MO472A PRELIMINARY STUDY OF POTENTIAL BIOMARKERS FOR EARLY DIAGNOSIS IN CHRONIC KIDNEY DISEASE

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Irina Lousa ◽  
Maria João Valente ◽  
Susana Rocha ◽  
Sofia D. Viana ◽  
Inês Preguiça ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Renal Function ◽  
Kidney Disease ◽  
Early Diagnosis ◽  
Primary Response ◽  
Therapeutic Interventions ◽  
Cellular Damage ◽  
Tubulointerstitial Injury ◽  
Circulating Levels ◽  
Potential Biomarkers

Abstract Background and Aims The conventionally used biomarkers for chronic kidney disease (CKD) diagnosis are not very sensitive for early diagnosis. Their values become clinically significant only when kidney damage is advanced, and a substantial filtration capacity has been lost. The reliance on these biomarkers may result in a long-time lapse in diagnosis, compromising the earlier use of successful therapeutic interventions to prevent CKD progression and reduce the risk of other common comorbidities. The study of earlier and more sensitive biomarkers for CKD diagnosis is an important medical need. Potentially new biomarkers reflecting different pathophysiological processes underlying CKD, such as changes in renal function, tubulointerstitial injury, inflammation and fibrosis, have been proposed. The use of a panel of biomarkers is likely to be synergetic in detecting CKD, since there are several different mechanisms by which CKD can initiate. Our aim was to identify markers of renal damage/dysfunction and evaluate their sensitivity for CKD detection, in patients at the earlier stages of the disease, stages 1 and 2. Method This study included 32 healthy controls and 29 CKD patients at stages 1 and 2, categorized according to the KDIGO guidelines, using the CKD-EPI equation based on serum creatinine to estimate the glomerular filtration rate (GFR). Causes of CKD in the studied patients were diabetes mellitus (n = 19), polycystic kidney disease (n = 1) and of unknown cause (n = 7) or other (n = 2). Circulating levels of creatinine and β-trace protein (BTP), as markers of renal function; interleukin 6 (IL-6), as a marker of inflammation; tissue inhibitor metalloproteinase 1 (TIMP 1), as a marker of tubulointerstitial injury; pro B-type natriuretic peptide (proBNP), as a marker of cardio-renal dysfunction; and cell-free DNA (cfDNA), as a marker of cellular damage, were evaluated. Results Compared to controls, we found significantly higher values of all studied markers in CKD patients (stage 1 and stage 2): BTP, TIMP-1, IL-6, pro-BNP, and cfDNA. In CKD patients, GFR was negatively correlated with circulating levels of pro-BNP (r = -0.610, P = 0.004, n = 20) and cfDNA (r = -0.408, P = 0.028, n = 29); and, microalbuminuria was positively correlated with circulating levels of BTP (r = 0.465, P = 0.013, n = 28). The biomarker cfDNA was positively correlated with TIMP-1 (r = 0.445, P = 0.16, n = 29) , a marker of tubulointerstitial injury, and with IL-6 (r = 0.670, P < 0.001, n = 29), a marker of inflammation. All patients presented at least two of the studied biomarkers with higher values than the median value presented by controls. Of all studied biomarkers, BTP was the one that was most altered in patients (86.2% presented higher values than the highest value presented by controls). Conclusion Our results suggest that the studied biomarkers are sensitive to the primary response to renal injury, being significantly elevated in the earlier stages of CKD, particularly BTP. Pro-BNP and cfDNA correlate well with disease severity assessed by GFR. The use of a panel comprising several biomarkers, related with different pathophysiological mechanisms underlying CKD initiation and progression, may increase the potential to detect patients at risk, when compared with the evaluation of each biomarker alone. Further validation for the use of these new potential biomarkers requires larger studies with standardized analytical methodologies. Acknowledgments: This work was supported by Applied Molecular Biosciences Unit (UCIBIO) and financed by FEDER COMPETE2020 funds UIDB/04378/2020 and UIDP/04539/2020 (CIBB); by POCI-01-0145-FEDER-007440; by FCT doctoral grant SFRH/BD/145939/2019; by funds from Portugal Regional Coordination and Development Commissions (Norte-01-0145-FEDER-000024).

