CE-marked – for IVD use in the EU
√   Widely cited for ICH
√   For kidney, heart, liver and other transplants
Check out the Biomedica anti-C4d antibodies for ICH and FITC.

Abstract

Liver transplantation has become a routine treatment for children with end stage liver failure. Recently, the long term survival of pediatric patients after liver transplantation has improved, with a life expectancy much longer than that of adult recipients, but also with longer exposition of the graft to various injuries, including immunological, inflammatory and others. Biochemical tests, although important, do not always reflect graft injury. The aim of our study was to analyze the histopathology of the graft in late protocol biopsies and correlate it with the clinical and biochemical status of these patients. We analyzed 61 protocol liver biopsies taken from 61 patients. Biopsies were taken 9.03-17.09 years (mean 12.68, median 11.74 years) after transplantation. Liver specimens were examined particularly for the presence and stage of liver fibrosis, inflammation, steatosis, and acute or chronic cellular and humoral rejection. We did not find any abnormalities in 26 (42.6%) liver specimens. None of the patients had signs of cellular or antibody mediated rejection or chronic rejection. In 23 liver biopsies (37.7%), we found non-specific lymphoid infiltrates. Another problem was fibrosis (equal to or more than three on the Ishak scale)-we found it in 17 patients, including seven liver specimens (11.5%) with severe fibrosis (Ishak 5-6). Conclusions: Various pathomorphological abnormalities were found in more than half of patients with a median 11.74 years post-transplant follow-up. Most of them presented normal laboratory liver tests at the same time, suggesting a slow subclinical process leading to pathomorphological abnormalities. No single factor for the development of these abnormalities was found, but our study supports the need for protocol liver biopsies even in patients with normal/almost normal biochemical liver tests.

Liver Transplant: antibody-mediated rejection monitored by C4d

 Related publications

Immunostaining Patterns of Posttransplant Liver Biopsies Using 2 Anti-C4d Antibodies  

Chen L, Himmelfarb EA, Sun M, Choi EK, Fan L, Lai J, Kim CJ, Xu H, Wang HL. Appl Immunohistochem Mol Morphol. 2020 Feb;28(2):146-153. doi: 10.1097/PAI.0000000000000723. PMID: 32044883.  

Citation Biomedica C4d antibody (purchased through Alpco, US, cat. no. BI-RC4D)

 Abstract

Histopathologic diagnosis of antibody-mediated rejection in posttransplant liver biopsies is challenging. The recently proposed diagnostic criteria by the Banff Working Group on Liver Allograft Pathology require positive C4d immunohistochemical staining to establish the diagnosis. However, the reported C4d staining patterns vary widely in different studies. One potential explanation may be due to different antibody preparations used by different investigators. In this study, posttransplant liver biopsies from 69 patients histopathologically diagnosed with acute cellular rejection, chronic rejection, or recurrent hepatitis C were immunohistochemically stained using 2 polyclonal anti-C4d antibodies. On the basis of the distribution of C4d immunoreactivity, 5 different staining patterns were observed: portal vein and capillary, hepatic artery, portal stroma, central vein, and sinusoids. The frequency, extent, and intensity of positive C4d staining with the 2 antibody preparations differed significantly for portal veins/capillaries and central veins, but not for hepatic arteries and portal stroma. Positive sinusoidal staining was seen in only 1 case. There were no significant differences in the frequency, extent, and intensity of positive C4d staining among the acute cellular rejection, chronic rejection, and recurrent hepatitis C groups with the 2 anti-C4d antibodies. These data show that different anti-C4d antibodies can show different staining patterns, which may lead to different interpretation. Caution is thus needed when selecting C4d antibodies for clinical use to aid in the diagnosis of antibody-mediated rejection.

Antibody-Mediated Rejection After Liver Transplant  

Lee M. Gastroenterol Clin North Am. 2017 Jun;46(2):297-309. doi: 10.1016/j.gtc.2017.01.005. PMID: 28506366.

Abstract

Antibody-mediated rejection (AMR) in liver transplants is a field in its infancy compared with its allograft cohorts of the kidney and lung. Acute AMR is diagnosed based on specific clinical and histopathologic criteria: serum donor specific antibodies, C4d staining, histopathologic findings on liver biopsy, and exclusion of other entities. In contrast, the histologic features of chronic AMR are not as specific and it is a more challenging diagnosis to make. Treatments of acute and chronic AMR include some combination of steroids, immune-modulating agents, intravenous immunoglobulin, plasmapheresis, and proteasome inhibitors.

Routine C4d immunohistochemistry in cardiac allografts: Long-term outcomes

Husain AN, Mirza KM, Fedson SE. J Heart Lung Transplant. 2017 Dec;36(12):1329-1335. doi: 10.1016/j.healun.2017.09.004. Epub 2017 Sep 14. PMID: 28988608.

 C4d immunostaining is an independent predictor of cardiac allograft vasculopathy and death in heart transplant recipients

Luk A, Alba AC, Butany J, Tinckam K, Delgado D, Ross HJ. Transpl Int. 2015 Jul;28(7):857-63. doi: 10.1111/tri.12560. Epub 2015 Mar 27. PMID: 25778989.

 

C4d has been regarded as an indirect footprint of an antibody-mediated response against an allograft. While C4d has emerged as a potential marker for antibody-mediated-rejection (AMR) after transplantation over the last decade, its use as a prognostic tool is still under debate.

A recent study has shown a positive association of C4d with cardiac allograft vasculopathy and death in heart transplant recipients. Late C4d positivity (> 1-year post-transplant) demonstrated an even higher risk for developing cardiac allograft vasculopathy and poor prognosis than early C4d positivity (within 1 year). The authors of the study suggest a prognostic role for C4d in heart transplantation warranting routine long-term detection of this marker in the pathologic evaluation of cardiac AMR.

Biomedica’s Anti C4d Antibodies allow the identification of human complement split product C4d in paraffin and frozen sections, and by flow cytometry.

