The predictive value of serum level of cystatin C for COVID-19 severity

AbstractTo investigate the potential prognostic value of Serum cystatin C (sCys C) in patients with COVID-19 and determine the association of sCys C with severe COVID-19 illness. We performed a retrospective review of medical records of 162 (61.7 ± 13.5 years) patients with COVID-19. We assessed the predictive accuracy of sCys C for COVID-19 severity by the receiver operating characteristic (ROC) curve analysis. The participants were divided into two groups based on the sCys C cut-off value. We evaluated the association between high sCys C level and the development of severe COVID-19 disease, using a COX proportional hazards regression model. The area under the ROC curve was 0.708 (95% CI 0.594–0.822), the cut-off value was 1.245 (mg/L), and the sensitivity and specificity was 79.1% and 60.7%, respectively. A multivariable Cox analysis showed that a higher level of sCys C (adjusted HR 2.78 95% CI 1.25–6.18, p = 0.012) was significantly associated with an increased risk of developing a severe COVID-19 illness. Patients with a higher sCys C level have an increased risk of severe COVID-19 disease. Our findings suggest that early assessing sCys C could help to identify potential severe COVID-19 patients.

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Association of pulse pressure with all-cause mortality in young adults

Postgraduate Medical Journal ◽

10.1136/postgradmedj-2019-137070 ◽

2019 ◽

Vol 96 (1138) ◽

pp. 461-466

Author(s):

Jie LI ◽

Jia-Yi Huang ◽

Kenneth Lo ◽

Bin Zhang ◽

Yu-Qing Huang ◽

...

Keyword(s):

Young Adults ◽

Pulse Pressure ◽

Subgroup Analysis ◽

Proportional Hazards ◽

Continuous Variable ◽

Cox Proportional Hazards ◽

Cox Proportional Hazards Models ◽

Increased Risk ◽

All Cause Mortality ◽

Cox Analysis

BackgroundPulse blood pressure was significantly associated with all-cause mortality in middle-aged and elderly populations, but less evidence was known in young adults.ObjectiveTo assess the association of pulse pressure (PP) with all-cause mortality in young adults.MethodsThis cohort from the 1999–2006 National Health and Nutrition Examination Survey included adults aged 18–40 years. All included participants were followed up until the date of death or 31 December 2015. PP was categorised into three groups: <50, 50~60, ≥60 mm Hg. Cox proportional hazards models and subgroup analysis were performed to estimate the adjusted HRs and 95% CIs for all-cause mortality.ResultsAfter applying the exclusion criteria, 8356 participants (median age 26.63±7.01 years, 4598 women (55.03%)) were included, of which 265 (3.17%) have died during a median follow-up duration of 152.96±30.45 months. When treating PP as a continuous variable, multivariate Cox analysis showed that PP was an independent risk factor for all-cause mortality (HR 1.94, 95% CI 1.02 to 3.69; p=0.0422). When using PP<50 mm Hg as referent, from the 50~60 mm Hg to the ≥60 mm Hg group, the risks of all-cause mortality for participants with PP ranging 50–60 mm Hg or ≥60 mm Hg were 0.93 (95% CI 0.42 to 2.04) and 1.15 (95% CI 0.32 to 4.07) (P for tend was 0.959). Subgroup analysis showed that PP (HR 2.00, 95% CI 1.05 to 3.82; p=0.0360) was associated with all-cause mortality among non-hypertensive participants.ConclusionAmong young adults, higher PP was significantly associated with an increased risk of all-cause mortality, particularly among those without hypertension.

