CysC Levels Research Articles

Is body composition important in the context of renal function in pediatric neurogenic bladder?

Neurogenic bladder due to myelomeningocele (MMC) is a significant risk factor for chronic kidney disease in children. Cystatin C (CysC) is a more accurate GFR marker than creatinine as it is unaffected by muscle mass but may be influenced by fat mass and BMI. This study evaluates: (1) GFR measurement accuracy using CysC and creatinine in MMC-related neurogenic bladder, (2) the relationship between body composition via bioelectrical impedance analysis (BIA) and renal parameters, and (3) the use of BIA for non-invasive GFR and body composition assessment. Forty children (median age 9.96years) underwent serum creatinine, CysC testing, and BIA measurements. We assessed age, sex, spinal lesion level, anthropometric measurements, BMI, and activity using Hoffer's scale. GFR was calculated using five creatinine-based formulas, three CysC-based, and three combining CysC and creatinine, including BIA GFR as an alternative approach. Creatinine-based GFR estimates were significantly higher than CysC-based GFR. Although only 30% of MMC patients met the traditional BMI criteria for overweight/obesity, 62.5% were obese based on BIA-measured body fat percentage. Significant differences were found in CysC and CysC-based GFR equations within BMI and fat mass groups. Positive correlations were observed between CysC and body weight, BMI percentiles, body fat mass and fat-to-muscle ratio. Muscle mass positively correlated with creatinine. BIA-determined fat mass percentage is a more sensitive obesity indicator than BMI in MMC patients. CysC levels and CysC-based GFR equations are influenced by body fat mass, requiring consideration of adiposity to avoid misestimating renal impairment.

Cystatin C: its correlation with some markers of immune system, inflammation, and its role in progression of diabetic retinopathy in type 2 diabetes

Aim: To study the correlations between Cystatin C (Cys-C) level and values of the markers of immune system and inflammation, and clinical manifestations of diabetic retinopathy (DR) in patients with type 2 diabetes mellitus (DM).Material and Methods. 3 groups of patients with type 2 diabetes and different stages of diabetic retinopathy were formed (21 people in each). Group I – with nonproliferative diabetic retinopathy (NPDR), Group II – with pre-proliferative diabetic retinopathy (PPDR), Group III – with proliferative diabetic retinopathy (PDR). The comparison group included patients with type 2 diabetes without vascular complications. Clinical study included: visometry, tonometry, assessing critical flicker fusion frequency, biomicroscopy of the anterior segment of the eye, ophthalmoscopy, biomicroscopy and ultrasound of the retina, crystalline lens, vitreous body, photographic recording of the fundus, optical coherence tomography. The content of Cystatin C (Cys-C), soluble forms of molecules B7.2 (CD86), 4-1BB, CTLA-4, Tim-3, LAG-3, PD-1, PD-L1, Galectin-9, proteins sICAM-1, SAA, NGAL and enzymes (MPO, MMP-2, MMP-9) was examined in the blood serum with the use of multiplex analysis.Results. As DR progresses, the level of Cys-C increases and becomes higher than in individuals with diabetes: with NPDR higher by 94.1% (p < 0.001), with PPDR – higher by 293.6% (p < 0.001). In individuals with PDR, the concentration of Cys-C is maximum. With DR, the amount of PD-1, PD-1L, NGAL, ICAM-1, MMP-9, and MPO increases in the blood serum; as the severity of DR worsens, the levels of ICAM-1, MPO, and MMP-9 increase. Direct correlations were found between the Cys-C values, on the one hand, and the values of some studied indicators, on the other.Conclusions. In type 2 diabetes and DR, the amount of Cys-C in the blood serum increases relative to individuals with diabetes without microangiopathy; in groups with worsening severity of ophthalmopathy, an increase in Cys-C concentration was recorded with a statistically significant difference between the groups. In groups with DR, the level of ICAM-1, MMP-9, and MPO increases with increasing severity. Moderate direct correlations were found between the amount of Cys-C on the one hand and PD-1, PD-L1, as well as the noticeable ones with the values of ICAM-1, NGAL, MMP-9, MPO on the other. A direct noticeable correlation was revealed between the level of Cys-C and the values of the fundus scale.

The Strong Effect of Propolis in Suppressing NF-κB, CysC, and ACE2 on a High-fat Diet

