CysC Concentration Research Articles

Cystatin C: factors affecting diagnostic and prognostic value in acute kidney injury

The level of serum and urinary cystatin C (CysC) can be modulated by some factors (weight, gender, age, ethnicity, smoking), diseases (sepsis, cardiovascular disease, diabetes mellitus, metabolic syndrome, obesity, hypo- and hyperthyroidism) as well as administration of glucocorticosteroids, but all of them do not affect its prognostic and diagnostic value in acute kidney injury (AKI). The CysC concentration can predict adverse outcomes, such as in-hospital and out-hospital mortality, chronicity of renal dysfunction, the demand and duration of renal replacement therapy (RRT). The sCysC is an independent predictor of RRT completion in critically ill AKI patients.

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.

An electrochemical immunosensor for sensitive and rapid detection of cystatin C based on Fe3O4/AuNPs-MWCNTs@PDA nanocomposite

Serum Cystatin C (CysC) is an impressive marker for early diagnosis of renal dysfunction. In this work, we established a novel electrochemical immunosensor based on Fe3O4/AuNPs-MWCNTs@PDA nanocomposite for the detection of CysC. The Fe3O4/AuNPs-MWCNTs@PDA nanozyme complex by polydopamine encapsulation can not only carry massive detection antibodies, but also bind the electroactive substance toluidine blue (TB) through electrostatic adsorption. By immobilizing AuNPs onto the electrode to bind the capture antibody (Ab1), we constructed a sandwich electrochemical immunosensor with low cost, high sensitivity, and repeatability. The detection range is 3.9–125.0 ng/mL with a significant linear relationship between the current peak difference (ip) and logarithm of the CysC concentration. Moreover, the detection limit of the immunosensor is 0.157 ng/mL. We have successfully utilized this novel immunosensor to detect CysC in human serum samples, and these results have implications for its potential use in clinical application.

Renal impairment may indicate postoperative low vision in young patients with proliferative diabetic retinopathy undergoing vitrectomy.

To innovatively evaluate the impact of renal impairment in young work age patients with proliferative diabetic retinopathy (PDR) on their visuality after vitrectomy. To find out whether it is possible to better predict the improvement of visual acuity after vitrectomy in working-age people without adding additional preoperative testing. In view of the fact that diabetic retinopathy and diabetic nephropathy are common diabetic complications of microvascular damage, it is considered whether preoperative renal function can be used as this evaluation index. This paper studies the design under this theme. This retrospective study included 306 patients (306 eyes) diagnosed with PDR and undergoing vitrectomy in our hospital from January 2016 to June 2023. Relevant baseline data were collected, including age, history of kidney disease and clinical laboratory test results. According to the International Standard Logarithmic Visual Acuity Checklist, the best corrected visual acuity was tested on the first day of admission and one month after surgery, and the difference between the two was subtracted. A difference >0 was defined as "vision improved". Patients were classified as vision-improved group (n=245) and non-improved group (n=61). The differences in baseline serum urea nitrogen, creatinine, uric acid, Cystatin C, estimated glomerular filtration rate (eGFR) and urine protein distribution between the two groups were statistically analyzed, binary regression analysis was performed for meaningful parameters, and random forest model ranked the characteristics in importance. 1.A higher level of serum cystatin C [1.02(0.80,1.48) mg/L vs 0.86(0.67,1.12) mg/L, P<0.001] and a lower eGFR [82.3(50.33, 115.11) ml/(min/1.73m²) vs 107.69(73.9, 126.01) ml/(min/1.73m²), P=0.002] appeared in the non-(vision-)improved group compared with the vision-improved group. 2. The occurrence of preoperation proteinuria history of nephropathy take a larger proportion in non-improved group. 3. Univariate regression analysis showed history of nephrology (OR=1.887, P=0.028), preoperative serum urea nitrogen (OR=0.939, P=0.043), cystatin C (Cys-C) concentration (OR=0.75, P=0.024), eGFR (OR=1.011, P=0.003) and proteinuria (OR=3.128, P<0.001) were influencing factors to postoperative visual acuity loss in young working age PDR patients. Excluding other confounding factors, preoperative proteinuria is an independent risk factor for postoperative vision improvement in working-age PDR populations (OR=2.722, P=0.009). 4. The accuracy of the prediction random forst model is 0.81. The model appears to be superior in terms of positive prediction. In young work aged PDR patients undergoing vitrectomy, preoperative urine protein can be an independent indicator of postoperative visual loss. Aggressive correction of kidney injury before surgery may help improve postoperative vision in patients with PDR.

