CysC Levels Research Articles

Serum Cystatin C Level in Liver Cirrhosis Patients with MELD-Na > 22

Background: Hepatorenal syndrome is a part of the prerenal acute kidney injury (AKI) characterized by kidney dysfunction which is secondary to the decreased renal blood flow that occurs in liver cirrhosis with portal hypertension and is a fatal complication. Hepatorenal syndrome (HRS) occurs in about 20% of liver cirrhosis patients with refractory ascites.Method: This study was conducted on 24 liver cirrhosis patients with ascites who visited Gastroenterohepatology Outpatient Ward and Internal Medicine Inpatient Unit, Dr. M. Djamil Padang. Samples were collected and data analyses were conducted in December 2019 to March 2020.Results: In this study, the model for end-stage liver disease (MELD)-Na score was used to determine the risk of HRS in liver cirrhosis patients with ascites, in which patients with a MELD-Na score 22 belonged to the group at risk of developing HRS. From 24 patients, the mean MELD-Na score was 24.58 ± 3.5. The lowest MELD-Na score was 22 in 8 patients (33.3%), while 1 patient (4.2%) had the highest MELD-Na score of 35. In this study, serum CysC levels were measured in patients with normal creatinine, and the mean serum CysC level was 2.69 ± 0.46 mg/L. The minimum value of CysC was 2.03 mg/L, while the maximum value was 3.9 mg/L. Serum CysC levels in all 24 patients were increased compared to the normal values.Conclusion: Liver cirrhosis patients who were at risk to develop HRS based on the MELD-Na score have increased serum Cystatin C levels, although serum creatinine levels were still normal.

Correlation Analysis of Early Renal Injury in Elderly Patients with Acute Exacerbations of Chronic Obstructive Pulmonary Disease.

ObjectiveTo investigate the correlation between serum cystatin C (Cys-C) and beta-2 (β2) microglobulin (β2-MG) levels and renal injury in elderly patients with acute exacerbations of chronic obstructive pulmonary disease (AECOPD) with a view to detecting renal injury in its early stages.MethodsA total of 106 patients with AECOPD were enrolled and divided into three groups according to their oxygen partial pressure (PO2) levels: severe hypoxia group, moderate hypoxia group, and mild hypoxia group. Another 60 healthy subjects were selected as the control group. General clinical data were collected from all the study subjects, along with measurements of arterial blood gas, Cys-C, β2-MG, serum creatinine (Scr), urea nitrogen (BUN), partial pressure of carbon dioxide (PCO2), and high-sensitivity C-reactive protein (hs-CRP).ResultsThe levels of hs-CRP, Cys-C, β2-MG, Scr, and BUN were highest in the severe hypoxia group, followed by the moderate hypoxia group, then the mild hypoxia group, and lowest in the control group. The differences between the groups were statistically significant for these indicators (P < 0.05). Apart from in the cases of Scr and BUN, there were no statistically significant differences between the mild group and the control group (P > 0.05). The levels of Cys-C and β2-MG were positively correlated with the levels of hs-CRP, PCO2, Scr, and BUN and negatively correlated with PO2 levels. hs-CRP and PO2 were high-risk factors influencing Cys-C levels, and β2-MG was a risk factor influencing Cys-C levels. The level of PO2 was a high-risk factor influencing β2-MG levels, and PCO2 and Cys-C were risk factors influencing β2-MG levels.ConclusionRenal injury was found to be present in patients with AECOPD and worsened with increasing degrees of hypoxia. Hypoxia and inflammation might be risk factors for renal injury in patients with AECOPD, Cys-C and β2-MG could be sensitive indicators for the early detection of renal injury.

Association between Serum Cystatin C levels and long-term cardiovascular outcomes and all-cause mortality in older patients with obstructive sleep apnea.