Background: A high fat diet (HFD)is one of the main causes of obesity and is closely linked to metabolic disorders brought on by stress and malfunctioning tissues. Propolis (Trigona Honey) is considered to be helpful in treating inflammatory diseases because it has also been demonstrated to have anti-inflammatory and anti-free radical properties. This study to demonstrate how much propolis supplementation affects BW, NF-κB, CysC, and ACE2 levels in Wistar rats (Rattus norvegicus) fed a HFD. Methods: Post-test and control group designs in an experimental setup. A total of twenty-four rats were randomly assigned to four groups of six. Group I received a normal diet for sixteen weeks (ND), Group II received a high fat diet (HFD) for sixteen weeks (HFD), Group III received an HFD for sixteen weeks plus propolis for eight weeks (HFD-8), and Group IV received an HFD and propolis for sixteen weeks (HFD-16). Using the Enzyme-Linked Immunosorbent Assay (ELISA), body weight (BW), serum NF-κB, Cys C, and ACE2 levels were measured before treatment (week 0), after 8 weeks of HFD (HFD-8) (week 8), and after 16 weeks of HFD (HFD-16). Results: The mean starting weight in the ND, HFD, HFD-8, and HFD-16 groups did not differ significantly (p > 0.001). By week eight, the HFD group's body weight had increased considerably (254.83 grams vs. 202.0 grams) in comparison to the ND group (p<0.001). The HFD and HFD-8 groups' body weight increased significantly at week 16 in comparison to the ND group (334.83 grams and 269.50 grams vs. 208.67 grams) (p<0.001). At week 16, there was no discernible difference in mean BW between ND and HFD-16 (p > 0.001). There was no significant difference found in the mean initial NF-κB levels between the ND, HFD, HFD-8, and HFD-16 groups (p > 0.001). At week 8, NF-κB levels in the HFD group were significantly higher (5,038 ng/ml vs. 3,655 ng/ml) (p<0.001) than in the ND group. At week 16, NF-κB levels in the HFD and HFD-8 groups were notably higher than those in the ND group (p<0.001), at 6,136 ng/ml and 4,378 ng/ml, respectively, compared to 3,775 ng/ml. Between ND and HFD-16, there was no significant distinction in the mean NF-κB levels at week 16 (p>0.001). There was no significant difference observed in the mean CysC and ACE2 between the ND, HFD, HFD-8, and HFD-16 groups (p > 0.001). CysC and ACE2 levels in the HFD group were significantly higher than those in the ND group at week 8, and in the HFD and HFD-8 groups, they were significantly higher than those in the ND group at week 16. When propolis is administered for eight weeks, the rise in BW, NF-κB, CysC, and ACE2 is suppressed until the eighth week, at which point it increases once more until the sixteenth week. Propolis administration, however, will halt the rise in BW, NF-κB, CysC, and ACE2 until the sixteenth week. Conclusion: Propolis administration for 16 weeks can suppress the increase in BW, LI, RI, NF-κB, CysC and ACE2 levels in rats given a high fat diet (HFD).

Investigating the relationship of co-exposure to multiple metals with chronic kidney disease: An integrated perspective from epidemiology and adverse outcome pathways

Systematic studies on the associations between co-exposure to multiple metals and chronic kidney disease (CKD), as well as the underlying mechanisms, remain insufficient. This study aimed to provide a comprehensive perspective on the risk of CKD induced by multiple metal co-exposures through the integration of occupational epidemiology and adverse outcome pathway (AOP). The study participants included 401 male mine workers whose blood metal, β2-microglobulin (β2-MG), and cystatin C (Cys-C) levels were measured. Generalized linear models (GLMs), quantile g-computation models (qgcomp), least absolute shrinkage and selection operator (LASSO), and bayesian kernel machine regression (BKMR) were utilized to identify critical nephrotoxic metals. The mean concentrations of lead, cadmium, mercury, arsenic, and manganese were 191.93, 3.92, 4.66, 3.11, 11.35, and 16.33 µg/L, respectively. GLM, LASSO, qgcomp, and BKMR models consistently identified lead, cadmium, mercury, and arsenic as the primary contributors to kidney toxicity. Based on our epidemiological analysis, we used a computational toxicology method to construct a chemical-genetic-phenotype-disease network (CGPDN) from the Comparative Toxicogenomics Database (CTD), DisGeNET, and GeneCard databases, and further linked key events (KEs) related to kidney toxicity from the AOP-Wiki and PubMed databases. Finally, an AOP framework of multiple metals was constructed by integrating the common molecular initiating events (reactive oxygen species) and KEs (MAPK signaling pathway, oxidative stress, mitochondrial dysfunction, DNA damage, inflammation, hypertension, cell death, and kidney toxicity). This is the first AOP network to elucidate the internal association between multiple metal co-exposures and CKD, providing a crucial basis for the risk assessment of multiple metal co-exposures.

Serum neutrophil gelatinase-associated lipocalin and cystatin C is associated with blood pressure in ex-preterm children and adolescents.

As preterm birth is a risk factor for hypertension (HTN), biomarkers for early prediction of HTN in childhood is an emerging need. The aims of the study were to evaluate serum biomarkers in ex-preterm children and examine for associations with office peripheral and central SBP (cSBP), ambulatory BP parameters and pulse wave velocity (PWV). This case-control study included children and adolescents born prematurely (ex-preterms) and at full term (controls). All participants underwent office and ambulatory BP monitoring, assessment of cSBP, PWV and serum biomarkers at the same visit. Neutrophil gelatinase-associated lipocalin (NGAL), matrix metalloproteinase-2, metalloproteinase-9 (MMP-2, MMP-9) and Cystatin C (CysC) were measured using ELISA. The study population included 52 ex-preterm individuals and 26 controls. Mean age was 10.7 ± 3.6 years. NGAL, MMP-2, MMP-9, and CysC levels were similar between the ex-preterm and the control group. In the ex-preterm group, NGAL is associated with office SBP z score (β = 1.007, 95% CI 1.001-0.014, P = 0.049), CysC with office DBP z score (β = 1.003, 95% CI 1.001-0.005, P = 0.018) and cSBP z score (β = 1.003, 95% CI 1.001-0.005, P = 0.006) independently of age, sex and BMI z score. Among ex-preterm children and adolescents 17% had ambulatory HTN and 31% had white-coat HTN. NGAL levels were higher in ex-preterm children with WCH compared with children with normal BP [57.9 (IQR 50.8) versus 34.6 (IQR 46.2)], P = 0.018]. WCH is common in ex-preterm children and adolescents and is associated with higher NGAL levels and CysC presents positive association with cSBP. The findings in this study provides preliminary evidence that NGAL and CysC may have a role in predicting the risk of developing hypertension later in life. Further studies are warranted.

