Particle-enhanced Nephelometric Immunoassay Research Articles

Longitudinal Three-Year Associations of Dietary Fruit and Vegetable Intake with Serum hs-C-Reactive Protein in Adults with and without Type 1 Diabetes.

High-sensitivity C-reactive protein (hs-CRP) is a widely used clinical biomarker of systemic inflammation, implicated in many chronic conditions, including type 1 diabetes (T1D). Despite the increasing emphasis on dietary intake as a modifiable risk factor for systemic inflammation, the association of hs-CRP with fruit and vegetable consumption is relatively underexplored in T1D. To address this gap, we investigated the longitudinal associations of dietary pattern-derived fruit and vegetable scores with hs-CRP in adults with and without T1D. Additionally, we examined the impact of berry consumption as a distinct food group. Data were collected in the Coronary Artery Calcification in Type 1 Diabetes study over two visits that were three years apart. At each visit, participants completed a food frequency questionnaire, and hs-CRP was measured using a particle-enhanced immunonephelometric assay. Mixed effect models were used to examine the three-year association of fruit and vegetable scores with hs-CRP. Adjusted models found a significant inverse association between blueberry intake and hs-CRP in the nondiabetic (non-DM) group. Dietary Approaches to Stop Hypertension- and Alternative Healthy Eating Index-derived vegetable scores were also inversely associated with hs-CRP in the non-DM group (all p-values ≤ 0.05). Conversely, no significant associations were observed in the T1D group. In conclusion, dietary pattern-derived vegetable scores are inversely associated with hs-CRP in non-DM adults. Nonetheless, in T1D, chronic hyperglycemia and related metabolic abnormalities may override the cardioprotective features of these food groups at habitually consumed servings.

Serum High-Sensitivity C-Reactive Protein Levels and the Risk of Atrial Fibrillation in Japanese Population: the Circulatory Risk in Communities Study.

Aim: This study aimed to investigate the association between the serum high-sensitivity C-reactive protein (hs-CRP) levels and incident atrial fibrillation risk in the general Japanese population, who have lower hs-CRP levels than the Western population, and assess whether the association is modified by sex, overweight, hypertension, and smoking status.Methods: We conducted a prospective study in 6517 Japanese men and women aged 40–79 years without atrial fibrillation at baseline and enrolled in the Circulatory Risk in Communities Study (2002–2008). The hs-CRP levels were measured using the latex particle-enhanced immunonephelometric assay. Atrial fibrillation was identified using standard 12-lead electrocardiograms and information on physician-diagnosed atrial fibrillation history from the follow-up surveys. We used a Cox proportional hazard regression stratified by community.Results: During a median follow-up of 11 years, 127 new cases of atrial fibrillation (74 and 53 cases among men and women, respectively) were found. Compared to the lowest quintile of hs-CRP levels, the multivariable hazard ratios (95% confidence intervals) were 2.54 (1.17–5.50), 2.28 (1.06–4.93), 2.92 (1.37–6.23), and 2.77 (1.30–5.91) for the second, third, fourth, and fifth (highest) quintiles, respectively. There was no significant effect modification by sex, overweight, hypertension, and smoking status (P for interaction > 0.05).Conclusions: Elevated hs-CRP levels were significantly associated with increased risk of atrial fibrillation in the Japanese population. The association of hs-CRP levels with incident atrial fibrillation did not vary according to sex, overweight, hypertension status, or smoking status.

Serum Neutrophil Gelatinase-Associated Lipocalin Independently Predicts for Renal Response in Myeloma Patients with Severe Renal Impairment