Husain et al. Routine C4d immunohistochemistry in cardiac allografts: Long-term outcomes. J Heart Lung Transplant 2017: 36(12):1329-1335

Check out the Biomedica anti-C4d antibodies for ICH and FITC.

Anti-C4d Antibody Highlights:

• 
  Most referenced for immunohistochemistry on paraffin embedded tissue sections
• 
  For kidney, heart, liver and other transplants

With more than 40 years of expertise in developing and manufacturing high-quality ELISA kits, we support scientists and healthcare professionals with reliable tests that drive discovery and help translate research into diagnostics.

All kits are developed and manufactured by Biomedica Immunoassays — Austrian quality you can trust.

Explore Our Biomarker ELISA Assays

Explore our trusted and widely cited ELISA assays for biomarkers in bone metabolism, cardiovascular and renal diseases, cancer, and oxidative stress.

Biomedica ELISA Kits: Features & Benefits

-Easy to use: Ready-to-use calibrators and controls included, with color-coded reagents

-Comprehensive validation package: Assays optimized for clinical samples in accordance with high-level international quality standards

-Guaranteed high quality: Reliable results you can trust

-Widely cited: Referenced in more than 2,500 publications

 

Biomedica provides high-quality ELISA kits for key bone biomarkers

Explore Our Biomarker ELISA Assays

 

BONE & MINERAL METABOLISM

 Biomedica provides high-quality ELISA kits for key bone biomarkers

SCLEROSTIN ELISA – SOST (cat. no. BI-20492)

OPG ELISA – Osteoprotegerin (cat. no. BI-20403)

RANKL ELISA–– soluble RANKL (cat. no. BI-20462)

DKK-1 ELISA – Dickkopf-1 (cat. no. BI-20413)

FGF23 intact ELISA – Fibroblast Growth Factor-23 intact (cat. no. BI-20700)

FGF23 C-terminal ELISA – Fibroblast Growth Factor-23 C-terminal (cat. no. BI-20702)

PERIOSTIN ELISA – POSTN (cat. no. BI-20433)

 related citations:

• Sclerostin ELISA (BI-20492) and DKK-1 ELISA (BI-20413): Sclerostin and DKK1 circulating levels associate with low bone turnover in patients with chronic kidney disease Stages 3 and 4.
• FGF23 C-terminal (BI-20702) and FGF intact ELISA (BI-20700): C-terminal and intact FGF23 in kidney transplant recipients and their associations with overall graft survival.  

 

CARDIOVASCULAR

NT-proBNP ELISA (cat.no. SK-1204)

rat NT-proBNP ELISA (cat.no. BI-1204R)

NT-proANP,  ELISA human, rodent  (cat.no. BI-20892)

NT-proCNP ELISA (cat.no. BI-20812)

Big Endothelin-1 ELISA (cat. no. BI-20082H)

Endostatin ELISA (cat. no. BI-20742)

Leucine-rich alpha-2-glycoprotein (LRG) ELISA (cat. no. BI-LRG)

 related citations:

•  Big Endothelin-1 ELISA (cat. no. BI-20082H) : Prognostic Value of Plasma Big Endothelin-1 in Patients Hospitalized for Heart Failure.
• NT-proBNP ELISA (cat.no. SK-1204): Intravenous mesenchymal stem cell transplantation mitigates pulmonary vascular remodeling but poses dose related risks in a pulmonary veno-occlusive disease model
• NT-proANP ELISA : Acute and Short‐Term Hemodynamic and Echocardiography Changes During and After Left Atrial Appendage Closure
• NT-proCNP ELISA (cat.no. BI-20812) : C-Type Natriuretic Peptide Preserves Vascular and Cardiac Function in Sepsis

 

KIDNEY & TRANSPLANT

Vanin-1 (urine) ELISA  (cat. no. BI-VAN1U)

FGF23 intact ELISA – Fibroblast Growth Factor-23 intact (cat. no. BI-20700)

FGF23 C-terminal ELISA – Fibroblast Growth Factor-23 C-terminal (cat. no. BI-20702)

Human IL-6 ELISA Kit (cat. no.  BI-IL6)

Human Endostatin ELISA (cat. no. BI-20742)

Anti-C4d Antibody (cat. no. BI-RC4D)

related citations:

• Human Vanin-1 (urine) ELISA (cat. no. BI-VAN1U): Urinary vanin-1 as a novel biomarker for survival in peripheral artery disease
• Vanin-1 ELISA (BI-VAN1U) and PERIOSTIN ELISA POSTN (cat. no. BI-20433): The Usefulness of Vanin-1 and Periostin as Markers of an Active Autoimmune Process or Renal Fibrosis in Children with IgA Nephropathy and IgA Vasculitis with Nephritis-A Pilot Study

• Anti-C4d Antibody (cat. no. BI-RC4D): Thirty-year follow-up of immunosuppression modulation: Impact on graft fibrosis and anti-HLA antibodies after pediatric liver transplantation

 

ONCOLOGY

FREE soluble RANKL HS ELISA | BI-20462

Human Periostin ELISA | BI-20433

Human DKK1 ELISA Kit | BI-20413

Leucine-rich alpha-2-glycoprotein (LRG1) ELISA | BI-LRG

related citations:

• LRG-1 ELISA (BI-LRG): High serum levels of leucine-rich α-2 glycoprotein 1 (LRG-1) are associated with poor survival in patients with early breast cancer. 
• FREE soluble RANKL HS ELISA | BI-20462: Retrospective Evaluation of Bone Turnover Markers in Serum for the Prediction of Metastases Development in Breast Cancer Patients: A Cohort Study

 

OXIDATIVE STRESS 

 oLAB (Anti-Oxidized LDL Autoantibodies) ELISA | BI-20032

OxyStat Assay – detection of biological peroxides | BI-5007

related citations:

•  oxLDL – oLAB ELISA (BI-20032): Overview of Clinical Relevance of Antibodies Against Oxidized Low-Density Lipoprotein (oLAb) Within Three Decades by ELISA Technology
• OxyStat Assay – The role of seminal reactive oxygen species assessment in the setting of infertility and early pregnancy loss

Understanding how immunosuppressants in transplant therapy cause blood vessel damage – C4d staining in liver tissue

The study titled “Modeling antithymocyte globulin-induced microvasculopathy using human iPSC-derived vascularized liver organoids” aims to better understand the vascular side effects caused by antithymocyte globulin (ATG), a drug used in transplant medicine. Researchers created vascularized liver organoids from human induced pluripotent stem cells (iPSCs) to simulate human liver blood vessels. Using this model, they investigated how ATG induces microvasculopathy, or small blood vessel damage. This platform offers new insights into the mechanisms of ATG-related vascular injury and could help develop safer treatments to reduce side effects in transplant patients.