Background and Aims: To investigate the association between obstructive sleep apnea (OSA) severity and baseline serum cystatin C (Cys-C) concentration and to explore the association between baseline serum Cys-C and long-term cardiovascular outcomes and mortality in older patients with OSA. Methods: Between January 2015 and October 2017, a total of 1107 consecutive eligible older patients (≥60 years) with OSA were included in this multicenter, prospective cohort study, and baseline demographics, clinical characteristics, sleep parameters, and follow-up outcomes were collected. Participants were divided into different groups based on baseline serum Cys-C levels. The primary end point was major adverse cardiovascular events (MACE) and the secondary end point was all-cause mortality. The correlation between OSA severity and baseline serum Cys-C was evaluated by Spearman correlation analysis. Multivariate Cox regression was used to analyze the association between Cys-C and the incidence of MACE and mortality. Results: Participants included 672 men and 435 women, with a median age of 66 (range, 60–96) years. At baseline, apnea–hypopnea index (AHI) (r = 0.128, p < 0.05), oxygen desaturation index (ODI) (r = 0.116, p < 0.05), and the lowest pulse oxygen saturation (LSpO2) (r = −0.097, p < 0.05) were correlated with serum Cys-C concentration. During the median follow-up period of 42 months, 97 patients (8.8%) experienced MACE and 40 patients (3.6%) experienced death. The association between serum Cys-C levels and the risk of MACE and all-cause mortality was slow rising shaped. The multivariable Cox regression analysis showed patients with a serum Cys-C concentration of ≥1.14 mg/L had higher risks of MACE (HR = 5.30, 95% CI: 2.28–12.30, p < 0.05) and all-cause mortality (HR = 9.66, 95% CI: 2.09–44.72, p < 0.05) compared with patients with serum Cys-C of ≤0.81 mg/L in older patients with OSA. The receiver-operating characteristic curve showed baseline serum Cys-C levels exhibited moderately capable of identifying patients with a long-term risk of clinical adverse events (MACE and mortality). Conclusion: OSA severity was positively correlated with serum Cys-C concentration. High levels of Cys-C were independently associated with increased risks of MACE and all-cause mortality in older patients with OSA, suggesting that lowering Cys-C levels should be considered as a therapeutic target, and monitoring serum Cys-C may be beneficial to the favorable prognosis of older patients with OSA.

Serum cystatin C level can be used to estimate GFR in patients with solid tumors: CON

Serum cystatin C (CysC) is being promoted by the major nephrology societies as a confirmatory biomarker to estimate glomerular filtration rate (GFR). Many clinicians have the impression that CysC may be a better biomarker for estimating GFR in cancer patients because it is less influenced by muscle mass and nutritional status. Cancer patients were not well represented in the cohorts from which the most frequently used Cr based eGFR estimating equations were derived. Clinical data supports that serum CysC levels are affected by the cancer milieu itself and by clinical factors that are often present in cancer patients. This article highlights data showing that serum CysC levels cannot be reliably used to estimate GFR in solid tumors.

Correlation of Blood Glucose and Pancreatic Islet Function with Serum Retinol-Binding Protein 4, Serum Cystatin C, and Human New Satiety Molecule Protein-1 in Pregnant Women with Gestational Diabetes Mellitus.

Objective To investigate the correlation of blood glucose and islet function with serum retinol-binding protein 4, serum cystatin C, and nesfatin-1 levels in women with gestational diabetes mellitus. Methods Between June 2018 and June 2020, 70 patients with gestational diabetes mellitus were included in a study group and 70 healthy pregnant women were recruited into a healthy group. Alterations in fasting blood glucose (FPG), glycated hemoglobin (HbA1c), fasting serum insulin (FINS), homeostatic model assessment for insulin resistance (HOMA-IR), serum retinol-binding protein 4 (RBP4), serum cystatin C (CysC), and nesfatin-1 of all eligible participants were analyzed, and the occurrence of complications was recorded. Correlation analysis of serum RBP4, serum CysC, and nesfatin-1 levels with blood glucose and islet function in women with gestational diabetes mellitus was performed. Results Gestational diabetes mellitus was associated with significantly higher levels of FPG, HbA1c, and HOMA-IR and lower levels of FINS (6.58 ± 1.41, 9.24 ± 1.09, 3.21 ± 2.03, 8.23 ± 2.21) versus a healthy condition (5.23 ± 0.85, 7.61 ± 0.67, 2.42 ± 1.14, 10.54 ± 2.15) (P < 0.05). Women with gestational diabetes mellitus showed significantly higher levels of serum RBP4, serum CysC, and nesfatin-1 (62.45 ± 7.86, 1.95 ± 0.59, 2.65 ± 0.49) versus healthy pregnant women (45.48 ± 6.15, 1.03 ± 0.67, 1.42 ± 0.62) (P < 0.05). With serum RBP4, serum CysC, and nesfatin-1 as dependent variables, univariate correlation analysis showed that serum RBP4, serum CysC, and nesfatin-1 levels were positively correlated with FPG and HbA1c levels and HOMA-IR, and negatively correlated with FINS in women with gestational diabetes mellitus (P < 0.05). Gestational diabetes mellitus resulted in a significantly higher incidence of preterm delivery, cesarean section, excess amniotic fluid, and premature rupture of membranes versus a healthy status (P < 0.05). Conclusion Glucose metabolism and islet function in women with gestational diabetes are significantly correlated with serum RBP4, serum CysC, and nesfatin-1 levels, which shows great potential for the prevention and treatment of gestational diabetes mellitus and perinatal complications.

