Serum cystatin-C Levels Research Articles

Relationship between serum cystatin-C levels and vibrating perception threshold in patients with Type 2 diabetes mellitus

To explore the relationship between serum cystatin-C (Cys-c) levels and vibrating perception threshold (VPT) in patients with Type 2 diabetes mellitus (T2DM). According to the symptoms, signs and results of lab examination, a total of 352 patients with T2DM were divided into a diabetic peripheral neuropathy group (DPN group, n=107) and a non-diabetic peripheral neuropathy group (NDPN group, n=245). Serum Cys-c levels were measured by radioimmunoassay method. The relationship between serum Cys-c levels and VPT, estimated glomerular filtration rate (eGFR), urinary albumin-to-creatinine ratio (ACR), glucose and blood pressure and other parameters were also analyzed by correlation and multiple regression analysis. All T2DM patients were divided into a high Cys-c levels group (n=89) and a low Cys-c levels group (n=263) according to the upper quartile of Cys-c, and the incidence of DPN and VPT levels in each group were compared. Risk factors of DPN in T2DM patients were analyzed by binary logistic regression analysis and receiver operating characteristic (ROC) curve was used to identify the optimal cutoff of serum Cys-c levels for predicting DPN in patients with T2DM. Serum Cys-c levels were significantly higher in the DPN group than that in the NDPN group [(1.04±0.43) vs (0.80±0.25) mg/L, P<0.01]. Correlation analysis showed that serum Cys-c levels were positively correlated with age, body mass index (BMI), serum creatinine (SCr), blood urea nitrogen (BUN), ACR, VPT, pulse pressure (PP), white blood cell( WBC) , red cell distribution width (RDW), hemoglobin A1c (HbA1c) and fasting blood glucose (FBG) (r=0.410, 0.115, 0.613, 0.433, 0.291, 0.300, 0.156, 0.129, 0.282, 0.314, 0.236, respectively, P<0.05 or P<0.01); and negatively correlated with diastolic blood pressure (DBP), eGFR and indirect bilirubin (IBIL) (r=-0.135, -0.647, -0.114, respectively, P<0.05 or P<0.01). Serum Cys-c levels in T2DM patients were positively correlated with VPT after adjusting for gender, age, BMI, ACR and eGFR (r=0.235, P<0.01). Multiple regression analysis revealed that VPT, age, SCr, eGFR, PP, ACR and HbA1C were independent related factors affecting serum Cys-c levels in T2DM patients. Compared with those in the low Cys-c levels group, the prevalence rate and VPT value was increased in the high Cys-c levels group (all P<0.01). Binary logistic regression analysis found that age, Cys-c and HbA1C were independent risk factors for predicting DPN in T2DM patients (all P<0.01). ROC curve analysis revealed that the optimal cutoff of Cys-c to predict DPN in T2DM patients was 0.996 mg/L, the sensitivity was 43.9%, the specificity was 83.7%, and the area under curve was 0.663. Serum Cys-c levels are well correlated with VPT in patients with T2DM. When the serum Cys-c levels>0.996 mg/L, the predicts have high risk of DPN in T2DM patients, which might be related to diabetic nephropathy, oxidative stress and inflammatory reaction induced by advanced age, hyperglycemia and hypertension.

Prediction of urine volume soon after birth using serum cystatin C.

Urine volume is an important clinical finding particularly during the early neonatal period. Oliguria is not a sign of impaired renal function but also a predictive factor for various complications and prognoses. It has been postulated that serum cystatin C (S-CysC) is a more sensitive biomarker for renal function than serum creatinine (S-Cr) in both adults and children. The objective of the current study was to investigate whether urine volume during 24h after birth can be predicted using S-CysC. The subjects were 87 infants. The average gestational age was 34.7±2.9weeks and the average birth weight was 2135±614g. Blood samples were obtained from either the umbilical cord or the peripheral veins or artery of the newborn at birth. Data regarding the amount of urine volume and fluid intake during the first 24h of life, maternal S-Cr and S-CysC levels within 48h before delivery, and neonatal S-Cr and S-CysC levels at birth were collected from the medical records. A significantly positive correlation was observed between maternal and neonatal S-Cr levels (r=0.84, p<0.0001) but not between maternal S-Cr levels and neonatal S-CysC levels (r=-0.069, p=0.52). A significant negative correlation was seen between neonatal S-CysC levels and urine volume (r=-0.47, p<0.0001). The present study findings indicate that it may be possible to use S-CysC levels at birth to predict urine volume during the first 24h of life.