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Significant association between Cystatin C, Gensini score, and Potential biomarker for Increased Risk of coronary artery lesions

10.21203/rs.3.rs-34296/v1 ◽

2020 ◽

Author(s):

jianyuan pan ◽

Zhenfei Chen ◽

Gaoliang Zhou ◽

Jun Feng ◽

Jing Zhang

Keyword(s):

Coronary Artery ◽

Cystatin C ◽

Elevated Serum ◽

Healthy Controls ◽

Gensini Score ◽

Coronary Artery Lesions ◽

Serum Cystatin C ◽

Serum Cystatin ◽

Potential Biomarker ◽

Increased Risk

Abstract Objective: Cystatin C (Cys C) has been proposed as a useful biomarker of early impaired kidney function and predictor of mortality risk. The present analysis is to investigate the association of serum Cystatin C with the severity of coronary artery lesions, Gensini score (GS) and the risk of CAD.Methods: 682 CAD patients (230 females, 452 males; mean age 62.6±10.7 years, range from 31 to 86 years) and 135 healthy controls (41 females, 94 males; mean age 58.0±10.3 years, range from 38 to 84 years) were recruited in the current study. ELISA was applied to measure serum Cystatin C levels. Estimated glomerular filtration rate (eGFR) and Gensini score were calculated. Results: Serum TC, LDL-C, UA, Cystatin C and HCY were significantly elevated in CAD patients compared to healthy controls. There were significant differences regarding to Cystatin C, eGFR and Gensini score among different type of CAD patients, of which AMI group had an elevated serum Cystatin C, LDL-C, HCY and Gensini score than the other two groups. When stratified by the quartiles of Cystatin C, we found that age, proportion of male patients and hypertension and diabetes, HCY and Gensini score were increased in Quartile fourth groups than in other quartile groups. Spearman's correlation test revealed positive relationship between Cystatin C, HCY and Gensini score. Multivariate logistic regression analysis revealed that serum Cystatin C level, presence of hypertension and diabetes, HCY, age and male were the risk factors for coronary artery lesions.Conclusions: In summary, our results suggested that Cystatin C is a promising clinical biomarker that provides complementary information to the established risk determinants. The serum Cystatin C level is strongly associated with Gensini score and could be used to evaluate the severity of coronary artery lesions.

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NGAL, albumin and cystatin C during cisplatin therapy

Physiological Research ◽

10.33549/physiolres.934212 ◽

2020 ◽

pp. 307-317

Author(s):

B. Florova ◽

D. Rajdl ◽

J. Racek ◽

O. Fiala ◽

V. M. Matejka ◽

...

Keyword(s):

Cystatin C ◽

Kidney Injury ◽

Cumulative Effect ◽

Serum Cystatin C ◽

Serum Cystatin ◽

Neutrophil Gelatinase Associated Lipocalin ◽

Cisplatin Nephrotoxicity ◽

Urine Albumin ◽

Increased Risk ◽

Neutrophil Gelatinase

Cisplatin is a commonly used chemotherapeutic drug. It is known for its nephrotoxic side effects with an increased risk of acute kidney injury. Finding of clinically feasible cisplatin nephrotoxicity markers is of importance. In our study, we compared neutrophil gelatinase-associated lipocalin (NGAL) in serum and urine, the estimated glomerular filtration rate (based on serum cystatin C) and urine albumin as markers of nephrotoxicity. The study involved 11 men and 9 women (mean ± SD age 58.2 ± 9.5 years) with different malignancies treated with cisplatin in four cycles of chemotherapy (I – IV). Samples 0 4 were taken before, immediately after, in 3, 6 and 24 hours after administering chemotherapy. We detected significant increase of ACR in Sample 2 (p=0.03) and decrease of eGFR in Sample 4 (p=0.03) up to 24 hours after cisplatin administration in the first chemotherapy cycle only. When cumulative effect of cisplatin was assessed, significantly increased values of urine albumin (vs cycle I) were found in Sample 0 (p=0.00058), 1 (p=0.00256), 2 (p=0.00456), 3 (p=0.00006) and 4 (p=0.00319) in cycles II to IV. We found a correlation between values of urine NGAL and urine albumin (r=0.68, p<0.0001). In conclusion, urine albumin was the only measured marker that consistently and statistically significantly increased after cisplatin containing chemotherapy cycles.