P0739PANEL OF SENSITIVE BIOMARKERS OF THE PRIMARY RESPONSE TO RENAL INJURY FOR AN EARLY DIAGNOSIS OF CHRONIC KIDNEY DISEASE

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Maria João Valente ◽  
Susana Rocha ◽  
Irina Lousa ◽  
Flávio Reis ◽  
Sara Nunes ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Renal Function ◽  
Kidney Disease ◽  
Renal Injury ◽  
Primary Response ◽  
Control Group ◽  
Tubulointerstitial Injury ◽  
Markers Of Inflammation ◽  
Tnf Α ◽  
Ckd Stage

Abstract Background and Aims The identification of early kidney injury biomarkers is of utmost importance, since most widely used markers of kidney function vary only after several biological changes. Biomarkers allowing an earlier diagnosis of chronic kidney disease (CKD) would avoid delays in the treatment of patients. It is unlikely that a single marker is sufficient to detect the onset of CKD considering the multiple pathophysiological changes underlying primary renal response to renal injury. Several markers of inflammation, endothelial (dys)function, glomerular and tubulointerstitial injuries have been proposed and could be used combined as a panel of markers with different specificities, allowing an early detection of renal injury. Our aim was to study a panel of biomarkers proposed as early markers of renal injury, with different specificities, to evaluate and compare their sensitivities at different CKD stages. Method In this preliminary study, we enrolled 22 healthy individuals and 27 CKD patients separated into 3 groups, according to the CKD stage: 9 in stages 1 and 2; 9 in stage 3, and 9 in stages 4 and 5. None of the patients presented inflammatory, infectious or neoplastic diseases. Diagnosis and CKD stage assignment were performed according to KDIGO guidelines. We evaluated circulating levels of cystatin C (CystC), creatinine (Cr), beta trace protein (BTP) as markers of renal function; tissue inhibitor metalloproteinase 1 (TIMP-1), neutrophil gelatinase-associated lipocalin (NGAL) and transforming growth factor-β (TGF-β) as markers of interstitial tubulointerstitial injury; asymmetric dimethylarginine (ADMA) and tissue plasminogen activator (t-PA), as markers of endothelial (dys)function; pentraxin 3 (PTX3), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), as markers of inflammation; and, pro B-type natriuretic peptides (proBNP), as a marker of cardiac (dys)function. Results In early stages of CKD (1 and 2), we found significant changes in markers of renal function (BTP, but not Cr and CystC), of tubular interstitial injury (TIMP-1 and TGF-β), of inflammation (TNF-α), of endothelial (ADMA) and cardiac (proBNP) dysfunction (vs. controls). In stage 3, we found significant changes (vs. stages 1-2) in markers of renal function (Cr and CystC), inflammation (TNF-α, IL-6), endothelial dysfunction (t-PA) and tubulointerstitial injury (TIMP-1); in stages 4-5 (vs. stage 3), we found significant changes only in the classic marker, Cr, and a trend towards increased CystC. Moreover, we found that at stages 1-2 all patients showed higher levels of BTP and proBNP when compared to the median value in the control group; TIMP-1 and ADMA were increased in 7/9 patients; TNF-α was increased in 7/9 patients; and 7/9 patients had lower values of TGF-β compared to the median value of controls. For the classical markers, Cr and CystC, we found that 5/9 and 4/9 patients, respectively, had lower values than the median value of controls; however, only 2/9 patients showed abnormal creatinine values (vs. reference values). Conclusion Our data suggest that a panel including classic (Cr and CystC) and more sensitive blood markers of the primary response to renal injury (BTP, TIMP-1 or TGF-β, ADMA, TNF-α and proBNP) would allow an earlier diagnosis of CKD, avoiding a delay in diagnosis and management of CKD patients.

scholarly journals Identification of Potential Biomarkers of Chronic Kidney Disease in Individuals with Diabetes: Protocol for a Cross-sectional Observational Study (Preprint)