Introduction: Severe renal impairment (RI) is a common complication of multiple myeloma (MM). Effective anti-MM therapy and supportive care can restore renal function in several patients, but we lack biomarkers that could predict renal outcomes. Neutrophil gelatinase-associated lipocalin (NGAL) is one of the earliest and most robust markers of acute kidney injury while serum Cystatin C (CysC) reflects renal function more accurately than creatinine and correlates with both tumor burden and renal function in MM. GDF-15 is secreted by bone marrow stromal cells and high serum levels indicate a poor treatment prognosis and a high risk of progression to dialysis in AL amyloidosis. Our aim was to evaluate serum NGAL, CysC, and GDF-15 in MM patients with severe RI defined as eGFR<30 ml/min/1.73m2, by CKD-EPI formula, including those on dialysis, as biomarkers for prediction of renal responses. Patients & Methods: MM patients who presented with myeloma-related severe RI in the Department of Clinical Therapeutics (Athens, Greece) were included in this study. NGAL, CysC and GDF-15 were measured in the same frozen serum sample collected before the administration of any therapy. Serum NGAL was measured using ELISA (BioPorto Diagnostics A/S, Gentofte, Denmark), while CysC was measured using a latex particle-enhanced nephelometric immunoassay (Dade Behring-Siemens Healthcare Diagnostics, Liederbach, Germany). GDF-15 was measured by a novel immunoassay, the Elecsys GDF-15 assay (Roche Diagnostics International Ltd, Rotkreuz, Switzerland), which is based on the sandwich immunoassay principle using biotin-streptavidin technology. Patients on dialysis received dialysis with regular membranes. IMWG renal response criteria were used. Results: In total, 101 newly diagnosed MM patients with severe RI were included in this analysis. Median creatinine was 4.6 mg/dl (range 2->10 mg/dl), median eGFR (ml/min/1.73 m2) was 11.3 (1.3-29.8) and dialysis was required in 35 (35%) patients. The median age was 71 years; median involved FLC was 4740 mg/L; hypercalcemia was found in 24%, LDH ≥ULN in 44% and high-risk cytogenetics in 25% of patients, while 98% of patients were classified as having ISS-3 and 49% as having R-ISS-3 disease stage. Treatment was bortezomib-based in all patients (in 21% VD and in 79% a triplet: VCD or VTD). Median NGAL levels were 182.3 ng/mL (range 20-550 ng/ml) and of CysC were 3.3 mg/L (0.9-8 mg/L); there was a strong correlation between NGAL and CysC levels (R2=0.653, p<0.001). There was also a strong correlation of both CysC and NGAL with eGFR (for CysC: R2=0.615, p<0.001 and for NGAL: R2=0.464, p<0.001). Both NGAL and CysC levels were higher in patients requiring dialysis vs those not in dialysis (median NGAL: 308 vs 166 ng/mL, p<0.002 and median CysC: 4.99 vs 2.83 mg/L, p=0.008). No significant correlations were observed with GDF-15 and the parameters tested. Renal response (Rrenal) was achieved in 63% of patients, including 45% with major Rrenal. Importantly, 40% of patients who required dialysis became dialysis independent. Median time to Rrenal was one month and median time to dialysis independence was two months. Lower levels of NGAL (p=0.0003) and CysC (p=0.03) were associated with higher probability of major Rrenal among patients with severe RI. Baseline eGFR, levels of sFLC and GDF-15 did not correlate with major Rrenal. None of these markers was associated with probability of dialysis independence among patients who required dialysis. Based on ROC analysis, in patients with severe RI (but not on dialysis), NGAL <138 ng/ml was strongly associated with major Rrenal (80% vs 20% at 3 months, p<0.001; Figure). Regarding CysC, levels <2.9 mg/L were associated with higher probability and shorter time to major Rrenal (p=0.012). In multivariate analysis performed in patients not on dialysis, that included age, NGAL, CysC and eGFR, only NGAL <138ng/ml remained a significant prognostic factor associated with major Rrenal (HR 5, 95% CI 2-18, p=0.002). Conclusions: Serum levels of NGAL were independent predictors of major renal response in MM patients with severe RI. Thus, serum NGAL could identify MM patients with severe RI who should be treated with more aggressive therapies and more effective and rapidly acting antimyeloma regimens. The absence of any predictive value of GDF-15 in MM-related severe RI in contrast to AL amyloidosis patients reflect the different biology of RI in these plasma cell dyscrasias. Figure Disclosures Dimopoulos: Sanofi Oncology: Research Funding. Kastritis:Amgen: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Genesis: Honoraria; Prothena: Honoraria; Pfizer: Honoraria; Takeda: Honoraria. Papassotiriou:Roche: Employment. Gavriatopoulou:Amgen: Honoraria; Janssen: Honoraria, Other: Travel expenses; Genesis: Honoraria, Other: Travel expenses; Takeda: Honoraria, Other: Travel expenses. Terpos:Janssen: Honoraria, Other: Travel expenses, Research Funding; Amgen: Honoraria, Research Funding; Celgene: Honoraria; Takeda: Honoraria, Other: Travel expenses, Research Funding; Genesis: Honoraria, Other: Travel expenses, Research Funding; Medison: Honoraria.

Disposable electrochemical immunosensor for analysis of cystatin C, a CKD biomarker

Specific monitoring of cystatin C (CysC) levels in biological fluids is critical for diagnosis, treatment and mechanistic understanding of a spectrum of diseases, particularly chronic kidney disease (CKD). Despite evidences that CysC correlates with the high risk and/or progression of CKD, its use in clinical practice is still scarce. In this context, we report the development of a simple and sensitive immunosensor for the detection of CysC. The biosensor combines the technology of cost-effective screen-printed electrodes with the high specificity of a sandwich immunoassay. Optimized conditions showed that the sensor operates in a linear range between 10 and 100 ng mL−1, with a detection limit and a sensitivity of 6.0 ng mL−1 and 6.4 ± 0.3 μA ng mL−1 cm−2, respectively. Moreover, the sensor provided precise results (RSD ≤ 6.2%) and the quantification of CysC in CKD serum samples revealed to be in agreement with the values obtained by a particle-enhanced nephelometric immunoassay. In this light, the proposed immunosensor qualifies for clinical application, constituting a step forward in the development of fast, sensitive and cost-effective diagnostic tools that can improve the current medical care settings of CKD patients.