C4d staining in Paraffin-Embedded (FFPE) liver tissue was performed with the BIOMEDICA anti-C4d antibody.

Anti-C4d Antibody | BI-RC4D 

for the identification of human complement split product C4d in paraffin and frozen sections as well as by flow cytometry.

 Product Highlights:

 Anti-C4d Antibody  cat. no. BI-RC4D

• TRUSTED – widely cited in over 100 citations
• MULTI-USE – for immunohistochemistry on paraffin embedded tissue and frozen sections
• The C4d antibody has been utilized in kidney, heart, liver and other transplants
• working protocol

 

Anti-C4d Antibody (FITC) | BI-RC4D-FITC

• Protocol for cell- or solid-phase bound C4 and C4d split product by flow cytometry
• working protocol

-Discover our anti-C4d antibodies for IHC and FITC.

 

How Immunosuppressants in Transplant Therapy cause Blood Vessel Damage

Publication: Modeling antithymocyte globulin-induced microvasculopathy using human iPSC-derived vascularized liver organoids. Kawamura S, Yoneyama Y, Saiki N, Wu Y, Moriya C, Ohmura R, Maezawa M, Shimada Y, Wang Y, Mori K, Okada N, Onishi Y, Sanada Y, Hirata Y, Sakuma Y, Takebe T. Cell Rep Med. 2025 Nov 18;6(11):102433. doi: 10.1016/j.xcrm.2025.102433. Epub 2025 Nov 6. PMID: 41202806; PMCID: PMC12711670.

Abstract

Antithymocyte globulin (ATG) is a widely used immunosuppressive agent, yet its off-target vascular effects remain a clinical challenge in part due to a lack of relevant human models. Here, we uncover a biphasic mechanism of ATG-induced microvasculopathy using a humanized liver organoid platform derived from induced pluripotent stem cells (iPSCs). We show that ATG triggers a rapid, complement-dependent phase of injury restricted to human iPSC-derived liver sinusoidal endothelial cells (iLSECs), leading to C3 deposition and acute thrombosis specifically in human but not in mouse vessels. Transcriptomics reveals a delayed transforming growth factor β (TGF-β) pathway-driven proinflammatory program that coincides with neutrophil recruitment and degranulation, while pharmacological TGF-β blockade attenuates thrombosis and flow disturbance. Our findings reveal a pathogenic sequence of complement and TGF-β pathway activation and establish a translational platform for dissecting human liver-specific microvasculopathy in vivo.

Related literature

Anti-thymocyte globulin-induced hyperbilirubinemia in patients with myelofibrosis undergoing allogeneic hematopoietic cell transplantation. Ecsedi M, Schmohl J, Zeiser R, Drexler B, Halter J, Medinger M, Duyster J, Kanz L, Passweg J, Finke J, Bethge W, Lengerke C. Ann Hematol. 2016 Oct;95(10):1627-36. doi: 10.1007/s00277-016-2758-z. Epub 2016 Aug 2. PMID: 27480090.

Complement component 4d immunostaining in liver allografts of patients with de novo immune hepatitis. Aguilera I, Sousa JM, Gavilan F, Gomez L, Alvarez-Márquez A, Núñez-Roldán A. Liver Transpl. 2011 Jul;17(7):779-88. doi: 10.1002/lt.22302. PMID: 21425430.

Influence of preformed donor-specific antibodies and C4d on early liver allograft function. Perera MT, Silva MA, Murphy N, Briggs D, Mirza DF, Neil DA. Scand J Gastroenterol. 2013 Dec;48(12):1444-51. doi: 10.3109/00365521.2013.845795. Epub 2013 Oct 16. PMID: 24131305.

 

 

Approximately 1 in 10 people are affected by chronic kidney disease (CKD), impacting over 800 million individuals globally (1-3). CKD is a progressive condition where the kidneys gradually lose their ability to function properly.

Early intervention is essential to preserving kidney health, slowing the progression of kidney disease and its complications, decreasing the risk of risk of cardiovascular disease, and preventing early death related to kidney and cardiovascular conditions (4).

World Kidney Day – March 12, 2026

What are the contributing factors to CKD?

Age over 60, diabetes, high blood pressure, heart disease, obesity, and certain medications are some of the known risk factors for kidney disease. 

 How can we maintain healthy kidneys?

Good nutrition, regular exercise, and adequate fluid intake are some of the ways to support kidney health.