2019 ◽  
Author(s):  
Ashani R Lecamwasam ◽  
Mohammadreza Mohebbi ◽  
Elif I Ekinci ◽  
Karen M Dwyer ◽  
Richard Saffery
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Data Collection ◽  
Gut Microbiome ◽  
Single Point ◽  
Therapeutic Interventions ◽  
Kidney Dysfunction ◽  
Early Diabetes ◽  
Cross Sectional ◽  
Potential Biomarkers

BACKGROUND The importance of identifying people with diabetes and progressive kidney dysfunction relates to the excess morbidity and mortality of this group. Rates of cardiovascular disease are much higher in people with both diabetes and kidney dysfunction than in those with only one of these conditions. By the time these people are identified in current clinical practice, proteinuria and renal dysfunction are already established, limiting the effectiveness of therapeutic interventions. The identification of an epigenetic or blood metabolite signature or gut microbiome profile may identify those with diabetes at risk of progressive chronic kidney disease, in turn providing targeted intervention to improve patient outcomes. OBJECTIVE This study aims to identify potential biomarkers in people with diabetes and chronic kidney disease (CKD) associated with progressive renal injury and to distinguish between stages of chronic kidney disease. Three sources of biomarkers will be explored, including DNA methylation profiles in blood lymphocytes, the metabolomic profile of blood-derived plasma and urine, and the gut microbiome. METHODS The cross-sectional study recruited 121 people with diabetes and varying stages (stages 1-5) of chronic kidney disease. Single-point data collection included blood, urine, and fecal samples in addition to clinical data such as anthropometric measurements and biochemical parameters. Additional information obtained from medical records included patient demographics, medical comorbidities, and medications. RESULTS Data collection commenced in January 2018 and was completed in June 2018. At the time of submission, 121 patients had been recruited, and 119 samples remained after quality control. There were 83 participants in the early diabetes-associated CKD group with a mean estimated glomerular filtration rate (eGFR) of 61.2 mL/min/1.73 m2 (early CKD group consisting of stage 1, 2, and 3a CKD), and 36 participants in the late diabetic CKD group with a mean eGFR of 23.9 mL/min/1.73 m2 (late CKD group, consisting of stage 3b, 4, and 5), <i>P</i><.001. We have successfully obtained DNA for methylation and microbiome analyses using the biospecimens collected via this protocol and are currently analyzing these results together with the metabolome of this cohort of individuals with diabetic CKD. CONCLUSIONS Recent advances have improved our understanding of the epigenome, metabolomics, and the influence of the gut microbiome on the incidence of diseases such as cancers, particularly those related to environmental exposures. However, there is a paucity of literature surrounding these influencers in renal disease. This study will provide insight into the fundamental understanding of the pathophysiology of CKD in individuals with diabetes, especially in novel areas such as epigenetics, metabolomics, and the kidney-gut axis. INTERNATIONAL REGISTERED REPORT DERR1-10.2196/16277

scholarly journals Identification of Potential Biomarkers of Chronic Kidney Disease in Individuals with Diabetes: Protocol for a Cross-sectional Observational Study

10.2196/16277 ◽  
2020 ◽  
Vol 9 (7) ◽  
pp. e16277
Author(s):  
Ashani R Lecamwasam ◽  
Mohammadreza Mohebbi ◽  
Elif I Ekinci ◽  
Karen M Dwyer ◽  
Richard Saffery
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Data Collection ◽  
Gut Microbiome ◽  
Single Point ◽  
Therapeutic Interventions ◽  
Kidney Dysfunction ◽  
Early Diabetes ◽  
Cross Sectional ◽  
Potential Biomarkers

