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BACKGROUND: Despite advances in lung cancer treatment, most lung cancers are diagnosed at an advanced stage. Expression of microRNA10b (miR-10b) and fibrinolytic activity, as reflected by soluble urokinase-type plasminogen activator receptor (suPAR) and plasminogen activator inhibitor 1 (PAI-1), are promising biomarker candidates. OBJECTIVE: To assess the expression of miR-10b, and serum levels of suPAR and PAI-1 in advanced stage non-small cell lung cancer (NSCLC) patients, and their correlation with progression, treatment response and prognosis. METHODS: The present prospective cohort and survival study was conducted at Dharmais National Cancer Hospital and included advanced stage NSCLC patients diagnosed between March 2015 and September 2016. Expression of miR-10b was quantified using qRT-PCR. Levels of suPAR and PAI-1 were assayed using ELISA. Treatment response was evaluated using the RECIST 1.1 criteria. Patients were followed up until death or at least 1 year after treatment. RESULTS: Among the 40 patients enrolled, 25 completed at least four cycles of chemotherapy and 15 patients died during treatment. Absolute miR-10b expression ⩾ 592,145 copies/ μ L or miR-10b fold change ⩾ 0.066 were protective for progressive disease and poor treatment response, whereas suPAR levels ⩾ 4,237 pg/mL was a risk factor for progressive disease and poor response. PAI-1 levels > 4.6 ng/mL was a protective factor for poor response. Multivariate analysis revealed suPAR as an independent risk factor for progression (OR a ⁢ d ⁢ j , 13.265; 95% confidence intervals (CI), 2.26577.701; P = 0.006) and poor response (OR a ⁢ d ⁢ j , 15.609; 95% CI, 2.221–109.704; P = 0.006), whereas PAI-1 was an independent protective factor of poor response (OR a ⁢ d ⁢ j , 0.127; 95% CI, 0.019–0.843; P = 0.033). CONCLUSIONS: Since miR-10b cannot be used as an independent risk factor for NSCLC progression and treatment response, we developed a model to predict progression using suPAR levels and treatment response using suPAR and PAI-1 levels. Further studies are needed to validate this model. [ABSTRACT FROM AUTHOR]

Caregivers are integral to the care of those with neurological disorders such as Parkinson's Disease (PD), but are often burdened by stress, anxiety, and depression. Previous research has suggested that the foundation of such stress is low-grade systemic inflammation, as evidenced by increased interleukin 6 (IL-6) and C-reactive protein (CRP) levels. Soluble urokinase-type plasminogen activator receptor (suPAR) is a kidney disease risk factor and marker of chronic inflammation that integrates psycho-social stress and organ dysfunction. Caregivers of PD experience an extraordinary amount of stress and suPAR's role as prognostic marker has not yet been assessed in caregivers of PD. The aim of this study was to determine the relationship between suPAR levels and PD caregiver burden. Healthy volunteers who accompanied patients with parkinsonism (n = 35) donated blood samples, and complete blood counts (CBC), CRP, and suPAR levels were measured. Participants were then interviewed by telephone and stratified into primary and non-primary caregiver groups. Their caregiver burden was quantified through the Zarit Caregiver Burden Short Form (ZBI-12). The resultant data demonstrated higher plasma levels of suPAR and ZBI-12 scores for the primary caregiver group relative to the non-primary caregiver group (suPAR level: 3.73 vs. 2.72 ng/mL, p = 0.01; ZBI-12: 18.57 vs. 5.4, p < 0.0001; Table). The data also revealed a moderate positive correlation between suPAR and ZBI-12 scores. These findings not only demonstrate a correlation between elevated suPAR and caregiving burden in PD, but also further support and raise awareness for the overall psychosocial burden and stress experienced by those caregivers. [ABSTRACT FROM AUTHOR]

Severe malaria (SM) is a leading cause of global morbidity and mortality, particularly in children in sub-Saharan Africa. However, existing malaria diagnostic tests do not reliably identify children at risk of severe and fatal outcomes. Dysregulated host immune and endothelial activation contributes to the pathogenesis of SM. Current research suggests that measuring markers of these pathways at presentation may have clinical utility as prognostic indicators of disease progression and risk of death. In this review, we focus on the available evidence implicating soluble urokinase-type plasminogen activator receptor (suPAR) as a novel and early predictor of severe and fatal malaria and discuss its potential utility for malaria triage and management. [ABSTRACT FROM AUTHOR]