Analytical performances of PENIA and PETIA urinary cystatin C determination allow tubular injury investigation.

The study was designed to evaluate the analytical performances of two ERM-DA471/IFCC traceable cystatin C (CysC) reagents available on the market for urinary CysC (u-CysC) quantification. In addition, clinical relevance was assessed by measuring u-CysC in healthy controls and in patients with tubular dysfunction. CysC in urine was measured by a particle-enhanced nephelometric immunoassay using Siemens reagents and by a particle-enhanced turbidimetric immunoassay using DiaSys reagents. Imprecision, linearity, limit of detection and limit of quantification were evaluated according to CLSI recommendations. The two methods were tested on 150 urinary samples from 50 healthy subjects, 50 HIV patients with tubular dysfunction and 50 patients who developed acute kidney acute injury. Within-laboratory coefficients of variations were below 4%. The lower limit of quantification of the assay was found at 0.043 and 0.046 mg/L for DiaSys and Siemens, respectively. The following Passing-Bablok regression equations were obtained: DiaSys = 0.99 Siemens + 0.00. Using Bland-Altman analysis, the mean bias was -0.004 mg/L on the analytical range between 0.02 and 1 mg/L. Median u-CysC in 50 HIV patients with tubular dysfunction and in 50 patients with AKI was higher than in control subjects. Both Siemens and DiaSys reagents demonstrated reliable and reproducible performances allowing easy determination of u-CysC on automated platforms in clinical practice with potential interest for the detection of tubular dysfunction.

Estimation of GFR in children using rescaled beta-trace protein

IntroductionBeta-trace protein (BTP) is a low molecular weight protein, produced mainly in the cerebrospinal fluid. It has been proposed as a marker for kidney function. Recently, a new method for GFR estimation using mean normal values to rescale GFR marker concentrations has been described for creatinine and cystatin C, two commonly used endogenous markers for kidney function. The aim of this study is to apply this approach to BTP in children. MethodWe retrospectively analyzed serum concentrations of creatinine, cystatin C and BTP measured during inulin clearance tests in children. BTP was measured using a particle-enhanced immunonephelometric assay (Siemens Healthcare). A novel BTP-based eGFR equation was developed using published normal values for children: eGFRBTP[ml/min/1.73m2] = 107.3/BTP/QBTP with QBTP = 0.69. Performance of this equation was compared to the established creatinine-based full age spectrum equation FASage and the cystatin C-based FAScys equations as well as the BTP-based Benlamri equation in terms of bias, % prediction error and P30 and P10 accuracy rates. Results322 inulin clearance tests were studied. Overall, our novel equation performed comparably to the creatinine-based FASage and the BTP-based Benlamri equations but was less accurate than FAScys (P30: 79.2 vs 86.3%, p = .008). Combining markers significantly enhanced performance compared to the single marker equations, with the exception of FAScys. ConclusionRescaled BTP concentrations are a simple method for estimating GFR in children. However, the additional value of BTP for the estimation of GFR compared to rescaled creatinine and cystatin C still remains to be demonstrated.

Serum cystatin C and cystatin C/albumin ratio for the evaluation of liver function in patients with cirrhosis

Purpose: The aim of this study is to analyze the serum cystatin C (Cys C) and cystatin C/albumin (Alb) ratio in patients with cirrhosis and evaluate the role of serum Cys C in the evaluation of liver function. Methods: The liver function of patients was graded according to the Child-Pugh Score. According to the serum Cys C levels (determined with particle-enhanced immunonephelometric assay), the patients were divided into two groups: the high Cys C level group and normal Cys C level group. The correlation between the Child-Pugh grades/scores and the serum Cys C level, Cys C/Alb ratio were investigated. Results: The Cys C values were not correlated to Child-Pugh grades and scores. Besides, the Cys C/Alb ratio of both groups had a linear regressive relationship with the Child-Pugh scores. Ninety-seven percentage sensitivity and 100% specificity were achieved for the evaluation of liver function in cirrhosis patients with high serum Cys C level. Conclusion: Cys C value and Cys C/Alb ratio are accurate for liver function evaluation in the cirrhosis patients with high serum Cys C levels. Compared with the Cys C value, the Cys C/Alb ratio is more related to the liver function and can be used as an indicator in cirrhosis patients with normal serum Cys C level for the evaluation of liver function.

Serum cystatin C is associated with kidney function but not with cardiovascular risk factors or subclinical atherosclerosis in patients with Systemic Lupus Erythematosus.

