Association of Serum Soluble Urokinase Receptor Levels With Progression of Kidney Disease in Children

Schaefer, Franz; Trachtman, Howard; Wühl, Elke; Kirchner, Marietta; Hayek, Salim S.; Anarat, Ali; Düzova, Ali; Mır, Sevgı; Paripović, Dušan; Yılmaz, Alev; Lugani, Francesca; Arbeiter, Klaus; Litwin, Mieczysław; Oh, Jun; Matteucci, Maria Chiara; Gellermann, Jutta; Wygoda, Simone; Jankauskienė, Augustina; Klaus, Günter; Dušek, Jiří; Testa, Sara; Zurowska, Aleksandra; Afonso, Alberto Caldas; Tracy, Melissa; Wei, Changli; Sever, Sanja; Smoyer, William E.; Reiser, Jochen

doi:10.1001/jamapediatrics.2017.2914

Cited by 44 publications

(34 citation statements)

References 30 publications

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“… 25 Well beyond being causally implicated in focal glomerulosclerosis, 26 suPAR, a 50-kDa protein, associates strongly with the GFR 17 and predicts the incidence of CKD in patients with suspected coronary heart disease 16 and individuals in the general population, 21 as well as the rate of GFR loss in children. 27 We found that in ESKD patients, circulating suPAR, a compound that is not removed by dialysis, exceeded the upper limit of the normal range in the vast majority (97%) of patients in our cohort.…”

Section: Discussionmentioning

confidence: 56%

Soluble Urokinase Plasminogen Activator Receptor (suPAR) and All-Cause and Cardiovascular Mortality in Diverse Hemodialysis Patients

Torino

Pizzini

Cutrupi

et al. 2018

Kidney International Reports

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IntroductionThe soluble receptor of urokinase plasminogen activator (suPAR) is an innate immunity/inflammation biomarker predicting cardiovascular (CV) and non-CV events in various conditions, including type 2 diabetic patients on dialysis. However, the relationship between suPAR and clinical outcomes in the hemodialysis population at large has not been tested.MethodsWe measured plasma suPAR levels (R&D enzyme-linked immunosorbent assay [ELISA]) in 1038 hemodialysis patients with a follow-up of 2.9 years (interquartile range = 1.7−4.2) who were enrolled in the PROGREDIRE study, a cohort study involving 35 dialysis units in 2 regions in Southern Italy.ResultssuPAR was strongly (P < 0.001) and independently related to female gender (β = −0.160), age (β = 0.216), dialysis vintage (β = 0.264), CV comorbidities (β = 0.105), alkaline phosphatase (β = 0.136), albumin (β = −0.147), and body mass index (BMI; β = 0.174) (all P < 0.006). In fully adjusted analyses, suPAR tertiles predicted the risk of all-cause mortality (third tertile vs. first tertile hazard ratio (HR) = 1.91, 95% confidence interval (CI) = 1.47 – 2.48, P < 0.001), CV mortality (HR = 1.47, 95% CI = 1.03–2.09, P = 0.03), and non-CV mortality (HR = 1.94, 95% CI = 1.28–2.93, P = 0.002); these relationships were not modified by diabetes or other risk factors. suPAR added only modest prognostic risk discrimination and reclassification power for these outcomes to parsimonious models based on simple clinical variables.ConclusionIn conclusion, suPAR robustly predicted all-cause and both CV and non-CV mortality in a large unselected hemodialysis population. Intervention studies are needed to definitively test the hypothesis that suPAR is causally implicated in clinical outcomes in this population.

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Section: Discussionmentioning

confidence: 56%

Soluble Urokinase Plasminogen Activator Receptor (suPAR) and All-Cause and Cardiovascular Mortality in Diverse Hemodialysis Patients

Torino

Pizzini

Cutrupi

et al. 2018

Kidney International Reports

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“…11,16,18 Levels of suPAR are strongly predictive of progressive decline in kidney function. 17,[19][20][21][22][23] Long-term exposure to elevated suPAR levels directly affects the kidneys by means of pathologic activation of αvβ3 integrin expressed in podocytes, resulting in proteinuria. 7,12,16,24 Whether suPAR has an effect on kidney tubular cells -the cells most affected in acute kidney injury -is unclear.…”

Section: Results-mentioning

confidence: 99%

Soluble Urokinase Receptor and Acute Kidney Injury

et al. 2020

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BACKGROUND-Acute kidney injury is common, with a major effect on morbidity and health care utilization. Soluble urokinase plasminogen activator receptor (suPAR) is a signaling glycoprotein thought to be involved in the pathogenesis of kidney disease. We investigated whether a high level of suPAR predisposed patients to acute kidney injury in multiple clinical contexts, and we used experimental models to identify mechanisms by which suPAR acts and to assess it as a therapeutic target. METHODS-We measured plasma levels of suPAR preprocedurally in patients who underwent coronary angiography and patients who underwent cardiac surgery and at the time of admission to the intensive care unit in critically ill patients. We assessed the risk of acute kidney injury at 7 days as the primary outcome and acute kidney injury or death at 90 days as a secondary outcome, according to quartile of suPAR level. In experimental studies, we used a monoclonal antibody to urokinase plasminogen activator receptor (uPAR) as a therapeutic strategy to attenuate acute kidney injury in transgenic mice receiving contrast material. We also assessed cellular bioenergetics and generation of reactive oxygen species in human kidney proximal tubular (HK-2) cells that were exposed to recombinant suPAR.

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“…Clinical studies have found suPAR to be associated with incidence and prevalence of disease and with disease severity and prognosis. This applies to acute as well as chronic diseases and infectious as well as noncommunicable diseases, including clinical conditions investigated in children (Schaefer et al, 2017;S ßirino glu et al, 2017;Wittenhagen et al, 2011;Wrotek, Jackowska, & Pawlik, 2015). suPAR appears to reflect the health status or inflammatory burden of an individual, and chronic multimorbid patients have higher suPAR levels than patients with fewer chronic diseases (Rasmussen et al, 2016), while healthy people have low suPAR levels (Haupt et al, 2014).…”

Section: Discussionmentioning

confidence: 99%

Cumulative childhood risk is associated with a new measure of chronic inflammation in adulthood

Rasmussen

Moffitt

Eugen‐Olsen

et al. 2018

Child Psychology Psychiatry

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Association of Serum Soluble Urokinase Receptor Levels With Progression of Kidney Disease in Children

Abstract: Schaefer et al.

Cited by 44 publications

References 30 publications

Soluble Urokinase Plasminogen Activator Receptor (suPAR) and All-Cause and Cardiovascular Mortality in Diverse Hemodialysis Patients

Soluble Urokinase Plasminogen Activator Receptor (suPAR) and All-Cause and Cardiovascular Mortality in Diverse Hemodialysis Patients

Soluble Urokinase Receptor and Acute Kidney Injury

Cumulative childhood risk is associated with a new measure of chronic inflammation in adulthood

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