Diagnostic and prognostic value of serum Cys-C, retinol-binding protein, and ischemia-modified albumin in patients with coronary heart disease: A diagnostic accuracy study.

The use of 3 biomarkers - cystatin-C (Cys-C), retinol-binding protein (RBP), and ischemia-modified albumin (IMA) - for the clinical classification and outcome of coronary heart disease (CHD) has not been adequately evaluated. We explored the serum levels of these 3 markers and evaluated their diagnostic and prognostic values in patients with CHD. This retrospective case-control study, conducted between June 2017 and June 2018, included 201 patients with CHD hospitalized at the Henan Provincial People's Hospital and 127 healthy individuals from Henan Provincial People's Hospital as controls. Cys-C, RBP, IMA levels, and other laboratory parameters in the 2 groups were determined, and patient outcomes were analyzed. Cys-C, RBP, and IMA levels were higher in the case group than in the control group (P < .05). Logistic regression analysis confirmed that these 3 biomarkers were independent risk factors for CHD. Each indicator has clinical significance in the diagnosis and prognosis of CHD, with RBP being the most significant. The AUC value for CHD detection using a combination of the 3 indicators was 0.783, and the sensitivity and specificity values were 78% and 74.6%, respectively. Simultaneous detection of Cys-C, RBP, and IMA could be an optimal method for early diagnosis and prognosis of CHD.

Simultaneous detection of multiple urinary biomarkers in patients with early-stage diabetic kidney disease using Luminex liquid suspension chip technology.

Several urinary biomarkers have good diagnostic value for diabetic kidney disease (DKD); however, the predictive value is limited with the use of single biomarkers. We investigated the clinical value of Luminex liquid suspension chip detection of several urinary biomarkers simultaneously. The study included 737 patients: 585 with diabetes mellitus (DM) and 152 with DKD. Propensity score matching (PSM) of demographic and medical characteristics identified a subset of 78 patients (DM = 39, DKD = 39). Two Luminex liquid suspension chips were used to detect 11 urinary biomarkers according to their molecular weight and concentration. The biomarkers, including cystatin C (CysC), nephrin, epidermal growth factor (EGF), kidney injury molecule-1 (KIM-1), retinol-binding protein4 (RBP4), α1-microglobulin (α1-MG), β2-microglobulin (β2-MG), vitamin D binding protein (VDBP), tissue inhibitor of metalloproteinases-1 (TIMP-1), tumor necrosis factor receptor-1 (TNFR-1), and tumor necrosis factor receptor-2 (TNFR-2) were compared in the DM and DKD groups. The diagnostic values of single biomarkers and various biomarker combinations for early diagnosis of DKD were assessed using receiver operating characteristic (ROC) curve analysis. Urinary levels of VDBP, RBP4, and KIM-1 were markedly higher in the DKD group than in the DM group (p < 0.05), whereas the TIMP-1, TNFR-1, TNFR-2, α1-MG, β2-MG, CysC, nephrin, and EGF levels were not significantly different between the groups. RBP4, KIM-1, TNFR-2, and VDBP reached p < 0.01 in univariate analysis and were entered into the final analysis. VDBP had the highest AUC (0.780, p < 0.01), followed by RBP4 (0.711, p < 0.01), KIM-1 (0.640, p = 0.044), and TNFR-2 (0.615, p = 0.081). However, a combination of these four urinary biomarkers had the highest AUC (0.812), with a sensitivity of 0.742 and a specificity of 0.760. The urinary levels of VDBP, RBP4, KIM-1, and TNFR-2 can be detected simultaneously using Luminex liquid suspension chip technology. The combination of these biomarkers, which reflect different mechanisms of kidney damage, had the highest diagnostic value for DKD. However, this finding should be explored further to understand the synergistic effects of these biomarkers.