Are your kidneys healthy? Take the quiz

 

 BIOMEDICA´s Biomarker ELISA Kits in Clinical Nephrology

• FGF23 (C-terminal) |BI-20700 and FGF23 intact ELISA |BI-20700
• Vanin-1 (urine) ELISA | BI-VAN1U  
• Endostatin ELISA | BI-20742
• Periostin ELISA | BI-20422
• Sclerostin ELISA |BI-20492 and Bioactive Sclerostin ELISA |BI-20472

 

 

Related Products:

Osteoprotegerin ELISA, NT-proBNP ELISA, Anti-C4d Antibody

Why laboratories choose BIOMEDICA ELISA kits

• ROBUST & RELIABLE ASSAYS
• Widely cited in over 1700 peer-reviewed publications
• Validated according to international guidelines
• High specificity, enabling reliable biomarker measurement in healthy individuals

 

Are you planning a clinical study ELISA kits for clinical research in kidney disease

Biomarkers in Clinical Nephrology – check out our broshure

 More information on kidney health can be found on the following websites:

1. ISN, World Kidney Day 2026 – International Society of Nephrology
2. Are your kidneys healthy- Quiz – 20 years World Kidney Day
3. Detect early, protect kidney health: World Kidney Day 2025. Waith FM, Bresolin NL, Antwi S. Pediatr Nephrol. 2025 May;40(5):1511-1514. doi: 10.1007/s00467-025-06714-4. Epub 2025 Feb 17. PMID: 39960639. For full publication- click here 
4. Are your kidneys ok? Detect early to protect kidney health. Vassalotti JA, Francis A, Soares Dos Santos AC Jr, Correa-Rotter R, Abdellatif D, Hsiao LL, Roumeliotis S, Haris A, Kumaraswami LA, Lui SF, Balducci A, Liakopoulos V; World Kidney Day Joint Steering Committee. Ren Fail. 2025 Dec;47(1):2503514. PMID: 40394853

 

Abstract

Early identification of kidney disease can protect kidney health, prevent kidney disease progression and related complications, reduce cardiovascular disease risk and decrease mortality. We must ask “Are your kidneys ok?” using serum creatinine to estimate kidney function and urine albumin to assess for kidney and endothelial damage. Evaluation for causes and risk factors for chronic kidney disease (CKD) includes testing for diabetes and measurement of blood pressure and body mass index. This World Kidney Day we assert that case-finding in high-risk populations, or even population level screening, can decrease the burden of kidney disease globally. Early-stage CKD is asymptomatic, simple to test for and recent paradigm shifting CKD treatments such as sodium glucose co-transporter-2 inhibitors dramatically improve outcomes and favor the cost-benefit analysis for screening or case-finding programs. Despite this, numerous barriers exist, including resource allocation, healthcare funding, healthcare infrastructure and healthcare-professional and population awareness of kidney disease. Coordinated efforts by major kidney non-governmental organizations to prioritize the kidney health agenda for governments and aligning early detection efforts with other current programs will maximize efficiencies.

Additonal publications:

IPNA’s commitment to world kidney day 2026: caring for little kidneys and protecting the planet. Shroff R, Sivaram P, Tarter A, Phiri EM, Antwi S, Ocheke I, Penido MG, Mccarthy F, Lou-Meda R, Adalat S, He G, Kermond R, Bayazit AK, Raina R; IPNA Green Nephrology Taskforce, IPNA Special Projects Committee. Pediatr Nephrol. 2026 Feb 24. PMID: 41733668.

Thirty-Year Outcomes of Immunosuppression Modulation

Over the past six decades, organ transplantation, especially pediatric liver transplantation, has revolutionized medical care by offering life-saving treatment options for children with end-stage liver disease (1). In a recent study, researchers investigated on how immunosuppressive therapy affects liver transplant outcomes in children during a thirty-year follow-up (2). Although pediatric liver transplantation is a life-saving procedure, it presents ongoing long-term challenges associated with immunosuppression (IS). Patients were classified according to their immunosuppression status at the final follow-up into three groups.

Pediatric Liver Transplantation

Thirty-Year Outcomes of Immunosuppression Modulation

Key Findings:
• The favorable histology and antibody profile observed in the IS-free group suggest the potential for sustained immune tolerance.
• Ongoing fibrosis in the IS-resumption group underscores the limitations of traditional immunosuppression strategies.
• Regular histological assessments and antibody monitoring may be beneficial for long-term immunosuppression management in pediatric liver transplant patients.

 

C4d a biomarker of transplant rejection

BIOMEDICA´s Anti-C4d Antibody Features – for the identification of human complement split product C4d in paraffin and frozen sections as well as by flow cytometry.

 

 Anti-C4d Antibody | BI-RC4D

• TRUSTED – widely cited in over 100 citations
• MULTI-USE – for immunohistochemistry on paraffin embedded tissue and frozen sections
• The C4d antibody has been utilized in kidney, heart, liver and other transplants
• working protocol

 

Anti-C4d Antibody (FITC) | BI-RC4D-FITC

• Protocol for cell- or solid-phase bound C4 and C4d split product by flow cytometry
• working protocol

 

-Explore our anti-C4d antibodies for IHC and FITC.

 

 

 

 

 

 

With over 30 years of experience in developing and manufacturing high quality ELISA kits we provide scientists and healthcare professionals with tests that enable discoveries and support the translation of research into diagnostics.

All Kits are developed & manufactured by Biomedica Immunoassays – Austrian Quality!

 

Discover our Biomarker ELISA Kit Collection

Trusted and widely cited ELISA assays for biomarkers in bone metabolism, cardiovascular and renal diseases, cancer and oxidative stress.

Biomedica´s ELISA Kits – Features & Benefits

• EASY – ready to use calibrators & controls included (color-coded reagents)
• FULL VALIDATION PACKAGE – assays are optimized for clinical samples following high level international quality standards.
• HIGH QUALITY GUARANTEED – results you can rely on
• WIDELY CITED in over 2500 publications

 

Discover our Biomarker ELISA Kit Collection

BONE 

Sclerostin (SOST), Osteoprotegerin (OPG), Free soluble RANKL (sRANKL), Periostin (POSTN)

Fibroblast Growth Factor (C-terminal and intact) FGF23 intact, FGF23 (C-terminal)

related citations:

• Sclerostin ELISA (BI-20492) : The effect of calcium supplementation on bone calcium balance and calcium and bone metabolism during load carriage in women: a randomized controlled crossover trial. 
• FGF23 ELISAs (BI-20702, BI-20700): C-terminal and intact FGF23 in kidney transplant recipients and their associations with overall graft survival. 