Ultrasensitive Silicon Nanowire Biosensor with Modulated Threshold Voltages and Ultra-Small Diameter for Early Kidney Failure Biomarker Cystatin C.

Acute kidney injury (AKI) is a frequently occurring severe disease with high mortality. Cystatin C (Cys-C), as a biomarker of early kidney failure, can be used to detect and prevent acute renal injury. In this paper, a biosensor based on a silicon nanowire field-effect transistor (SiNW FET) was studied for the quantitative detection of Cys-C. Based on the spacer image transfer (SIT) processes and channel doping optimization for higher sensitivity, a wafer-scale, highly controllable SiNW FET was designed and fabricated with a 13.5 nm SiNW. In order to improve the specificity, Cys-C antibodies were modified on the oxide layer of the SiNW surface by oxygen plasma treatment and silanization. Furthermore, a polydimethylsiloxane (PDMS) microchannel was involved in improving the effectiveness and stability of detection. The experimental results show that the SiNW FET sensors realize the lower limit of detection (LOD) of 0.25 ag/mL and have a good linear correlation in the range of Cys-C concentration from 1 ag/mL to 10 pg/mL, exhibiting its great potential in the future real-time application.

Prognostic value of serum cystatin C concentration in dogs with myxomatous mitral valve disease.

Impaired renal function is 1 of the poor prognostic factors in dogs with myxomatous mitral valve disease (MMVD). However, the value of cystatin C (Cys-C), a marker of renal function, as a prognostic marker for MMVD in dogs has not yet been explored. This study aims to investigate the prognostic value of Cys-C in dogs with MMVD. Fifty client-owned small-breed dogs with MMVD were included in this study. This is a retrospective, cross-sectional study. The prognostic value of serum Cys-C concentration was assessed using univariable and multivariable Cox hazard regression analyses. Kaplan-Meier survival curves for MMVD-specific survival in dogs stratified into high and low Cys-C groups were generated and analyzed using the log-rank test. Serum Cys-C concentrations were significantly associated with MMVD-related death (P < .01) in both univariable (hazard ratio [HR], 5.086; 95% confidence interval [CI], 1.950-13.270) and multivariable Cox hazard regression analysis (HR, 4.657; 95% CI, 1.767-12.270). The high Cys-C group (n=14) had a significantly shorter MMVD-specific survival time than the low Cys-C group (n=36; P < .01). In dogs with normal blood creatinine concentrations, the high Cys-C group (n=10) had a significantly shorter MMVD-specific survival time than the low Cys-C group (n=36; P < .01). High serum Cys-C concentrations were associated with a worse prognosis of MMVD. Furthermore, serum Cys-C could be a predictor of MMVD prognosis even in dogs with normal blood creatinineconcentration.

Performance of Glomerular Filtration Rate Estimating Equations in Cancer Patients Evaluated for Chimeric Antigen Receptor T-Cell Therapy