Serum Cystatin C levels increase with increasing visceral fat area in patients with type 2 diabetes mellitus

The present study aimed to explore the association between serum cystatin C (Cys-C) levels and visceral fat area (VFA) in patients with type 2 diabetes mellitus (T2DM). A total of 208 previously diagnosed T2DM patients who visited our hospital from September 2019 to December 2021 were included and divided into three groups based on tertiles of Cys-C levels, namely, Groups C1, C2, and C3. The clinical data of the subjects were collected, biochemical parameters such as Cys-C levels were determined, and bioelectrical impedance analysis was applied to determine the VFA and subcutaneous fat area (SFA). The VFA in Group C1 was lower than that in Groups C2 and C3 (all P < 0.05), with no significant difference in VFA between Groups C2 and C3 (P > 0.05). Spearman’s correlation analysis revealed that the serum Cys-C level was positively correlated with age, VFA, SFA, insulin resistance index, waist circumference, body mass index, systolic blood pressure, serum creatinine level, and blood uric acid level (r = 0.543, 0.353, 0.168, 0.148, 0.365, 0.264, 0.25, 0.497, and 0.155, respectively; P < 0.05) and negatively correlated with glycated haemoglobin levels (r = -0.175, P < 0.05). Univariate linear regression analysis revealed that VFA was positively correlated with the Cys-C level (β = 0.002, 95% CI = 0.001–0.003, P < 0.05), with an increase of 0.002 mg/L in the Cys-C level for each 1 cm2 increase in VFA. Further multivariate linear regression analysis was performed with the serum Cys-C level as the dependent variable and age, VFA, SFA, insulin resistance (HOMA-IR), WC, BMI, SBP, Cr, UA, and HbA1c as the independent variables. The results suggested that VFA was positively correlated with serum Cys-C level (β = 0.001, 95% CI = 0.000–0.002, P < 0.05), with serum Cys-C levels increasing by 0.001 mg/L for every 1 cm2 increase in VFA. Using a VFA ≥ 100 cm2 as the criterion for visceral obesity, ROC analysis revealed that the Cys-C level was a better predictor of visceral obesity, with an area under the ROC curve (AUC) of 0.701 (95% CI = 0.631–0.771, P < 0.05), an optimal cut-off of 0.905 mg/L, and a sensitivity and specificity of 58.3% and 75.2%, respectively. The results suggested that the serum Cys-C level was correlated with the VFA in patients with T2DM and that Cys-C may play a vital role in T2DM patients with visceral obesity.

Cystatin C: diagnostic and prognostic value in acute kidney injury

Acute kidney injury (AKI) is a life-threatening condition that occupies one of the leading places in the structure of mortality in intensive care units. AKI markers common in clinical practice are characterized by a number of disadvantages: serum creatinine – late response to damage to the kidney tubules, an increase in damage to more than 50% of nephrons; urine volume – limited diagnostic value and overdiagnosis of AKI in dehydration, the impossibility of assessing on the basis of a single measurement, as well as the need for regular and frequent dynamic monitoring. The review considers the diagnostic and prognostic possibilities of cystatin C (CysC) in AKI. The results of 55 researches were analyzed. The influence of a number of physiological conditions and non-renal diseases on blood serum and urinary CysC levels were shown. These indicators proved to be highly sensitive and specific biomarkers for AKI diagnosis and prognosis, allowing the specialists to verify renal dysfunction at an early stage of development, ahead of structural changes, and thereby to timely correct treatment, including withdrawal of nephrotoxic drugs and initiation of nephroprotection therapy.

Cystatin C and the difference between cystatin C and serum creatinine: Improved metrics to predict waitlist mortality among patients with decompensated cirrhosis.

Among patients with decompensated cirrhosis, serum creatinine (sCr) is biased by sex, frailty, and hepatic synthetic function, while Cystatin C (cysC) is not. We found that sCr would better associate with waitlist mortality and that the difference between cysC and sCr (cysCsCr diff ) would quantify this bias and be independently associated with outcomes. We measured cysC levels at ambulatory liver transplant visits among 525 consecutive patients seen at our center. We defined the cysCsCr diff as the difference between cysC minus sCr. We compared demographics and clinical characteristics in patients with low, intermediate, and high cysCsCr diff , divided by tertile. We used Cox regression to compare the association between sCr and cysC and waitlist mortality and demonstrate the independent association between cysCsCr diff and waitlist mortality. In Cox regression, cysC was significantly more associated with waitlist mortality than sCr ( p < 0.001). We found that as compared to those with a low cysCsCr diff , those with an intermediate or high cysCsCr diff were more likely to be female, have ascites, have higher frailty, and have higher MELD 3.0 scores ( p < 0.05 for all). Compared to those with a low cysCsCr diff , we found that those in the intermediate and high groups were more likely to die during follow-up (low: 6% vs. intermediate: 8% vs. high: 11%, p = 0.007). We found that after adjusting for the components of the MELD 3.0 score, each 1-point increase in the cysCsCr diff was associated with 1.72× (1.27-2.32) the hazard of waitlist mortality. Our study demonstrates that not only is cysC more associated with waitlist mortality than sCr, but that cysCsCr diff represents a novel independent metric associated with waitlist mortality.