Background The importance of identifying people with diabetes and progressive kidney dysfunction relates to the excess morbidity and mortality of this group. Rates of cardiovascular disease are much higher in people with both diabetes and kidney dysfunction than in those with only one of these conditions. By the time these people are identified in current clinical practice, proteinuria and renal dysfunction are already established, limiting the effectiveness of therapeutic interventions. The identification of an epigenetic or blood metabolite signature or gut microbiome profile may identify those with diabetes at risk of progressive chronic kidney disease, in turn providing targeted intervention to improve patient outcomes. Objective This study aims to identify potential biomarkers in people with diabetes and chronic kidney disease (CKD) associated with progressive renal injury and to distinguish between stages of chronic kidney disease. Three sources of biomarkers will be explored, including DNA methylation profiles in blood lymphocytes, the metabolomic profile of blood-derived plasma and urine, and the gut microbiome. Methods The cross-sectional study recruited 121 people with diabetes and varying stages (stages 1-5) of chronic kidney disease. Single-point data collection included blood, urine, and fecal samples in addition to clinical data such as anthropometric measurements and biochemical parameters. Additional information obtained from medical records included patient demographics, medical comorbidities, and medications. Results Data collection commenced in January 2018 and was completed in June 2018. At the time of submission, 121 patients had been recruited, and 119 samples remained after quality control. There were 83 participants in the early diabetes-associated CKD group with a mean estimated glomerular filtration rate (eGFR) of 61.2 mL/min/1.73 m2 (early CKD group consisting of stage 1, 2, and 3a CKD), and 36 participants in the late diabetic CKD group with a mean eGFR of 23.9 mL/min/1.73 m2 (late CKD group, consisting of stage 3b, 4, and 5), P<.001. We have successfully obtained DNA for methylation and microbiome analyses using the biospecimens collected via this protocol and are currently analyzing these results together with the metabolome of this cohort of individuals with diabetic CKD. Conclusions Recent advances have improved our understanding of the epigenome, metabolomics, and the influence of the gut microbiome on the incidence of diseases such as cancers, particularly those related to environmental exposures. However, there is a paucity of literature surrounding these influencers in renal disease. This study will provide insight into the fundamental understanding of the pathophysiology of CKD in individuals with diabetes, especially in novel areas such as epigenetics, metabolomics, and the kidney-gut axis. International Registered Report Identifier (IRRID) DERR1-10.2196/16277

EFFECTIVENESS OF ANTIAGGREGANT THERAPY ON KIDNEY ACTIVITY IN THE PREDIALYSIS STAGE OF CHRONIC KIDNEY DISEASE

2020 ◽  
Vol 6 (1) ◽  
pp. 55-60
Author(s):  
Khabib Barnoev ◽  
◽  
Sherali Toshpulatov ◽  
Nozima Babajanova ◽  
Keyword(s):  
Chronic Kidney Disease ◽  
Renal Function ◽  
Kidney Disease ◽  
Comparative Study ◽  
Functional Status ◽  
Stage Ii ◽  
Term Administration ◽  
Antiaggregant Therapy

The article presents the results of a study to evaluate the effectiveness of antiaggregant therapy on the functional status of the kidneys in 115 patients with stage II and III chronic kidney disease on the basis of a comparative study of dipyridamole and allthrombosepin. Studies have shown that long-term administration of allthrombosepin to patients has led to improved renal function.

scholarly journals Renal Function as a Predictor of Reamputation After Initial Transmetatarsal Amputation in the Perioperative Period

2018 ◽  
Vol 3 (3) ◽  
pp. 2473011418S0001
Author(s):  
Junho Ahn ◽  
Katherine Raspovic ◽  
Dane Wukich ◽  
George Liu
Keyword(s):  
Chronic Kidney Disease ◽  
Renal Failure ◽  
Renal Function ◽  
Kidney Disease ◽  
Lower Extremity ◽  
Perioperative Period ◽  
Improvement Program ◽  
Acs Nsqip ◽  
Cell Counts ◽  
Insulin Dependent