Serum cystatin C and CRP are early predictive biomarkers for emergence of hypoxia in COVID-19.

BackgroundIn Japan, during the coronavirus disease 2019 (COVID-19) pandemic, patients with non-hypoxia are recommended to recuperate at home or in pre-hospital facilities. However, it was observed that unexpected hypoxia may occur and become severe subsequently in patients whose symptoms were initially expected to improve naturally. The aim of this study is to validate biomarkers that can predict at an early stage the emergence of hypoxia in COVID-19 patients without hypoxia.MethodsWe retrospectively enrolled 193 patients with COVID-19, excluding patients with hypoxia and severe disease from the onset. Participants were classified into two groups according to the emergence of hypoxia during the clinical course, and the laboratory data were compared to identify biomarkers that could predict early the emergence of hypoxia.ResultsThe areas under the curve for serum cystatin C (CysC) and C-reactive protein (CRP) levels for the emergence of hypoxia during the clinical course were higher than those for other biomarkers (CysC, 0.84 and CRP, 0.83). Multivariate analysis showed that high serum CysC and CRP levels were associated with the emergence of hypoxia during the clinical course.ConclusionsElevated serum CysC and CRP levels were associated with the emergence of hypoxia during the clinical course in COVID-19 patients without hypoxia. These findings may help determine the need for hospitalization in initially non-hypoxic COVID-19 patients.

The relationship between serum cystatin C levels and Hughes motor scale in Guillain-Barré syndrome

Objectives:To study the clinical features of Guillain–Barré syndrome (GBS) and the relationship between serum cystatin C (cysC) levels and Hughes motor scale (HMS) in GBS.Methods:One hundred and one GBS patients between January 2017 and January 2020 were reviewed retrospectively. Their epidemiological characteristics, clinical manifestations and auxiliary examinations were assessed. The HMS was used to measure the peak deficit. The influencing factors of GBS severity were analyzed by univariate and multivariate analyses.Results:The serum cysC levels were significantly higher in the severe group than in the mild group [0.98 (0.85-1.20) vs. 0.81 (0.76-0.95), p=0.004], and there was a positive correlation between serum cysC levels and HMS in GBS patients (r=0.376, p=0.001). On multivariate analysis, respiratory muscle palsy (p=0.003), time to peak deficit (p=0.017), serum cysC (p=0.045) and hyponatremia (p=0.015) were independent risk factors for a poor functional outcome (HMS>3). Combining serum cysC and respiratory muscle palsy was more valuable for assessing disease severity than respiratory muscle palsy alone (AUC 0.863 vs. 0.787, p=0.001).Conclusion:Serum cysC was an independent risk factor in GBS, and positively correlated with HMS. It might be used to assess the severity of GBS with other negative prognostic factors.

Correlation between Serum Homocysteine Level and Cystatin C Elevation in Patients with H-type Hypertension

[Objective] To investigate the correlation between serum levels of homocysteine (Hcy) and cystatin C (CysC), a sensitive marker of renal function, in patients with H-type hypertension. [Methods] A total of 857 patients with essential hypertension without moderate to severe renal impairment (estimated glomerular filtration rate ≥ 60 ml/(min-1.73 m2) by Modification of Diet in Renal Disease equation) visited the Seventh Affiliated Hospital of Sun Yat-sen University from May 2018 to May 2020 were selected as the research subjects. The observation group (n = 635) consisted of patients with H-type hypertension (essential hypertension with Hcy ≥ 10 mmol/l) and the control group (n = 222) consisted of patients with non-H-type hypertension (essential hypertension with Hcy &lt; 10 mmol/l). Multivariate logistic regression analysis, curve fitting, and threshold analysis were used to evaluate the correlation between elevated CysC and serum Hcy levels. [Results]CysC in observation group was significantly higher than that in control group (0.96 ± 0.160 vs 0.84 ± 0.13 mmol/l; p &lt; 0.001). Multivariate logistic regression analysis, curve fitting, and threshold analysis showed that there was a significant difference in the risk of CysC elevation between Hcy levels at 10-25 mmol/L and Hcy levels below 10 mmol/L; there was no significant difference in the risk of CysC elevation between Hcy levels above 25 mmol/L and Hcy levels below 10 mmol/L. The inflection point of Hcy was 15.23 mmol/L, and when Hcy was &lt; 15.23 mmol/L, the probability of CysC elevation increased by 27\% for each 1 mmol/L increase in Hcy (OR 1.27, 95\% Cl: 1.12, 1.44; P = 0.0002). When Hcy was &gt; 15.23 mmol/l, the probability of CysC elevation was reduced by 4\% for each 1 mmol/l increase in Hcy (OR 0.96, 95\% Cl: 0.92, 1.01; P = 0.1085). [Conclusions] The risk of CysC in patients with H-type hypertension is higher than that in patients with non-H-type hypertension when Hcy is between 10-25 mmol/L; and the probability of cystatin C elevation is the highest when Hcy is at 15.23 mmol/L.

