Abstract MP07: Soluble Urokinase-type Plasminogen Activator Receptor is associated with progression of hypertension-attributed chronic kidney disease in African Americans

Circulation ◽  
2018 ◽  
Vol 137 (suppl_1) ◽  
Author(s):  
Shengyuan Luo ◽  
Josef Coresh ◽  
Adrienne Tin ◽  
Casey M Rebholz ◽  
Teresa K Chen ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
African Americans ◽  
Kidney Disease ◽  
Plasminogen Activator ◽  
Cox Proportional Hazards ◽  
Adverse Outcomes ◽  
Ckd Progression ◽  
Type Plasminogen Activator ◽  
Urokinase Type Plasminogen Activator ◽  
Plasminogen Activator Receptor

Introduction: Soluble urokinase-type plasminogen activator receptor (suPAR), a circulating signaling protein and marker of immune activation, has been linked to incident and progressive chronic kidney disease (CKD) in select patient populations, often with few African Americans. Hypothesis: We assessed the hypothesis that higher circulating levels of suPAR are associated with risk for progression of hypertension-attributed CKD in African Americans. Methods: We quantified baseline plasma levels of suPAR in participants of the African-American Study of Kidney Disease and Hypertension (AASK), a clinical trial of African Americans with hypertension-attributed CKD, and regular assessment of measured glomerular filtration rate (mGFR), and proteinuria. We used Cox proportional hazards regression to assess the associations of suPAR with CKD progression (defined as doubling of serum creatinine or end-stage renal disease [ESRD]), ESRD, worsening proteinuria (pre-ESRD doubling of 24-hour urine protein to creatinine ratio [UPCR] to ≥220 mg/g), and all-cause death. Results: Among 955 AASK participants, the median baseline suPAR was 4462 pg/mL (25 th to 75 th percentile: 3425-5923 pg/mL), mean mGFR was 46 mL/min per 1.73 m 2 , and median 24-hour UPCR was 79.6 mg/g. After controlling for baseline demographics, AASK trial arm, mGFR, proteinuria, APOL1 risk status, and clinical risk factors, there was a 1.42-times higher risk for CKD progression per two-fold higher baseline suPAR (HR 1.42, 95% CI: 1.17-1.71, p <0.001). Higher suPAR was also independently associated with ESRD (HR 1.59, 95% CI: 1.26-2.00, p <0.001) and death (HR 1.40, 95% CI: 1.12-1.75, p =0.003). Only in patients with two APOL1 risk alleles was suPAR associated with worsening proteinuria (HR 1.77, 95% CI 1.11-2.82, p =0.016; p interaction =0.008). Conclusion: Our study provides evidence of associations between higher suPAR levels and risk for various adverse outcomes in African Americans with hypertension-attributed CKD, independent of proteinuria and GFR.

scholarly journals Soluble Urokinase‐Type Plasminogen Activator Receptor, Changes of 24‐Hour Blood Pressure, and Progression of Chronic Kidney Disease

2021 ◽  
Vol 10 (1) ◽  
Author(s):  
Jong Hyun Jhee ◽  
Bo Young Nam ◽  
Chan Joo Lee ◽  
Jung Tak Park ◽  
Seung Hyeok Han ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Plasminogen Activator ◽  
Interquartile Range ◽  
Ckd Progression ◽  
Type Plasminogen Activator ◽  
Urokinase Type Plasminogen Activator ◽  
Plasminogen Activator Receptor ◽  
The Relationship

Background Soluble urokinase‐type plasminogen activator receptor (suPAR) is associated with cardiovascular risks and poor renal outcomes. However, whether elevated suPAR levels are associated with 24‐hour blood pressure patterns or kidney disease progression in patients with chronic kidney disease (CKD) is unclear. Methods and Results A total of 751 patients with CKD stage 1 to 5 were recruited from CMERC‐HI (Cardiovascular and Metabolic Disease Etiology Research Center–High Risk) cohort study (2013–2018). The relationship of serum suPAR levels to 24‐hour blood pressure parameters and CKD progression was analyzed. The median serum suPAR level was 1439.0 (interquartile range, 1026.2–2150.1) pg/mL, and the mean estimated glomerular filtration rate was 52.8±28.5 mL/min per 1.73 m 2 at baseline. Patients with higher suPAR levels had significantly higher levels of office, 24‐hour, daytime, and nighttime systolic blood pressure and nighttime diastolic blood pressure than those with lower suPAR levels. The highest suPAR tertile was associated with an increased risk of a reverse dipping pattern (odds ratio, 2.93; 95% CI, 1.27–6.76; P =0.01). During a follow‐up of 43.2 (interquartile range, 27.0–55.6) months, the CKD progression occurred in 271 (36.1%) patients. The highest suPAR tertile was significantly associated with higher risk of CKD progression than the lowest tertile (hazard ratio [HR], 2.09; 95% CI, 1.37–3.21; P =0.001). When the relationship was reevaluated with respect to each dipping pattern (dipper, extreme dipper, nondipper, and reverse dipper), this association was consistent only in reverse dippers in whom the risk of CKD progression increased (HR, 1.43; 95% CI, 1.02–2.01; P =0.03) with every 1‐unit increase in serum suPAR levels. Conclusions Elevated suPAR levels are independently associated with CKD progression, and this association is prominent in reverse dippers.

scholarly journals Elevated Plasma Soluble Urokinase-Type Plasminogen Activator Receptor (suPAR) in Sickle Cell Disease - a Marker of Chronic Kidney Disease