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Integrated analysis of two-lncRNA signature as a potential prognostic biomarker in cervical cancer: a study based on public database

PeerJ ◽

10.7717/peerj.6761 ◽

2019 ◽

Vol 7 ◽

pp. e6761 ◽

Cited By ~ 9

Author(s):

Wenjuan Wu ◽

Jing Sui ◽

Tong Liu ◽

Sheng Yang ◽

Siyi Xu ◽

...

Keyword(s):

Cervical Cancer ◽

Roc Curve ◽

Proportional Hazards ◽

Cox Proportional Hazards ◽

The Cancer Genome Atlas ◽

Differentially Expressed ◽

Integrated Analysis ◽

Roc Curve Analysis ◽

Gynecological Malignancy ◽

Lncrna Expression

Background Cervical cancer (CC) is a common gynecological malignancy in women worldwide. Evidence suggests that long non-coding RNAs (lncRNAs) can be used as biomarkers in patients with CC. However, prognostic biomarkers for CC are still lacking. The aim of our study was to find lncRNA biomarkers which are able to predict prognosis in CC based on the data from The Cancer Genome Atlas (TCGA). Methods The patients were divided into three groups according to FIGO stage. Differentially expressed lncRNAs were identified in CC tissue compared to adjacent normal tissues based on a fold change >2 and <0.5 at P < 0.05 for up- and downregulated lncRNA, respectively. The relationship between survival outcome and lncRNA expression was assessed with univariate and multivariate Cox proportional hazards regression analysis. We constructed a risk score as a method to evaluate prognosis. We used receiver operating characteristic (ROC) curve and the area under curve (AUC) analyses to assess the diagnostic value of a two-lncRNA signature. We detected the expression levels of the two lncRNAs in 31 pairs of newly diagnosed CC specimens and paired adjacent non-cancerous tissue specimens, and also in CC cell lines. Finally, the results were statistically compared using t-tests. Results In total, 289 RNA sequencing profiles and accompanying clinical data were obtained. We identified 49 differentially expressed lncRNAs, of which two related to overall survival (OS) in CC patients. These two lncRNAs (ILF3-AS1 and RASA4CP) were found together as a single prognostic signature. Meanwhile, the prognosis of patients with low-risk CC was better and positively correlated with OS (P < 0.001). Further analysis showed that the combined two-lncRNA expression signature could be used as an independent biomarker to evaluate the prognosis in CC. qRT-PCR results were consistent with TCGA, confirming downregulated expression of both lncRNAs. Furthermore, upon ROC curve analysis, the AUC of the combined lncRNAs was greater than that of the single lncRNAs alone (0.723 vs 0.704 and 0.685), respectively; P < 0.05. Conclusions Our study showed that the two-lncRNA signature of ILF3-AS1 and RASA4CP can be used as an independent biomarker for the prognosis of CC, based on bioinformatic analysis.

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Combining Serum Cystatin C and Urinary N-Acetyl-Beta-D-Glucosaminidase Improves the Precision for Acute Kidney Injury Diagnosis after Resection of Intracranial Space-Occupying Lesions

Kidney & Blood Pressure Research ◽

10.1159/000504599 ◽

2020 ◽

Vol 45 (1) ◽

pp. 142-156 ◽

Cited By ~ 1

Author(s):

Yujun Deng ◽

Jianchao Ma ◽

Yating Hou ◽

Dong Zhou ◽

Tieying Hou ◽

...

Keyword(s):