Background: An accurate assessment of kidney function is necessary to evaluate candidates seeking chimeric antigen receptor T-cell (CAR-T) therapy.(Jain, et al, 2019, Yakoub-Agha, et al, 2019) Additionally, kidney function quantification is essential to selecting the appropriate dose for fludarabine-based lymphodepleting chemotherapy prior to CAR-T cell infusion in order to optimize outcomes.(Hirayama, et al, 2019) Treatment decisions are currently guided by a glomerular filtration rate (GFR) that is estimated using serum creatinine. However, estimated GFR (eGFR) utilizing cystatin C-based equations has been suggested to overcome the known limitations of creatinine-based eGFR in patients with cancer.(Kellum, et al, 2012, Hersh, et al, 1986) The accuracy and precision of these eGFR assessment strategies in potential CAR-T therapy recipients has not been explored, and the preferred method for quantifying GFR in this patient population remains unknown. Methods: This IRB-approved, single-center, observational study evaluated the performance of contemporary eGFR equations in any adult patient being evaluated for CAR-T therapy with a measured GFR (mGFR) by iothalamate clearance. Excluded individuals were those without a serum creatinine (SCr) and serum cystatin C (cysC) concentration performed within 14 days of the mGFR. Baseline characteristics and pertinent laboratory values were abstracted from the medical record. eGFR was calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations, including the most recent iterations that were developed without the race parameter.(Levey, et al, 2009, Inker, et al, 2012, Inker, et al, 2021) Bias, accuracy (percentage of estimates within 10% and 30% of mGFR), and precision (SD of the difference between the eGFR and the mGFR) were assessed. The prediction of mGFR by each eGFR equation was assessed with scatterplots. Results: The 135 patients that were included had a median age of 63 (IQR: 56, 69) years and 77 (57%) were male. Two patients (1%) were African American and 123 (91%) were White. Relapsed lymphoma was the most common cancer diagnosis (n=94, 70%), followed by multiple myeloma (n=38, 28%) and acute lymphoblastic leukemia (n=3, 2%). Median mGFR was 73 ml/min/1.73m2 (IQR: 57, 92) with mGFR >60 ml/ml/1.73m2 in 95 (70%) patients. Table 1 summarizes baseline characteristics, laboratory values, and eGFR. The average absolute bias ranged from -10.1 to -0.1 ml/min/1.73m2 indicating that all equations underestimated mGFR to some degree. CKD-EPI 2021 SCr and CKD-EPI 2021 cysC+SCr had the least bias at -0.1 ml/min/1.73m2 and -4.0 ml/min/1.73m2, respectively. CKD-EPI 2021 cysC+SCr had the greatest accuracy within 10% of GFR and within 30% of mGFR. Additional bias, precision, and accuracy details of each estimating equation are summarized in table 1. The CKD-EPI 2012 cysC+SCr and the CKD-EPI 2021 cysC+SCr equations most closely correlated with mGFR in all patients (r=0.82 and 0.81, respectively). Correlation of measured glomerular filtration rate (GFR) with each of the GFR estimating equations is depicted in figure 1. Conclusion: CKD-EPI 2021 SCr and CKD-EPI 2021 cysC+SCr were the equations with the least bias. Contemporary eGFR equations had the greatest correlation with mGFR and seem acceptable when evaluating CAR-T therapy candidacy. Accuracy when dosing medications with a narrow therapeutic index, such as chemotherapy, is paramount, and all eGFR methods had limited accuracy within 10% of mGFR. Though the CKD-EPI 2021 cysC+SCr demonstrated the highest degree of accuracy within 10% of mGFR and within 30% of mGFR, iothalamate clearance should be the preferred method for kidney function assessment in patients seeking and receiving CAR-T therapy. Future research should investigate the impact of fludarabine dose selection on clinical outcomes of CAR-T recipients. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

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.

Cystatin C Concentration During the First Three Postnatal Days in Healthy Term Newborns.

Cystatin C (Cys-C) concentration has not been examined sufficiently among healthy newborn population, particularly in terms of reference values. This study aimed to establish gender-, postnatal age- and birth weight-specific Cys-C concentration for healthy term newborns. Its objective was also to examine if there were any differences between our measured concentration and the reference interval established by the CALIPER study. Serum samples from a total of 90 healthy term newborns were used to determine Cys-C concentration. Cys-C was measured within first three days of birth using particle-enhanced turbidimetric immunoassay (PETIA) on the Architect plus ci8200 analyzer. Median concentration of the Cys-C was 2.05 mg/L. There were no statistically significant differences in Cys-C concentration regarding gender (p=0.779), birth weight (p=0.505), postnatal age (p=0.512) or Apgar score (p=0.799). The value of the 2.5th and 97.5th percentile for Cys-C concentrations for girls was 0.93-3.15 mg/L and for boys it was 1.5-3.36 mg/L. Cys-C concentration in healthy term newborns does not depend on gender, birth weight, postnatal age, or Apgar score. Our measured concentration range of CyS-C in healthy newborns turned out to be slightly wider than the interval determined in the CALIPER study.