Effects of Serum LDL-C, CysC, and D-D in Patients with Coronary Atherosclerotic Heart Disease

Objective To investigate the effects of low-density lipoprotein cholesterol (LDL-C) and serum cystatin C (CysC) combined with D-dimer (D-D) on patients with coronary atherosclerotic heart disease (CHD). Methods 90 patients with CHD who were admitted to our hospital and diagnosed by coronary angiography (CAG) from February 2020 to June 2021 were selected as the study subjects. 90 patients were grouped according to different types and branches of coronary lesions, and 30 patients with outpatient health check-ups at the same period were selected as the control group, and the differences in serum LDL-C, CysC, and D-D levels between the groups were compared. The logistic regression model was built to explore risk factors affecting the occurrence of CHD. Also, receiver operating characteristic (ROC) curves were drawn to analyze the diagnostic value of LDL-C, CysC, and D-D in CHD. Results In the comparison of LDL-C, CysC, and D-D levels, CHD group > control group (P < 0.05); stable angina (SAP) group > unstable angina (UAP) group > acute myocardial infarction (AMI) group (P < 0.05); three-branch group > two-branch group > single-branch group (P < 0.05). The logistic regression model showed that high expression levels of LDL-C, CysC, and D-D, male gender, and combined hypertension were risk factors for CHD. The area under the curve (AUC) of the combination of LDL-C, CysC, and D-D was 0.868, and the sensitivity and specificity were 88.89% and 73.33%, respectively, which are higher than those in single diagnosis (P < 0.05). Conclusions LDL-C, CysC, and D-D are highly expressed in CHD samples, and the combination of the three is beneficial to enhance the diagnostic accuracy of clinical CHD.

Assessment of Fasudil on Contrast-Associated Acute Kidney Injury Using Multiparametric Renal MRI.

Aims: To evaluate the utility of fasudil in a rat model of contrast-associated acute kidney injury (CA-AKI) and explore its underlying mechanism through multiparametric renal magnetic resonance imaging (mpMRI). Methods: Experimental rats (n = 72) were grouped as follows: controls (n = 24), CA-AKI (n = 24), or CA-AKI + Fasudil (n = 24). All animals underwent two mpMRI studies (arterial spin labeling, T1 and T2 mapping) at baseline and post iopromide/fasudil injection (Days 1, 3, 7, and 13 respectively). Relative change in renal blood flow (ΔRBF), T1 (ΔT1) and T2 (ΔT2) values were assessed at specified time points. Serum levels of cystatin C (CysC) and interleukin-1β (IL-1β), and urinary neutrophil gelatinase-associated lipocalin (NGAL) concentrations were tested as laboratory biomarkers, in addition to examining renal histology and expression levels of various proteins (Rho-kinase [ROCK], α-smooth muscle actin [α-SMA]), hypoxia-inducible factor-1α (HIF-1α), and transforming growth factor-β1 (TGF-β1) that regulate renal fibrosis and hypoxia. Results: Compared with the control group, serum levels of CysC and IL-1β, and urinary NGAL concentrations were clearly increased from Day 1 to Day 13 in the CA-AKI group (all p < 0.05). There were significant reductions in ΔT2 values on Days 1 and 3, and ΔT1 reductions were significantly more pronounced at all time points (Days 1–13) in the CA-AKI + Fasudil group (vs. CA-AKI) (all p < 0.05). Fasudil treatment lowered expression levels of ROCK-1, and p-MYPT1/MYPT1 proteins induced by iopromide, decreasing TGF-β1 expression and suppressing both extracellular matrix accumulation and α-SMA expression relative to untreated status (all p < 0.05). Fasudil also enhanced PHD2 transcription and inhibition of HIF-1α expression after CA-AKI. Conclusions: In the context of CA-AKI, fasudil appears to reduce renal hypoxia, fibrosis, and dysfunction by activating (Rho/ROCK) or inhibiting (TGF-β1, HIF-1α) certain signaling pathways and reducing α-SMA expression. Multiparametric MRI may be a viable noninvasive tool for monitoring CA-AKI pathophysiology during fasudil therapy.

A low serum uric acid concentration predicts a poor prognosis in adult patients with candidemia.