Cystatin C (CysC) is a protein considered as an excellent marker of renal function, and it has been suggested as an independent predictor of cardiovascular (CV) risk. We evaluated the association of serum CysC with renal function, CV risk factors, inflammation, and subclinical atherosclerosis in Systemic Lupus Erythematosus (SLE) patients. Sixty-one SLE female patients were selected according to estimated glomerular filtration rate (GFR) > 60ml/min/1.73m2. Renal function parameters, SLE specific factors, CV risk factors, and inflammatory markers were assessed. Subclinical atherosclerosis was assessed by measuring the carotid-femoral pulse wave velocity (PWV) by Doppler velocimetry. Serum CysC concentration was measured using a particle-enhanced immunonephelometric assay that established 0.59-1.01mg/l as reference values. Patients with high CysC showed significantly altered creatinine, microalbuminuria, and GFR in addition to a significant higher presence of traditional CV risk factors such as arterial hypertension (p<0.001), metabolic syndrome (p<0.001), hypertrigliceridemia (p<0.001), tobacco habit (p<0.05), and a strong association with arterial stiffness (p=0.017). Positive correlation between CysC, homocysteine (r=0.511; p<0.001) and fibrinogen levels (r=0.304; p<0.02) were also observed. A significantly higher SLICC/ACR score was related to high CysC level (p=0.011), together with higher endothelin-1 and lower TNF serum concentration (p<0.005). Considering only patients without any renal impairment (microalbumin/creatinine <30mg/g), no association between CysC level and CV risk factors, arterial stiffness, or SLE-related factors was found. Serum CysC is a good marker of renal function in SLE patients, but it is not independently associated with cardiovascular risk factor or subclinical atherosclerosis.

Diagnostic value of serum cystatin C for acute kidney injury in patients with liver cirrhosis

Objective: To determine the diagnostic value of serum cystatin C (Cys C) for acute kidney injury (AKI) in patients with liver cirrhosis. Methods: Serum Cys C levels in 150 liver cirrhosis patients (88 AKI and 62 non-AKI patients) were measured by the Particle-Enhanced Nephelometric Immuno-Assay. The accuracy of serum Cys C for the diagnosis of AKI in liver cirrhosis was evaluated by the ROC curve. Results: Liver cirrhosis patients with AKI had significantly higher serum Cys C levels [2.37 (1.75-2.83) mg/L] than those without AKI [0.97 (0.85-1.09) g/L] (P <0.001). Serum Cys C level was highest in the acute tubular necrosis group [5.41 (2.77-6.19) mg/L], followed by the hepatorenal syndrome group [2.55 (2.28-3.59) mg/L] and prerenal azotemia group [2.07 (1.70-2.41) mg/L], and the serum Cys C level was significantly different between the three groups (P <0.001). In addition, patients with AKI were further divided into infection group and non-infection group. Serum Cys C level was significantly higher in the infection group than in the non-infection group (P <0.05). The area under the ROC curve of serum Cys C for the diagnosis of AKI in liver cirrhosis was 0.99 (0.98-1.00) at a cut-off value of 1.36 mg/L, and the sensitivity and specificity were 97% and 95%, respectively. Conclusion: Serum Cys C is a good marker for detecting AKI in liver cirrhosis, and the different levels of increase in Cys C may be useful in differentiating the different types of AKI.

Quantification of cystatin-C in human serum by stable isotope dilution liquid chromatography electrospray ionization tandem mass spectrometry.

Cystatin C (CysC)-based estimated glomerular filtration rate is an excellent marker for early diagnosis of Chronic Kidney Disease (CKD). Particle-enhanced nephelometric immunoassay (PENIA) and particle-enhanced turbidimetric immunoassay (PETIA) are commonly used methods for CysC quantification in clinical testing. However, both of them lack of specificity which mass spectrometry offers. In this paper, an isotope dilution liquid chromatography tandem mass spectrometry (ID-LC-MS/MS) method was established for quantification of CysC in human serum. After CysC denaturation, reduction and alkylation of cysteine residues, trypsin was added for proteolytic digestion of CysC. Specific peptide ALDFAVGEYNK was selected as surrogates for intact CysC protein, then quantified CysC by stable isotope-labelled internal standard peptide A[13C615N]LDFAVGEYNK based on calibration curve method. The calibration curves were y=0.1565x-1.6715 (R2=0.988) and y=1.8785x-2.2497 (R2=0.991) for y9 and y6, respectively. The linear range was 0.1-10mg/L and 0.5-15mg/L for y9 and y6, respectively. The limit of quantification (LOQ) was 0.052mg/L. At different concentrations of CysC, the recoveries were in the range of 80.5%-93.7%, the intraday precisions were in the range of 0.3%-2.2%, and the inter-day precisions were in the range of 0.2%-2.8%. The results show that ID-LC-MS/MS and PETIA methods have higher consistency (y=0.8021x+0.6611, p=0.14), and the mean difference of the two methods was -0.29mg/L, and 95% of the individual difference values were in the range of -0.91mg/L-0.33mg/L.