Effect of age, sex, and breed on serum cystatin C and creatinine concentrations in dogs.

This study investigated the effects of age, sex and breed on serum cystatin C (Cys-C) and creatinine in small breed dogs. This retrospective study included 250 dogs weighing less than 15kg without azotemia. Serum Cys-C and creatinine concentrations were analyzed, along with their correlation with age, and the difference between sexes or dog breeds. Serum Cys-C concentration correlated with age (P < 0.001), and did not differ between sexes or dog breeds. By contrast, serum creatinine concentration did not correlate with age. Serum creatinine concentration was higher in males than females (P < 0.05), and was lower in Miniature Dachshunds and Chihuahuas, and was higher in Shiba Inus compared to the general study population (P < 0.001). Serum Cys-C concentration correlates with age, and might be more sensitive to aging-associated subclinical renal dysfunction than serum creatinine concentration in dogs. Unlike serum creatinine concentration, serum Cys-C concentration is not affected by sex or dog breed.

Indoor solid fuel use and renal function among middle-aged and older adults: A national study in rural China

Solid fuel use is the main source of indoor air pollution, especially in rural areas of developing countries. Nevertheless, the evidence linking indoor solid fuel use and renal function is very limited. Therefore, we investigated the association between indoor solid fuel use and renal function among middle-aged and older adults in rural China. Cystatin C (CysC) concentration of each participant was used to calculate the estimated glomerular filtration rate (eGFR). We used the baseline data to investigate the associations between solid fuel use for cooking and heating and eGFR through a linear-mixed effects model. Then, we applied the generalized linear-mixed effects model with binary distribution to examine the relationship between renal function decline and cooking fuel switching from 2011 to 2015. A total of 4959 participants were included at baseline, and 3536 participants were included in the follow-up analysis. Compared to participants who used clean fuel for both cooking and heating, the eGFR was significantly lower among participants who cooked with solid fuel and heated with clean fuel (β: -2.81; 95% CI: -5.53, -0.09). In the follow-up analysis, the risks of renal function decline for participants using solid fuel for cooking were significantly higher in males (OR: 2.74; 95% CI: 1.68, 4.49), smokers (OR: 5.70; 95% CI: 2.82, 11.55), and drinkers (OR: 7.11; 95% CI: 3.15, 16.02) compared to females, non-smokers, and non-drinkers. Moreover, 45–65 years aged participants (OR: 0.54; 95% CI: 0.33, 0.89) and non-drinkers (OR: 0.61; 95% CI: 0.41, 0.92) who switched from solid to clean cooking fuel had a lower risk of renal function decline. In conclusion, our findings show that household solid fuel use is likely to be an important risk factor for renal function decline in rural China. And switching to cleaner fuel may provide significant public health benefits.

Association Cystatin C and Risk of Stroke in Elderly Patients With Obstructive Sleep Apnea: A Prospective Cohort Study.