This study aimed to determine the relation of serum uric acid (UA) level with outcomes in adults with candidemia. Medical records of patients with candidemia treated from 2014 to 2017 were retrospectively reviewed. Patients were age- and sex-matched with healthy control subjects. The associations of UA and cystatin C (CysC) levels with diagnosis and prognosis of candidemia were determined. Sixty-four patients with candidemia (13 females and 51 males; mean age 48.5 years) and 64 matched control subjects were included. The median UA level of patients with candidemia was 255 μmol/L (range, 158–395 μmol/L), and of healthy controls was 398 μmol/L (range, 345–450 μmol/L) (P < 0.001). The median CysC level of patients with candidemia was 1.07 mg/L (range, 0.89–1.59 mg/L), and of the healthy controls was 0.82 mg/L (range, 0.74–0.95 mg/L) (P < 0.001). Patients with a favorable prognosis had significantly higher serum UA levels than those with a poor prognosis (181 μmol/L vs 344 μmol/L; P = 0.001). It was indicated that the estimated OR for UA was significantly > 1 (P = 0.009), and the AUC was 0.734. In summary, a lower serum UA level is associated with a diagnosis of candidemia, and a poor outcome.

The preventive effects of different doses of atorvastatin on contrast‐induced acute kidney injury after CT perfusion

BackgroundContrast‐induced acute kidney injury (CI‐AKI) is a severe complication among patients receiving intravascular contrast media. The purpose of this study was to investigate the preventive effects of pretreatment of atorvastatin at intensive doses on CI‐AKI after computed tomography (CT) perfusion.MethodsThe levels of serum creatinine (SCR), blood urea nitrogen (BUN), Cystatin C (CysC), estimated glomerular filtration rate (eGFR), high‐sensitivity C‐reactive protein (hs‐CRP), and interleukin‐6 (IL‐6) in patients were compared between the observation group receiving 40 mg/kg atorvastatin and the control group receiving 20 mg/kg atorvastatin before and 72 h after CT examination. In addition, the incidence of CI‐AKI was recorded.ResultsCompared with the control group, the incidence of renal injury in the observation group was significantly reduced, from 8% to 2% (χ 2 = 6.62, p = 0.010). In addition, there was no notable difference in the levels of Scr, BUN, CysC, hs‐CRP, and IL‐6 before CT examination between two groups (p > 0.05). The levels of SCR, BUN, CysC, hs‐CRP, and IL‐6 were increased, while the levels of eGFR were decreased in the control group at 72 h after CT examination (p < 0.05). At 72 h after CT enhancement, the levels of BUN, CysC, and hs‐CRP were prominently increased in the observation group (p < 0.05), while SCR, eGFR, and IL‐6 did not change (p > 0.05). Compared with the control group, the levels of SCR, BUN, CysC, eGFR, hs‐CRP, and IL‐6 in the observation group were significantly decreased at 72 h after CT examination (p < 0.05).ConclusionIntensive dose of atorvastatin pretreatment can prevent CI‐AKI undergoing CT perfusion through lowering inflammation as well as renal function indexes SCR, CysC, BUN, and eGFR.

JNK and Jag1/Notch2 co-regulate CXCL16 to facilitate cypermethrin-induced kidney damage

Cypermethrin (CYP), a widely-used composite pyrethroid pesticide, has underlying nephrotoxic effects. To elucidate potential roles of the MAPK pathway, the Jag/Notch pathway, and miRNAs in CYP-mediated kidney lesion, Sprague-Dawley rats and glomerular mesangial cells were used in this work. Results displayed that β-CYP abnormally altered renal histomorphology and ultrastructures, induced renal DNA damage, and impaired renal functions, as evidenced by the increase in plasma levels of Cys-C and β2-Mg. β-CYP activated the JNK/c-Jun pathway by inducing ROS and oxidative stress. Meanwhile, β-CYP changed the miRNA expression profile, miR-21–5p showing the most significant increase. Moreover, the Jag1/Notch2/Hes1 pathway was directly targeted by miR-21–5p, the mRNA and protein expression of Jag1, Notch2, and Hes1 being declined in vivo and in vitro. The chemokine CXCL16 was induced by β-CYP, accompanied by the inflammatory factor production and inflammatory cell infiltration in kidneys. The specific JNK inhibitor, Jag1 overexpression, Hes1 overexpression, bidirectional Co-IP, ChIP, and CXCL16 silencing demonstrated that CXCL16 co-regulated by the JNK/c-Jun and Jag1/Notch2/Hes1 pathways elicited renal inflammation. Collectively, our findings indicate that β-CYP is of nephrotoxicity and it not only directly changes renal histomorphology and ultrastructures, but induces CXCL16 to trigger renal inflammation via the JNK/c-Jun and Jag1/Notch2/Hes1 pathways, finally synergistically contributing to kidney damage.