Severe malaria (SM) is a leading cause of global morbidity and mortality, particularly in children in sub-Saharan Africa. However, existing malaria diagnostic tests do not reliably identify children at risk of severe and fatal outcomes. Dysregulated host immune and endothelial activation contributes to the pathogenesis of SM. Current research suggests that measuring markers of these pathways at presentation may have clinical utility as prognostic indicators of disease progression and risk of death. In this review, we focus on the available evidence implicating soluble urokinase-type plasminogen activator receptor (suPAR) as a novel and early predictor of severe and fatal malaria and discuss its potential utility for malaria triage and management.

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Introduction: The soluble urokinase-type plasminogen activator receptor (suPAR) potentially plays a role in immune-thrombosis, possibly by modulating plasmin activity or contributing to chemotaxis in a complex, poorly understood context. The role of suPAR levels in the short-term prognostic of patients with pulmonary embolism (PE) has not been evaluated., Material and Methods: This observational, prospective, single-center study enrolled consecutive patients aged 18 and above with confirmed acute symptomatic PE and no prior anticoagulant therapy. The primary objective was to assess the prognostic capacity of suPAR levels measured at the time of diagnosis in terms of mortality., Results: Fifty-two patients, with a mean age of 73.8 years (±17), were included, with gender distribution evenly split at 50%. Seven (13.5%) patients died. The ROC curve for mortality yielded an AUC of 0.72 (95% CI 0.48-0.96), with an optimal suPAR cut-off of 5.5ng/mL. Bivariate analysis for suPAR>5.5ng/mL was associated with a crude odds ratio of 10 (95% CI 1.63-61.27; p=0.01) for 30-day mortality. Survival analysis showed a 30-day mortality hazard ratio of 8.33 (95% CI 1.69-40.99; p<0.01)., Conclusion: suPAR emerges as a potential biomarker for short-term mortality prediction and holds the potential for enhanced stratification in patients with acute symptomatic PE., (Copyright © 2024 Elsevier España, S.L.U. All rights reserved.)

Inflammation is a hallmark of heart failure (HF) and among inflammatory biomarkers, the most studied remains the C-reactive protein (CRP). In recent years several biomarkers have emerged, such as sST2 and soluble urokinase–type plasminogen activator receptor (suPAR). This study set out to examine the relative importance of long-time prognostic strength of suPAR and the potential additive information on patient risk with chronic HF in comparison with pronostic value of CRP and sST2. Demographics, clinical and biological variables were assessed in a total of 182 patients with chronic HF over median follow-up period of 80 months. Inflammatory biomarkers (i.e., CRP, sST2, and suPAR) were performed. In univariate Cox regression analysis age, NYHA class, MAGGIC score and the five biomarkers (N-terminal pro brain natriuretic peptide [NT-proBNP], high-sensitive cardiac troponin T [hs-cTnT], CRP, sST2, and suPAR) were associated with both all-cause and cardiovascular mortality. In the multivariate model, only NT-proBNP, suPAR, and MAGGIC score remained independent predictors of all-cause mortality as well as of cardiovascular mortality. Risk classification analysis was significantly improved with the addition of suPAR particularly for all-cause short- and long-term mortality. Using a classification tree approach, the same three variables could be considered as significant classifier variables to predict all-cause or cardiovascular mortality and an algorithm were reported. We demonstrated the favorable outcome associated with patients with a low MAGGIC score and a low suPAR level by comparison to patients with low MAGGIC score but high suPAR values. The main findings of our study are (1) that among the three inflammatory biomarkers, only suPAR levels were independently associated with 96-month mortality for patients with chronic HF and (2) that an algorithm based on clinical score, a cardiomyocyte stress biomarker and an inflammatory biomarker could help to a more reliable long term risk stratification in heart failure. [ABSTRACT FROM AUTHOR]