 

CARDIOASCULAR

Natriuretic Peptides: NT-proANP (for human and preclinical use), NT-proBNP, NT-proCNP,                  

Endothelins: Big Endothelin-1 (Big ET-1)

Rat NT-proBNP

• related citation: rat NT-proBNP ELISA (BI-1204R): Leucine Supplementation Improves Diastolic Function in HFpEF by HDAC4 Inhibition.

 

KIDNEY   

Endostatin, Vanin-1

• related citation Vanin-1 ELISA (BI-VAN1U): The Usefulness of Vanin-1 and Periostin as Markers of an Active Autoimmune Process or Renal Fibrosis in Children with IgA Nephropathy and IgA Vasculitis with Nephritis-A Pilot Study. 

 

CANCER

Semaphorin 4D, Neuropilin-1, Leucine-rich alpha-2-glycoprotein (LRG1), Periostin 

• related citation LRG-1 ELISA (BI-LRG): High serum levels of leucine-rich α-2 glycoprotein 1 (LRG-1) are associated with poor survival in patients with early breast cancer. 

 

OXIDATIVE STRESS   

Autoantibodies to oxidized low density lipoprotein (anti-oxLDL AB – oLAB)

OxyStat – detection of biological peroxides

• related citation oxLDL – oLAB ELISA (BI-20032): Novel approaches for the assessment of relative body weight and body fat in diagnosis and treatment of anorexia nervosa: A cross-sectional study.

 

TRANSPLANTATION    

anti-C4D antibody

• related citation anti-C4d Antibody (BI-RC4D): Complement Activation Is Associated With Crescents in IgA Nephropathy. 

 

Biomedica also offers Custom Analytical Service Measurements

• ELISA & LUMINEX
• NEXT-GENERATION SEQUENCING
• RT-QPCR MICRORNA SERVICES

Does active Vitamin D prevent bone loss?

Kidney transplant recipients are at increased risk of bone loss due to the effects of medication and metabolic changes. In a study by Khairallah P et al, researchers evaluated whether oral calcitriol (active vitamin D) could help prevent bone loss in patients managed with steroid-free immunosuppression. Sixty-seven patients were randomized to receive either calcitriol or a placebo for 12 months. The results showed no significant differences in bone density, quality, or strength between the two groups. Biochemical markers evolved similarly in both groups as well. However, the incidence of hypercalcemia was higher among those taking calcitriol compared to placebo. The study concluded that calcitriol does not prevent bone loss and may raise the risk of hypercalcemia, suggesting that routine use may not be necessary if vitamin D levels are sufficient.

Osteoporosis after Kidney Transplantation

Calcitriol supplementation after kidney transplantation: results of a double-blinded, randomized, placebo-controlled trial. Khairallah P et al., J Bone Miner Res. 2025 May 24;40(5):603-616. doi: 10.1093/jbmr/zjaf044. PMID: 40089990; PMCID: PMC12103722.

Abstract

A significant number of kidney transplant recipients have low BMD. We hypothesized that calcitriol administration over the first year posttransplantation would protect the cortical skeleton in recipients managed without corticosteroids by suppressing PTH and bone remodeling. In this double-blind, placebo-controlled trial, 67 participants aged ≥18 yr on corticosteroid-sparing immunosuppressive regimen were randomized to daily calcitriol 0.5 μg or placebo for 12 mo after transplantation. The primary endpoint was the percent change in cortical density at the radius and tibia from pre- to postcalcitriol treatment compared to placebo as measured by HR-pQCT. Areal BMD was measured by DXA. Cortical and trabecular volumetric BMD and microarchitecture and total estimated bone strength were measured by HR-pQCT. Blood samples for bone metabolic markers were obtained at baseline, 1- and 12 mo. All primary analyses were intent to treat. Safety was assessed for hypercalcemia and progression of vascular calcifications. Thirty-two participants received calcitriol and 29 received placebo; 27 and 27 participants completed the study, respectively. Most participants were male and Caucasian. Baseline Z-scores at all sites were within 0.5 SD of the general population. At 12 mo posttransplantation, there were no between-group differences in areal BMD, volumetric BMD, microarchitecture or bone strength, or serum levels of bone markers. Participants with versus without bone loss had a blunted anabolic response over 12 mo measured by serum bone markers. Hypercalcemia was higher in the calcitriol group compared to placebo (p < .001). No changes in arterial calcification scores were observed. In this randomized placebo-controlled study of calcitriol administration in kidney transplant recipients on corticosteroid-sparing immunosuppression, calcitriol did not improve bone quality and strength but was associated with higher rates of hypercalcemia.

One of the biochemical markers analysed in the study above was FGF23, measured with the BIOMEDICA.

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

• RELIABLE – validated following international quality guidelines
• CITED in over 80 publications
• EASY – 8 standards and 2 controls included
• For SERUM & PLASMA samples
• HIGH QUALITY guaranteed!

 

 

 

 

Literature

Osteoporosis after kidney transplantation-no place for active vitamin D in the prevention of bone loss. Jørgensen HS, Evenepoel P. J Bone Miner Res. 2025 May 24;40(5):567-568. doi: 10.1093/jbmr/zjaf049. PMID: 40156932.

Bone Disease in Chronic Kidney Disease and Kidney Transplant. Bellorin-Font E, Rojas E, Martin KJ. Nutrients. 2022 Dec 29;15(1):167. doi: 10.3390/nu15010167. PMID: 36615824; PMCID: PMC9824497.

Big ENDOTHELIN-1 a prognostic marker in CAD.  Endothelin-1 (ET-1) is the most potent vasoconstrictor peptide. This 21 amino acid peptide is the biologically active from that is rapidly cleared from the circulation. Its low concentrations and short half-life make it challenging to detect in serum and plasma samples. Big-Endothelin-1 (BigET-1) is the precursor peptide in the synthesis of Endothelin-1 (ET-1).  It circulates in higher concentrations  and also has a much longer half-life than ET-1. Therefore, measurement of plasma BigET-1 levels are an alternative approach for the indirect estimation of ET-1 release (1).

