Serum-soluble urokinase receptor levels do not distinguish focal segmental glomerulosclerosis from other causes of nephrotic syndrome in children

Sinha, Aditi; Bajpai, Jaya; Saini, Sharanjot; Bhatia, Divya; Gupta, Akshat; Puraswani, Mamta; Dinda, Amit Kumar; Agarwal, Sanjay Kumar; Sopory, Shailaja; Pandey, Ravindra Mohan; Hari, Pankaj; Bagga, Arvind

doi:10.1038/ki.2013.546

Cited by 94 publications

(71 citation statements)

References 33 publications

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“…In addition, lower levels were associated with male sex and increased estimated GFR [38]. Findings in other cohorts have raised questions about the role of suPAR in the pathogenesis of proteinuria, its ability to discriminate FSGS from other forms of primary glomerular disease, and its predictive value in identifying recurrent disease post-transplant [39][40][41]. Additional studies are needed to determine the role of this specific molecule in primary FSGS in native kidneys and recurrent disease in renal allografts.…”

Section: Pathogenesismentioning

confidence: 99%

Recurrent focal segmental glomerulosclerosis after kidney transplantation

2015

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Focal segmental glomerulosclerosis (FSGS) is an important cause of glomerular disease in children and adolescents and nearly 50 % of affected patients will progress to endstage kidney disease over a 5 to 10-year period. Unfortunately, there is no established treatment for disease in the native kidney. Moreover, up to 55 % of patients develop recurrent disease after receiving a kidney transplant, with a substantially higher risk in patients who have already experienced recurrent disease in a prior transplant. A number of clinical and laboratory factors have been identified as risk factors for this complication. In addition, new investigations into podocyte biology and circulating permeability factors have shed light on the cause of recurrent the disease. While a number of novel therapeutic agents have been applied in the management of this problem, there still is no proven treatment. In this review, we summarize recent advances in the epidemiology, pathophysiology, and treatment of recurrent FSGS in pediatric patients who have received a kidney transplant.

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Section: Pathogenesismentioning

confidence: 99%

Recurrent focal segmental glomerulosclerosis after kidney transplantation

2015

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“…In addition, circulating suPAR has been reported to positively associate with carotid atherosclerosis and increased cardiovascular risk in CKD (29,30), and is also reported to be involved in renal damage that might progress to CKD (31). suPAR was previously postulated to represent a specific biomarker for primary FSGS, but recently has been identified in other glomerular diseases and negatively correlated with GFR (23,30,32). In this study, the systemic level of suPAR in RVH was higher than observed in primary FSGS (approximately 4.6 ng/ml) (22,33).…”

Section: Discussionmentioning

confidence: 99%

Biomarkers of Kidney Injury and Klotho in Patients with Atherosclerotic Renovascular Disease

Park

Herrmann

Saad

et al. 2015

Clinical Journal of the American Society of Nephrology

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Background and objectives Occlusive renovascular disease and hypertension may progress to CKD. Circulating levels of several biomarkers, including fibroblast growth factor (FGF)-23, Klotho, and soluble urokinase plasminogen activator receptor (suPAR), are altered in patients with CKD, but their role in essential hypertension (EH) and renovascular hypertension (RVH) remains unclear.Design, setting, participants, & measurements Levels of FGF-23, Klotho, suPAR, plasminogen activator inhibitor (PAI)-1, tissue factor, and tissue factor pathway inhibitor (TFI) were measured in the inferior vena cava and renal vein of hypertensive patients with atherosclerotic renal artery stenosis (n=12) or age-matched participants with EH (n=12) and relatively preserved renal function. Single-kidney blood flow was measured to calculate renal release of markers. For control, peripheral vein levels were measured in healthy volunteers (HVs; n=12).Results FGF-23 levels did not differ among the groups, whereas Klotho levels were lower in participants with RVH and EH than in HVs, and suPAR levels were elevated in patients with RVH compared with HVs and patients with EH (6.161.5 versus 4.461.9 and 3.261.2 ng/ml, P,0.05). PAI-1 levels were higher in patients with RVH than in patients with EH, but tissue factor and TFI levels were not statistically significantly different. After adjustment for GFR, Klotho levels remained decreased in both RVH and EH, and suPAR and PAI-1 levels remained elevated in RVH. eGFR correlated inversely with systemic and renal vein suPAR levels, and directly with systemic Klotho levels.Conclusions Klotho levels are low in hypertensive patients, whereas suPAR and PAI-1 levels are specifically elevated in RVH, correlating with GFR. Klotho, PAI-1, and suPAR may be markers of kidney injury in hypertensive patients.

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“…However, the postulated central role and direct pathological action of suPAR in FSGS is debated intensively. 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].…”

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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Serum-soluble urokinase receptor levels do not distinguish focal segmental glomerulosclerosis from other causes of nephrotic syndrome in children

Cited by 94 publications

References 33 publications

Recurrent focal segmental glomerulosclerosis after kidney transplantation

Recurrent focal segmental glomerulosclerosis after kidney transplantation

Biomarkers of Kidney Injury and Klotho in Patients with Atherosclerotic Renovascular Disease

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

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