Predictive Value Of Serum Cystatin Research Articles

Higher serum cystatin C and matrix metalloproteinase 9 levels effectively predict in-stent restenosis after stent implantation for intracranial and extracranial arterial stenosis

ObjectiveThis paper was performed to unravel the predictive value of serum cystatin C (Cys C) and matrix metalloproteinase 9 (MMP-9) levels before vascular stent implantation for in-stent restenosis (ISR) 6-12 months after stent implantation for intracranial and extracranial arterial stenosis. MethodsOne hundred and ninety-eight patients who underwent dilatation stenting for intracranial and extracranial arterial stenosis and completed Digital Subtraction Angiography or head and neck CT- Angiography review were selected for the study and were divided into ISR group (n = 33) and no ISR (NISR) group (n = 165) according to the presence or absence of ISR. Serum levels of Cys C, MMP-9, triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), uric acid (UA), creatinine (Cr), homocysteine (Hcy), fibrinogen (FIB), total bilirubin (TBIL), endothelin-1 (ET-1), nitric oxide (NO), angiotensin II (Ang II), interleukin-6 (IL-6), tumor necrosis factor (TNF-α), and C-reactive protein (CRP) levels before vascular stent implantation were examined and compared between groups. ROC curves were employed for analyzing the predictive value of serum Cys C and MMP-9 alone or in combination for ISR. Pearson test was utilized for analyzing the serum Cys C and MMP-9 with vasoactive substances and inflammatory cytokines in patients in the ISR group. Logistic regression analysis was implemented to analyze the factors influencing ISR 6-12 months after stent implantation for intracranial and extracranial arterial stenosis. ResultsCys C, MMP-9, LDL, UA, Cr, Hcy, FIB, ET-1, NO, Ang II, IL-6, TNF-α, and CRP were higher in the ISR group than in the NISR group, and TBIL was lower than in the NISR group (P < 0.05). The AUC of the combined serum Cys C and MMP-9 (AUC = 0.900) was greater than that of Cys C (AUC = 0.685) or MMP-9 (AUC = 0.870) alone (P < 0.05). Cys C and MMP-9 levels were positively correlated with ET-1, NO, Ang II, IL-6, TNF-α, and CRP (r > 0, P < 0.05). Increased levels of Cys C, MMP-9, LDL-C, UA, Cr, Hcy, FIB, ET-1, NO, Ang II, IL-6, TNF-α, and CRP, and diabetes were risk factors for the development of ISR (OR > 1, P < 0.05), and TBil was protective factor (OR < 1, P < 0.05). ConclusionSerum Cys C combined with MMP-9 levels are effective in predicting ISR.

Association of serum cystatin C level and major adverse cardiovascular events in patients with percutaneous coronary intervention.

Recurrent acute myocardial infarction requiring unplanned percutaneous coronary intervention (PCI) is one of the major adverse cardiovascular events (MACEs) in patients with acute coronary syndrome (ACS) after PCI. There is a continuing controversy about the association between serum cystatin C, a biomarker for the evaluation of renal function, and the prognosis of ACS patients following PCI. The retrospective study evaluated the association between serum cystatin C level and MACE in ACS patients after PCI. Data were retrieved for 330 patients with ACS for primary PCI in a single center. Serum cystatin C levels were measured before PCI. All patients underwent regular follow-ups after PCI, and the studied endpoint was MACE, defined as the need for a repeat revascularization in the heart. The predictive value of serum cystatin C for MACE was analyzed using univariate and multivariate analysis. Restricted cubic spline (RCS) analysis was applied to evaluate the dose-response relationship between serum cystatin C level and MACE in ACS patients following PCI. After a median follow-up of 63 months (range, 1-148 months), 121 of the 330 patients experienced MACE. Compared to patients who did not have MACE, patients who had MACE showed a significant decrease in serum cystatin C levels (0.99±0.32 vs. 1.15±0.78 mg/L, P=0.03). In multivariate regression analysis, serum cystatin C level was an independent risk factor for MACE. According to the serum cystatin C level, patients were divided into 4 categories, Cox regression analysis illustrated that the second quartile of serum cystatin C level indicated an increased risk of MACE in patients with PCI for primary ACS compared to the highest quartile [Q2: adjusted hazard ratio (HR) =2.109; 95% confidence interval (CI): 1.193-3.727; P=0.01]. RCS analysis showed a significant U-shaped dose-response relationship between cystatin C level and MACE in patients with PCI for ACS (P for non-linearity =0.004). These results indicated an association between serum cystatin C level and post-PCI MACE in ACS patients.