Prospective Comparison of Urinary Measured Creatinine Clearance With eGFR and Cystatin C Based Cis-eGFR, Including Kinetic eGFR in the Immediate Post-transplant Period With Prompt Allograft Function

IntroductioneGFR and KeGFR have not been compared, with urinary measured creatinine clearance (mCrCl) or serum Cystatin C eGFR, soon after kidney transplant with prompt primary function. The study aims to compare post-KTx, urinary mCrCl, and eGFRCysC with eGFR and KeGFR. MethodPost-KTx, urine was collected every 12 hours from 25 of the 34 consenting subjects to calculate mCrCl and compare with MDRD-4, Jelliffe eGFR, Cockcroft-Gault Creatinine-Clearance, and KeGFR by Chen and Brater formulae. Serum CysC levels were also measured in the last 14 subjects to compare with creatinine, mCrCl, and eGFRCysC. FindingsAt 12 to 96 hours post-KTx (n=25), mCrCl was 55.8% to 13.6% higher than MDRD-4 eGFR. The mean CysC level (n=14) was 58% to 14% lower than creatinine for up to 3.0 days post-KTx, with higher MDRD-4 eGFRCysC. Chen and Brater KeGFR were significantly lower than mCrCl and eGFR (figure-1B, table-1). Within three days post KTx, a 50% decrease in creatinine provided ≥ 50 mL/min CrCl in 90% of cases (mean mCrCl 61.7± 22.8). This difference was greater when the initial creatinine was higher with the rapid decrease in creatinine. Conclusion1) Post-KTx eGFR/KeGFR formulae underestimate mCrCl. 2) Serum CysC levels were lower than creatinine, corresponding higher eGFRCysC. 3) A 50% decrease from initial serum creatinine; mean mCrCl was 61.7±22.8 mL/min, and 90% of them have mCrCl > 50 mL/min. Post KTx, until creatinine is stabilized, recipients are often receiving subtherapeutic dosing of renally adjusted medications. More prospective studies are necessary, including radioisotope clearance.

Kidney function assessment using cystatin C and serum creatinine in heart transplantation recipients: Implications for valganciclovir dosing

BackgroundAmong heart transplantation (HT) recipients, the accuracy of serum creatinine (sCr)-based estimated glomerular filtration rate (eGFR) may be limited by fluctuations in extrarenal variables (e.g., muscle mass). Cystatin C (cysC) is less influenced by muscle mass; however, obesity and steroid use may increase cysC levels. Herein, we: i) longitudinally compared changes in eGFRcysC and eGFRsCr among HT recipients; ii) investigated the association of body mass index (BMI), steroid use and muscle mass with discrepancies between eGFRs; and iii) explored the implications of eGFRcysC use on valganciclovir (VGC) dosing. MethodscysC and sCr were measured in 294 blood samples obtained from 80 HT recipients. Intra-individual differences between eGFRs (eGFRdiffcysC-sCr) were calculated. Negative eGFRdiffcysC-sCr values correspond to eGFRsCr > eGFRcysC and positive values to eGFRcysC > eGFRsCr. In a patient subset (n=21), pectoralis muscle measures were derived from computed tomography scans. ResultsMarked differences between eGFRcysC and eGFRsCr were observed, particularly early post-HT (1-week post-HT, median eGFRdiffcysC-sCr -28 ml/min/1.73 m2). eGFRcysC demonstrated stability following a transient post-operative decline, while eGFRsCr decreased in the first year post-HT. Lower BMI and higher prednisone dose displayed a modest association with more negative eGFRdiffcysC-sCr values. Conversely, pectoralis muscle measures indicative of greater muscle mass and better tissue quality exhibited a stronger association with more positive eGFRdiffcysC-sCr values. The use of eGFRcysC would have led to VGC dose adjustment in 46% of samples, predominantly resulting in dose reduction. ConclusionsAmong HT recipients, eGFRcysC and eGFRsCr markedly differ with implications for VGC dosing. The observed discrepancies may reflect changes in body composition and steroid use.

Serum cystatin C, monocyte/high-density lipoprotein-C ratio, and uric acid for the diagnosis of coronary heart disease and heart failure

BACKGROUND Coronary heart disease (CHD) and heart failure (HF) are the major causes of morbidity and mortality worldwide. Early and accurate diagnoses of CHD and HF are essential for optimal management and prognosis. However, conventional diagnostic methods such as electrocardiography, echocardiography, and cardiac biomarkers have certain limitations, such as low sensitivity, specificity, availability, and cost-effectiveness. Therefore, there is a need for simple, noninvasive, and reliable biomarkers to diagnose CHD and HF. AIM To investigate serum cystatin C (Cys-C), monocyte/high-density lipoprotein cholesterol ratio (MHR), and uric acid (UA) diagnostic values for CHD and HF. METHODS We enrolled 80 patients with suspected CHD or HF who were admitted to our hospital between July 2022 and July 2023. The patients were divided into CHD (n = 20), HF (n = 20), CHD + HF (n = 20), and control groups (n = 20). The serum levels of Cys-C, MHR, and UA were measured using immunonephelometry and an enzymatic method, respectively, and the diagnostic values for CHD and HF were evaluated using receiver operating characteristic (ROC) curve analysis. RESULTS Serum levels of Cys-C, MHR, and UA were significantly higher in the CHD, HF, and CHD + HF groups than those in the control group. The serum levels of Cys-C, MHR, and UA were significantly higher in the CHD + HF group than those in the CHD or HF group. The ROC curve analysis showed that serum Cys-C, MHR, and UA had good diagnostic performance for CHD and HF, with areas under the curve ranging from 0.78 to 0.93. The optimal cutoff values of serum Cys-C, MHR, and UA for diagnosing CHD, HF, and CHD+HF were 1.2 mg/L, 0.9 × 109, and 389 µmol/L; 1.4 mg/L, 1.0 × 109, and 449 µmol/L; and 1.6 mg/L, 1.1 × 109, and 508 µmol/L, respectively. CONCLUSION Serum Cys-C, MHR, and UA are useful biomarkers for diagnosing CHD and HF, and CHD+HF. These can provide information for decision-making and risk stratification in patients with CHD and HF.