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 968-968
Author(s):  
Nowah Kokou Apeadoufia Afangbedji ◽  
James G. Taylor ◽  
Sergei Nekhai ◽  
Marina Jerebtsova
Keyword(s):  
Chronic Kidney Disease ◽  
Sickle Cell Disease ◽  
Kidney Disease ◽  
Renal Disease ◽  
Plasminogen Activator ◽  
Sickle Cell ◽  
Cell Disease ◽  
Type Plasminogen Activator ◽  
Urokinase Type Plasminogen Activator ◽  
Plasminogen Activator Receptor

Abstract Background: Sickle cell nephropathy (SCN) is one of the most common complications of SCD, leading in most cases to chronic kidney disease (CKD) and end-stage renal disease (ESRD). Despite the high prevalence of CKD in sickle cell disease (SCD) patients, there remains a poor understanding of the pathophysiological mechanism of SCN and a lack of biomarkers for early detection of SCD-associated CKD. Soluble urokinase-type plasminogen activator receptor (suPAR) is an emerging biomarker of CKD. suPAR is a member of the fibrinolytic system, which is dysregulated in SCD patients. Objective: To evaluate suPAR as a biomarker of SCD-associated nephropathy and identify plasma proteases responsible for its increase in SCD. Methods: The study was approved by Howard University review board (IRB) and all subjects provided written inform consent prior to the sample collection. Whole blood and urine samples were collected from 77 SCD patients and 10 healthy individuals, and plasma was isolated. Levels of creatinine and cystatin C in plasma and albumin and creatinine in urine were measured by ELISA. eGFR was calculated using CKD-EPI creatinine-cystatin equation, and CKD stages were assigned. Plasma suPAR was measured by ELISA and was correlated with CKD stages. The activities of candidates uPAR proteases: Neutrophile elastase (NE), urokinase-type plasminogen activator (uPA) and plasmin in plasma samples from SCD patients were measured and compared to healthy participants. Results: The average age of SCD patients was 42.5 years (range 18-67 years). Most patients had HbSS genotype (67.5%),19.5% of patients were HbSC (hemoglobin C sickle cell compound heterozygous), and 13% had HbS β-thalassemia. More than half (53.2 %) were females. We observed an increased level of plasma suPAR (&gt;3ng/ml) in more than 60% of SCA patients without renal disease, representing a risk factor for CKD progression. Plasma suPAR levels further increased in the patients with CKD and positively correlated with stages of CKD (r=0.419, R2=0.1696). Analysis of plasma proteases that cleaved uPAR producing soluble peptides (suPAR) demonstrated increased urokinase-type plasminogen activator (uPA) activity without significant changes in neutrophile elastase. Conclusion: This study validated plasma suPAR as a potential marker of CKD in SCD patients and identified plasma uPA as a uPAR protease that may increase circulating suPAR in SCD. Future longitudinal analysis of suPAR levels in patients with SCA is needed. Acknowledgments: We thank Drs. Namita Kumari and Xiaomei Niu for their help in samples identification. This work was supported by NIH Research Grants 1R01HL125005-06A1, 5U54MD007597, 1P30AI117970-06,1UM1AI26617, and 1SC1HL150685. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

scholarly journals Clinical value of soluble urokinase type plasminogen activator receptors in chronic kidney disease

Medicine ◽  
2019 ◽  
Vol 98 (38) ◽  
pp. e17146
Author(s):  
Reem M. Ahmed ◽  
Mona A. Khalil ◽  
Amal H. Ibrahim ◽  
Hanaa M. Eid ◽  
Walid Kamal Abdelbasset ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Plasminogen Activator ◽  
Clinical Value ◽  
Type Plasminogen Activator ◽  
Urokinase Type Plasminogen Activator

Soluble urokinase-type plasminogen activator receptor and incident end-stage renal disease in Chinese patients with chronic kidney disease

2018 ◽  
Vol 35 (3) ◽  
pp. 465-470 ◽  
Author(s):  
Li Lv ◽  
Fang Wang ◽  
Liang Wu ◽  
Jin-Wei Wang ◽  
Zhao Cui ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Renal Disease ◽  
End Stage Renal Disease ◽  
Type Plasminogen Activator ◽  
Urokinase Type Plasminogen Activator ◽  
Increased Risk ◽  
Plasminogen Activator Receptor ◽  
Stage Renal Disease ◽  
End Stage

Abstract Background Soluble urokinase-type plasminogen activator receptor (suPAR), a marker of immune activation, was shown to be associated with outcomes and kidney disease among various patient populations. The prognostic role of circulating suPAR levels in patients with chronic kidney disease (CKD) needs to be investigated in a cohort with large sample size of renal diseases. Methods We measured serum suPAR concentration in 2391 CKD patients in the multicenter Chinese Cohort Study of Chronic Kidney Disease, and investigated the association of serum suPAR with the prespecified endpoint event, end-stage renal disease (ESRD), using Cox proportional hazards regression model. Results Altogether, 407 ESRD events occurred during the median follow-up of 54.8 (interquartile range: 47.5–62.2) months. The higher levels of serum suPAR were independently associated with increased risk of incident ESRD after adjusting for potential confounders including the baseline estimated glomerular filtration rate categories, with the hazard ratios (HRs) of 1.53 [95% confidence intervals (CIs) 1.10–2.12] for the top tertile (≥3904 pg/mL) compared with the bottom tertile (&lt;2532 pg/mL). When stratified by the etiologies of CKD, among patients with glomerulonephritis (GN), serum suPAR levels were also independently associated with the higher risk of ESRD, with an HR of 1.61 (95% CI 1.03–2.53) in the top tertile compared with the bottom tertile. Conclusions Circulating suPAR level was independently associated with an increased risk of progression to ESRD in Chinese CKD patients, especially in those with an etiology of GN.

Sign in / Sign up

Export Citation Format

Share Document