Serum NGAL, cystatin C and urinary NAG measurements for early diagnosis of contrast-induced nephropathy in children

Aim: The study investigated a number of biomarkers for the early diagnosis of contrast-induced nephropathy (CIN), which is an important cause of acute kidney injury (AKI). Material and methods: The study included 91 children scheduled for elective cardiac angiography and 50 healthy controls. Biomarkers including serum (s) and urinary (u) sodium, serum and u-creatinine, s-cystatin-C, serum neutrophil gelatinase-associated lipocalin (NGAL) and urinary N-acetyl beta glucosaminidase (u-NAG)/creatinine ratio were measured 4 times sequentially in the patients and once in the controls. Results: The patient group comprised 40 males (44%) and 51 females (56%) while the control group comprised 16 males (32%) and 34 females (68%). Age, gender, s-creatinine, estimated-glomerular filtration rate (eGFR), s-cystatin-C and fractional-excretion of sodium did not differ significantly between the groups. Serum sodium and s-NGAL were found to be lower in the patients than those of in the controls, while their u-NAG/creatinine ratio was found to be higher. Sequential data analysis revealed that s-NGAL and u-NAG/creatinine ratio increased in the first 6 h after radiocontrast media (RCM) administration and decreased at 12 and 24 h. Serum BUN and s-cystatin-C levels also showed a significant difference during the 24-h follow-up. eGFR, s-sodium and s-creatinine levels did not change in the following period. Serum cystatin-C levels revealed a significant negative correlation with eGFR. Administered RCM doses showed a positive correlation only with u-NAG/creatinine ratios. Conclusion: In the first 24 h, s-cystatin-C, s-NGAL and especially u-NAG/creatinine ratio showed promise as biomarkers, but eGFR is not adequate for early diagnosis of CIN. Sequential measurement of biomarkers may contribute to more accurate diagnosis of AKI.

Cerium oxide nanoparticles attenuate acute kidney injury induced by intra-abdominal infection in Sprague-Dawley rats.

BackgroundIntra-abdominal infection or peritonitis is a cause for great concern due to high mortality rates. The prognosis of severe intra-abdominal infection is significantly diminished in the presence of acute kidney injury (AKI) which is often characterized by renal tubular cell death that can lead to renal failure. The purpose of the current study is to examine the therapeutic efficacy of cerium oxide (CeO2) nanoparticles for the treatment of peritonitis-induced AKI by polymicrobial insult.ResultsA one-time administration of CeO2 nanoparticles (0.5 mg/kg) in the absence of antibiotics or other supportive care, attenuated peritonitis-induced tubular dilatation and the loss of brush border in male Sprague–Dawley rats. These improvements in renal structure were accompanied by decreases in serum cystatin-C levels, reduced renal oxidative stress, diminished Stat-3 phosphorylation and an attenuation of caspase-3 cleavage suggesting that the nanoparticle treatment improved renal glomerular filtration rate, diminished renal inflammation and reduced renal apoptosis. Consistent with these data, further analysis demonstrated that the CeO2 nanoparticle treatment diminished peritonitis-induced increases in serum kidney injury molecule-1 (KIM-1), osteopontin, β-2 microglobulin and vascular endothelial growth factor-A (VEGF-A) levels. In addition, the nanoparticle attenuated peritonitis-induced hyperglycemia along with increases in blood urea nitrogen (BUN), serum potassium and sodium.ConclusionCeO2 nanoparticles scavenge reactive oxygen species and attenuate polymicrobial insult induced increase in inflammatory mediators and subsequent AKI. Taken together, the data indicate that CeO2 nanoparticles may be useful as an alternative therapeutic agent or in conjunction with standard medical care for the treatment of peritonitis induced acute kidney injury.