Association between Cystatin C and Cardiac Function in Acute Myocardial Infarction Patients: A Real-World Analysis.

Background Acute myocardial infarction (AMI), as well as its long-term and short-term complications, is known to present with high morbidity and mortality. Cardiac function deterioration and ventricular remodelling after AMI are known to be correlated to worse long-term outcomes. However, the underlying mechanism remains elusive and there is a shortage of serum prediction markers. This study investigates the relationship between in-hospital Cystatin C (CysC) and cardiac function and subsequent prognosis among AMI patients. Research Design and Methods. We measured admission CysC and cardiac function parameters, including ejection fraction (EF) and pro-BNP value in 5956 patients diagnosed with AMI. Simple and multiregression analyses were performed to investigate the correlation between CysC and cardiac function in AMI patients. Major adverse cardiovascular events (MACE), cardiovascular, and all-cause mortality were documented, and 351 participants with high cystatin (≥1.09 mg/L) and 714 low cystatin (<1.09 mg/L) were investigated for survival analysis during a 48-month follow-up. Results 5956 patients with AMI were enrolled in the initial observational analysis, and 1065 patients of the whole cohort were included in the follow-up survival analysis. The admission CysC level was found to be significantly positively correlated to the pro-BNP level (R square = 0.2142, 95% CI 4758 to 5265, p < 0.0001) and negatively correlated to the EF value (R square = 0.0095, 95% CI -3.503 to -1.605, p < 0.0001). Kaplan-Meier survival analysis revealed significantly increased MACE incidence (HR = 2.293, 95% CI 1.400 to 3.755, p < 0.0001), cardiovascular mortality (HR = 3.016, 95% CI 1.694 to 5.371, p = 0.0002), and all-cause mortality (HR = 3.424, 95% CI 2.010 to 5.835, p < 0.0001) in high-admission CysC cohort with AMI at the end of 4-year follow-up. Conclusions Admission CysC is negatively correlated with cardiac function in AMI patients and acts as a novel predictor for MACE incidence in the whole population. Further studies are needed to investigate the specific mechanism of CysC in the cardiac function deterioration among AMI patients.

Renoprotective Effect of Vardenafil and Avanafil in Contrast-Induced Nephropathy: Emerging Evidence from an Animal Model.

The potential renoprotective effects of vardenafil (VAR) have been evaluated in a very limited number of studies using acute kidney injury animal models other than contrast-induced nephropathy (CIN) with promising results, while avanafil (AVA) has not been evaluated in this respect before. The purpose of this study was to evaluate for the first time the potential renoprotective effect of VAR and AVA in a rat model of CIN. Twenty-five male Wistar rats were equally assigned into five groups: control, CIN, CIN+N-acetyl cysteine (NAC) (100 mg/kg/day) as a positive control, CIN+VAR (10 mg/kg/day) and CIN+AVA (50 mg/kg/day). CIN was induced by dehydration, inhibition of prostaglandin and nitric oxide synthesis as well as exposure to the contrast medium (CM). Serum Cr (sCr) levels were measured at 24 and 48 h after CIN induction. At 48 h of CM exposure, animals were sacrificed. Matrix metalloproteinase (MMP) 2 (MMP-2) and MMP-9, kidney injury molecule 1 (KIM-1) and cystatin-C (Cys-C) were measured on renal tissue. Histopathological findings were evaluated on kidney tissue. All treatment groups had close to normal kidney appearance. sCr levels subsided in all treatment groups compared to CIN group at 48 h following CIN induction. A significant decline in the levels of MMP-2, MMP-9, KIM-1 and Cys-C compared to CIN group was observed. These results provide emerging evidence that VAR and AVA may have the potential to prevent CIN.

The effectiveness of the sarcopenia index in predicting septic\xa0shock and death in elderly patients with community-acquired\xa0pneumonia