CYSTATIN C, HbA1c, DAN RASIO ALBUMIN KREATININ

Prevalence of type 2 diabetes mellitus and chronic kidney disease is increasing nowdays. Cystatin C is a more sensitive marker in detecting kidney disturbance at an early stage. Microalbuminuria indicates that there is an increasing risk in kidney disorders in diabetes mellitus patients. HbA1c is used to assess average blood glucose in three (3) months. An evaluation about the relation among Cystatin C, HbA1c, and ACR is needed to decide which test will be appropriate for the patient. Cystatin C was determined using Particleenhanced nephelometric immunoassay (PENIA) method from BN Prospec. High Performance Liquid Chromatography (HPLC) method from BioRad was used for HbA1c test, while random urine sample was used for Albumin Creatinine Ratio (ACR) test. Urine and serum creatinine were tested by immunoturbidimetric assay from Cobas C501. Correlation among Cystatin C, HbA1c, and ACR was estimated using Spearman's correlation test. There was a significant correlation among Cystatin, HbA1c, and ACR. Spearman correlation value showed a positive weak correlation. There was a strong relation between Cystatin C and HbA1c, but weak relations between Cystatin C and ACR, and between HbA1c and ACR. It can be concluded that due to the weak correlation between ACR and kidney function as well as between ACR and HbA1c, ACR is not a good assessment to predict diabetic nephropathy progressiveness.

Long-term follow-up of renal function assessing serum cystatin C in dogs with diabetes mellitus or hyperadrenocorticism.

Serum cystatin C (sCysC) is used as biomarker for glomerular filtration rate (GFR). The effects of diabetes mellitus (DM) on renal function in dogs are unclear. Some renal variables have been evaluated in dogs with hyperadrenocorticism (HAC), but not sCysC. The purpose of this study was the validation of a particle-enhanced nephelometric immunoassay (PENIA) for measuring canine sCysC, and to assess renal function in dogs with DM or HAC. A PENIA was analytically validated for canine sCysC by determining imprecision and linearity. In a longitudinal 6-month study, renal function of 14 DM dogs was assessed, using serum creatinine, GFR, urinary protein-to-creatinine (UPC) ratio, urinary markers, systolic blood pressure (SBP), and sCysC, and compared to 17 healthy dogs at baseline. Furthermore, sCysC was measured at initial presentation and during a 12-month follow-up in 22 HAC dogs. The sCysC intra- and inter-assay variation coefficients were < 8% and highly linear (r = .997). About 33% and 67% of DM dogs had persistent proteinuria and systemic hypertension, respectively, but there were no significant differences in GFR, UPC, and urinary markers over time, and compared with healthy dogs at initial presentation. Serum CysC decreased significantly (P < .05) over time within the DM group. It did not change significantly over time within the HAC group. A PENIA measured sCysC linearly and precisely. There were no clinically relevant renal alterations over time in dogs with DM, although persistent proteinuria was observed. In dogs with HAC, sCysC measurement was not useful, although significant GFR changes occurred over time.

Can admission serum cystatin C level be an early marker subclinical acute kidney injury in critical care patients?

Background In critical care patients, the diagnosis of subclinical acute kidney injury (AKI) might be difficult with measurements of serum creatinine and estimated glomerular filtration rate (eGFR). Their ‘sensitive kidneys’ can easily be affected from sepsis, underlying diseases, medications and volume status and if they can be detected earlier, some preventive measures might be taken. In this study we aimed to determine whether admission serum cystatin C (sCys-C) and other clinical parameters can identify subclinical AKI in medical intensive care unit (ICU) patients with normal creatinine-based eGFR at admission. Methods A prospective cohort study, performed in an adult ICU of a university hospital between January 2008 and March 2013. The blood samples were obtained within the first 24-48 hours of admission and sCys-C levels were analyzed with particle-enhanced immunonephelometric assay. AKI development was assessed according to RIFLE criteria. The cutoff value of sCys-C for the prediction of AKI was determined with receiver operating characteristic (ROC) curve analysis. Results A total of 72 patients were included in the study and 19 (26%) of them developed AKI. Among the patients with AKI admission sCys-C levels were significantly higher when compared with non-AKI patients (1.06 ± 0.29 vs. 0.89 ± 0.28 respectively, p = 0.026). With ROC curve analysis, the threshold level for sCys-C was 0.94 mg/L with 63% sensitivity and 66% specificity [AUC: 0.67, p = 0.026]. With logistic regression analysis ‘high sCys-C levels at admission’ (OR = 4.73; 95%CI 1.03–21.5, p = 0.044) was found as one of the independent variables for the prediction of AKI development, in addition to ‘being intubated before ICU admission’ (OR = 10.2; 95%CI 1.72–60.4, p = 0.01) and ‘hypotension during ICU follow-up’ (OR = 12.3; 95%CI 2.5–60.1, p = 0.002). Conclusion In this cohort of patients, a high sCys-C level at admission was found to be a predictor of subclinical AKI arising during their ICU stay. If supported with further studies, it might be used to provide more accurate and earlier knowledge about renal dysfunction and to take appropriate preventive measures.

Diagnostic accuracy of serum cystatin C in chronic kidney disease: a meta-analysis.