Abstract Background There is still a challenge in discriminating between vertebral osteomyelitis and degenerative diseases of the spine. To this end, we determined the suitability of soluble urokinase-type plasminogen activator receptor (suPAR) and compared the diagnostic potential of suPAR to CRP. Methods Patients underwent surgical stabilization of the lumbar and/or thoracic spine with removal of one or more affected intervertebral discs, as therapy for vertebral osteomyelitis (n = 16) or for erosive osteochondrosis (control group, n = 20). In this prospective study, we evaluated the suPAR and CRP levels before (pre-OP) and after surgery (post-OP) on days 3–5, 6–11, 40–56, and 63–142. Results The suPAR levels in vertebral osteomyelitis patients were significantly higher than those from controls pre-OP, 3–5 days post-OP, and 6–11 days post-OP. Significantly higher CRP levels were observed in the vertebral osteomyelitis group than in the controls pre-OP and 6–11 days post-OP. Levels of suPAR and CRP correlated positively in all patients in the pre-OP period: r = 0.63 (95% CI: 0.37–0.79), p

Soluble urokinase-type plasminogen activator receptor (suPAR) is associated with chronic kidney disease (CKD) severity and peripheral artery disease (PAD). We hypothesize an association of PAD severity and suPAR in patients without advanced CKD and further risk stratification according to the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines. For study purposes, suPAR was measured in 334 PAD patients (34% women, age 69 (62–78) years, eGFR 68 ± 20 mL/min/1.72 m2) by commercial ELISA. Patients were followed for 10 years to assess long-term all-cause survival by Cox regression. Higher suPAR levels were associated with lower ankle–brachial index (R = −0.215, p = 0.001) in patients with PAD without media-sclerosis (n = 236). suPAR levels inversely correlated with decreased glomerular filtration rate (R = −0.476, p < 0.001) and directly correlated with urinary albumin-to-creatinine ratio (R = 0.207, p < 0.001). Furthermore, higher suPAR levels associated with a higher KDIGO risk score (p < 0.001). Baseline suPAR was significantly associated with all-cause mortality (HR 1.40 (95% CI 1.16–1.68), p < 0.001) over 10 years. suPAR remained associated with mortality (HR 1.29 (1.03–1.61), p = 0.026) after multivariable adjustment for age, sex, cardiovascular risk factors, and eGFR. Future research may define a standard role for suPAR assessment in PAD's work-up and treatment, especially in patients with CKD. [ABSTRACT FROM AUTHOR]

Background: Soluble urokinase-type plasminogen activator receptor (suPAR) is positively correlated with immune system activity. Inflammation can promote the development of chronic obstructive pulmonary disease (COPD). Therefore, this study conducted a systematic review and meta-analysis to assess the association between suPAR levels and the pathogenesis of COPD, and further assess the exact clinical value of suPAR in COPD. Methods: PubMed, Excerpt Medica Database (Embase), Web of Science (WOS), and Cochrane Library databases were searched for studies that reported the value of suPAR diagnosis for adult COPD patients. Results: A total of 11 studies were included, involving 4520 participants. Both COPD patients with predicted forced expiratory volume in 1 s (FEV1)⩾80% [weighted mean difference (WMD) = 320.25; 95% confidence interval (CI): 99.79–540.71] and FEV1 < 80% (WMD = 2950.74; 95% CI: 2647.06–3254.43) showed higher suPAR level. The sensitivity and specificity of suPAR for diagnosis of COPD were 87% and 79%, respectively, and AUC was 84%. This can not only effectively identify acute exacerbation of COPD (AECOPD) in a healthy population (WMD = 3114.77; 95% CI: 2814.66–3414.88), but also has the potential to distinguish AECOPD from stable COPD (WMD = 351.40; 95% CI: 215.88–486.93). There was a significant decrease of suPAR level after treatment [WMD = –1226.97; 95% CI: –1380.91– (–1073.03)]. Conclusion: suPAR as a novel biomarker has potential for early diagnosis of COPD and prediction of AECOPD. There is a potential correlation between the level of suPAR and the state of COPD, which may also indicate the early state and severity of COPD. When the suPAR level of COPD patients is further increased, the risk of acute exacerbation increases and should be highly valued. This also shows potential as a measure of treatment response, and as a guide to the clinical management in COPD. The reviews of this paper are available via the supplemental material section. [ABSTRACT FROM AUTHOR]

Focal segmental glomerulosclerosis (FSGS) in children, which is a kind of nephrotic syndrome showing steroid resistance, usually progresses to a substantial number of end stage renal disease (ESRD). Although the pathogenesis of primary FSGS is unclear, several recent studies have reported that FSGS is associated with circulating immune factors such as soluble urokinase-type plasminogen activator receptor (suPAR) or anti-CD40 autoantibody. We report a successfully treated case of a 19-year-old female patient who experienced a recurrence of primary FSGS. After the diagnosis of FSGS, the patient progressed to ESRD and received a kidney transplantation (KT). Three days later, recurrence was suspected through proteinuria and hypoalbuminemia. She has been performed plasmapheresis and high dose methylprednisolone pulse therapy and shown remission status without increasing proteinuria for four years after KT. In conclusion, strong immunosuppressive therapy may be helpful for a good prognosis of recurrent FSGS, suppressing several immunologic circulating factors related disease pathogenesis.

