OPG a marker of cardiovascular mortality in CKD
Biomedica´s Osteoprotegerin (OPG) and Fibroblast Growth Factor (FGF23) assays were highlighted in the German Chronic Kidney Disease (CKD) cohort study to investigate the prognostic value of a total of nine mineral and bone disease biomarkers (MBD) (1). Brief, 4246 participants were enrolled and baseline serum samples of the MBD markers were prospectively observed for a median time of 6.5 years. The markers were compared to study the association of each biomarker with adverse cardiovascular (CV) outcomes and mortality. Of the nine biomarkers examined, Osteoprotegerin (OPG) best identified CKD patients who had the highest risk. The findings mirror the link between bone metabolism and CV disease in CKD patients and may help clinicians to identify patients who are at high risk for CV disease (1).
OPG a marker of cardiovascular mortality in CKD
The Kidney, Bone, and Heart Connection
Chronic Kidney Disease (CKD), is a condition involving a gradual loss of kidney function. The kidneys lose their ability to filter toxins and extra fluid from the blood. There is no cure for this progressive disease and it is associated with a high morbidity and mortality rate that occurs especially in people with diabetes and hypertension (2). Worldwide, it is estimated that CKD is present in one out of ten adults (3).
Bone Disorders in Chronic Kidney Disease
Other important roles of the kidney include maintaining bone health and balancing important minerals in the body. A majority of patients with CKD have an elevated risk of developing disturbances of bone and mineral metabolism that lead to bone lesions (4). Thus, mineral an bone disorders (MBD) with biochemical and hormonal alterations are part of the complications associated with the progression of CKD (5).
Cardiovascular Events in Chronic Kidney Disease (CKD)
Mineral and bone disorder in CKD can not only affect the bones but also other organs including the heart and blood vessels. It is well recognized that both atherosclerosis and arteriosclerosis are accelerated in patients with kidney failure (6). The high cardiovascular morbidity and mortality in CKD patients is mainly caused by progressive vascular calcification.
Osteoprotegerin (OPG) a Cardiovascular Risk Factor in CKD
Osteoprotegerin (OPG) is a protein that regulates bone mass by inhibiting bone resorption. Apart from its traditional role in bone, OPG plays an important role in vascular disease and calcification as it interacts with endothelial and smooth muscle cells (7).
In a large prospective, population based study, severity, initiation, and progression of atherosclerosis was assessed in carotid arteries (8). The researchers demonstrated that OPG was an independent risk factor for the progression of atherosclerosis and onset of cardiovascular disease (CV) (8).
Serum OPG has also been shown to be a predictor of progression of atherosclerosis and coronary calcification in hemodialysis patients (9) and OPG serum levels increase with CKD disease progression and are associated with mortality in these patients (10). Moreover, high OPG levels are also associated with CV events in the general population as demonstrated in a large community based cohort (10). These data strongly reinforce OPG as marker for CV disease risk factor burden and predictor of CVD and mortality in the community (11).
Finally, the data from the recent German Chronic Kidney Disease cohort study investigating the prognostic value of nine mineral and bone disease associated biomarkers (MBD) showed that only serum OPG levels consistently identified the CKD patients who had the highest risk for adverse CV outcomes and mortality (1).
Osteoprotegerin (OPG) and Fibroblast Growth Factor (FGF23) can reliably be measured with a conventional ELISA assay
Biomedica OPG ELISA (cat. no. BI-20403)
- Method: Sandwich ELISA, HRP/TMB, 12×8-well detachable strips
- Sample: Serum, plasma (EDTA, citrate, heparin)
- Sample volume: 20μl / well
- Detection range: 1.25-20 pmol/L (= 25 – 400 pg/mL)
- Sensitivity: 0.07 pmol/L (= 1.4 pg/mL)
- Incubation time: 4 h + 1 h + 30 min (room temperature)
- Precision: In-between-run (n=12): ≤ 5 % CV: Within-run (n=5): ≤ 3 % CV
- Widely cited in over 250 publications!
Biomedica FGF23 (C-terminal) ELISA (cat. no. BI-20702)
- Method: Sandwich ELISA, HRP/TMB, 12×8-well detachable strips
- Sample: Serum, plasma (EDTA, citrate, heparin)
- Sample volume: 50μl / well
- Detection range: 0.2 – 20 pmol/mL (= 1.54 – 150.4 pg/mL)
- Sensitivity: 0.08 pmol/L (= 0.6 pg/mL)
- Incubation time: 20-24 h + 1 h+ 30 min (room temperature)
- Precision: In-between (n=10): ≤ 10 % CV; Within-run (n=6): ≤ 12 % CV
Publications
- Association of mineral and bone biomarkers with adverse cardiovascular outcomes and mortality in the German Chronic Kidney Disease (GCKD) cohort. Reimer KC, Nadal J, Meiselbach H, Schmid M, Schultheiss UT, Kotsis F, Stockmann H, Friedrich N, Nauck M, Krane V, Eckardt KU, Schneider MP, Kramann R, Floege J, Saritas T; GCKD study investigators. Bone Res. 2023 Oct 20;11(1):52. doi: 10.1038/s41413-023-00291-8. PMID: 37857629; PMCID: PMC10587182.