Cystatin-C levels in healthy children and adolescents: Influence of age, gender, body mass index and blood pressure

ObjectivesCystatin-C is considered a more sensitive and specific marker of kidney function than creatinine since it can diagnose patients with earlier-stage of renal dysfunction. The aim of this study is to determine the levels of Cystatin-C in healthy children and adolescents as well as any correlations to age, gender, body-mass index (BMI) and blood pressure (BP). Design and methodsCystatin-C was measured in 536 healthy Greek children and adolescents (295 males and 241 females) using a nephelometric immunoassay. Additionally, the age, body mass index and blood pressure was recorded for each subject. ResultsOverall, the mean serum Cystatin-C level was 0.79±0.10mg/L. Cystatin-C was found to be statistically significantly lower in females than in males (p<0.001) as well as in prepubertal children compared to adolescents (p<0.001). Higher values of Cystatin-C were observed in subjects with increased BMI (p<0.001). Neither systolic nor diastolic blood pressure was found to significantly affect Cystatin-C levels. ConclusionsThe levels of Cystatin-C were statistically significantly higher in males, compared to age-matched females and also positively correlated with age and BMI.

Lead poisoning and cystatin-C in children

Background Lead pollution is a global problem both in developed and developing countries. Lead poisoning is associated with decreased glomerular filtration rate (GFR) and is a risk factor for acute kidney injury (AKI). Serum cystatin-C is a more precise test of GFR than serum creatinine level, as serum cystatin-C levels rise earlier than serum creatinine, when GFR decreases. Objective To assess for a possible correlation between lead poisoning and cystatin-C levels in children. Methods We conducted a cross-sectional study in children aged 6-11 years with a history of lead poisoning from elementary schools in Talawaan District, North Minahasa Regency from July to October 2013. Cystatin-C and blood lead levels (BLL) were measured in all subjects. Spearman’s rho test was used to analyze a potential correlation between BLL and cystatin-C level. Results This study included 41 children, comprising 21 boys and 20 girls. Their median age was 8.50 (range 6.8-10.7) years. Elevated levels of cystatin-C did not exceed normal values, however, we found a positive correlation between BLL and cystatin C (r=0.419, P=0.006). Conclusion There is a positive correlation between BLL and cystatin C level in children with lead poisoning. Regular monitoring of BLL, medical intervention, and an epidemiological study to help find the sources of contamination are needed for children with lead poisoning.

Association between graft function and serum TNF-α, TNFR1 and TNFR2 levels in patients with kidney transplantation

Introduction: This prospective observational study aimed to assess the relevance of serial postoperative serum TNF-α, TNFR1 and TNFR2 measurements for predicting graft function and acute rejection episodes (AR) after transplantation. Materials and methods: We studied 50 kidney transplant recipients (31 female, 19 male; mean age: 38.36 ± 12.88). Blood samples were collected immediately before and after surgery at day 7, month 1 and month 3. Serum TNF-α, TNFR1 and TNFR2 levels were measured by ELISA using a commercial kit (Invitrogen ELISA). Serum cystatin-C levels were measured by particle-enhanced immunonephelometric method. Glomerular filtration rate (GFR) was estimated by Chronic Kidney Disease-Epidemiology (CKD-EPI) equation. Patients were assigned to their transplant outcomes in terms of acute rejection [AR(+) and AR(−)] and slow (SGF) or immediate graft function (IGF). Results: Among 50 recipients, six had AR(+) and 44 had AR(−), depending on graft function: 17 had SGF and 33 had IGF. Serum creatinine, cystatin-C, TNF-α, TNFR1 and TNFR2 levels demonstrated consistent significantly decreases after transplantation while GFR values had consistent increases (p = 0.001). Pretransplant levels were not statistically different between AR(+) and AR(−) groups (TNF-α: 30.79 ± 5.96 vs. 27.95 ± 2.43 pg/mL, TNFR1: 55.96 ± 21.6 vs. 40.52 ± 7.41 ng/mL, TNFR2: 58.31 ± 8.06 vs. 50.9 ± 3.34 ng/mL, respectively) (p > 0.05). Serum TNF-α, TNFR1 and TNFR2 levels on day 7 and month 1 were also significantly higher in AR(+) group compared to AR(−) (p = 0.012, p = 0.049 for TNF-α, p = 0.001, p = 0.002 for TNFR1, p = 0.001, p = 0.002 for TNFR2). Conclusions: Our preliminary findings suggest that serum TNF-α, TNFR1 and TNFR2 levels might be considered useful markers of evaluating graft function after renal transplantation.