BackgroundCommunity-acquired pneumonia (CAP) causes high morbidity and mortality in all age groups worldwide. Lower muscle radiodensity was associated with worse clinical outcomes (including shock) and higher in-hospital mortality. Prompt detection of sarcopenia in older adults with CAP is important. The measurement of muscle mass often involves specialized and expensive techniques. A relatively simple and inexpensive method such as the sarcopenia index (SI) to measure muscle mass would be helpful. Therefore, we performed a retrospective cohort study to assess the association between SI and septic shock risk and mortality in older patients with CAP.Study designIn this retrospective cohort study, information on hospitalized CAP patients, including general information and septic shock, were obtained from the medical record database of the Southwest Medical University Zigong Affiliated Hospital, China. Data on patient survival and mortality (all-cause) were acquired from government authorities and telephonic follow-up. Serum creatinine (Cr) and cystatin-C (CysC) levels on admission were included in the database. The SI was determined as the serum Cr/CysC ratio × 100 and the participants were assigned to low and high SI groups. The association between SI and septic shock was evaluated by logistic regression, and that between SI and mortality by Cox regression analysis.ResultsIn total, 769 older adults (≥ 60 years) with CAP were included, of which 480(62.4%) were male and 289(37.6%)were female. We found that the total prevalence of septic shock in older adults with CAP was 16.0%. In the female group, septic shock was more prevalent in the low SI group than in the high SI group (low SI vs. high SI, 22.22% vs. 11.52%, p = 0.024). Following adjustment for confounders, there was a significant association between high SI and a lower risk of septic shock in female patients (OR = 0.38, 95%CI: 0.16–0.94; p < 0.05). The total death toll of older adults with CAP was 332(43.2%). Irrespective of sex, there was a higher risk of mortality in the low SI group (total group: low SI vs. high SI, 63.02% vs. 36.57%, p < 0.001; male group: low SI vs. high SI, 63.03% vs. 39.34%, p < 0.001; female group: low SI vs. high SI, 73.61% vs. 28.57%, p < 0.001) and, after adjustment for confounding factors and irrespective of sex, high SI was a protective factor for mortality in older adults with CAP (total group: HR = 0.64, 95%CI: 0.48–0.84; p < 0.05; male: HR = 0.69, 95%CI: 0.49–0.97; p < 0.05; female: HR = 0.39, 95%CI: 0.24–0.62; p < 0.05).ConclusionWhile the SI effectively predicts mortality in older adults with CAP, it was only found to be associated with septic shock in older females.

The value of cystatin C in evaluating the severity and prognosis of patients with severe fever with thrombocytopenia syndrome

BackgroundSevere fever with thrombocytopenia syndrome (SFTS) is a novel emerging viral infectious disease. We explore the value of cystatin C (CysC) level in the evaluation of disease severity and prognosis in patients with SFTS.Methods254 patients with SFTS were enrolled in this study. According to the classification and the outcome of the disease, the patients were divided into the general group and the severe group, the severe patients were divided into the fatal group and the non-fatal group. We compared the laboratory indexes by univariate and multivariate logistic regression analysis to explore the severity and prognostic risk factors of SFTS disease, ROC curve and Kaplan–Meier survival analysis curve were drawn to analyze the independent risk factors and the predictive value of disease severity and prognosis.ResultsUnivariate analysis showed that the CysC level in severe group and fatal group was significantly higher than general group and non-fatal group (P < 0.05), respectively. Multivariate logistic regression showed that the CysC level was an independent risk factor for severe and death in SFTS patients, and it can effectively predict the risk of severe (AUC = 0.711, 95% CI: 0.645–0.777) and death (AUC = 0.814, 95% CI: 0.737–0.89). The risk of death in patients with cystatin C ≥ 1.23 mg/L was 5.487 times higher than that in patients with cystatin C < 1.23 mg/L.ConclusionsThe CysC level have good predictive value for disease severity and prognosis in patients with SFTS.Trial registration Not applicable

Human urinary kallidinogenase decreases the incidence of post-stroke cognitive impairment in acute ischemic stroke patients.

Post-stroke cognitive impairment (PSCI) is a common symptom of stroke and affects the quality of life and prognosis of stroke survivors. In our study, we evaluated the efficacy of Human urinary kallidinogenase (HUK) on cognitive function in acute ischemic stroke (AIS) patients, and discussed the role of cystatin C (CysC) in improving PSCI. We enrolled a retrospective cohort with prospective follow-up. From August 2020 to May 2021, 130 patients completed the final follow-up. Among them, 61 patients received HUK combined with basic treatment, which we defined as the HUK group, and 69 patients received basic treatment, which we defined as the control group. We compared the changes of CysC, urea nitrogen and creatinine levels after one week of treatment between the two groups. Cognitive function was assessed by Montreal Cognitive Assessment (MoCA) at 3-month after AIS. No significant differences in demographic data and Laboratory tests between two groups before treatment. A total of 67 patients (51.5%) were diagnosed as PSCI at 3-month follow-up, among which, 25 patients were in the HUK group and 42 patients were in the control group. Compared with the control group (60.9%), the incidence of PSCI was significantly lower in the HUK group (41.0%). In addition, the serum CysC level after a week of treatment significantly decreased from baseline in HUK group (p = 0.037), in comparison, the serum CysC level in the control group was basically unchanged (p = 0.951). There was a significant negative correlation between MoCA score and the level of CysC after treatment (p = 0.003, r = -0.373). HUK can reduce the risk of PSCI at 3-month in AIS patients. The decrease of serum CysC level may be one of the mechanisms by which HUK reduces the incidence of PSCI.