- Chronic kidney disease. Kalantar-Zadeh K, Jafar TH, Nitsch D, Neuen BL, Perkovic V. Lancet. 2021 Aug 28;398(10302):786-802. doi: 10.1016/S0140-6736(21)00519-5. Epub 2021 Jun 24. PMID: 34175022.
- Prevalence, outcomes, and cost of chronic kidney disease in a contemporary population of 2·4 million patients from 11 countries: The CaReMe CKD study. Sundström J, Bodegard J, Bollmann A, Vervloet MG, Mark PB, Karasik A, Taveira-Gomes T, Botana M, Birkeland KI, Thuresson M, Jäger L, Sood MM, VanPottelbergh G, Tangri N; CaReMe CKD Investigators. Lancet Reg Health Eur. 2022. 20:100438. doi: 10.1016/j.lanepe.2022.100438. PMID: 36090671; PMCID: PMC9459126.
- Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD): Current Perspectives. Waziri B, Duarte R, Naicker S. Int J Nephrol Renovasc Dis. 2019 Dec 24;12:263-276. doi: 10.2147/IJNRD.S191156. PMID: 31920363; PMCID: PMC6935280.
- Mineral Bone Disorders in Kidney Disease Patients: The Ever-Current Topic. Hu L, Napoletano A, Provenzano M, Garofalo C, Bini C, Comai G, La Manna G. Int J Mol Sci. 2022 Oct 13;23(20):12223. doi: 10.3390/ijms232012223. PMID: 36293076; PMCID: PMC9603742
- Role of Chronic Kidney Disease (CKD)-Mineral and Bone Disorder (MBD) in the Pathogenesis of Cardiovascular Disease in CKD. Yamada S, Nakano T J Atheroscler Thromb. 2023 Aug 1;30(8):835-850. doi: 10.5551/jat.RV22006. Epub 2023 May 30. PMID: 37258233; PMCID: PMC10406631.
- Role of crosstalk between endothelial cells and smooth muscle cells in vascular calcification in chronic kidney disease. Zhang YX, Tang RN, Wang LT, Liu BC. Cell Prolif. 2021. 54(3):e12980. doi: 10.1111/cpr.12980. Epub 2021 Jan 27. PMID: 33502070; PMCID: PMC7941222.
- Osteoprotegerin is a risk factor for progressive atherosclerosis and cardiovascular disease. Kiechl S, Schett G, Wenning G, Redlich K, Oberhollenzer M, Mayr A, Santer P, Smolen J, Poewe W, Willeit J. Circulation. .109(18):2175-80. doi: 10.1161/01.CIR.0000127957.43874.BB. Epub 2004 Apr 26. PMID: 15117849.
- Serum osteoprotegerin is a predictor of progression of atherosclerosis and coronary calcification in hemodialysis patients. Kurnatowska I, Grzelak P, Kaczmarska M, Stefańczyk L, Nowicki M. Nephron Clin Pract. 2011;117(4):c297-304. doi: 10.1159/000321169. Epub 2010 Sep 22. PMID: 20861651.
- Circulating Osteoprotegerin in Chronic Kidney Disease and All-Cause Mortality. Kamińska J, Stopiński M, Mucha K, Pac M, Gołębiowski M, Niewczas MA, Pączek L, Foroncewicz B. Int J Gen Med. 2021 Jun 9;14:2413-2420. doi: 10.2147/IJGM.S302251. PMID: 34135625; PMCID: PMC8200134.
- Biomarkers of the osteoprotegerin pathway: clinical correlates, subclinical disease, incident cardiovascular disease, and mortality. Lieb W, Gona P, Larson MG, Massaro JM, Lipinska I, Keaney JF Jr, Rong J, Corey D, Hoffmann U, Fox CS, Vasan RS, Benjamin EJ, O’Donnell CJ, Kathiresan S. Arterioscler Thromb Vasc Biol. 2010 Sep;30(9):1849-54. doi: 10.1161/ATVBAHA.109.199661. Epub 2010 May 6. PMID: 20448212; PMCID: PMC3039214.
- Association of mineral and bone biomarkers with adverse cardiovascular outcomes and mortality in the German Chronic Kidney Disease (GCKD) cohort. Reimer KC, Nadal J, Meiselbach H, Schmid M, Schultheiss UT, Kotsis F, Stockmann H, Friedrich N, Nauck M, Krane V, Eckardt KU, Schneider MP, Kramann R, Floege J, Saritas T; GCKD study investigators. Bone Res. 2023 Oct 20;11(1):52. doi: 10.1038/s41413-023-00291-8. PMID: 37857629; PMCID: PMC10587182.