A comparison of the effects of ketamine and remifentanil on renal functions in coronary artery bypass graft surgery

We have investigated the effects of ketamine-based and remifentanil-based anesthetic protocol on perioperative serum cystatin-C levels, and creatinine and/or cystatin-C-based eGFR equations in terms of acute kidney injury in coronary artery bypass graft (CABG) surgery. Using a simple randomization method (coin tossing), patients were divided into the two groups and not-blinded to the anesthetist. Remifentanil–midazolam–propofol or ketamine–midazolam–propofol-based anesthetic regimen was chosen. Different eGFR formulas using creatinine (MDRD, CKD-EPI, Cockrauft Gault); cystatin-C (eGFR1, eGFR2) or a combination of creatinine and cystatin-C (eGFR 3) were used to calculate estimated glomerular filtration rates (eGFRs). High-sensitive troponin T was used to determine if ketamine use in coronary surgery contributed to myocardial cell damage. Thirty-seven patients were included in the study (remifentanil group = 19, ketamine Group = 18). Urea, creatinine, cystatin-C levels were comparable between the groups in all the measurement times and also postoperative day 2 samples showed statistically higher results compared to baseline (p < 0.001). Effects of ketamine and remifentanil on renal functions were found similar. Creatinine and cystatin-C-based eGFR equations resulted similar in our study. Reversible stage 1 acute kidney injury (AKI) was observed on postoperative day 2 in seven patients from the remifentanil group and six patients from the ketamine group. Hs-troponin T was found to be higher in postoperative day 1 samples; there were no significant difference between the groups. Our results indicated that patients who have normal renal functions undergoing on-pump coronary bypass surgery, effects of ketamine and remifentanil on renal functions in terms of AKI were found to be similar.

Cystatin-C as an early marker of diabetic nephropathy in diabetic patients

Chronic kidney disease (CKD) is a major trouble in public health worldwide due to its rapid and random prevalence especially in diabetic patients. Further, diabetic nephropathy is a common cause of renal failure occurred in diabetic patients accompanied with low level of albumin in urine at early stage. Notably, early recognition of structural and functional alteration in the kidney is required and essential to identify the appropriate treatment at the beginning of renal syndromes. Several studies exhibit the essential role of serum creatinine in assessment of glomerular filtration rate (GFR) as a biomarker of renal failure. Alternatively, here findings demonstrate that level of serum cystatin-c is an efficacious candidate that can be revealing the possible alternations in renal function including children patients. Thus, blood samples collected from renal and/or diabetic patients showed contradictory relationship between serum cystatin-c level and GFR independent from diabetic syndromes. The results strongly indicate the possible exploiting of serum cystatin-c as an early indicator for renal disease. Collectively, current data further confirm the crucial role of serum cystatin-c in early detection of renal failure via reverse connection with GFR particularly in diabetic children.

Myeloid Mineralocorticoid Receptor Activation Contributes to Progressive Kidney Disease

Clinical and experimental studies have shown that mineralocorticoid receptor (MR) antagonists substantially reduce kidney injury. However, the specific cellular targets and mechanisms by which MR antagonists protect against kidney injury must be identified. We used conditional gene deletion of MR signaling in myeloid cells (MR(flox/flox) LysM(Cre) mice; MyMRKO) or podocytes (MR(flox/flox) Pod(Cre) mice; PodMRKO) to establish the role of MR in these cell types in the development of mouse GN. Accelerated anti-glomerular basement membrane GN was examined in groups of mice: MyMRKO, PodMRKO, wild-type (WT) littermates, and WT mice receiving eplerenone (100 mg/kg twice a day; EPL-treated). At day 15 of disease, WT mice had glomerular crescents (37%±5%), severe proteinuria, and a 6-fold increase in serum cystatin-C. MyMRKO, PodMRKO, and EPL-treated mice with GN displayed proteinuria similar to that in these disease controls. However, MyMRKO and EPL-treated groups had a 35% reduction in serum cystatin-C levels and reduced crescent numbers compared with WT mice, whereas PodMRKO mice were not protected. The protection observed in MyMRKO mice appeared to result predominantly from reduced recruitment of macrophages and neutrophils into the inflamed kidney. Suppression of kidney leukocyte accumulation in MyMRKO mice correlated with reductions in gene expression of proinflammatory molecules (TNF-α, inducible nitric oxide synthase, chemokine (C-C motif) ligand 2, matrix metalloproteinase-12), tubular damage, and renal fibrosis and was similar in EPL-treated mice. In conclusion, MR signaling in myeloid cells, but not podocytes, contributes to the progression of renal injury in mouse GN, and myeloid deficiency of MR provides protection similar to eplerenone in this disease.