Background: Early risk stratification of patients with suspected acute myocardial infarction (AMI) constitutes an unmet need in current daily clinical practice. We aimed to evaluate the predictive value of soluble urokinase-type plasminogen activator receptor (suPAR) levels for 1-year mortality in patients with suspected AMI. Methods and results: suPAR levels were determined in 1314 patients presenting to the emergency department with suspected AMI. Patients were followed up for 12 months to assess all-cause mortality. Of 1314 patients included, 308 were diagnosed with AMI. Median suPAR levels did not differ between subjects with AMI compared to non-AMI (3.5 ng/ml vs. 3.2 ng/ml, p = 0.066). suPAR levels reliably predicted all-cause mortality after 1 year. Hazard ratio for 1-year mortality was 12.6 (p < 0.001) in the quartile with the highest suPAR levels compared to the first quartile. The prognostic value for 6-month mortality was comparable to an established risk prediction model, the Global Registry of Acute Coronary Events (GRACE) score, with an AUC of 0.79 (95% CI 0.72–0.86) for the GRACE score and 0.77 (95% CI 0.69–0.84) for suPAR. Addition of suPAR improved the GRACE score, as shown by integrated discrimination improvement statistics of 0.036 (p = 0.03) suggesting a further discrimination of events from non-events by the addition of suPAR. Conclusions: suPAR levels reliably predicted mortality in patients with suspected AMI. Study registration: http://www.clinicaltrials.gov (NCT02355457). [ABSTRACT FROM AUTHOR]

Background: There is still a challenge in discriminating between vertebral osteomyelitis and degenerative diseases of the spine. To this end, we determined the suitability of soluble urokinase-type plasminogen activator receptor (suPAR) and compared the diagnostic potential of suPAR to CRP. Methods: Patients underwent surgical stabilization of the lumbar and/or thoracic spine with removal of one or more affected intervertebral discs, as therapy for vertebral osteomyelitis (n = 16) or for erosive osteochondrosis (control group, n = 20). In this prospective study, we evaluated the suPAR and CRP levels before (pre-OP) and after surgery (post-OP) on days 3–5, 6–11, 40–56, and 63–142. Results: The suPAR levels in vertebral osteomyelitis patients were significantly higher than those from controls pre-OP, 3–5 days post-OP, and 6–11 days post-OP. Significantly higher CRP levels were observed in the vertebral osteomyelitis group than in the controls pre-OP and 6–11 days post-OP. Levels of suPAR and CRP correlated positively in all patients in the pre-OP period: r = 0.63 (95% CI: 0.37–0.79), p < 0.0001. The values for the area under the receiver operating characteristics curve (AUC) for pre-OP and the overall model post-OP were 0.88 (95% CI: 0.76–1.00) and 0.84 (95% CI: 0.71–0.97) for suPAR, 0.93 (95% CI: 0.85–1.00) and 0.77 (95% CI: 0.62–0.93) for CRP, and 0.98 (95% CI: 0.96–1.00) and 0.91 (95% CI: 0.82–1.00) for the combination of suPAR and CRP. The AUC for suPAR pre-OP revealed an optimum cut-off value, sensitivity, specificity, NPV, and PPV of 2.96 ng/mL, 0.69, 1.00, 0.80, and 1.00, respectively. For CRP, these values were 11.58 mg/L, 0.88, 0.90, 0.90, and 0.88, respectively. Conclusion: The present results show that CRP is more sensitive than suPAR whereas suPAR is more specific than CRP. Moreso, our study demonstrated that improvement in the diagnostic power for discrimination of vertebral osteomyelitis and degenerative diseases of the spine can be achieved by a combination of both suPAR and CRP. Trial registration: ClinicalTrials.gov, NCT02554227, posted Sept. 18, 2015, and updated Aug. 13, 2019 [ABSTRACT FROM AUTHOR]