BigET-1 is primarily produced by endothelial cells and is produced through cleavage of “preproendothelin”, a larger precurser protein. The conversion of BigET-1 to the biologically active 21 amino acid ET-1, is a result the proteolytic cleavage by endothelin-converting enzymes (ECEs) (2). Big-ET-1 has been reported as an independent predictor of cardiovascular mortality in patients with chronic heart failure as determined in a large cohort study in more than 2800 individuals (3). In addition, Big ET-1 has been shown to be a strong and independent predictor of mortality in patients with moderate to severe light chain cardiac amyloidosis (AL-CA) , which may indicate a possible role for risk stratification in patients with this disease (4).

Big ENDOTHELIN-1 can easily be measured in serum and plasma samples.

Biomedica Big Endothelin ELISA Assay 

• EASY – can be used in every lab
• ROBUST & fully VALIDATED (following international quality guidelines)
• HIGHLY SENSTIVE – 0.02 pmol/l (= 0.086 pg/ml)
• GOOD ANALYTE STABILITY in serum and plasma

 

Download your protocol booklet  here

Big ENDOTHELIN-1 a prognostic marker in CAD

The Biomedica BigET-1 ELISA assay was highlighted in this large cohort study of nearly 8000 prediabetic and diabetic patients with stable Coronary Artery Disease (CAD): Prognostic Value of Plasma Endothelin-1 in Predicting Worse Outcomes in Patients with Prediabetes and Diabetes and Stable Coronary Artery Diseases. Yang C et al., Diabetes Metab J. 2024. 

Key findings

• Plasma BigET-1 level is an independent predictor of #cardiovascular events (CVEs) in patients with stable CAD. 

• BigET-1 remains independently associated with worse cardiovascular outcomes in prediabetic and diabetic patients but not in patients with normoglycemia.

• Patients with diabetes and high BigET-1 levels were associated with the highest risk of CVEs in patients with stable CAD.
• Targeting ET-1 pathways may help manage CAD in individuals with dysglycemia.

 

Literature

1. Biomarkers and Precision Medicine in Heart Failure . Nasrien E. Ibrahim et al., Heart Failure: a Companion to Braunwald’s Heart Disease (Fourth Edition), 2020.
2. Endothelin-1 levels and cardiovascular events. Jankowich M, Choudhary G. Trends Cardiovasc Med. 2020 Jan;30(1):1-8. doi: 10.1016/j.tcm.2019.01.007.PMID: 30765295.
3. Propeptide big-endothelin, N-terminal-pro brain natriuretic peptide and mortality. The Ludwigshafen risk and cardiovascular health (LURIC) study. Gergei I, Krämer BK, Scharnagl H, Stojakovic T, März W, Mondorf U. Biomarkers. 2017; 22(3-4):315-320. doi: 10.1080/1354750X.2016.1252969. PMID: 27788598.
4. Prognostic value of plasma big endothelin-1 in patients with light chain cardiac amyloidosis. Chen Z, Shi A, Wang Z, Chen Y, Lin Y, Su M, Dong H, Laptseva N, Hu Y, Flammer AJ, Duru F, Jin W, Chen L. Heart. 2024; 26;110(18):1124-1132. doi: 10.1136/heartjnl-2024-324000. PMID: 39084705.
5. Prognostic Value of Plasma Endothelin-1 in Predicting Worse Outcomes in Patients with Prediabetes and Diabetes and Stable Coronary Artery Diseases. Yang C, Zhu CG, Guo YL, Wu NQ, Dong Q, Xu RX, Wu YJ, Qian J, Li JJ. Diabetes Metab J. 2024 Sep;48(5):993-1002. doi: 10.4093/dmj.2023.0410. Epub 2024 Aug 21. PMID: 39165112.

 

Further reading

• Plasma concentration of big endothelin-1 and its relation with plasma NT-proBNP and ventricular function in heart failure patients. Rivera M, Cortés R, Portolés M, Valero R, et al., Rev Esp Cardiol. 2005 Mar;58(3):278-84. Spanish. PMID: 15766450.

• Endothelin: 30 Years From Discovery to Therapy. Barton M, Yanagisawa M. Hypertension. 2019; 74(6):1232-1265.

 

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

1. 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.
2. 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.
3. 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.
4. 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.
5. Vanin1 (VNN1) in chronic diseases: Future directions for targeted therapy. Yu H, Cui Y, Guo F, Zhu Y, Zhang X, Shang D, Dong D, Xiang H. Eur J Pharmacol. 2024; 962:176220. doi: 10.1016/j.ejphar.2023.176220. PMID: 38042463.
6. Urinary vanin-1 for predicting acute pyelonephritis in young children with urinary tract infection: a pilot study. Krzemień G, Pańczyk-Tomaszewska M, Górska E, Szmigielska A Biomarkers. 2021; 26(4):318-324. doi: 10.1080/1354750X.2021.1893813. PMID: 33656956
7. A Novel Biomarker for Acute Kidney Injury, Vanin-1, for Obstructive Nephropathy: A Prospective Cohort Pilot Study. Washino S, Hosohata K, Oshima M, Okochi T, Konishi T, Nakamura Y, Saito K, Miyagawa T. Int J Mol Sci. 2019; 20(4):899. doi: 10.3390/ijms20040899. PMID: 30791405.

The Biomedica SCLEROSTIN ELISA Assay Kit (# BI-20492) was utilized in a recent publication assessing the associations between serum and bone sclerostin levels and biomarkers of bone turnover and bone histomorphometry. Read more: Sclerostin, Osteocytes, and Wnt Signaling in Pediatric Renal Osteodystrophy.