Acute Kidney Injury ◽

Cystatin C ◽

Predictive Accuracy ◽

Characteristic Curve ◽

Kidney Injury ◽

Adverse Outcomes ◽

Superior Performance ◽

Tubular Damage ◽

Serum Cystatin C ◽

Serum Cystatin

Background: Postoperative acute kidney injury (AKI) is frequent and associated with adverse outcomes. Unfortunately, the early diagnosis of AKI remains a challenge. Combining functional and tubular damage biomarkers may provide better precision for AKI detection. However, the diagnostic accuracy of this combination for AKI after neurosurgery is unclear. Serum cystatin C (sCysC) and urinary albumin/creatinine ratio (uACR) are considered functional biomarkers, while urinary N-acetyl-β-D-glucosaminidase (uNAG) represents tubular damage. We aimed to assess the performances of these clinical available biomarkers and their combinations for AKI prediction after resection of intracranial space-occupying lesions. Methods: A prospective study was conducted, enrolling adults undergoing resection of intracranial space-occupying lesions and admitted to the neurosurgical intensive care unit. The discriminative abilities of postoperative sCysC, uNAG, uACR, and their combinations in predicting AKI were compared using the area under the receiver operating characteristic curve (AUC-ROC), continuous net reclassification index (cNRI), and incremental discrimination improvement (IDI). Results: Of 605 enrolled patients, AKI occurred in 67 patients. The cutoff values of sCysC, uNAG, and uACR to predict postoperative AKI were 0.72 mg/L, 19.98 U/g creatinine, and 44.21 mg/g creatinine, respectively. For predicting AKI, the composite of sCysC and uNAG (AUC-ROC = 0.785) outperformed either individual biomarkers or the other two panels (uNAG plus uACR or sCysC plus uACR). Adding this panel to the predictive model improved the AUC-ROC to 0.808. Moreover, this combination significantly improved risk reclassification over the clinical model alone, with cNRI (0.633) and IDI (0.076). Superior performance of this panel was further confirmed with bootstrap internal validation. Conclusions: Combination of functional and tubular damage biomarkers improves the predictive accuracy for AKI after resection of intracranial space-occupying lesions.

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Correlation of Serum Cystatin C with Glomerular Filtration Rate in Patients Receiving Platinum-Based Chemotherapy

Analytical Cellular Pathology ◽

10.1155/2016/4918325 ◽

2016 ◽

Vol 2016 ◽

pp. 1-5 ◽

Cited By ~ 2

Author(s):

Ernesta Cavalcanti ◽

Vittoria Barchiesi ◽

Dionigio Cerasuolo ◽

Flaviano Di Paola ◽

Monica Cantile ◽

...

Keyword(s):

Renal Failure ◽

Glomerular Filtration Rate ◽

Serum Creatinine ◽

Cancer Patients ◽

Cystatin C ◽

Roc Curve ◽

Filtration Rate ◽

Serum Cystatin C ◽

Serum Cystatin ◽

Platinum Based Chemotherapy

Objectives. Serum cystatin C seems to be an accurate marker of glomerular filtration rate (GFR) compared to serum creatinine. The aim of this work was to explore the possibility of using serum cystatin C instead of serum creatinine to early predict renal failure in cancer patients who received platinum based chemotherapy.Design and Methods. Serum creatinine, serum cystatin C concentrations, and GFR were determined simultaneously in 52 cancer patients received carboplatin-based or cisplatin-based chemotherapy. Serum creatinine was assayed on Cobas C6000-Roche, serum cystatin C assay was performed on AIA 360-Tosoh, and GFR was determined in all patients, before the first cycle of chemotherapy and before the subsequent administrations.Results. In the overall series, for the prediction of a fall of GFR < 80 mL/min/1.73 m2, the AUC of the ROC curve for cystatin C was 0,667 and the best threshold was 1.135 mg/L (sensitivity 90.5%, specificity 61.1%). For a GFR fall < 60 mL/min/1.73 m2, the AUC of ROC curve for cystatin C was 74.3% and the best threshold was 1.415 mg/L (sensitivity 66.7%, specificity 73.2%).Conclusions. Baseline cystatin C values were not able to predict renal failure during subsequent treatment. In conclusion, serum cystatin C is not a reliable early marker to efficiently predict renal failure in patients receiving chemotherapy.

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Prognostic value of fibrinogen to albumin ratios among critically ill patients with acute kidney injury

Internal and Emergency Medicine ◽

10.1007/s11739-021-02898-3 ◽

2021 ◽

Author(s):

Wenkai Xia ◽

Chenyu Li ◽

Xiajuan Yao ◽

Yan Chen ◽

Yaoquan Zhang ◽

...