Background: Focal segmental glomerulosclerosis (FSGS) is frequently associated with heavy proteinuria and progressive renal failure requiring dialysis or kidney transplantation. However, primary FSGS also has a ~40% risk of recurrence of disease in the transplanted kidney (rFSGS). Multiple circulating factors have been identified to contribute to the pathogenesis of primary and rFSGS including soluble urokinase-type plasminogen activator receptor (suPAR) and patient-derived CD40 autoantibody (CD40autoAb). However, the downstream effector pathways specific to individual factors require further study. The tumor necrosis factor, TNF pathway activation by one or more circulating factors present in the sera of patients with FSGS has been supported by multiple studies., Methods: A human in vitro model was used to study podocyte injury measured as the loss of actin stress fibers. Anti-CD40 autoantibody was isolated from FSGS patients (recurrent and non-recurrent) and control patients with ESRD due to non-FSGS related causes. Two novel human antibodies-anti-uPAR (2G10) and anti-CD40 antibody (Bristol Meyer Squibb, 986090) were tested for their ability to rescue podocyte injury. Podocytes treated with patient derived antibody were transcriptionally profiled using whole human genome microarray., Results: Here we show that podocyte injury caused by sera from FSGS patients is mediated by CD40 and suPAR and can be blocked by human anti-uPAR and anti-CD40 antibodies. Transcriptomic studies to compare the molecules and pathways activated in response to CD40 autoantibody from rFSGS patients (rFSGS/CD40autoAb) and suPAR, identified unique inflammatory pathways associated with FSGS injury., Conclusions: We identified several novel and previously described genes associated with FSGS progression. Targeted blockade of suPAR and CD40 pathways with novel human antibodies showed inhibition of podocyte injury in FSGS., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://atm.amegroups.com/article/view/10.21037/atm-22-3670/coif). MMS is a founder of technology for the assessment of kidney injury, owned by the regents, University of California. As the founder she has financial or non-financial interests in Nephrosant. JR reports that he receives consulting fees from Reata, Novateur Ventures, Walden Biosciences, Biomarin, Astellas, Massachusetts General Hospital, Genentech, Up to Date, Merck, Insceptionsci, GL, Visterra, Aclipse and MantraBio. JR also has several patents: US20110212083-Role of soluble uPAR in the Pathogenesis of Proteinuric Kidney Disease, S9867923-Reducing Solucble Rokinase Receptor in the Circulation, JP2016530510-Non-Glycoslyated suPAR Biomarkers and Uses thereof, US20160296592-Methods/Compositions for the Treatment of Proteinuric Diseases, US9144594-Dynamin Mediated Diseases and US8809386-Dynamin Ring Stabilizers. JR is on Scientific advisory board of Walden Biosciences and has stocks/stock options at Walden Biosciences and Aclipse. The other authors have no conflicts of interest to declare., (2023 Annals of Translational Medicine. All rights reserved.)

Background: Soluble urokinase-type plasminogen activator receptor (suPAR) could be a causative factor in idiopathic focal segmental glomerulosclerosis (FSGS). It is currently unknown to what extent suPAR levels could be affected by treatment with immunosuppressive drugs such as cyclosporin A (CsA) and mycophenolate mofetil (MMF). Treatment with CsA, but not MMF, is accompanied by nephrotoxicity, and since suPAR levels correlate with glomerular filtration rate (GFR), treatment with these drugs could indirectly modulate suPAR levels by their effect on renal function. Methods: We measured suPAR levels in a recent prospective multicenter crossover trial comparing the efficacy of MMF and CsA in pediatric patients with minimal change disease (MCD) and frequently relapsing steroid-sensitive nephrotic syndrome (FR-SSNS). All patients had biopsy-proven MCD and normal renal function; they were treated with each drug for 1 year in a crossover study design. Serum suPAR levels were measured before and after 1 year of therapy with MMF ( n = 40) and CsA ( n = 35). Results: The suPAR levels decreased after 1 year of treatment with MMF ( p < 0.05). Conversely, suPAR levels increased after 1 year of treatment with CsA in the same patients ( p = 0.01). These changes in suPAR levels were not correlated to the estimated glomerular filtration rate (eGFR) or changes in the GFR. Conclusions: Data from this prospective randomized trial suggest that treatment with MMF and CsA is associated with different effects on suPAR levels in children with MCD and that these are independent of their effects on GFR. [ABSTRACT FROM AUTHOR]

