Circulating levels of osteopontin are closely related to glomerular filtration rate and cardiovascular risk markers in patients with chronic kidney disease

Lorenzen, Johan M.; Kramer, Robert S.; Kliem, Volker; Bode-Boeger, Stefanie M.; Veldink, Hendrik; Haller, Hermann; Fliser, Danilo; Kielstein, Jan T.

doi:10.1111/j.1365-2362.2010.02271.x

Cited by 59 publications

(41 citation statements)

References 38 publications

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“…A recent study by Evenepoel et al demonstrated that microscopic nephrocalcinosis was quite common in patients with CKD and prevalence increased with worsening glomerular filtration rate and correlated with elevated serum phosphate and parathyroid hormone levels 52 . It is likely that OPN is involved in this process as Lorenzen et al discovered that OPN levels increased with worsening GFR 53 . These increased levels also correlated closely with serum phosphate and intact parathyroid hormone.…”

Section: Discussionmentioning

confidence: 99%

Osteopontin protects against high phosphate-induced nephrocalcinosis and vascular calcification

Paloian

Leaf

Giachelli

2016

Kidney International

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Pathologic calcification is a significant cause of increased morbidity and mortality in patients with chronic kidney disease (CKD). The precise mechanisms of ectopic calcification are not fully elucidated, but it is known to be caused by an imbalance of pro-calcific and anti-calcific factors. In the CKD population, an elevated phosphate burden is both highly prevalent and a known risk factor for ectopic calcification. Here we tested whether osteopontin, an inhibitor of calcification, protects against high phosphate load-induced nephrocalcinosis and vascular calcification. Osteopontin knockout mice were placed on a high phosphate diet for eleven weeks. Osteopontin deficiency together with phosphate overload caused uremia, nephrocalcinosis characterized by substantial renal tubular and interstitial calcium deposition, and marked vascular calcification when compared to controls. While the osteopontin-deficient mice did not exhibit hypercalcemia or hyperphosphatemia, they did show abnormalities in the mineral metabolism hormone fibroblast growth factor 23. Thus, endogenous osteopontin plays a critical role in the prevention of phosphate induced nephrocalcinosis and vascular calcification in response to high phosphate load. A better understanding of osteopontin’s role in phosphate induced calcification will hopefully lead to better biomarkers and therapies for this disease, especially in patients with CKD and other at risk populations.

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Section: Discussionmentioning

confidence: 99%

Osteopontin protects against high phosphate-induced nephrocalcinosis and vascular calcification

Paloian

Leaf

Giachelli

2016

Kidney International

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“…Osteopontin is an extracellular matrix protein that contributes to the development of atherosclerosis as it acts as a pro-inflammatory cytokine to induce macrophage adhesion and migration, it promotes vascular smooth muscle cell proliferation and may mediate vascular calcification [29]. Osteopontin mRNA is expressed in aortic atherosclerotic plaques in patients with CAD, but not in the arteries of healthy controls, and expression is proportional to severity of disease [30].…”

Section: Discussionmentioning

confidence: 99%

Impaired renal function impacts negatively on vascular stiffness in patients with coronary artery disease

et al. 2013

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BackgroundChronic kidney disease (CKD) and coronary artery disease (CAD) are independently associated with increased vascular stiffness. We examined whether renal function contributes to vascular stiffness independently of CAD status.MethodsWe studied 160 patients with CAD and 169 subjects without CAD. The 4-variable MDRD formula was used to estimate glomerular filtration rate (eGFR); impaired renal function was defined as eGFR <60 mL/min. Carotid-femoral pulse wave velocity (PWV) was measured with the SphygmoCor® device. Circulating biomarkers were assessed in plasma using xMAP® multiplexing technology.ResultsPatients with CAD and impaired renal function had greater PWV compared to those with CAD and normal renal function (10.2 [9.1;11.2] vs 7.3 [6.9;7.7] m/s; P < 0.001). In all patients, PWV was a function of eGFR (β = −0.293; P < 0.001) even after adjustment for age, sex, systolic blood pressure, body mass index and presence or absence of CAD. Patients with CAD and impaired renal function had higher levels of adhesion and inflammatory molecules including E-selectin and osteopontin (all P < 0.05) compared to those with CAD alone, but had similar levels of markers of oxidative stress.ConclusionsRenal function is a determinant of vascular stiffness even in patients with severe atherosclerotic disease. This was paralleled by differences in markers of cell adhesion and inflammation. Increased vascular stiffness may therefore be linked to inflammatory remodeling of the vasculature in people with impaired renal function, irrespective of concomitant atherosclerotic disease.

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“…21 Moreover, OPN expression is involved in the coordinated regulation of the NFkB, ERK1/2 and AP-1 signaling pathways, which have been found to be involved in various pathologies, including immunological disorders, neoplastic transformation and renal disorders. 22,23 This pleiotropic pattern may explain why OPN is not a good predictor of vascular calcification specifically, despite that its presence was documented in calcified coronary artery plaques. 8,20 OPN is expressed in adipose tissue and in the livers of obese subjects; thus, obesity-induced inflammation may obscure OPN involvement in vascular calcification.…”

Section: Biomarkers Of Vascular Calcification In Normotension E Stępimentioning

confidence: 99%

Osteoprotegerin, but not osteopontin, as a potential predictor of vascular calcification in normotensive subjects

et al. 2012

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We conducted a cross-sectional observation study that included 500 asymptomatic subjects to investigate the relationship between bone metabolism and coronary artery calcification (CAC) in hypertensive conditions. Osteoprotegerin (OPG) and osteopontin (OPN) levels and their associations with hypertension were analyzed to predict CAC in 316 subjects. Multislice computed tomography was used to quantify CAC. Multivariate analysis of variance was used to test the non-interactive effects of hypertension, CAC severity and biomarker levels, and the logistic regression model was applied to predict the risk of CAC. OPG and OPN concentrations were significantly higher in the hypertensive than the normotensive subjects, at 3.0 (2.3-4.0) pmol l À1 and 51 (21-136) ng ml À1 vs. 2.4 (2.0-3.0) pmol l À1 and 41 (13-63) ng ml À1 , respectively. The OPG level, but not OPN level, increased with age (r¼0.29; P¼0.0001). Zero or minimal CAC (o10 Agatston units (AU)) was observed in 63% of the subjects, mild (11-100 AU) in 17%, moderate (101-400 AU) in 12% and severe (401-1000 AU)-to-extensive (41000 AU) in 8%. In hypertensive subjects, only glomerular filtration rate (GFR) (b¼À0.67) and gender (b¼0.52) were significant predictors for CAC (R¼0.68). In normotensive patients, GFR (b¼À0.81), gender (b¼0.48) and log-transformed OPG levels (b¼0.15) were significant predictors for CAC. OPG levels were associated with an increased risk of CAC in normotensive subjects only (odds ratio: 3.37; 95% confidence interval (1.63-6.57); P¼0.0002). OPG predicted a premature state of vascular calcification in asymptomatic normotensive individuals, and renal function significantly contributed to this process in both hypertensive and normotensive subjects.

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Circulating levels of osteopontin are closely related to glomerular filtration rate and cardiovascular risk markers in patients with chronic kidney disease

Cited by 59 publications

References 38 publications

Osteopontin protects against high phosphate-induced nephrocalcinosis and vascular calcification

Osteopontin protects against high phosphate-induced nephrocalcinosis and vascular calcification

Impaired renal function impacts negatively on vascular stiffness in patients with coronary artery disease

Osteoprotegerin, but not osteopontin, as a potential predictor of vascular calcification in normotensive subjects

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