Evaluation of serum cystatin C levels in multiple myeloma: diagnostic significance and clinical implications

Cystatin C (CysC) levels in patients with multiple myeloma (MM) have been linked to tumour load and outcomes’ prediction. This study aimed at assessing the diagnostic utility of CysC in distinguishing MM patients from controls and advanced stages of MM. In total, 98 MM patients and 57 healthy controls participated in this cross-sectional case-control study. Demographic, clinical, and biochemical data were assessed. The study groups exhibited significantly diverse measures of urea, creatinine, CysC, β2-microglobulin, and lactate dehydrogenase activity. β2-Microglobulin was found to be a reliable predictor for both the MM staging and its diagnosis, but CysC was found to only possess a partial capacity of predicting advanced MM stages. Our results highlight the significance of taking into account many biomarkers in the therapy of MM, so as to achieve effective clinical evaluation. More research is required in order to clarify the CysC implication in the prognosis and management of MM.

Role of Urinary Biomarkers (Transforming Growth Factor β1, Neutrophil Gelatinase-Associated Lipocalin, and Cystatin C) as a Prognostic Factor of Renal Outcome in the Posterior Urethral Valve.

The urinary biomarker response precedes the appearance of any renal structural or functional derangement. Transforming growth factor-β1 (TGF-β1), neutrophil gelatinase associated lipocalin (NGAL), and Cystatin C (CysC) can act as the early prognostic markers in posterior urethral valve (PUV) patients. To compare the urinary levels of TGF-β1, NGAL, and CysC between PUV cases and age matched controls and to correlate these with renal structural and functional parameters. This prospective study included children with PUV diagnosed using the standard investigations and an equal number of age-matched controls with nonurological problems. For the study subjects, the urinary samples were collected at three different time points (pre- and postoperatively at 3 and 6 months), whereas for controls, only single-voided samples were studied. The urinary levels of TGF-β1, NGAL, and CysC were estimated by the standardized techniques using the ELISA kits. Statistical methods were used to drive the comparisons between cases and controls. Fifteen children with a median age of 10 (5-48) months were enrolled in each of the two groups. The mean uTGF-β1 in the case group was significantly higher at all three time points (43.20 ± 6.13 pg/ml, 43.33 ± 11.89 pg/ml and 40.71 ± 9.01 pg/ml) as compared to the control group (29.12 ± 8.31 pg/ml) (P ≤ 0.001). The median uNGAL in the case group was also higher (17.78 ng/ml, 2.35 ng/ml and 2.536 ng/ml) as compared to the control group (1.31 ng/ml). However, the difference was significant only preoperatively (P = 0.02). The median uCysC in case group was similarly higher (0.347 μg/ml, 0.439 μg/ml, and 0.382 μg/ml) than the control group (0.243 μg/ml) (P > 0.05). Serum creatinine in the case group (0.49 mg/dl) showed no significant rise above that of control (0.24 mg/dl). A cutoff value of uTGF-β1 = 36.55 pg/ml (P < 0.001), uNGAL = 0.879 ng/ml (P = 0.02), and uCysC = 0.25 μg/ml (P = 0.22) was found to be associated with renal damage in PUV. A significant correlation was found between uNGAL and S. creatinine at 3 months (r = 0.43, P = 0.017) and 6 months (r = 0.47, P = 0.08). The elevated uTGF-β1, a decline in uNGAL and an increase in uCysC suggests ongoing inflammation, improvement in hydronephrosis and a prolonged proximal tubular dysfunction in PUV patients, respectively.