Keyword(s):

Acute Kidney Injury ◽

Hospital Mortality ◽

Critically Ill ◽

Critically Ill Patients ◽

Proportional Hazards ◽

Predictive Accuracy ◽

Prognostic Significance ◽

Kidney Injury ◽

Cox Proportional Hazards ◽

Increased Risk

AbstractFibrinogen to albumin ratios (FAR) have shown to be a promising prognostic factor for improving the predictive accuracy in various diseases. This study explores FAR's prognostic significance in critically ill patients with acute kidney injury (AKI). All clinical data were extracted from the Multiparameter Intelligent Monitoring in Intensive Care Database III version 1.4. All patients were divided into four groups based on FAR quartiles. The primary endpoint was in-hospital mortality. A generalized additive model was applied to explore a nonlinear association between FAR and in-hospital mortality. The Cox proportional hazards models were used to determine the association between FAR and in-hospital mortality. A total of 5001 eligible subjects were enrolled. Multivariate analysis demonstrated that higher FAR was an independent predictor of in-hospital mortality after adjusting for potential confounders (HR, 95% CI 1.23, 1.03–1.48, P = 0.025). A nonlinear relationship between FAR and in-hospital mortality was observed. FAR may serve as a potential prognostic biomarker in critically patients with AKI and higher FAR was associated with increased risk of in-hospital mortality among these patients.

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Transcranial Doppler combined with quantitative electroencephalography brain function monitoring for estimating the prognosis of patients with posterior circulation cerebral infarction

10.21203/rs.3.rs-64085/v1 ◽

2020 ◽

Author(s):

Yanting Cao ◽

Xiaonan Song ◽

Lijuan Wang ◽

Yajie Qi ◽

Ying Chen ◽

...

Keyword(s):

Cerebral Infarction ◽

Roc Curve ◽

Transcranial Doppler ◽

Brain Function ◽

Predictive Accuracy ◽

Cox Proportional Hazards ◽

Posterior Circulation ◽

Quantitative Electroencephalography ◽

Roc Curve Analysis ◽

Brain Function Monitoring

Abstract Background: Posterior circulation cerebral infarction (PCCI) leads to decreased cerebral blood flow (CBF) and metabolism. Neural activity is closely related to regional CBF both spatially and temporally. Transcranial Doppler (TCD) combined with quantitative electroencephalography (QEEG) can evaluate neurovascular coupling and involves synergy between the metabolic and vascular systems. This study aimed to monitor brain function using TCD-QEEG and estimate its efficacy in predicting the prognosis of patients with PCCI.Methods: We used TCD-QEEG to perform quantitative brain function monitoring; we recorded the related clinical variables simultaneously. The data were analyzed using a Cox proportional hazards regression model. Receiver-operating characteristic (ROC) curve analysis was used to evaluate the cut-off for the diastolic flow velocity (VD) and (delta+theta)/(alpha+beta) ratio (DTABR). The area under the ROC curve (AUROC) was calculated to assess the predictive validity of the study variables. Results: Forty patients (aged 63.7±9.9 years; 30 men) were assessed. Mortality at 90 days was 40%. The TCD indicators of VD (hazards ratio [HR] 0.168, confidence interval [CI] 0.047–0.597, p=0.006), and QEEG indicators of DTABR (HR 12.527, CI 1.637–95.846, p=0.015) were the independent predictors of the clinical outcomes. The AUROC after the combination of VD and DTABR was 0.896 and showed better predictive accuracy than the Glasgow Coma Scale score (0.75), VD (0.76), and DTABR (0.781; all p<0.05).Conclusion: TCD-QEEG provides a good understanding of the coupling mechanisms in the brain and can improve our ability to predict the prognosis of patients with PCCI.