Abstract: Background: We reported that the soluble LDL receptor relative with 11 ligand-binding repeats (sLR11) is a promising biomarker for follicular lymphoma (FL). In this study, we evaluated the fluctuations in serum sLR11 levels compared with those of serum soluble urokinase-type plasminogen activator receptor (suPAR) and soluble interleukin-2 receptor (sIL-2R) in patients with non-Hodgkin's lymphoma (NHL). Methods: Serum sLR11, suPAR, and sIL-2R levels were measured using ELISA in 175 NHL patients and 57 healthy controls. The levels at diagnosis and at remission were evaluated in 64 paired samples. Results: Serum sLR11 levels were significantly increased in FL, diffuse large B-cell lymphoma (DLBCL), and peripheral T-cell lymphoma patients compared with healthy controls. Serum sLR11 levels revealed significant positive correlations with serum suPAR and sIL-2R levels. Serum sLR11 levels at remission were decreased compared with those at diagnosis, and the declines at remission expressed a slope of approximately −1 with an intercept near that of controls. The receiver operating characteristic–area under the curve of serum sLR11 concentrations was equivalent to that of serum suPAR and sIL-2R concentrations in an early-stage DLBCL and FL. Conclusions: sLR11 may be a novel soluble receptor indicative of early-stage NHL, with potential use for evaluating therapeutic efficacy. [Copyright &y& Elsevier]

Summary. The urokinase-type plasminogen activator (uPA) system, which consists of a proteinase (uPA), a receptor (uPAR or CD87) and inhibitors, is involved in proteolysis, cell migration, tissue remodelling, angiogenesis and cell adhesion. Recent findings suggest that malignant plasma cells express uPA and uPAR. The expression of these factors could represent a process by which myeloma plasma cells interact with the bone marrow (BM) environment and influence important biological events such as bone matrix degradation, plasma cell invasion and homing and, possibly, clinical evolution. We evaluated uPAR (CD87) and its soluble form (suPAR) in 49 multiple myeloma (MM) patients and correlated their expression and levels with clinico-biological characteristics of the disease. Flow cytometric analysis demonstrated that CD87 was expressed in all MM patients. High CD87 expression was associated with higher intensity of expression of CD56 (P = 0·038), CD38 (P = 0·058) and CD138 (P = 0·054) and CD45bright positivity (P = 0·014). suPAR levels correlated positively with soluble serum CD138 (P = 0·001), creatinine (P = 0·001), beta2 -microglobulin (P < 0·001), disease stage (P = 0·017) and extra-BM involvement (P = 0·002). In the 46 evaluable patients, multivariate analysis showed that high levels of suPAR (P = 0·0214) and disease stage (P = 0·0064) were predictive of extra-BM involvement. In multivariate Cox analysis, 13q deletion (P = 0·0278), high soluble serum CD138 (P = 0·0201) and high suPAR (P = 0·0229) were the only parameters that independently affected survival. We conclude that CD87 is expressed on myeloma plasma cells and that suPAR, which predicts extra-BM involvement and poor prognosis, possibly represents a molecule with a relevant role in the biology of MM. [ABSTRACT FROM AUTHOR]