Category: Midfoot/Forefoot Introduction/Purpose: With increasing rates of patients being newly diagnosed with diabetes mellitus, foot complications are becoming more common, which often lead to amputation. Compared to major lower extremity amputations, transmetatarsal amputations (TMA) are associated with lower cost, better function, and more aesthetically satisfactory results for patients. Renal failure has been shown to be a significant predictor of morbidity and mortality in lower extremity amputations at various levels. However, previous reports examining the effect of renal function on reamputation rates after TMA have been mixed. As a result, the purpose of this study was to evaluate renal dysfunction as a risk factor for reamputation after initial TMA during the 30-day perioperative period in a large population database. Methods: Patients under 90 years of age who underwent a TMA between 2012 and 2015 were retrospectively identified in the prospectively collected American College of Surgeons-National Surgical Quality Improvement Program® (ACS-NSQIP®) database using the Current Procedure Terminology (CPT) code 28805. Failure of the initial TMA was defined as reamputation in the 30-day perioperative period through corresponding CPT codes. From these criteria, a total of 1,775 patients were identified. More than 150 unique patient factors were included in the study, but glycated hemoglobin (HbA1C) was not reported by the ACS-NSQIP® database. Diabetes status was categorized into four groups: “Insulin” dependent, “Non-Insulin” dependent, or “None.” Filtration rate was estimated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation, and patients were categorized into stages of chronic kidney disease (CKD). Results: Over the 30-day perioperative period, the rate of reamputation after TMA was 6.5%. No statistical differences in age, gender, race, body-mass index, or level of pre-operative functional status were found between groups. Reamputation rates after TMA was significantly correlated with higher white blood cell counts (p<.00001), greater serum creatinine (p=.021), higher blood urea nitrogen (p=.021), type of glycemic control (p=.002), stage of CKD (p=.003), dialysis (p=.001), and pre-operative blood transfusion (p=.042). Stage IV-V CKD was associated with 75% increased odds of reamputation (OR=1.75, 95% CI=1.12-2.73), and higher stage of CKD was associated with greater reamputation rates (p=.003) where stage II CKD had the lowest reamputation rate (3.6%) and stage V with the highest reamputation rate (10.9%). A similar trend was seen with 30-day mortality (p<.00001). Conclusion: In the current study, CKD was significantly correlated with reamputation rates after TMA as well as 30-day mortality. In contrast to a previous report, dialysis was also associated with TMA failure and need for reamputation. Our findings corroborate previous findings correlating dialysis-dependent renal failure and mortality. Whether patients in certain stages of CKD would achieve better outcomes with higher-level amputation rather than a TMA should be investigated in future studies.

scholarly journals Sex modulates the association of radial artery augmentation index with renal function decline in individuals without chronic kidney disease

2021 ◽  
Author(s):  
Qiao Qin ◽  
Fangfang Fan ◽  
Jia Jia ◽  
Yan Zhang ◽  
Bo Zheng
Keyword(s):  
Chronic Kidney Disease ◽  
Renal Function ◽  
Kidney Disease ◽  
Arterial Stiffness ◽  
Confidence Interval ◽  
Odds Ratio ◽  
Adjusted Odds Ratio ◽  
Augmentation Index ◽  
Renal Function Decline

Abstract Purpose An increase in arterial stiffness is associated with rapid renal function decline (RFD) in patients with chronic kidney disease (CKD). The aim of this study was to investigate whether the radial augmentation index (rAI), a surrogate marker of arterial stiffness, affects RFD in individuals without CKD. Methods A total of 3165 Chinese participants from an atherosclerosis cohort with estimated glomerular filtration rates (eGFR) of ≥ 60 mL/min/1.73 m2 were included in this study. The baseline rAI normalized to a heart rate of 75 beats/min (rAIp75) was obtained using an arterial applanation tonometry probe. The eGFRs at both baseline and follow-up were calculated using the equation derived from the Chronic Kidney Disease Epidemiology Collaboration. The association of the rAIp75 with RFD (defined as a drop in the eGFR category accompanied by a ≥ 25% drop in eGFR from baseline or a sustained decline in eGFR of > 5 mL/min/1.73 m2/year) was evaluated using the multivariate regression model. Results During the 2.35-year follow-up, the incidence of RFD was 7.30%. The rAIp75 had no statistically independent association with RFD after adjustment for possible confounders (adjusted odds ratio = 1.12, 95% confidence interval: 0.99–1.27, p = 0.074). When stratified according to sex, the rAIp75 was significantly associated with RFD in women, but not in men (adjusted odds ratio and 95% confidence interval: 1.23[1.06–1.43], p = 0.007 for women, 0.94[0.76–1.16], p = 0.542 for men; p for interaction = 0.038). Conclusion The rAI might help screen for those at high risk of early rapid RFD in women without CKD.

scholarly journals Efficacy and safety of gout flare prophylaxis and therapy use in people with chronic kidney disease: a Gout, Hyperuricemia and Crystal-Associated Disease Network (G-CAN)-initiated literature review