Predictive value of serum cystatin C for risk of mortality in severe and critically ill patients with COVID-19.

BACKGROUNDThe outbreak of coronavirus disease 2019 (COVID-19) has rapidly evolved into a global pandemic. COVID-19 is clinically categorized into mild, moderate, severe, and critical illness. Acute kidney injury is an independent risk factor for poor prognosis in patients with. Serum cystatin C (sCys C) is considered a more sensitive biomarker for early renal insufficiency than conventional indicators of renal function. Early detection of risk factors that affect the prognosis of severe and critically ill patients while using active and effective treatment measures is very important and can effectively reduce the potential mortality rate.AIMTo determine the predictive value of sCys C for the prognosis of patients with COVID-19.METHODSThe clinical data of 101 severe and critically ill patients with COVID-19 at a designated hospital in Wuhan, Hubei Province, China were analyzed retrospectively. According to the clinical outcome, the patients were divided into a discharge group (64 cases) and a death group (37 cases). The general information, underlying diseases, and laboratory examination indexes of the two groups were compared. Multivariate Cox regression was used to explore the relationship between sCys C and prognosis. The receiver operating characteristic (ROC) curve was used to demonstrate the sensitivity and specificity of sCys C and its optimal cut-off value for predicting death.RESULTSThere were significant differences in age, sCys C, creatinine, C-reactive protein, serum albumin, creatine kinase-MB, alkaline phosphatase, lactate dehydrogenase, neutrophil count, and lymphocyte count between the two groups (P < 0.001). Multivariate logistic regression analysis showed that sCys C was an independent risk factor for death in patients with COVID-19 (Odds ratio = 1.812, 95% confidence interval [CI]: 1.300-2.527, P < 0.001). The area under the ROC curve was 0.755 (95%CI: 1.300-2.527), the cut-off value was 0.80, the specificity was 0.562, and the sensitivity was 0.865.CONCLUSIONsCys C is an independent risk factor for death in patients with COVID-19. Patients with a sCys C level of 0.80 mg/L or greater are at a high risk of death.

Evaluation of cystatin C and neutrophil gelatinase-associated lipocalin as predictors of mortality in patients undergoing percutaneous mitral valve repair (MitraClip).

Compromised renal function is a major risk factor that is strongly associated with poor outcome in patients with mitral regurgitation (MR) and heart failure. Cystatin C, a cysteine protease inhibitor, has been used as a specific and sensitive biomarker of renal function. Neutrophil gelatinase-associated lipocalin (NGAL) is another sensitive biomarker that specifically indicates functional and structural kidney damage. The aim of the present study was to determine the predictive value of serum cystatin C and urinary NGAL as indicators of mortality in patients undergoing percutaneous mitral valve repair (PMVR). A total of 120 consecutive patients (age: 77.3 years [±11.2]) undergoing PMVR using the MitraClip system were included in this study. Venous blood and urinary samples were collected for biomarker analysis prior to PMVR. Physiological parameters, medication use, safety events, and all-cause mortality were assessed 12 months after the procedure. Twelve months after PMVR, there was a significant reduction in the severity of MR (P < 0.001), and an improvement in the New York Heart Association class (P < 0.01) was documented. Baseline levels of serum cystatin C (nonsurvivors: 2.4 mg/L [interquartile, IQR: 1.7;3.1] vs survivors: 1.7 mg/L [IQR: 1,3;2.1], P < 0.001) and urinary NGAL (nonsurvivors: 242.0 ng/mL [IQR: 154.5;281.5] vs survivors: 132.0 ng/mL [IQR:107.0;177.3], P < 0.001) were significantly higher in patients who died during the 12-month follow-up period. Cystatin C and urinary NGAL were found to be predictors of long-term mortality in high-risk patients undergoing PMVR. Thus, cystatin C and NGAL assessment may be helpful in risk stratification in patients undergoing PMVR.