Background: Few prospective cohort studies have assessed the relationship between Cystatin C (Cys-C) and risk of stroke in elderly patients with obstructive sleep apnea (OSA). The study sought to examine the association between baseline serum Cys-C and long-term risk of stroke among elderly OSA patients.Methods: A total of 932 patients with OSA, no history of stroke, ≥60 years of age, and complete serum Cys-C records were included in this study. All patients had completed polysomnography (PSG). OSA was defined as an apnea-hypopnea index (AHI) of ≥5 events per hour. Participants were categorized into four groups according to baseline serum Cys-C concentration, split into quartiles. Multivariate Cox regression were used to evaluate the association between Cys-C and the incidence of new-onset stroke.Results: Stroke occurred in 61 patients during the median 42-month follow-up period. The cumulative incidence rate of stroke was 6.5%, which included 54 patients with ischemic stroke and 7 patients with hemorrhagic stroke. The cumulative incidence of stroke was higher among patients with baseline serum Cys-C concentration of ≥1.15 mg/L when compared with other groups (PLog–rank < 0.001). After adjusting for potential confounding factors in the Cox regression model, patients with a serum Cys-C concentration of ≥1.15 mg/L had a 2.16-fold higher risk of developing stroke compared with patients with serum Cys-C ≤ 0.81 mg/L (HR, 2.16, 95%CI, 1.09–6.60; P = 0.017). Additionally, there was a higher risk in those of age ≥70 years (HR, 3.23, 95%CI, 1.05–9.24; P = 0.010). The receiver-operating characteristic curves showed that the capability of Cys-C to identify elderly patients with OSA who had a long-time risk of stroke was moderate (AUC = 0.731, 95% CI: 0.683–0.779, P = 0.001).Conclusion: Increased Cys-C concentration was identified as a risk factor in the incidence of stroke in elderly patients with OSA, independent of gender, BMI, hypertension and other risk factors. Additionally, it conferred a higher risk in patients of age ≥70 years.

Cystatin C kidney functional reserve: a simple method to predict outcome in chronic kidney disease.

Kidney functional reserve (KFR), the only clinical kidney stress test, is not routinely measured because the complexity of measurement has limited clinical application. We investigated the utility of plasma cystatin C (CysC) after oral protein loading (PL) to determine KFR in Stages 3 and 4 chronic kidney disease (CKD). Following a 24-h low-protein diet, KFR was measured after oral protein by hourly plasma CysC and compared with simultaneous creatinine clearance (CrCl) and radionuclide 99technetium diethylenetriaminepentaacetatic acid (Tc-99m-DTPA) measured glomerular filtration rate (mGFR) measurement in an observational, single-centre cohort study of adults with CKD Stages 3 and 4. Subjects were followed for 3 years for fast (F) or slow (S) CKD progression, dialysis requirement or death or a combination of major adverse kidney events (MAKEs). CysC, CrCl and Tc-99m-DTPA mGFR measurements of KFR in 19 CKD Stage 3 and 21 CKD Stage 4 patients yielded good agreement. KFR was not correlated with baseline kidney function. Eight CKD Stage 3 (42%) and 11 CKD Stage 4 (52%) subjects reached their lowest serum CysC concentration 4 h after PL. CysC KFR and baseline serum creatinine (sCr) predicted death or dialysis or MAKE-F with a respective area under the curve (AUC) of 0.73 [95% confidence interval (CI) 0.48-0.89] and 0.71 (95% CI 0.51-0.84). Including CysC KFR, age, baseline sCr and nadir CysC predicted a decrease in sCr-estimated GFR >1.2 mL/min/year (MAKE-S) with an AUC of 0.89. Serial CysC avoided timed urine collection and radionuclide exposure and yielded equivalent estimates of KFR. Serial CysC may facilitate monitoring of KFR in clinical practice.

Predictive Value of Cystatin C for Stroke Recurrence in Patients With Acute Ischemic Stroke.

This study explored the value of cystatin C (CysC) in predicting stroke recurrence in patients with acute ischemic stroke. This was a post hoc analysis of the China Antihypertensive Trial in Acute Ischemic Stroke (CATIS) on 3,474 acute ischemic stroke patients with documented serum CysC and high-sensitivity C-reactive protein (hsCRP) concentrations. Study outcomes included stroke recurrence and combined vascular events within 2 years after stroke. In stroke patients with higher (i.e., ≥4.8ng/mL), but not lower, hsCRP concentrations, a higher CysC concentration (i.e., ≥0.78 mg/L) was associated with a 2.48-fold increase in the risk of recurrent stroke (95% confidence interval [CI] 1.37-4.51; P=0.003) and a 2.04-fold increase in the risk of vascular events (95% CI 1.27-3.28; P=0.003). Serum hsCRP concentrations significantly modified the association of serum CysC with recurrent stroke (Pinteraction=0.001) and vascular events (Pinteraction=0.007). Moreover, CysC may improve reclassification of stroke recurrence (net reclassification improvement [NRI] 42.9%, P=0.001; integrated discrimination improvement [IDI] 1.2%, P=0.001) and vascular events (NRI 35.8%, P=0.001; IDI 1.1%, P=0.004). In ischemic stroke patients with high hsCRP concentrations, higher CysC concentrations increased the risk of stroke recurrence and vascular events. This indicates that the predictive value of CysC on stroke recurrence may depend on the inflammation status of patients.