Chronic kidney disease (CKD) is a major health problem worldwide with dramatically increasing incidence and prevalence. Serum cystatin C (sCysC) has been clarified by many studies as a relatively accurate marker to evaluate renal function. Meta-analysis of diagnostic test studies. Various clinical settings of CKD, including adult patients with diabetes, renal transplant patients, and so on. A computerized search of PubMed, Cochrane clinical trial database, and Current Contents (from inception until June 16, 2014) was performed to identify potentially relevant articles. Increased sCysC concentration. The measured glomerular filtration rate measured by nuclear medicine techniques such as 99Tc-diethylene triamine pentacaetic acid (99Tc-DTPA) or 51Cr-ethylenediamine tetra-acetic acid (51Cr-EDTA), or calculated by Cockcroft-Gault (CG) or Modification of Diet in Renal Disease (MDRD) formula or 24 hours creatinine clearance rate. In total 19 studies were included in this study. Across all settings, the diagnostic odds ratio (DOR) of sCysC in predicting CKD was 40 (95% CI, 26 - 61) when sensitivity and specificity was 0.85 (95% CI, 0.81 - 0.89) and 0.87 (95% CI, 0.84 - 0.90), respectively. The area under the curve for the receiver-operating characteristic (AUROC) of sCysC to predict CKD was 0.92 (95% CI, 0.90 - 0.94). For the diagnostic value of sCysC in diabetics with CKD, the DOR was 51 (95% CI, 22 - 122), with sensitivity and specificity of 0.89 and 0.87, respectively. Subgroup analysis showed that sCysC was of better diagnostic value in the West than in Asia, and the diagnostic value of sCysC assayed by particle-enhanced nephelometric immunoassay (PENIA) was higher than sCysC assayed by particle-enhanced turbidimetric immunoassay (PETIA). SCysC appears to be a good biomarker in the definition of CKD. However, its performance is different in subgroups restricted by clinical settings, race, and sCysC assay.

Serum and urinary cystatin C in cats with feline immunodeficiency virus infection and cats with hyperthyroidism.

The objective of this study was to investigate serum cystatin C (sCysC) and urinary cystatin C (uCysC) in cats with hyperthyroidism and cats with feline immunodeficiency virus (FIV). Thirty cats with FIV, 26 hyperthyroid cats and 28 healthy cats were included. sCysC and uCysC:creatinine (uCysC/uCr) ratio were measured with a human particle-enhanced nephelometric immunoassay, previously validated for feline CysC measurement. Routine renal variables (serum creatinine [sCr], urine specific gravity, urinary protein:creatinine ratio [UPC]) were also measured in the three groups. Cats with hyperthyroidism had significantly higher sCysC and higher uCysC/uCr ratio, lower sCr and a higher UPC than healthy cats. Cats with FIV infection did not show a significantly higher sCysC concentration but had a significantly higher sCr and UPC than healthy cats. uCysC could be detected in only four of them. This study demonstrated that sCysC is increased in cats with hyperthyroidism, in contrast with sCr, but not in cats with FIV. Many hyperthyroid cats, but only four cats with FIV, had an elevated uCysC/uCr ratio. Further studies may reveal if uCysC might be a valuable marker for tubular dysfunction in cats.

Biological validation of feline serum cystatin C: The effect of breed, age and sex and establishment of a reference interval

Chronic kidney disease (CKD) is common in cats, but the routine renal markers, serum creatinine (sCr) and urea, are not sensitive or specific enough to detect early CKD. Serum cystatin C (sCysC) has advantages over sCr, both in humans and dogs, and sCysC concentration is significantly higher in cats with CKD than in healthy cats. The objective of this study was to determine the effect of age, sex and breed on feline sCysC and to establish a reference interval for feline sCysC. In total, 130 healthy cats aged 1–16 years were included. sCysC was determined using a validated particle-enhanced nephelometric immunoassay. sCr, urea, urine specific gravity, urinary protein:creatinine ratio (UPC) and systolic blood pressure (SBP) were also measured.No significant differences in sCysC concentration were observed among young, middle-aged and geriatric cats, female intact, female neutered cats, male intact and male neutered cats, or among purebred and domestic short-or longhaired cats. The 95% reference interval for feline sCysC was determined to be 0.58–1.95 mg/L. sCr was significantly higher in geriatric cats than young cats. Serum urea in geriatric cats was significantly higher than in middle-aged and young cats (P = 0.004 and P < 0.001, respectively). SBP in geriatric cats was significantly higher than in both middle-aged and young cats (P = 0.004 and P = 0.040, respectively). Male neutered and female neutered cats had significantly higher serum urea concentrations than female intact cats (P = 0.003 and P = 0.006, respectively). Male intact cats had a significantly higher UPC than female intact and female neutered cats (P = 0.02 for each comparison). There were no significant differences among sex groups for USG. It is of concern that sCysC in the majority of cats with CKD in previous studies falls within the reference interval calculated in this study. Further studies are warranted to evaluate the diagnostic value of sCysC as a renal marker in cats.