Association between preoperative serum Cystatin-C levels and postsurgical oncological prognosis in patients with PRCC: A retrospective cohort study.

Cystatin-C (Cys-C) is a predictor of several malignancies. However, whether Cys-C levels predict prognosis in patients with papillary renal cell carcinoma (PRCC) remains uncertain. The aim of this study was to assess the correlation between Cys-C and clinical outcomes in patients with PRCC. The medical records of 137 patients with PRCC who underwent surgery at our institution from January 2008 to December 2020 were retrospectively analyzed. Data were divided into two subgroups based on cutoff values and the relationship between the Cys-C group and their clinical outcomes was assessed. By the last follow-up, 62 patients had died of various causes, 53 of whom died from PRCC. Sixty patients suffered recurrence or metastasis during follow-up. Based on the cutoff value, the patients were divided into two groups: low Cys-C group (Cys-C < 1.25 mg/L, n=92) and high Cys-C group (Cys-C ≥ 1.25 mg/L, n=45). Pathological classification and serum Cys-C levels were shown to be independent prognostic factors affecting clinical outcomes, according to multivariate Cox regression analysis (p < 0.05). After adjusting the Cox proportional hazards model, the risk of death was elevated in the high Cys-C group. The results of the area under the curve for time-dependent receiver operating characteristics analysis indicated that Cys-C is a stable and reliable prognostic biomarker for predicting survival in patients with PRCC. Forest plots, constructed to better reflect the comparison of hazard ratios between the two groups, confirmed that Cys-C levels were significantly associated with worsening overall survival. This study is the first to examine the relationship between preoperative serum Cys-C levels and prognostic overall survival in patients with PRCC. Cys-C may be a useful biomarker for preoperative screening of high-risk patients who may require adjuvant therapy.

Expression and Clinical Significance of Serum MiR-424 and MiR-765 in Multiple Myeloma

To investigate the expression and clinical significance of miR-424 and miR-765 in patients with multiple myeloma (MM). The eighty-one MM patients admitted to Sanya Central Hospital from January 2017 to July 2020 were divided into phase Ⅰ (n=16), phase Ⅱ (n=25) and phase Ⅲ (n=40) according to the international staging system, while they were divided into IgG type (n=46), IgA type (n=19), light chain type (n=10) and non secretory type (n=6) according to the results of immunotyping. Another 50 healthy normal persons in the same period were selected as the control group. The levels of serum miR-424, miR-765 and Cystatin C (Cys-C) were measured in each group. The diagnostic value of serum miR-424, miR-765 and Cys-C in MM was estimated by ROC curve. Pearson correlation was used to analyze the correlation between serum levels of miR-424, miR-765 and Cys-C in MM patients. The serum levels of miR-424 (2.74±1.30 vs 0.85±0.26), miR-765 (2.05±0.82 vs 0.63±0.17) and Cys-C ［(2.18±0.86 vs 0.72±0.15) mg/L］ in MM group were significantly higher than those in control group (P<0.001). The serum levels of miR-424 (5.08±2.36 vs 1.12±0.34, 2.24±0.93), miR-765 (3.50±1.52 vs 0.74±0.20, 1.78±0.65) and Cys-C ［(3.81±1.30 vs 0.92±0.24, 1.68±0.55) mg/L］ in MM patients at stage Ⅲ were significantly higher than those in patients at stage Ⅰ and Ⅱ (P<0.001). Also the serum levels of the three molecules in phase II were significantly higher than those in phase I (P<0.001). The serum levels of miR-424 and miR-765 in MM patients at IgG type were significantly higher than those at IgA, light chain and non secretory types (P<0.001). ROC curve analysis showed that the area under the curve (0.952，95%CI: 0.890-0.993) was greatest for the combination of miR-424, miR-765 and Cys-C for diagnosis of MM, and its sensitivity and specificity were 95.0% and 87.2%. The results of correlation analysis showed that the serum levels of miR-424 and miR-765 were positively correlated with Cys-C (r=0.795，r=0.760). The serum levels of miR-424 and miR-765 in MM patients are significantly increased in the pattern increasing with the progression of MM stage. Combined with Cys-C, miR-424 and miR-765 have high value in the diagnosis of MM.