The effect of rheumatoid factor on three commercial immunoassays for serum cystatin C

Cystatin C (CysC) can be used to diagnose early changes in renal insufficiency. However, there are little researches to study whether there is an interference between the level of CysC and RF. Thus, we conducted this study to investigate it. We randomly selected 30 patients with high RF (RF concentration: 552.05 ± 476.23 IU/mL) and 33 healthy subjects with RF concentration <11.1 IU/mL and CysC were measured with different reagents and instruments; Interference experiment was also be included. The results showed that the measured CysC concentration increases with increasing RF concentration in a dose-dependent manner and CysC levels are falsely increased by RF interference depends on the reagents used (CysC reagent: Whitman, Nanjing, China). Reagent manufacturers should fully consider RF interference when developing CysC reagents, and evaluate them before they are sold. When selecting CysC reagents, we should evaluate RF interference to the measurement to avoid misleading results.

Clinical effect and mechanism of total glucosides of paeony in the adjuvant therapy for children with Henoch-Schönlein purpura nephritis: a prospective randomized controlled study

OBJECTIVE To study the clinical effect and mechanism of total glucosides of paeony (TGP) in the adjuvant therapy for children with Henoch-Schonlein purpura nephritis (HSPN). METHODS Sixty-four HSPN children with moderate proteinuria were divided into a TGP treatment group (n=34) and a routine treatment group (n=30) using a random number table. Thirty healthy children who underwent physical examination were enrolled as the healthy control group. The children in the routine treatment group were given conventional treatment alone, and those in the observation group were given TGP in addition to the conventional treatment. The two groups were compared in the clinical outcome after 4 weeks of treatment. The proportion of follicular helper T (Tfh) cells in peripheral blood and the plasma levels of interleukin-21 (IL-21) and interleukin-4 (IL-4) were measured in the healthy control group and the two HSPN groups. The changes in serum cystatin C (CysC) level and urinary alpha 1-microglobulin (A1M) concentration were compared before and after treatment in the two HSPN groups. RESULTS Compared with the healthy children before treatment, the children with HSPN had higher proportion of Tfh cells and expression levels of IL-21 and IL-4 (P < 0.01). The TGP treatment group had a higher overall response rate to treatment than the routine treatment group (94% vs 67%, P < 0.05). After treatment, both groups had reductions in the proportion of Tfh cells in peripheral blood, the expression levels of IL-21, IL-4, serum CysC, and urinary A1M concentration. The TGP treatment group had greater reductions in these indices than the routine treatment group (P < 0.01). CONCLUSIONS TGP has a marked clinical effect in the treatment of HSPN and can reduce the inflammatory response of the kidney and exert a protective effect on the kidney by inhibiting the proliferation of Tfh cells and downregulating the expression of IL-21 and IL-4 in plasma.

Dissecting the Genetic Architecture of Cystatin C in Diversity Outbred Mice.

Plasma concentration of Cystatin C (CysC) level is a biomarker of glomerular filtration rate in the kidney. We use a Systems Genetics approach to investigate the genetic determinants of plasma CysC concentration. To do so we perform Quantitative Trait Loci (QTL) and expression QTL (eQTL) analysis of 120 Diversity Outbred (DO) female mice, 56 weeks of age. We performed network analysis of kidney gene expression to determine if the gene modules with common functions are associated with kidney biomarkers of chronic kidney diseases. Our data demonstrates that plasma concentrations and kidney mRNA levels of CysC are associated with genetic variation and are transcriptionally coregulated by immune genes. Specifically, Type-I interferon signaling genes are coexpressed with Cst3 mRNA levels and associated with CysC concentrations in plasma. Our findings demonstrate the complex control of CysC by genetic polymorphisms and inflammatory pathways.