Sclerostin (SOST) ELISA  (cat. no. BI-20492)

• Most referenced Sclerostin ELISA in over 290 citations
• Low sample volume – 20µl / well
• Validation following international guidelines

 

Sclerostin a biomarker in renal pediatric bone disease

Sclerostin, Osteocytes, and Wnt Signaling in Pediatric Renal Osteodystrophy. Laster M. et al., Nutrients. 2023 Sep 25;15(19):4127. doi: 10.3390/nu15194127. PMID: 37836411; PMCID: PMC10574198 . link to full text

Abstract

The pathophysiology of chronic kidney disease-mineral and bone disorder (CKD-MBD) is not well understood. Specific factors secreted by osteocytes are elevated in the serum of adults and pediatric patients with CKD-MBD, including FGF-23 and sclerostin, a known inhibitor of the Wnt signaling pathway. The molecular mechanisms that promote bone disease during the progression of CKD are incompletely understood. In this study, we performed a cross-sectional analysis of 87 pediatric patients with pre-dialysis CKD and post-dialysis (CKD 5D). We assessed the associations between serum and bone sclerostin levels and biomarkers of bone turnover and bone histomorphometry. We report that serum sclerostin levels were elevated in both early and late CKD. Higher circulating and bone sclerostin levels were associated with histomorphometric parameters of bone turnover and mineralization. Immunofluorescence analyses of bone biopsies evaluated osteocyte staining of antibodies towards the canonical Wnt target, β-catenin, in the phosphorylated (inhibited) or unphosphorylated (active) forms. Bone sclerostin was found to be colocalized with phosphorylated β-catenin, which suggests that Wnt signaling was inhibited. In patients with low serum sclerostin levels, increased unphosphorylated “active” β-catenin staining was observed in osteocytes. These data provide new mechanistic insight into the pathogenesis of CKD-MBD and suggest that sclerostin may offer a potential biomarker or therapeutic target in pediatric renal osteodystrophy.

 

Related Literature

FGF-23 and sclerostin in serum and bone of CKD patients. Lima F, Monier-Faugere MC, Mawad H, David V, Malluche HH. Clin Nephrol. 2023 May;99(5):209-218. doi: 10.5414/CN111111. PMID: 36970967; PMCID: PMC10286735. (Biomedica Sclerostin ELISA Assay Kit, cat. no. BI-20492 citation)

Sclerostin and Dickkopf-1 in renal osteodystrophy. Cejka D, Herberth J, Branscum AJ, Fardo DW, Monier-Faugere MC, Diarra D, Haas M, Malluche HH. Clin J Am Soc Nephrol. 2011 Apr;6(4):877-82. doi: 10.2215/CJN.06550810. Epub 2010 Dec 16. PMID: 21164019; PMCID: PMC3069382. (Biomedica Sclerostin ELISA Assay Kit, cat. no. BI-20492 citation)

Bone Disorders in Pediatric Chronic Kidney Disease: A Literature Review. Capossela L, Ferretti S, D’Alonzo S, Di Sarno L, Pansini V, Curatola A, Chiaretti A, Gatto A.Biology (Basel). 2023 Nov 2;12(11):1395. doi: 10.3390/biology12111395. PMID: 37997994; PMCID: PMC10669025.

 

Discover Biomedica Biomarker ELISA Kits for Biomarkers in Bone-Kidney-Heart diseases.

Developed & manufactured by Biomedica` Immunoassays
Austrian Quality!

√  WIDELY CITED  in +1500  publications

Discover Biomedica Biomarker ELISA Kits

Biomarker Assays

√  Natriuretic Peptides                           NT-proBNP, NT-proANP (for human and rat samples), NT-proCNP

√  Endothelins                                              Big Endothelin-1

√  Wnt inhibitors                                        Sclerostin, Dickkopf-1 (DKK-1)

√  Bone metabilism                                   Osteoprotegerin (OPG), soluble free RANKL (sRANKL)

√  Nephrology & transplant                  Fibroblast growth factor 23 (FGF23 c-terminal and FGF23 intact),
                                                                              Endostatin, Angiopoietin-2 (human, mouse and rat) , Neuropilin-1,
                                                                              Vanin-1 urine (human, mouse and rat), anti-C4d antibody

 

RELATED CITATIONS

Big Endothelin-1 (BigET-1)

Plasma Big Endothelin-1 Level Predicted 5-Year Major Adverse Cardiovascular Events in Patients With Coronary Artery Ectasia. Cai Z, Wang H, Yuan S, Yin D, Song W, Dou K.Front Cardiovasc Med. 2021 Nov 29;8:768431. doi: 10.3389/fcvm.2021.768431. PMID: 34912865; PMCID: PMC8667227.

Abstract

Sepsis is a life-threatening organ dysfunction and has become the main cause of in-hospital death in severe trauma patients. It is caused by an extreme response of the body to an infection. The early recognition of sepsis is critical for timely initiation of treatment and new biomarkers may help for early diagnosis.  Researchers recently investigated the use of Vanin-1 as a possible predictive biomarker of traumatic sepsis. The study demonstrated that Vanin-1 increased among trauma patients and was independently associated with the risk of sepsis, especially in the first 3 days after injury.

View abstract:  Plasma Vanin-1 as a Novel Biomarker of Sepsis for Trauma Patients: A Prospective Multicenter Cohort Study. Lu H et al. , J Infect Dis Ther. 2021. 10(2):739-751.

Abstract:
Introduction: Vanin-1 plays a pivotal role in oxidative stress and the inflammatory response. However, its relationship with traumatic sepsis remains unknown. The aim of our study was to evaluate whether plasma vanin-1 could be used for the early prediction of traumatic sepsis.

Methods: In this three-stage prospective cohort study, severe trauma patients admitted from January 2015 to October 2018 at two hospitals were enrolled. Plasma vanin-1 levels were measured by enzyme-linked immunosorbent assay (ELISA). The associations among variables and traumatic sepsis were identified by logistic regression models and the receiver operating characteristic (ROC) curve was analyzed to evaluate the diagnostic efficiency.