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Correlation of Serum Cystatin C level with Coronary Artery Disease and Its Severity

The Journal of Medical Research ◽

10.31254/jmr.2021.7302 ◽

2021 ◽

Vol 7 (3) ◽

pp. 65-69

Author(s):

Mahmoud Moustafa Mohammed ◽

◽

Keyword(s):

Renal Function ◽

Heart Disease ◽

Cystatin C ◽

Coronary Atherosclerosis ◽

The Body ◽

Serum Cystatin C ◽

Serum Cystatin ◽

Coronary Syndrome ◽

Normal Ranges ◽

Increased Risk

Background: Atherosclerosis is an important cause of cardiovascular mortality and morbidity in the world and its progression might be slowed in many people with appropriate lifestyle and drug interventions. Hence a lot of researches are targeting the atherosclerotic process and its mediators. Cystatin C is considered to be an active cysteine protease inhibitor found in all body fluids and expressed in all nucleated cells in the body and is a better marker of renal function when compared to creatinine. Elevated plasma levels of cystatin C is thought to be associated with increased risk of cardiovascular disease (CVD) and mortality in different populations. This may be due to the fact that it represents occult impaired renal function, which is associated with increased risk of CVD. However, in several studies, cystatin C has been associated with CVD even within normal ranges of eGFR. Aim: To evaluate the relation of the serum cystatin C level and atherosclerotic burden in coronary arteries Methods: Our study included 80 patients of both sexes with known or suspected ischemic heart disease who were candidates for coronary angiography. Their serum Cystatin C level was measured using ELISA technique and correlated with coronary atherosclerosis using Gensini score. Results: No association was found between coronary atherosclerosis severity and serum cystatin C level. There was also no difference in serum cystatin C level between patients presenting with acute coronary syndrome and those presenting with stable ischaemic heart disease. Conclusion: The relation between serum cystatin C level and coronary atherosclerosis is still unclear

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Serum Cystatin C Predicts Stroke Clinical Outcomes at 1 Year Independent of Renal Function

Frontiers in Neurology ◽

10.3389/fneur.2021.676872 ◽

2021 ◽

Vol 12 ◽

Author(s):

Yarong Ding ◽

Liping Liu ◽

Zimo Chen ◽

Hao Li ◽

Yuesong Pan ◽

...

Keyword(s):

Renal Function ◽

Clinical Outcomes ◽

Cystatin C ◽

Primary Outcome ◽

Cox Proportional Hazards ◽

Stroke Recurrence ◽

Serum Cystatin C ◽

Vascular Events ◽

Serum Cystatin ◽

All Cause Mortality

Objective: Serum cystatin C (CysC) is a sensitive marker of renal function to predict cardiovascular diseases. We aimed to investigate the predictive value of CysC for clinical outcomes independent of renal function in patients with acute ischemic stroke (AIS).Methods: We measured serum CysC levels in 10,256 AIS patients from Third China National Stroke Registry (CNSR-III). The primary outcome was a combination of all-cause mortality and major disability (modified Rankin scale score, 3–6). Secondary outcomes included stroke recurrence and combined vascular events at 1 year. Outcomes were analyzed using logistic regression and Cox proportional hazards models, respectively.Results: The median CysC of included patients was 0.95 mg/l (interquartile range, 0.83–1.10 mg/l). A U-shaped association was observed between CysC and primary outcome (all-cause mortality or major disability) [quartile (Q)1 vs. Q2: adjusted odds ratio (aOR) 1.29, 95% CI 1.06–1.58, p = 0.012; Q3 vs. Q2: aOR 1.12, 95% CI 0.93–1.35, p = 0.242; Q4 vs. Q2: aOR 1.35, 95% CI 1.10–1.65, p = 0.004]. A similar trend also existed in “preserved renal function” patients. Adding CysC to a model containing conventional risk factors improved the model performance with integrated discrimination improvement (IDI) of 0.13% (p = 0.016) and net reclassification index (NRI) of 13.10% (p <0.001) for primary outcome. No significant association was observed for stroke recurrence or combined vascular event rate in different CysC quartiles.Conclusions: CysC showed a U-shaped correlation with 1-year stroke clinical outcome, suggesting that serum CysC may not only be a simple candidate marker of renal function.

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