Serum cystatin C concentration measured routinely is a prognostic marker for renal disease in dogs

This study examined the predictive value of serum cystatin C (Cys-C) concentration, measured during routine periodic health examinations, in the renal prognosis of dogs. A cohort of 140 dogs weighing <15 kg whose serum Cys-C concentrations were measured during periodic health examinations from December 2013 to March 2016 were prospectively studied, with renal disease-related death the predicted end point. Of the 140 dogs, nine died from renal diseases during the follow-up period (539 ± 249 days). Serum Cys-C concentrations were higher in the dogs that subsequently died of renal disease than in the censored group (0.8 ± 0.25 vs. 0.3 ± 0.1 mg/dl, respectively; P < .01). Dogs with high serum Cys-C concentrations (>0.55 mg/dl) had a shorter (P < .01) renal disease-specific survival period than those with low serum Cys-C concentrations (≤0.55 mg/dl). In conclusion, high serum Cys-C concentrations in periodic health examinations in dogs <15 kg predicted poorer prognosis for renal function.

A Prospective Observational Study on the Predictive Value of Serum Cystatin C for Successful Weaning from Continuous Renal Replacement Therapy

Background/Aims: There is a paucity of literature that investigates a biomarker associated with successful renal recovery following continuous renal replacement therapy (CRRT). Our study aimed to identify potential renal biomarkers or clinical indicators that could predict the successful weaning from CRRT. Methods: We conducted a prospective, observational study of 110 patients who had received CRRT and were weaned after renal recovery. Patients were considered to have successfully weaned from CRRT once there was no need for renal replacement therapy (RRT) for at least 14 days. For patients who had to restart dialysis within 14 days were considered unsuccessful. Results: Of the 110 patients evaluated, 89 (80.9%) were successfully weaned from CRRT. These patients had lower serum cystatin C (CysC) levels and higher urine output than the group that restarted RRT at the time of CRRT cessation. However, the levels of serum creatinine and neutrophil gelatinase-associated lipocalin were not significantly lower in the successful group compared to the restart-RRT group. A multivariable logistic regression showed that serum CysC was an independent predictor for the successful weaning from CRRT. Furthermore, in a multivariable Cox proportional hazards analysis, the group that was successfully weaned from CRRT had a lower in-hospital mortality compared to the restarted RRT group. Conclusion: Serum CysC, at the time of CRRT cessation, is an independent predictor of the successful weaning from CRRT in critically ill patients with acute kidney injury.

Serum cystatin C versus creatinine in the assessment of allograft function in early periods of kidney transplantation

Introduction: Serum cystatin C is not routinely used in the evaluation of renal function and this may be due to its high cost, lack of adequate studies to approve the use of cystatin C and lack of accessibility and reliability. Many kidney transplanted patients encounter with decreased performance before creatinine rising and go toward rejection without certain actions. Certainly, the early detection of renal function reduction can prevent spiritual and physical damage among patients. Objectives: This study was aimed to determine the predictive value of serum cystatin C and creatinine in the assessment of allograft function in the early period after kidney transplantation in Urmia city, Iran. Patients and Methods: In this prospective study, serum creatinine, cystatin C and glomerular filtration rate (GFR) of 49 kidney transplanted patients in the 3rd, 8th and 14th day were measured and compared together. The correlation of creatinine and cystatin C was examined using Spearman’s correlation. ROC curves were used to investigate sensitivity and specificity. Results: In this study, there was a statistically significant relationship between serum levels of creatinine and serum levels of cystatin C in 3rd, 8th and 14th day. The sensitivity and specificity of cystatin C in 14th day were 76% and 91.2%, respectively and for creatinine were 72% and 75% respectively, indicating cystatin C is a more sensitive indicator compared to creatinine on the 14th day in the presence of loss of GFR below 60 mL/cc. Conclusion: Serum cystatin C as a valuable marker can be an effective predictor marker of renal function reduction beside creatinine. Due to high cost of measuring kits of serum cystatin C, it is not possible to use this marker in all transplanted patients in the world. Therefore, we can use this marker in high-risk patients with probability of transplantation rejection.

