Detection of suPAR in the Saliva of Healthy Young Adults: Comparison with Plasma Levels

Gustafsson, Anna; Ajeti, Vjosa; Ljunggren, Lennart

doi:10.4137/bmi.s8326

Cited by 45 publications

(46 citation statements)

References 22 publications

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“…Literature on variation by sex in serum suPAR levels is limited mostly to homogenous northern European populations, and contrary to our findings, demonstrated that suPAR levels are higher in female patients than in male patients (27,30,31). Again, the discrepancy in our findings may be explained by the age ranges of our cohort.…”

Section: Discussioncontrasting

confidence: 99%

Serum Soluble Urokinase-Type Plasminogen Activator Receptor Levels and Idiopathic FSGS in Children

Bock

Price

Gallon

et al. 2013

Clinical Journal of the American Society of Nephrology

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SummaryBackground and objectives FSGS is the primary cause of childhood nephrotic syndrome leading to ESRD. Permeability factors, including circulating serum soluble urokinase-type plasminogen activator receptor (suPAR), have been postulated as putative causes in adults with primary FSGS. Similar results have yet to be proven in children.Design, setting, participants, & measurements This cross-sectional single-center study assessed the association of serum suPAR in children with FSGS or other glomerular and nonglomerular kidney diseases.Results This study examined 110 samples retrieved from 99 individuals (between January 2011 and April 2012), aged 1-21 years; of these individuals, 20 had primary FSGS, 24 had non-FSGS glomerular disease, 26 had nonglomerular kidney disease, and 29 were healthy controls. suPAR levels were not significantly different in children with FSGS, non-FSGS glomerular disease, and healthy controls (P.0.05). However, suPAR levels (median [25%-75%]) were higher in children with nonglomerular kidney disease (3385 pg/ml ) versus FSGS (2487 pg/ml [2191-3351]; P,0.05). Female patients with nephrotic-range proteinuria (U-Pr/Cr .2) had lower suPAR levels than those without proteinuria (2380 pg/ml versus 3125 pg/ml , respectively; P,0.001). This trend was not seen among male participants; suPAR levels in all female participants were lower than in male participants (P=0.03). Thirty-four patients studied were kidney transplant recipients; transplant status was not associated with suPAR levels in patients with FSGS or non-FSGS diagnoses, independent of proteinuria, race, or sex (P.0.05).Conclusions On the basis of these results, circulating suPAR is unlikely the leading cause for childhood idiopathic FSGS.

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Section: Discussioncontrasting

confidence: 99%

Serum Soluble Urokinase-Type Plasminogen Activator Receptor Levels and Idiopathic FSGS in Children

Bock

Price

Gallon

et al. 2013

Clinical Journal of the American Society of Nephrology

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“…6 The circulating form is produced by cleavage of membrane-bound urokinase-type plasminogen activator receptor and is readily detected in plasma, serum, urine, and other bodily fluids. 9–11 Elevated suPAR levels have been associated with poor outcomes in various patient populations. 12–20 In addition, suPAR has been implicated in the pathogenesis of kidney disease, specifically focal segmental glomerulosclerosis and diabetic nephropathy, through interference with podocyte migration and apoptosis.…”

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confidence: 99%

Soluble Urokinase Receptor and Chronic Kidney Disease

et al. 2015

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BACKGROUND Relatively high plasma levels of soluble urokinase-type plasminogen activator receptor (suPAR) have been associated with focal segmental glomerulosclerosis and poor clinical outcomes in patients with various conditions. It is unknown whether elevated suPAR levels in patients with normal kidney function are associated with future decline in the estimated glomerular filtration rate (eGFR) and with incident chronic kidney disease. METHODS We measured plasma suPAR levels in 3683 persons enrolled in the Emory Cardiovascular Biobank (mean age, 63 years; 65% men; median suPAR level, 3040 pg per milliliter) and determined renal function at enrollment and at subsequent visits in 2292 persons. The relationship between suPAR levels and the eGFR at baseline, the change in the eGFR over time, and the development of chronic kidney disease (eGFR <60 ml per minute per 1.73 m2 of body-surface area) were analyzed with the use of linear mixed models and Cox regression after adjustment for demographic and clinical variables. RESULTS A higher suPAR level at baseline was associated with a greater decline in the eGFR during follow-up; the annual change in the eGFR was −0.9 ml per minute per 1.73 m2 among participants in the lowest quartile of suPAR levels as compared with −4.2 ml per minute per 1.73 m2 among participants in the highest quartile (P<0.001). The 921 participants with a normal eGFR (≥90 ml per minute per 1.73 m2) at baseline had the largest suPAR-related decline in the eGFR. In 1335 participants with a baseline eGFR of at least 60 ml per minute per 1.73 m2, the risk of progression to chronic kidney disease in the highest quartile of suPAR levels was 3.13 times as high (95% confidence interval, 2.11 to 4.65) as that in the lowest quartile. CONCLUSIONS An elevated level of suPAR was independently associated with incident chronic kidney disease and an accelerated decline in the eGFR in the groups studied. (Funded by the Abraham J. and Phyllis Katz Foundation and others.)