CYSTATIN C BASED EGFR IS SUPERIOR FOR THE ASSESSMENT OF CARDIOVASCULAR RISK IN PRETERM CHILDREN

Objective: Preterm birth is a risk factor for hypertension (HTN), chronic kidney disease (CKD) and adverse cardiovascular (CV) outcomes. The aims of the study were to evaluate the utility of eGFR based on cystatin C (Cys C) compared to creatinine in regard to associations with office blood pressure (BP) and central systolic BP (cSBP). Design and method: This case-control study included 52 children and adolescents born prematurely (ex-preterms) and 26 at full term (controls) matched for age in 2:1 ratio. All participants underwent office BP and cSBP measurement and laboratory evaluation including assessment of CysC values at the same visit. Results: Mean age of the population was 10.74±3.55 years. There were no significant differences in BP levels, eGFR(creatinine) and eGFR(CysC) between ex-preterm and control group. CysC levels were similar between the ex-preterm and the control group. CysC significantly correlated with cSBP z score (r=0.32, p=0.02, Spearman test). This association remained significant after adjustment for age, sex and BMI z score in the ex-preterm group (B=1.003, 95%CI 1.001-0.005, p=0.006). 42% (n=22) of the ex-preterm children presented cSBP levels greater than the 95th percentile. eGFR(CysC) presented positive association with office DBP (r=-0.37, p= 0.006, Spearman test) and cSBP z score (r= -0.32, p=0.022, Spearman test) in the ex-preterm group, but not in the control group (Figure). eGFR(creatinine) did not associate with BP parameters. eGFR(creatinine) overestimated eGFR levels in ex-preterm group (mean difference 20.56±22.66, p &lt;0.001). Two (3%) and 17(32.6%) ex preterm children had GFR &lt; 90 ml/min/1.73m2 by creatinine-based eGFR compared by eGFR(CysC). Conclusions: eGFR(CysC) presents apositive association with cSBP and thus, may better classify future cardiovascular risk in ex-preterm children. cSBP elevation and its association with CysC maybe a target for future studies to elucidate the role of central hemodynamic alterations in the development of HTN and CV disease in the ex-preterm individuals.

Cystatin C Attenuates Perihematomal Secondary Brain Injury by Inhibiting the Cathepsin B/NLRP3 Signaling Pathway in a Rat Model of Intracerebral Hemorrhage.

Secondary brain injury (SBI) is a noticeable contributor to the high mortality and morbidity rates associated with intracerebral hemorrhage (ICH), and effective treatment options remain limited. Cystatin C (CysC) emerges as a novel candidate for SBI intervention. The therapeutic effects and underlying mechanisms of CysC in mitigating SBI following ICH were explored in the current research. An in vivo ICH rat model was established by injecting autologous blood into the right caudate nucleus. Western blotting (WB) was utilized to assess the levels of CysC, cathepsin B (CTSB), and the NLRP3 inflammasome. Subsequently, the ICH rat model was treated with exogenous CysC supplementation or CysC knockdown plasmids. Various parameters, including Evans blue (EB) extravasation, brain water content, and neurological function in rats, were examined. RT-qPCR and WB were employed to determine the expression levels of CTSB and the NLRP3 inflammasome. The co-expression of CTSB, CysC, and NLRP3 inflammasome with GFAP, NeuN, and Iba1 was assessed through double-labeled immunofluorescence. The interaction between CysC and CTSB was investigated using double-labeled immunofluorescence and co-immunoprecipitation. The findings revealed an elevation of CysC expression level, particularly at 24h after ICH. Exogenous CysC supplementation alleviated severe brain edema, neurological deficit scores, and EB extravasation induced by ICH. Conversely, CysC knockdown produced opposite effects. The expression levels of CTSB and the NLRP3 inflammasome were significantly risen following ICH, and exogenous CysC supplement attenuated their expression levels. Double-labeled immunofluorescence illustrated that CysC, CTSB, and the NLRP3 inflammasome were predominantly expressed in microglial cells, and the interaction between CysC and CTSB was evidenced. CysC exhibited potential in ameliorating SBI following ICH via effectively suppressing the activation of the NLRP3 inflammasome mediated by CTSB specifically in microglial cells. These findings underscore the prospective therapeutic efficacy of CysC in the treatment of ICH-induced complications.

Efficacy of Flexible Ureteroscopy Lithotripsy and Percutaneous Nephrolithotomy in the Treatment of Patients with Kidney Stones and Their Impact on Inflammatory Response and Renal Function.

Kidney stones are one of the most common benign diseases in urology. As technology updates and iterates, more minimally invasive and laparoscopic surgeries with higher safety performance appear. This paper explores the effectiveness of retrograde intrarenal surgery (RIRS) and percutaneous nephrolithotomy (PCNL) in treating kidney stones, focusing on their effects on inflammatory responses and renal function. We conducted a retrospective analysis of 200 patients with kidney stones treated in our hospital between June 2019 and June 2023. 100 patients who underwent RIRS were included in the RIRS group. Another 100 patients who underwent PCNL treatment were included in the PCNL group. The intraoperative blood loss, operation duration, and hospitalization time of the two groups of patients were recorded and compared. The enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of inflammatory factors in the serum of the two groups of patients: [serum amyloid A (SAA), interleukin-6 (IL-6) and high-sensitivity C-reactive protein (CRP)] and renal function index [blood urea nitrogen (BUN), creatinine (Scr) and serum cystatin (Cys-c)]. The two groups of patients were recorded separately: Postoperative complications and stone-free rate. Operation duration was longer for the RIRS group than the PCNL group, which exhibited significantly less intraoperative blood loss and shorter hospital stays (p < 0.05). Before surgery, there was no statistically significant difference in the serum levels of SAA, IL-6, and CRP between the two groups of patients (p > 0.05). On the first day after surgery, the serum SAA levels in both groups were lower than before surgery, IL-6 and CRP levels were higher than before surgery, and the serum levels of SAA, IL-6, and CRP in the RIRS group were significantly lower than those in the PCNL group. The difference was statistically significant (p < 0.05). Before surgery, there was no statistically significant difference in the serum BUN, Scr, and Cys-c levels between the two groups of patients (p > 0.05). On the first day after surgery, the serum BUN, Scr, and Cys-c levels of the two groups of patients were significantly higher than those before surgery. The serum BUN, Scr, and Cys-c levels of the RIRS group were significantly lower than those of the PCNL group, and the difference was statistically significant (p < 0.05). Both surgical methods have sound stone-clearing effects regarding long-term stone clearance rates 1 month and 3 months after surgery (p > 0.05). PCNL had a better stone clearance rate on the 2nd postoperative day (p < 0.05). The incidence of postoperative complications in the RIRS group was significantly lower than that in the PCNL group, and the difference was statistically significant (p < 0.05). For kidney stones ≤2 cm, PCNL showed higher stone clearance rates on the second postoperative day. However, RIRS and PCNL demonstrated adequate long-term stone clearance at 1 and 3 months post-surgery. Both surgical methods are safe and effective, and RIRS is safer than PCNL. Compared with PCNL, RIRS is a new method of kidney stone operation, which has less trauma to the patient's body and fewer complications after the operation, speeding up the recovery process of the patient.