Predictive value of serum cystatin C for acute kidney injury in adults: a meta-analysis of prospective cohort trials

The role of serum cystatin C (Scys) for the detection of acute kidney injury (AKI) has not been fully discussed. This meta-analysis was aimed to investigate the overall diagnostic accuracy of Scys for AKI in adults, and further identify factors affecting its performance. Studies before Sept. 2016 were retrieved from PubMed, Embase, Web of Science and the Cochrane Library. A total of 30 prospective cohort studies (involving 4247 adults from 15 countries, 982 patients occurring AKI) were included. The revised Quality Assessment for Studies of Diagnostic Accuracy (QUADAS-2) tools demonstrated no significant bias had influenced the methodological quality of the included studies. Scys showed a high predictive power for all-cause AKI, that the area under the receiver operating characteristic curve was 0.89. The detailed assessment parameters, such as sensitivity, specificity, positive likelihood ratio, negative likelihood ratio and diagnostic odds ratio for Scys were 0.82, 0.82, 4.6, 0.22 and 21, respectively. Although Scys could be slightly influenced by the following factors: settings, AKI diagnostic criteria, ethnicity, determination method, age and gender, these factors above did not reach statistically significance. In conclusion, Scys could be a vital promising marker to screen out AKI.

Serum Cystatin C, Creatinine-Based Estimated Glomerular Filtration Rate, and the Risk of Incident Hypertension in Middle-Aged Men

The aim of this study was to examine the predictive value of serum cystatin C (CysC) and that of creatinine-based estimated glomerular filtration rate (eGFRCreat) for the risk of incident hypertension in a middle-aged male population. Serum CysC levels were measured in 904 nonhypertensive, Japanese male subjects (mean age = 44±6 years) who received an annual general health examination in a company. Serum creatinine levels were simultaneously measured, and eGFRCreat was calculated. Subjects were followed-up for a maximum period of 4 years, and annual blood pressure measurements were recorded. During the follow-up period, 124 subjects developed hypertension, defined as systolic/diastolic blood pressure ≥140/90 mmHg or use of antihypertensive medications. In the Kaplan-Meier analysis, both the third quintile of CysC and that of eGFRCreat showed the lowest 4-year cumulative incident rate of hypertension. The multiadjusted hazard ratio for incident hypertension was significantly increased in the highest quintile of CysC compared with the third quintile (2.60; 95% confidence interval (CI) = 1.41-4.77; P = 0.002), as well as compared with the lowest 4 quintiles combined (1.89; 95% CI = 1.26-2.84; P = 0.002). However, eGFRCreat did not show significant hazard ratios for incident hypertension in any of the adjusted models. Elevated serum CysC levels could predict the risk of incident hypertension in this study population with a maximum follow-up period of 4 years. In contrast, eGFRCreat did not show predictive value for the risk of incident hypertension.

Is serum cystatin C an early predictor for acute kidney injury following cardiopulmonary bypass surgery in infants and young children?

Acute kidney injury (AKI) is a potential complication following cardiopulmonary bypass (CPB) surgery in infants and young children with congenital heart disease (CHD). The current pilot study evaluates the predictive value of serum cystatin C (CysC) for AKI after pediatric CPB surgery. We prospectively enrolled 43 children with CHD (30 males and 13 females) who underwent CPB surgery. They were aged 3 years or younger. Serum CysC was measured at baseline and at 6 hours, 12 hours, 24 hours, and 48 hours after initiating CBP. Twenty-one (48.8%) patients developed AKI after cardiac surgery. Children who developed AKI had more complex cardiac surgical procedures (based on the Risk Adjustment for Congenital Heart Surgery 1 [RACHS-1] category), a longer CPB duration, and a longer aortic clamping time (ACT). Serum concentrations of CysC postoperatively demonstrated an initial decline at 6 hours, a subsequent increase at 12 hours, and stabilized at 24–48 hours. The best predictive performance was achieved 6 hours after CPB with an area under receiver operating characteristic curve (AUC) value of 0.69. The optimal cut-off value was 0.47 mg/L (sensitivity, 85.7%; specificity, 50%). By contrast, the RACHS-1 category, CPB duration, and ACT had higher AUC values at 0.735, 0.791, and 0.731, respectively. In conclusion, serum CysC had limited predictive capacity and was not superior to clinical risk factors for the early detection of AKI after CPB surgery in this pilot study, which focused on infants and young children.