Plasma cystatin-C and risk of developing gestational diabetes mellitus

AimsCystatin-C, a low molecular weight protein, is effectively applied to evaluate the risk of developing renal insufficiency, cardiovascular disorders, neural defects, and inflammatory states. However, the role of this biomarker to monitor different pregnancy-related complications remains controversial. Materials and methodsIn the present study, we compared serum cystatin-C concentration between pregnant women with gestational diabetes mellitus (GDM) and healthy pregnant women to assess value of this biomarker to predict presence of GDM in these women. The study consisted of 60 consecutive pregnant women (30 women suffered GDM and 30 healthy pregnant women) enrolled in Afzalipour hospital in Kerman, Iran in 2012. Fasting blood sample was collected to perform measurements on plasma glucose, lipids, serum creatinine, and C-cystatin. Serum cystatin-C level was quantified using ELISA techniques. ResultsUnadjusted comparison of cystatin-C level between the two study group showed no significant discrepancy between them so that the level of this biomarker in GDM group was 593.00±204.81mg/L and in healthy group was 531.67±87.52mg/L (P=0.137); while in multivariable linear model with the presence of associated variables, GDM was a main determinant for increased level of cystatin-C (standardized beta of 0.355, P-value of 0.014). ConclusionGestational age was also identified to be another indicator of elevated cystatin-C. In final, our study showed that cystatin-C can be a reliable, useful and promising marker of GDM appearance in pregnant women.

Response to letter to the editor ‘Serum cystatin-C levels correlate with endothelial dysfunction in patients with the metabolic syndrome’

Response to letter to the editor ‘Serum cystatin-C levels correlate with endothelial dysfunction in patients with the metabolic syndrome’

Comparison of Serum Cystatin C, Serum Creatinine, Measured GFR, and Estimated GFR to Assess the Risk of Kidney Failure in American Indians With Diabetic Nephropathy

We compared values of baseline serum cystatin C (SCysC), serum creatinine (SCr), and measured glomerular filtration rate (mGFR) for predicting end-stage renal disease (ESRD) in patients with type 2 diabetes and elevated albuminuria. Observational longitudinal study. Pima Indians with type 2 diabetes and elevated albumin-creatinine ratio (ACR ≥30 mg/g). Baseline SCysC, SCr, and mGFR. Individuals were followed up from their first examination with diabetes and ACR ≥30 mg/g until December 2010, onset of ESRD, or death, whichever came first. Incidence rates adjusted for age and sex were computed by Mantel-Haenszel stratification. The abilities of SCysC, SCr, and mGFR values to predict ESRD were compared with receiver operating characteristic curves. Of 234 Pima Indians with a mean age of 42.8 years who were followed up for a median of 10.7 (range, 0.6-21.3) years, 68 (29%) developed ESRD. The incidence of ESRD was significantly higher in patients in the lowest versus highest tertile of 1/SCysC (incidence rate ratio, 2.43; 95% CI, 1.31-4.50). By contrast, mGFR and 1/SCr had J-shaped associations with ESRD. In unadjusted analyses, 1/SCysC had the highest area under the receiver operating characteristic curve (AUROC; 0.719 ± 0.035) and mGFR had the lowest (0.585 ± 0.042; P < 0.001); the AUROC for 1/SCr was intermediate (0.672 ± 0.040; P = 0.1 and P = 0.03 vs 1/SCysC and mGFR, respectively). In analyses adjusted for age, sex, diabetes duration, height, weight, hemoglobin A1c level, and ACR, 1/SCysC had the highest AUROC (0.845 ± 0.026). Models with mGFR or 1/SCr alone had similar AUROCs (P = 0.9) and both were lower than the model with 1/SCysC alone (P = 0.02 and P = 0.03, respectively). The predictive values of the filtration markers are limited to the extent that their precision is based on a single measurement. SCysC level was a better predictor of ESRD than mGFR or SCr level in Pima Indians with type 2 diabetes and elevated albuminuria.