Rationale & Objective: Most circulating biomarkers of chronic kidney disease (CKD) progression focus on factors reflecting glomerular filtration. Few biomarkers capture nonglomerular pathways of kidney injury or damage, which may be particularly informative in populations at high risk for CKD progression such as individuals with diabetes., Study Design: Cohort study., Setting & Participants: 594 participants (mean age, 70 years; 53% women) of the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study who had diabetes and an estimated glomerular filtration rate (eGFR)<60mL/min/1.73m 2 at baseline., Exposures: Plasma biomarkers of inflammation/fibrosis (TNFR1 and TNFR2, suPAR, MCP-1, YKL-40) and tubular injury (KIM-1) measured at the baseline visit., Outcomes: Incident kidney failure with replacement therapy (KFRT)., Analytical Approach: Cox proportional hazards regression and least absolute shrinkage and selection operator regression adjusted for established risk factors for kidney function decline, baseline eGFR, and urinary albumin-creatinine ratio (UACR)., Results: A total of 98 KFRT events were observed over a mean of 6.2±3.5 (standard deviation) years of follow-up. Plasma biomarkers were modestly associated with baseline eGFR (correlation coefficients ranging from-0.08 to-0.65) and UACR (0.14 to 0.56). In individual biomarker models adjusted for eGFR, UACR, and established risk factors, hazard ratios for incident KFRT per 2-fold higher biomarker concentrations were 1.52 (95% CI, 1.25-1.84) for plasma KIM-1, 1.54 (95% CI, 1.08-2.21) for TNFR1, 1.91 (95% CI, 1.16-3.14) for TNFR2, and 1.39 (95% CI, 1.05-1.84) for YKL-40. In least absolute shrinkage and selection operator regression models accounting for biomarkers in parallel, plasma KIM-1 and TNFR1 remained associated with incident KFRT., Limitations: Single biomarker measurement, lack of follow-up eGFR assessments., Conclusions: Individual plasma markers of inflammation/fibrosis (TNFR1, TNFR2, YKL-40) and tubular injury (KIM-1) were associated with risk of incident KFRT in adults with diabetes and an eGFR<60mL/min/1.73m 2 after adjustment for established risk factors., (Copyright © 2021 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Introduction: Severe, nonresponsive, primary focal segmental glomerular sclerosis (FSGS) can progress to end-stage kidney disease (ESKD) in <5 years. Soluble urokinase-type plasminogen activator receptor (suPAR) may contribute to podocyte effacement by activating podocyte β3 integrin. It has been reported as a potential permeability factor and biomarker for primary FSGS. Rituximab was found to have efficacy in case reports and small series. Whether rituximab is efficacious in patients with treatment-resistant FSGS in the context of high suPAR levels and evidence of podocyte B3 integrin activation remains unknown., Methods: In this nonblinded, open-label pilot study, the safety and efficacy of rituximab were evaluated in treatment-resistant adult patients with primary FSGS and a suPAR level > 3500 pg/ml with evidence of β3 integrin activation. Rituximab (1 g) was given on days 1 and 15. The primary outcome was proteinuria at 12 months., Results: Only 13 of 38 screened patients qualified for the study, of whom 9 consented to participate. The baseline proteinuria and glomerular filtration rate (GFR) levels were 7.70 ± 4.61 g/d and 67 ± 38 ml/min, respectively. A transient response at 6 months was noted in 2 patients without a parallel change in suPAR level. At 12 months, there was no statistically significant improvement in proteinuria level with all participants remaining nephrotic (7.27 ± 7.30 g/d). GFR level marginally declined to 60 ± 38 ml/min with one patient progressing to ESKD. There were 2 serious infections, an infusion-related reaction and leucopenia attributed to rituximab., Conclusion: Rituximab was ineffective when administered to adult patients with treatment-resistant primary FSGS with a high suPAR and evidence of podocyte activation., (© 2021 International Society of Nephrology. Published by Elsevier Inc.)

Background: Various biomarkers have been associated with coronary artery disease (CAD) and ischemic heart failure. The aim of this study was to investigate the correlation of serum levels of soluble urokinase-type plasminogen activator receptor (suPAR), growth differentiation factor 15 (GDF-15), heart-type fatty acid-binding protein (H-FABP), and soluble suppression of tumorigenicity 2 (sST2) with left ventricular ejection fraction (EF) in CAD patients and controls. Methods and Results: CAD patients were divided into three groups according to their EF as measured by the biplane Simpson method (53–84%, 31–52%, ≤30%). Overall, 361 subjects were analyzed. In total, 155 CAD patients had an EF of 53–84%, 71 patients had an EF of 31–52%, and 23 patients had an EF of ≤30% as compared to 112 healthy controls (age 51.3 ± 9.0 years, 44.6% female). Mean ages according to EF were 62.1 ± 10.9, 65.2 ± 10.1, and 66.6 ± 8.2 years, respectively, with females representing 29.0, 29.6, and 13.0%. suPAR, GDF-15, H-FABP, and sST2 values were significantly higher in CAD patients and showed an exponential increase with decreasing EF. In a multiple logistic regression model, GDF-15 (p = 0.009), and NT-brain natriuretic peptide (p = 0.003) were independently associated with EF. Conclusion: Biomarkers such as suPAR, GDF-15, H-FABP, and sST2 are increased in CAD patients, especially in highly impaired EF. Besides NT-proBNP as a well-known marker for risk prediction, GDF-15 may be an additional tool for diagnosis and clinical follow-up. [ABSTRACT FROM AUTHOR]