Relationship of serum uric acid, serum creatinine and serum cystatin C with maternal and fetal outcomes in rural Indian pregnant women

BackgroundHypertensive disorders are the most common in pregnancy. Several studies showed a positive correlation between elevated maternal serum uric acid (UA), serum creatinine and adverse maternal and fetal outcomes, but only a few studies are available on serum cystatin C and maternal and fetal outcomes. The present study was undertaken to study the association of serum UA, creatinine and cystatin C with maternal and fetal outcomes.MethodsOut of 116 pregnant women 69 women had no hypertension and 47 had hypertension with or without proteinuria. Serum UA, creatinine and cystatin C was measured by modified Uricase method, modified kinetic Jaffe’s reaction and particle-enhanced immunonephelometric assay respectively. Multivariate logistic regression was performed to determine the independent effects of serum UA, creatinine and cystatin C on maternal and fetal outcomes using stata 13.1.ResultsThe adjusted odds ratio (OR) was 3.73 (95% CI: 1.18-11.75; P=0.024) for UA; 15.79 (95% CI: 3.04-81.94; P=0.001) for creatinine and 2.03 (95% CI: 0.70-5.87; P=0.192) for cystatin C in hypertensive disorders of pregnancy. All the three renal parameters were not significantly associated with birth weight, gestational age of delivery and mode of delivery after adjusting for the confounding factors.ConclusionsSerum creatinine and uric acid are independent risk factors for hypertensive disorders of pregnancy. High serum uric acid is associated with low birth weight and delivery by caesarian section whereas high serum creatinine with preterm delivery only before adjustment for confounding factors and not after adjustment. Serum cystatin C was not significantly associated with the maternal and fetal outcomes.

Evaluation of Early Glomerulopathy and Tubulopathy in Patients with Transfusion Dependent Thalassemia

Background: We have less information about renal injury in patients with transfusion dependent ß thalassemia (TDT).Cystatin C (Cys-C) is a marker to predict glomerular dysfunction with higher sensitivity and specificity than serum creatinine. Asymptomatic renal tubular dysfunction demonstrated in patients with Beta-thalassaemia who receive deferasirox although age and dose-dependent toxicity profile could not be fully understood.Aim: The aim of this study was to evaluate renal tubular and glomeruler functions and the etiology of early glomerulopathy and tubulopathy in patients with TDT.Patients and methods: Fifty TDT patients (2-45years, 28 F and 22 M, mean age:18.4±11.8 years), were evaluated for glomerulopatrhy and tubulopathy by using standard hematology and biochemistry, urine pH, blood pH, urine ca/crea ratio and meanFractional Na excretion (FENe) and compared to reference values. Thirthy healthy volunteer (18 F and 12 M, mean age: 21,6 ± 11, age ranged 3-44 years) were evaluated as control group. Thirthy-eight (75.5%) patients were receiving Deferasirox (DFX), 8 (16.3%) were Deferipron (DFP), 4 small children (8%) were none. Serum Cys-C and urine β-2MG were measured using a latex particle-enhanced nephelometric immunoassay. Patients with known renal disease were excluded.Results: The main results of the study for tubulopathy were: a. Mean Na, K, Ca, P, urine and blood pH were within normal ranged. b. Eight older patients (16%) had high FENe. 7/8 of these patients received long term DFX therapy (mean 6,1±2.3 years) with 20-30mg/kg/day dose, c. Mean Ca/crea ratio (0.22 ± 0.11)and mean urine pH were found higher than normal level e. Eighteen percent (n=9) of patients had high urine β-2 MG (p<0.01). For glomerulopaty; a. No patient had increased serum Crea according to age. b. Mean urea, creatinin and albumin level determined within normal ranged b. eGFR was determinated above normal reference values according to age. c. 25/50 patients (50%) had higher serum Cys-C values compared with controls (p<0.001).When we evaluated the etiology of early glomerulopathy and tubulopathy,we found that; a. There were no statistically significant differences between pretransfusion Hb, liver iron overload, cardiac iron overload, and sistatin C, β-2 MG, FENa, Ca/Kreatinin, and GFR. b. Cys- C, urea, creatinine increases with the age, β-2 MG and FENe does not change with age. c. There was no statistically significant difference between Cys-C and β-2 MG levels in patients used DFP and control groups’ but statistically difference was found between DFX and control group(Table 1). d. B-2 MG level significantly increased who received high dose DFX (20-30 and 30-40 mg/kg/day compared to 15-20 mg/kg/day dose and controls (Table 2). e. β-2MG level were higher in patients with ferritin level <500 ng/ml and >1000 ng/ mL than in control group (p<0.000). Low and high ferritin level were risk for tubulopathy in TDT patients (Table 3). f. There was positive correlation between Cys-C and age. g. Cys- C is significantly higher than the control group in all patients and not related to DFX dose. h. Cys C were detected significantly higher than the control group in all patients not related to ferrtin levels.Conclusion: Early identification of subclinical renal glomerular and tubular ýnjury in TDT patients had great importance and it may allow specific measures to delay the progression of renal damage.We suggest to evaluate intermittently early marker of glomerulopathy and tubulopathy in addition to routine renal function tests to prevent major renal injury in TDT patients.Table-1Beta 2 MG, Cys-C levels in different chelationsChelationAll pts(n=50)Deferipron(n=8)Deferasirox(n=38)Control (n=30)Mean±SDMean±SDMean±SDMean±SDΒ-2MG mg/L0,35±0,430,20±0,000,39±0,490,20±0,01Cys-C mg/L0,75±0,120,73±0,090,75±0,130,66±0,09Table-2Effect of DFX doses on Beta-2 microglobulin and Cys- C levelsDose15-20(n=11)20-30(n=13)30-40(n=14)Control(n=30)PMean±SDMean±SDMean±SDMean±SDΒ-2MG mg/L0,20±0,000,28±0,200,56±0,700,20±0,010,011Cys-C mg/L0,76±0,090,73±0,160,77±0,090,66±0,090,013Table-3:Beta-2 microglobulin, Cys-C levels according to Ferritin.Ferritin ( ng/mL)<500 (n=7)500-1000(n=10)>1000(n=33)Control (n=30)PMean±SDMean±SDMean±SDMean±SDΒ-2 MG mg/L0,49±0,600,28±0,240,34±0,450,20±0,010,000Cys-C mg/L0,79±0,160,80±0,100,73±0,110,66±0,090,001 DisclosuresNo relevant conflicts of interest to declare.