GFR Estimation Using Standardized Cystatin C in Kidney Transplant Recipients

The utility of serum cystatin C (SCysC) as a filtration marker in kidney transplantation is uncertain. We took advantage of the recent validation of a reference calibrator for SCysC and of newly developed CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) equations (2012) expressed for use with standardized SCysC level to reassess the performance of SCysC as a filtration marker in kidney transplant recipients. Study of diagnostic test accuracy. 670 kidney transplant recipients from 3 centers undergoing glomerular filtration rate (GFR) measurements from December 2006 to November 2012. Estimated GFR (eGFR) using the 2012 SCysC-based and serum creatinine (SCr)/SCysC-based CKD-EPI equations (eGFR(cys) and eGFR(cr-cys), respectively) and the 2009 SCr-based CKD-EPI equation (eGFR(cr)), with SCysC and SCr measured at a single laboratory between April 2011 and June 2011. Measured GFR (mGFR) using urinary clearance of inulin. Bias (the difference between mGFR and eGFR) was significantly smaller for eGFR(cys) and eGFR(cr-cys) versus eGFR(cr) (-2.82 and -0.54 vs +4.4 mL/min/1.73 m(2), respectively; P < 0.001). Precision (standard deviation of the mean bias) also was better for eGFR(cys) and eGFR(cr-cys) versus eGFR(cr) (12 and 11 vs 13 mL/min/1.73 m(2) [P < 0.001 for both comparisons]). Accuracy (percentage of GFR estimates within 30% of mGFR) was greater for eGFR(cys) and eGFR(cr-cys) versus eGFR(cr) (81% and 86% vs 75%, respectively [P = 0.004 and P < 0.001]). Net reclassification index with respect to mGFR of 30 mL/min/1.73 m(2) for eGFR(cr-cys) and eGFR(cys) versus eGFR(cr) was 18.8% [95% CI, 8.6%-28.9%] and 22.5% [95% CI, 10.2%-34.9%]. Patients were exclusively of European descent; association with transplant outcome was not evaluated. Our data validate the use of both the newly developed SCysC-based and SCr/SCysC-based CKD-EPI equations (2012) in kidney transplant recipients. Both equations perform better than the SCr-based CKD-EPI equation (2009).

Cystatin-C marker in diabetic and non diabetic patients with ischemic heart disease

Background:recent data indicate the prevalence of cardiovascular disease in patientswith high cystatin-C level;it can be used as a good predictor for assessment of mortality in cardiovascular diseases regardless of the status of renal function.Patients and methods: Onehundred twenty (120) patients with ischemic heart disease admitted to this study at Baghdad teaching hospital for the period from January 2011 to September2011,Those patients categorized into two groups (60) diabetic and (60) non diabetic in comparison to fifty healthy control.Fasting serum cystatin-C was measured in all patients and controls.Results: The level of serum cystatin-C, in diabetic patients with ischemic heart disease was (2.05±0.55 μg/L). Its level in non diabetic patients with ischemic heart disease was (1.19±0.59 μg/L)both were significantly higher(p&lt;0.001)than its level in healthy control(0.38±0.062 μg/L).Conclusion:Cystatin-C is good prognostic biomarker in patients with ischemic heart disease with or without diabetes mellitus.

Cystatin-C as a predictor for major adverse cardiac events in patients with acute coronary syndrome

Abstract Cystatin-C (CYS-C) has emerged as a highly sensitive marker of even a mildly impaired glomerular filtration rate. Experimental studies have suggested that its inhibitory effects on cysteine protease may help to prevent plaque destabilisation. We aimed to evaluate the predictive value of CYS-C level for major adverse cardiac events (MACE) including mortality and morbidity during the hospital stay and 3-month follow-up period. Methods Seventy-five patients were hospitalised for acute coronary syndrome (ACS). Another control group consisted of patients who were presented with chest pain but no evidence of ischaemic heart disease documented by laboratory markers and angiography. Serum CYS-C levels were measured during the first 24 h of admission. Patients with an abnormal creatinine-derived glomerular filtration rate (GFR) were excluded. Coronary angiography was performed for the entire study population. Results In group I, the mean CYS-C was 1.836 ± 0.782 mg/l vs. 0.991 ± 0.163 mg/l in the control group ( P r = 0.5) and with LDL ( r = 0.367, P r = 0.419, P r = 0.349). Smoking was the only predictor associated with a high CYS-C level in the multivariate regression analysis ( P = 0.033). CYS-C was an independent predictor of MACE and heart failure complications either in-hospital or during follow-up ( P Conclusions CYS-C could be a useful marker for diagnosing coronary arteriosclerosis. An elevated CYS-C in patients with ACS is an independent predictor of MACE either in-hospital or during follow-up.