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“…Several studies report lack of differences in suPAR levels between FSGS and other kidney diseases and suggests rather a reduced glomerular filtration as a major cause of increased suPAR in patients with renal disorders [64][65][66][67][68][69]. suPAR is readily detected in both plasma and serum [50,70] and it is also found in urine [50], cerebrospinal fluid [71] and saliva [72]. Blood levels of suPAR are dependent on age and sex [7] with slightly increased levels in elderly and females.…”

Section: Supar As a Clinical Marker Of Inflammation And Organ Damagementioning

confidence: 99%

Soluble urokinase plasminogen activator receptor—A valuable biomarker in systemic lupus erythematosus?

Enocsson¹,

Sjöwall²,

Wetterö³

2015

Clinica Chimica Acta

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The expression of uPAR is mainly regulated by growth factors and pro-inflammatory cytokines like basic fibroblast growth factor, epidermal growth factor, tumor necrosis factor, interleukin ( suPAR as a clinical marker of inflammation and organ damagePlasma membrane expression of uPAR as well as the levels of circulating suPAR have been investigated in relation to a broad range of conditions and suPAR has been referred to as a "molecular crystal ball" due to its prognostic value in diseases like tuberculosis, HIV, sepsis and cancer [2,6,13,26,58,59]. Further, it has been reported that it reflects overall immune activation and systemic inflammation [2]. suPAR has also emerged as a potential biomarker of fibrosis in chronic liver diseases of diverse etiology [10,11,[60][61][62].Recently, suPAR attracted significant attention in primary focal segmental glomerulosclerosis (FSGS). data from this pilot study revealed significantly higher suPAR levels among patients with moderately or highly elevated SDI after study inclusion, compared to patients without SDI increase (Figure 2).Furthermore, there were higher death rates among patients in the two groups with SDI increase (Figure 2). However, it is well known that present organ damage predicts further organ damage [17,100], and thus, adjustment for SDI at baseline should be performed to reduce the risk of bias. A stepwise linear multiple regression analysis was therefore performed to evaluate the impact of suPAR on future SDI increase. After adjusting for age, sex and SDI at study inclusion, we found suPAR levels to have a significant impact on future SDI increase (p = 0.005, standardized β = 0.20) whereas SDI at study inclusion was excluded from the model. Since recent studies have revealed an inverse correlation between serum suPAR and glomerular filtration [67,68,96], we also included estimated glomerular filtration (eGFR) (calculated by the 4-variable Modification of Diet in Renal Disease StudyGroup formula [101]) in the analysis, but eGFR was not retained in the model. From these results, we suggest that suPAR can actually predict organ damage independent of present SDI score or eGFR, but that a prospective study examining the association between suPAR levels at the time of diagnosis with future SDI would be preferable.In line with these findings, elevated suPAR levels have previously been demonstrated to associate with the risk of developing cancer, cardiovascular disease and type 2 diabetes later in life in the general population [7]. Importantly, these associations were independent of CRP, which is known for its predictive value in cardiovascular disease [7,102].7 Potential roles of suPAR in SLE pathogenesisAssessment of circulating suPAR levels at the clinical laboratory could possibly become a future way to estimate organ damage in SLE, and suPAR would be an even more appealing biomarker candidate if the levels could be mechanistically linked to the disease. The pathogenesis of SLE is notoriously complex and not fully understood, but includes disturbances in t...

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Detection of suPAR in the Saliva of Healthy Young Adults: Comparison with Plasma Levels

Cited by 45 publications

References 22 publications

Serum Soluble Urokinase-Type Plasminogen Activator Receptor Levels and Idiopathic FSGS in Children

Serum Soluble Urokinase-Type Plasminogen Activator Receptor Levels and Idiopathic FSGS in Children

Soluble Urokinase Receptor and Chronic Kidney Disease

Soluble urokinase plasminogen activator receptor—A valuable biomarker in systemic lupus erythematosus?

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