Predictive value of serum cystatin C, β2-microglobulin, and urinary liver-type fatty acid-binding protein on the development of contrast-induced nephropathy

Contrast-induced nephropathy (CIN) is associated with prolonged hospitalization and adverse clinical outcomes. Useful predictors of CIN are necessary to minimize the risk of developing CIN. The purpose of this study was to identify the useful predictors of CIN. We prospectively measured serum cystatin C (CysC) and β2-microglobulin (β2-MG), and urinary liver-type fatty acid-binding protein (L-FABP), β2-MG and N-acetyl-β-D-glucosaminidase (NAG) before and 1day after percutaneous coronary intervention (PCI) in 96 patients with stable angina who underwent elective PCI. The frequency of CIN was 5% (5/96). Baseline levels of serum β2-MG (4.2±2.6 vs. 2.2±1.0mg/L, p=0.0007) and CysC (1.51±0.52 vs. 1.11±0.34mg/L, p=0.013) were significantly higher in the CIN group. Urinary β2-MG, NAG, and L-FABP levels became significantly elevated after PCI. Of these, the mean change of urinary L-FABP was significantly higher in the CIN group (25.2±31.5 vs. 8.9±16.3ng/mL, p=0.044). Univariate linear regression analyses showed that the change of urinary L-FABP correlated positively with the volume of contrast medium (r=0.460, p<0.0001). Receiver-operating characteristic analysis showed that baseline serum β2-MG exhibited 75% sensitivity and 80% specificity at a cut-off point of >2.8mg/L, and baseline serum CysC exhibited 75% sensitivity and 73% at a cut-off point of >1.26mg/L for predicting CIN. In conclusion, baseline serum β2-MG and CysC were useful predictors of CIN. The change of urinary L-FABP serves as an indicator of renal injury due to contrast medium and as an adjunct predictor of CIN.

Evolution and predictive power of serum cystatin C in acute renal failure

The serum concentration of cystatin C has recently been proposed as a better indicator of glomerular filtration rate (GFR) than plasma creatinine. Little is known about cystatin C in critical illness. We assessed serum cystatin C as a marker of renal function in acute renal failure (ARF) and its power in predicting survival of ARF patients. 202 consecutive adult patients admitted into the intensive care unit (ICU) during a period of 9 months. Serum cystatin C, plasma creatinine and plasma urea were measured on admission, daily during the first 3 days, and 5-7 times a week during the rest of the ICU stay. The patients with and without ARF were compared by the Mann-Whitney U-test. The correlation between different variables was calculated by Spearman's correlation. Forward stepwise multiple regression analysis was performed to test independent predictors of mortality. The positive predictive value of serum cystatin C and plasma creatinine for ARF and mortality was calculated by ROC analysis. ARF occurred in 54 patients (27%). Serum cystatin C showed excellent positive predictive value for ARF in critical illness by ROC analysis. In acute renal dysfunction, abnormal values of serum cystatin C and plasma creatinine appeared equally quickly (median 3 days). The diagnosis of ARF, the day 1 Apache II score and admission plasma creatinine appeared as independent predictors of hospital mortality. ROC analysis showed only weak predictive power for serum cystatin C and plasma creatinine regarding hospital mortality. Serum cystatin C was as good as plasma creatinine in detecting ARF in intensive care patients. Neither marker was clinically useful in predicting mortality.