The removal of cystatin C during continuous venovenous hemofiltration

Dear Editor, With interest we read the paper by Kiers et al. [1] suggesting that cystatin C (CyC) is not a useful parameter for residual renal function during continuous venovenous hemofiltration (CVVH). We previously found that the sieving coefficient (SC) for the cellulose triacetate membrane for CyC is approximately 0.50 [2]. On the basis of the constant CyC production reported in the literature, we hypothesized that predilution CVVH (2 l/h) is unlikely to influence serum CyC levels, although we did not determine changes in serum CyC [2]. Using the same dose (2 l/h, predilution) but a different membrane (polyacrylonitrile), Kiers et al. report a significant decrease of CyC after 24 h of CVVH in six patients with acute kidney injury (AKI). The authors do not report whether the patients were anuric during CVVH. Several factors may explain the opposite results. First, the cellulose triacetate membrane and the polyacrylonitrile membrane may behave differently in their ability to remove CyC [3]. Unfortunately, Kiers et al. did not measure CyC in the ultrafiltrate, and thus we are not informed on the SC. Second, it is possible that the patients in the study by Kiers et al. had recovering renal function during CVVH, although this is not very likely. Finally, the assumption that the generation rate of CyC in critically ill and non-critically ill patients is comparable may be wrong. To date, only few circumstances have been identified that have an impact on the production of CyC; nevertheless, this was never studied in critically ill patients [4]. We performed a small pilot study in six consecutive patients in order to determine the removal of CyC during CVVH and its effect on serum CyC levels. Patients were included if filter-down time was no longer than 2 h. We applied postdilution CVVH (35 ml/kg/h) and used either a polysulfone membrane (AV 600; Fresenius, Oberursel, Germany) or a cellulose triacetate membrane (UF 205; Nipro Europe, Zaventem, Belgium). Serum CyC decreased after the initiation of CVVH both in oligo-anuric and non-oliguric patients (Fig. 1). In the non-oliguric patients CyC levels increased after cessation of CVVH, suggesting that CVVH played an important role in the removal of CyC. When corrected for possible incomplete mixing by using the SC of urea, which should be 1 by definition, we found an SC of 0.49 ± 0.04 for the cellulose triacetate membrane and 0.45 ± 12 for the polysulfone membrane (p = 1.00). The CVVH dose in the present study was higher than in our earlier study and this may account for the decrease of CyC. Another possibility is that contrary to what we proposed earlier, CyC production is reduced in critically ill patients. The present pilot study and the study by Kiers et al. are limited by the small number of patients. Both studies, however, reach the same conclusion suggesting that during CVVH serum CyC is of little value in monitoring residual renal function, because CVVH removes CyC and decreases its serum levels. Fig. 1 Time course of serum cystatin C and serum creatinine during continuous venovenous hemofiltration (CVVH). Curves represent individual patients. Open circles, cellulose triacetate membrane, closed circles polysulfone membrane. Left panel oligo-anuric patients. ...

Elevated level of serum cystatin-C concentration is a useful predictor for myelosuppression induced by methotrexate for treatment of rheumatoid arthritis

Methotrexate (MTX) is indispensable for the treatment of rheumatoid arthritis (RA). However, a small number of patients treated with MTX occasionally encounter some life-threatening events, including myelosuppression. Renal insufficiency, one of risk factors for these events, is difficult to assess because the serum creatinine concentration level and estimated glomerular filtration rate are sometimes inaccurately determined in aged RA patients. As a better indicator to evaluate this pathology, we measured the serum cystatin-C (Cys-C) level in 78 RA patients ≥50 years who were treated with MTX and observed for a year. The measurement achieved successful screening of two patients with leukocytopenia, one with interstitial lung disease (ILD), and two with liver dysfunction. An additional four referral inpatients with MTX-induced adverse events (three with pancytopenia, one with ILD) were enrolled for analysis, amounting to 82 patients. The logistic regression analysis showed that a correlation was observed between myelotoxicity and serum Cys-C level (elevation per 0.1 mg/dl; odds ratio 2.34, 95% confidence interval 1.08–5.09, p = 0.03). In conclusion, elderly RA patients potentially have subclinical renal insufficiency detected by the serum Cys-C concentration level. The elevated level of serum Cys-C is a more sensitive indicator to predict MTX-induced myelotoxicity than that of serum creatinine.