Sensitivity and Specificity of Cystatin C in Detecting Early Renal Impairment in Hypertensive Pregnancies

Purpose: To determine the cutoff point of cystatin C for the detection of renal impairment in hypertensive pregnancies.Methods: A cross-sectional study was conducted in an antenatal clinic and ward at Hospital Universiti Sains Malaysia, Kelantan, Malaysia from January 2009 until January 2010. Sixty four pregnant patients beginning at 2nd trimester, aged of 16 to 55 years and hypertensive, including gestational hypertension, chronic hypertension with superimposed preeclampsia, preeclampsia and unclassified hypertension, were included in the study. Consenting patients were required to provide 5 ml of blood and 24-h urine. Serum and reagent, N Latex cystatin C, were equilibrated at room temperature and measured by particle-enhanced nephelometric immunoassay (PENIA) using a BN II Dade Behring Nephelometer SystemResults: The mean age of the patients was 37.06 ±4.32 (range: 24 to 46 years). A majority (64.1 %) of the patients were in the second trimester of pregnancy and delivered in the gestational period of 38 - 40 weeks (54.7 %). The number of patients in chronic kidney disease (CKD) stages I, II, III, IV and V were 25 (39.1 %), 18 (28.1 %), 18 (28.1 %), 2 (3.1 %) and 1 (1.6 %), respectively. The mean systolic blood pressure was 149.59 ± 18.79 mm Hg, and diastolic blood pressure 91.53 ± 10.33 mm Hg. The cutoff point in detecting renal impairment using cystatin C was &gt; 0.74 with 84.6 % sensitivity and 86.7 % specificity for second trimester and &gt; 0.81 with sensitivity of 76.9 % and specificity of 60.0 % in detecting renal impairment for third trimester.Conclusion: The cutoff point in detecting renal impairment for second trimester is better than for third trimester since it maximizes the value of sensitivity and specificity.Keywords: Cystatin C, Sensitivity, Specificity, Renal impairment, Hypertension; Pregnancy

C-reactive protein levels and risk of disabling dementia with and without stroke in Japanese: The Circulatory Risk in Communities Study (CIRCS)

ObjectiveStudies have shown that elevated high-sensitivity C-reactive protein (hs-CRP) predicts stroke, which is a risk factor for dementia. It remains, however, unclear whether hs-CRP increases risk of dementia. MethodsA prospective nested case–control study of Japanese 40–69 years of age was conducted using frozen serum samples collected from approximately 7531men and women who participated in cardiovascular risk surveys from 1984 to 1994 in one community and 1989–1995 in another community under the Circulatory Risk in Communities Study (CIRCS). Two control subjects per case were matched by sex, age, community, and year of serum storage. The hs-CRP was measured using a latex particle-enhanced immunonephelometric assay. ResultsBetween 1999 and 2013, we identified 275 disabling dementia cases (96 cases with history of stroke and 179 without it). There was a positive association between hs-CRP levels and risk of dementia with history of stroke. No significant association was observed between hs-CRP levels and risk of dementia without history of stroke. After adjustment for hypertension, diabetes and other confounding variables, the positive association remained statistically significant. The multivariable odds ratios associated with 1-SD increment of log hs-CRP were 1.02 (0.87–1.20) for total dementia, 1.35 (1.02–1.79) for dementia with history of stroke, and 0.89 (0.72–1.10) for dementia without history of stroke. ConclusionElevated hs-CRP levels were associated with increased risk of disabling dementia in individuals with history of stroke but not in those without it.