Cystatin C is a predictor for long-term All-Cause and Cardiovascular Mortality in US Adults with Metabolic Syndrome.

This study examined the relationship between Cystatin C (CysC) levels and all-cause, CVD, and cancer mortality in US metabolic syndrome (MetS) patients. The 1999-2002 National Health and Nutrition Examination Survey (NHANES) prospective cohort research included 1,980 MetS participants. To assess CysC levels and all-cause, CVD, and cancer mortality, fitted curves, Kaplan-Meier survival curves, cox regression analysis, and ROC curves were performed. During a mean follow-up of 15.3 ± 5.4 years, a total of 819 deaths occurred. The fitted and Kaplan-Meier survival curves revealed that greater CysC levels were linked to higher all-cause, CVD, and cancer mortality rates (P<0.05). After adjusting for variables, CysC level was associated with all-cause, CVD, and cancer mortality at 1.63 (1.42-1.88), 1.53 (1.19-1.95), and 1.53 (1∼2.32), respectively (P<0.05). Later tertile models showed consistent results. High CysC tertile participants showed higher risk of all-cause mortality (HR 1.87; 1.43-2.45), CVD mortality (HR 1.97, 1.15∼3.38), and cancer mortality (HR 1.72, 1.01∼2.91) compared to those in the lowest tertile (P<0.05). Subgroup studies by sex and other characteristics confirmed the findings. CysC demonstrated the higher predictive efficacy across mortality outcomes, followed by eGFR, outperforming Urea nitrogen, Creatinine, Uric acid, and CRP. CysC alone exhibited substantial predictive value for all-cause (AUC 0.773; P<0.05) and CVD mortality (AUC 0.726; P<0.05). Combining CysC with age enhanced the predictive value for all-cause mortality to 0.861 and CVD mortality to 0.771 (P<0.05). MetS patients with elevated CysC levels have a higher risk of all-cause, CVD, and cancer death. CysC may predict MetS all-cause and CVD mortality.

Lower glomerular filtration rate after mild stroke induces cognitive impairment by causing endothelial dysfunction

The incidence of post stroke cognitive impairment (PSCI) is high in patients with mild stroke (MIS), and the risk factors and mechanism are uncertain. Increased cystatin C (CysC) levels after stroke may reflect lower glomerular filtration rate (GFR) and renal impairment. Previous studies have suggested endothelial dysfunction (ED) is closely related to renal impairment and cognitive impairment, respectively. We aimed to observe whether lower GFR estimated by CysC after MIS leaded to a high incidence of PSCI, and the role of ED in this process. 256 patients were enrolled in this prospective observational study. Renal function was assessed using GFR estimated by serum CysC. Endothelial function was evaluated by reactive hyperemia index (RHI) which calculated automatically by peripheral arterial tonometry (PAT). The cognitive function at baseline and 3 months was evaluated by MoCA score, and MoCA score ≤ 26 indicates the presence of PSCI. Spearman correlation analysis and linear regression were conducted to explore the factors affecting ED. Univariate and multivariate analysis was used to identify the independent risk factors of PSCI. The receiver operating characteristic (ROC) curve was applied to explore the optimal cutoff value of the independent risk factors levels for predicting PSCI. A total of 141 patients (55.1%) suffered from ED. Multiple linear regression analysis showed that there was a strong linear correlation between eGFRcys and RHI (p < 0.001). At the three-month follow-up, a total of 150 (58.6%) patients had been diagnosed with PSCI. Multivariate logistic regression analysis showed that RHI was an independent factor affecting the occurrence of PSCI (p < 0.05). ROC curve showed that the area under the curve was 0.724, and the optimal cut-off value of RHI was 1.655, with the sensitivity and specificity for PSCI were 72.7% and 73.6%, respectively. The lower eGFRcys level after MIS was significantly associated with ED, and ED may mediate the higher incidence of PSCI at 3 months after MIS.