Cystatin C Is an Important Biomarker for Cardiovascular Autonomic Dysfunction in Chinese Type 2 Diabetic Patients.

Background Cardiovascular autonomic dysfunction is closely related to increased mortality in patients with diabetes. Previous studies have proved that cystatin C (CysC) is an important predictor of both peripheral neuropathy and cardiovascular events. However, whether CysC is also associated with cardiovascular autonomic dysfunction remains unclear. Therefore, the aim of this study was to investigate the relationship between CysC and cardiovascular autonomic dysfunction in type 2 diabetic patients without renal dysfunction. Methods A total of 161 type 2 diabetic patients with normal serum creatinine (less than 133 μmol/l) and estimated glomerular filtration rate (eGFR) higher than 60 ml/min per 1.73 m2 were recruited in our study. Cardiovascular autonomic dysfunction was determined by heart rate variability (HRV) measured by a 24-hour Holter monitor. Serum CysC was tested by particle-enhanced turbidimetric immunoassay, and subjects were divided into three groups based on the tertiles of CysC. Pearson correlation analysis was used to evaluate the association between different indexes, and the association of CysC with HRV indexes was assessed by multivariate linear regression analysis. Results The HRV parameters were lower in the group with the highest CysC concentration than in the groups with lower levels of CysC (P < 0.05). Pearson correlation analysis showed a negative relationship between CysC and the HRV parameters, including SDNN (r = −0.31, P < 0.001), SDANN (r = −0.25, P = 0.002), and logLF (r = −0.18, P = 0.023). Furthermore, multivariate linear regression analysis revealed that CysC was independently correlated with SDNN (β = −24.11, P = 0.015) and SDANN (β = −19.88, P = 0.047) after adjusting for the confounding factors of gender, age, blood pressure, body mass index, eGFR, and hemoglobin A1c. Conclusions Serum CysC levels are associated with cardiovascular autonomic dysfunction; furthermore, CysC may be a reliable and convenient biomarker for detecting cardiovascular autonomic dysfunction.

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

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

Utility of cystatin C as a potential bladder tumour biomarker confirmed by surface plasmon resonance technique.

Background & objectives:The determination of cystatin C (cysC) may be helpful in diagnosis and monitoring of cancer because the pathogenesis of cancer is linked with an increased activity of cysteine peptidases (cathepsins) and a decrease of cysC concentration. This study was aimed to examine the utility of cysC as a marker of bladder cancer (BCa) to be used in the diagnosis.Methods:This study was conducted with 90 patients with BCa and 27 healthy people. Patients with other cancers, inflammation process and impaired renal function were excluded from the study. The concentrations of cysC in the plasma and urine were measured by surface plasmon resonance imaging technique.Results:The concentration of cysC in the serum taken from the patients with BCa [0.35±0.02 μg/ml (range: 0.20-0.78 μg/ml)] was significantly (P <0.001) lower than the serum cysC concentration of the healthy people [0.68±0.05 μg/ml (range: 0.52-0.89 μg/ml)]. The urinary cysC concentration of the BCa patients [0.19±0.01 μg/ml (range: 0.09-0.34 μg/ml)] was not significantly different from the urinary cysC concentration of the healthy people [0.24±0.02 μg/ml (range: 0.16-0.33 μg/ml)]. Receiver operating characteristic (ROC) curve showed that BCa patients with cysC concentration <0.54 μg/ml [sensitivity: 87%; specificity: 92%; area under the curve (AUC) of ROC: 0.927; P =0.02] could be optimally separated from healthy people. The ROC curve further showed that superficial low-grade patients with cysC concentration lower than 0.36 μg/ml (sensitivity: 0.63%; specificity: 0.58%; AUC of ROC: 0.635; P =0.08) could not be optimally separated from high-risk tumour patients.Interpretation & conclusions:BCa patients have lower serum cysC concentration than the control group. Serum cysC may be considered as a potential marker of BCa but not its aggressiveness.