Results: A total of 426 trauma patients (22 in the discovery cohort, 283 in the internal test cohort, and 121 in the external validation cohort) and 16 healthy volunteers were recruited. The plasma vanin-1 of trauma patients was significantly higher than that of healthy volunteers (P < 0.05). Patients with sepsis had higher plasma vanin-1 than patients without sepsis in the discovery trauma cohort (P < 0.05). In the internal test cohort, plasma vanin-1 at day 1 after trauma was significantly associated with the incidence of sepsis (OR = 3.92, 95% CI 2.68-5.72, P = 1.62 × 10^-12). As a predictive biomarker, vanin-1 afforded a better area under the curve (AUC) (0.82, 95% CI 0.77-0.87) than C-reaction protein (CRP) (0.62, 95% CI 0.56-0.68, P < 0.0001), procalcitonin (PCT) (0.66, 95% CI 0.60-0.71, P < 0.0001), and Acute Physiology and Chronic Health Evaluation II (APACHE II) (0.71, 95% CI 0.65-0.76, P = 6.70 × 10^-3). The relevance was further validated in the external validation cohort (OR = 4.26, 95% CI 2.22-8.17, P = 1.28 × 10^-5), with an AUC of 0.83 (95% CI 0.75-0.89). Vanin-1 could also improve the diagnostic efficiency of APACHE II (AUC = 0.85).

Conclusions: Our study demonstrated that plasma vanin-1 increased among trauma patients and was independently associated with the risk of sepsis. Vanin-1 might be a potential biomarker for the early prediction of traumatic sepsis.

Human VANIN -1  can reliably be measured in urine samples by ELISA

√  Optimized for human urine samples

√  Highly SPECIFIC and DEFINED characterized antibodies

√   RELIABLE rigorously validated according to FDA/ICH/EMEA guidelines

√   QUICK one-step ELISA

Related products:

Mouse/rat Vanin-1 ELISA

Nephrology: FGF23, Endostatin, Anti C4d
Cardiology: NT-proBNP, Endothelins, proANP, NT-proCNP

First commercially available fully validated ELISA to reliably measure Vanin-1 in human urine samples from Biomedica.

Vanin-1 is a glycoprotein that is selectively expressed in renal tubular cells.

Urinary Vanin-1

• has as superior predictive value for drug induced AKI than KIM-1 or NGAL
  
  
• is a novel biomarker to detect and monitor the clinical course of obstructive nephropathy
  

Biomedica offers the FIRST fully validated VANIN-1 (urine) ELISA for reliable results

Try our  VANIN-1 (urine) ELISA  and contact us for your evaluation discount.

Related Literature & Findings:

Urinary Vanin-1 As a Novel Biomarker for Early Detection of Drug-Induced Acute Kidney Injury. Hosohata K et al., J Pharmoc Exp Therapeut, 2012; 656–62.

A Novel Biomarker for Acute Kidney Injury, Vanin-1, for Obstructive Nephropathy: A Prospective Cohort Pilot Study. Washino S. et al., Int J Mol Sci, 2019; 20, 4.

Pharmacological inhibition of Vanin-1 is not protective in models of acute and chronic kidney disease. Unterschemmann K, Ehrmann A, Herzig I, Andreevski AL, Lustig K, Schmeck C, Eitner F, Grundmann M. Am J Physiol Renal Physiol. 2021 Jan 1;320(1):F61-F73. doi: 10.1152/ajprenal.00373.2020. Epub 2020 Nov 16. PMID: 33196323.

Abstract

BI-VAN1U –  human VANIN-1 ELISA Assay Highlights:

√  Optimized for human urine samples

√  Highly SPECIFIC and DEFINED characterized antibodies

√   RELIABLE rigorously validated according to FDA/ICH/EMEA guidelines

√   QUICK one-step ELISA

Related products:

Nephrology: FGF23, Endostatin, Anti C4d
Cardiology: NT-proBNP, Endothelins, proANP, NT-proCNP

Meet us at poster #P163 to learn about our C-terminal FGF23 ELISA and our nephrology product line!

From 27th-30th September, Biomedica will participate at the Annual Congress for German Nephrology taking place at the Estrel Convention Center in Berlin. The congress is hosted by the German Society for Nephrology (Deutsche Gesellschaft für Nephrologie, DGfN), which celebrates its 10th anniversary this year.

According to the DGfN, between four and six million Germans live with reduced kidney function. 80,000 of these patients are currently being treated with dialysis. Another 25,000 patients are under medical surveillance after a successful kidney transplant. Therapy for kidney diseases is cost-intensive; treatment for an average dialysis patient amounts to 40,000 Euros per year, amounting to 3 billion Euros health care costs annually. For more information go to http://www.die-nephrologen.de/fakten.html.

To ameliorate current treatment regimens and bring innovative technology to the clinic, the DGfN supports cooperation between ambulant and stationary clinicians and promotes the development of innovative and coordinated strategies to tackle the challenge of improving early diagnosis and long-term treatment of patients with kidney diseases.

One important aspect of improving outcomes is to stratify risk and detect diseases in an early stage. For this reason, Biomedica specialises in developing high-quality biomarker ELISAs for clinical research and application.

As our contribution to the scientific programme of the Kongress Für Nephrologie 2018, Biomedica will be presenting a poster about our C-terminal FGF-23 ELISA kit, a biomarker that has been linked to the clinical outcomes in both acute kidney injury and chronic kidney disease.

Dr. Annegret Bitzer, one of our Biomedica Product managers, is going to present the C-terminal FGF-23 poster (Poster #P163) on Friday 28th September from 2-3:30 pm, and will be happy to chat with you about the clinical significance of intact FGF-23 in kidney disease, as well as about the biomarkers in our innovative nephrology product line, which includes:

Human and mouse/rat Endostatin ELISAs
C-terminal FGF-23 ELISA
Bioactive Sclerostin ELISA
Osteoprotegerin ELISA
Total soluble Neuropilin-1 ELISA
Anti-C4d Antibodies

Coming soon:

Vanin-1 ELISA
intact FGF23 ELISA

We look forward to meeting you at the Congress!