The Value of Beta2 Microglobulin, Retinol Binding Protein, Endothelin-1, N Amino ß-d-Glucoaminodase and Cystatin C for the Evaluation Sickle Cell Nephropathy

AbstractAbstract 4817 Introduction:Sickle Cell Anemia (SCA) is a chronic disease characterized by broad clinical manifestations and multi-organ disease. Sickle cell nephropathy is one of the major side effects in the patients with SCA. This study was planned to determine the incidence of renal complications of the patients with SCA and to evaluate the renal complications by using new markers such as ß2 microglobulin, retinol binding protein (RBP), endothelin-1, N amino ß-d-glucoaminodase (NAG) and cystatin C. Methods:45 children (mean age 8.4 ± 1.21, range: 1–15 years), 10 adult patients with SCA (mean age:31.4 ± 10.11, range: 16–45 years) and 20 healthy children (mean age:8.45 ± 4.05, range: 1–15 years), 10 healthy adults (mean age: 26.6 ± 8.62, range: 16–45 years) as control groups were included in the study. A detailed history was taken from each child, and a full physical examination was performed. Serum and urine electrolytes, urine analysis, urine culture and renal ultrasonography were performed for all patients. 24 hour urine was collected both in patient and control groups, and GFR was measured. Tubular phosphate reabsorbtion, 24 hour urine protein and calcium excretion, fractional excretion of Na, K, Urea and Cl were calculated from 24 hour urine samples. ß2 microglobulin, endothelin-1 RBP and NAG levels were measured in spot urine samples of patients and controls. Serum cystatin C level was measured in both patient and control groups. ß2 microglobulin, endothelin-1, RBP and cystatin C were measured with micro-elisa method. On the other hand colorimetric assay was used to measure NAG. Results:35 patients (63%) had enuresis nocturna, 34 patients (61%) had moderate proteinuria and 9 patient (16%) had poliuria. 26 patients (47%) had past history of urinary tract infection and 3 patients had past history of hematuria. Although all the markers to evaluate tubular functions were in normal ranges, ß2 microglobulin/creatinine ratio was found to be high in 10 patients (18%). GFR measured with creatinine was in normal ranges in all of the patients. Hovewer GFR measured with cystatin-C was low in 3 patients (0.5%). Urine ß2 microglobulin, endothelin-1, RBP, NAG, and serum cystatin-C levels were all in normal ranges both in patient and control groups. Conclusions:The commonly observed renal side effects in the patients with SCA are enuresis nocturna, proteinuria and increased tendency to urinary tract infections. It could be suspected that ß2 microglobulin/creatinin ratio and GFR that is calculated by the use of cystatin C could be use in order to evaluate the tubular and glomerular functions in those patients with SCA during the early stages of sickle cell nephropathy. Besides, urine endothelin-1, RBP and NAG levels could not be considered as good markers for determining the sickle cell nephropathy. Disclosures:No relevant conflicts of interest to declare.

Elevated level of serum cystatin-C concentration is a useful predictor for myelosuppression induced by methotrexate for treatment of rheumatoid arthritis

Methotrexate (MTX) is indispensable for the treatment of rheumatoid arthritis (RA). However, a small number of patients treated with MTX occasionally encounter some life-threatening events, including myelosuppression. Renal insufficiency, one of risk factors for these events, is difficult to assess because the serum creatinine concentration level and estimated glomerular filtration rate are sometimes inaccurately determined in aged RA patients. As a better indicator to evaluate this pathology, we measured the serum cystatin-C (Cys-C) level in 78 RA patients ≥ 50 years who were treated with MTX and observed for a year. The measurement achieved successful screening of two patients with leukocytopenia, one with interstitial lung disease (ILD), and two with liver dysfunction. An additional four referral inpatients with MTX-induced adverse events (three with pancytopenia, one with ILD) were enrolled for analysis, amounting to 82 patients. The logistic regression analysis showed that a correlation was observed between myelotoxicity and serum Cys-C level (elevation per 0.1 mg/dl; odds ratio 2.34, 95% confidence interval 1.08-5.09, p = 0.03). In conclusion, elderly RA patients potentially have subclinical renal insufficiency detected by the serum Cys-C concentration level. The elevated level of serum Cys-C is a more sensitive indicator to predict MTX-induced myelotoxicity than that of serum creatinine.