2021 ◽  
Vol 23 (1) ◽  
Author(s):  
Huai Leng Pisaniello ◽  
Mark C. Fisher ◽  
Hamish Farquhar ◽  
Ana Beatriz Vargas-Santos ◽  
Catherine L. Hill ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Renal Function ◽  
Kidney Disease ◽  
Literature Review ◽  
Interleukin 1 ◽  
Treatment Options ◽  
Cochrane Library ◽  
Efficacy And Safety ◽  
Clinical Trial Results ◽  
Gout Flare

AbstractGout flare prophylaxis and therapy use in people with underlying chronic kidney disease (CKD) is challenging, given limited treatment options and risk of worsening renal function with inappropriate treatment dosing. This literature review aimed to describe the current literature on the efficacy and safety of gout flare prophylaxis and therapy use in people with CKD stages 3–5. A literature search via PubMed, the Cochrane Library, and EMBASE was performed from 1 January 1959 to 31 January 2018. Inclusion criteria were studies with people with gout and renal impairment (i.e. estimated glomerular filtration rate (eGFR) or creatinine clearance (CrCl) < 60 ml/min/1.73 m2), and with exposure to colchicine, interleukin-1 inhibitors, non-steroidal anti-inflammatory drugs (NSAIDs), and glucocorticoids. All study designs were included. A total of 33 studies with efficacy and/or safety analysis stratified by renal function were reviewed—colchicine (n = 20), anakinra (n = 7), canakinumab (n = 1), NSAIDs (n = 3), and glucocorticoids (n = 2). A total of 58 studies reported these primary outcomes without renal function stratification—colchicine (n = 29), anakinra (n = 10), canakinumab (n = 6), rilonacept (n = 2), NSAIDs (n = 1), and glucocorticoids (n = 10). Most clinical trials excluded study participants with severe CKD (i.e. eGFR or CrCl of < 30 mL/min/1.73 m2). Information on the efficacy and safety outcomes of gout flare prophylaxis and therapy use stratified by renal function is lacking. Clinical trial results cannot be extrapolated for those with advanced CKD. Where possible, current and future gout flare studies should include patients with CKD and with study outcomes reported based on renal function and using standardised gout flare definition.

scholarly journals High-sensitive cardiac troponin for the diagnosis of acute myocardial infarction in different chronic kidney disease stages

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Daijin Ren ◽  
Tianlun Huang ◽  
Xin Liu ◽  
Gaosi Xu
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Chronic Kidney Disease ◽  
Renal Function ◽  
Kidney Disease ◽  
Cardiac Troponin ◽  
Optimal Cutoff ◽  
Cutoff Values ◽  
Optimal Value ◽  
Disease Stages

Abstract Background Chronic kidney disease (CKD) are associated with acute myocardial infarction (AMI). High-sensitive cardiac troponin (hs-cTn) has been evidenced to enhance the early diagnostic accuracy of AMI, but hs-cTn levels are often chronically elevated in CKD patients, which reduces their diagnostic utility. The aim of this study was to derive optimal cutoff-values of hs-cTn levels in patients with CKD and suspected AMI. Methods In this retrospective paper, a total of 3295 patients with chest pain (2758 in AMI group and 537 in Non-AMI group) were recruited, of whom 23.1% were had an estimated glomerular filtration rate (eGFR) of < 60 mL min−1 (1.73 m2)−1. Hs-cTnI values were measured at presentation. Results AMI was diagnosed in 83.7% of all patients. The optimal value of hs-TnI in diagnosing AMI was 1.15 ng mL−1, which were higher in males than females comparing different cutoff-values of subgroups divided by age, gender and renal function, and which increased monotonically with decreasing of eGFR because in patients with CKD without AMI, the correlation between hs-cTnI and renal function is low but significant (r2 = 0.067, P < 0.001). Conclusions Different optimal cutoff-values of hs-cTnI in the diagnosis of AMI in patients with CKD were helpful to the clinical diagnosis of AMI in various populations and were higher in males than females, but which was needed to be validated by multicenter randomized controlled clinical studies in the future.

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