Elevated Serum Cystatin Research Articles

Evaluating the role of serum cystatin C as a circulating biomarker of diabetic retinopathy from a rural Indian population

Abstract PURPOSE: This study aimed to evaluate serum cystatin C as a potential biomarker for diabetic retinopathy (DR) in a rural Indian population, addressing the urgent need for effective screening tools amidst rising diabetes prevalence. MATERIALS AND METHODS: A cross-sectional study recruited 112 patients with diabetes mellitus from Sambalpur, Odisha, India, categorized into groups with and without DR. Serum cystatin C levels were measured alongside clinical and demographic parameters, using established diagnostic methods. RESULTS: Patients with DR exhibited significantly higher serum cystatin C levels compared to those without DR (mean: 0.99 ± 0.50 mg/L vs. 0.80 ± 0.36 mg/L, P = 0.027). Adjusted analysis showed a notable association between higher cystatin C tertiles and DR (adjusted odd’s ratio: 7.65, 95% confidence interval: 1.49–39.08, P = 0.01), highlighting its potential as an independent predictor. CONCLUSION: Elevated serum cystatin C levels were strongly associated with the presence of DR, suggesting its utility as a biomarker for early identification and risk stratification in diabetic patients. Integration of cystatin C measurement into routine clinical practice may enhance DR screening and management strategies, offering potential benefits in reducing vision loss and improving patient outcomes. This study underscores the need for further longitudinal research to validate these findings and elucidate the temporal relationship between cystatin C levels and DR progression.

Associations Between CYP3A5 (c.6986A>G) Gene Polymorphism and Kidney Impairment in Hypertensive Adults Without Cystatin C Elevation.

This study aimed to explore the potential role of CYP3A5 (c. 6986A>G) gene polymorphism in predicting kidney function impairment in patients with hypertension who did not have elevated serum cystatin C. We recruited a group of patients with hypertension who did not have elevated cystatin C and analyzed the CYP3A5 (c. 6986A>G) gene polymorphism. Chi-square tests were used to compare the clinical characteristics and genotypic distribution between the two groups. Logistic regression analysis was used to explore the association between CYP3A5 (c.6986A>G) gene polymorphism and renal function impairment in hypertension with non-elevated cystatin. In patients with hypertension who participated in the study, there was a significant association between CYP3A5 (c. 6986A>G) gene polymorphism and kidney function impairment (p < 0.05). Patients with the CYP3A5 (c. 6986A>G) mutation display a greater risk of kidney function impairment. CYP3A5 (c. 6986A>G) gene AA homozygote polymorphism significantly increases risk of kidney function impairment in patients with hypertension with normal cystatin C. However, further studies are needed to validate this association and to further understand the mechanism of CYP3A5 (c. 6986A>G) gene polymorphism in kidney function impairment in patients with hypertension.

2,5-Dihydroxyacetophenone attenuates acute kidney injury induced by intra-abdominal infection in rats.

As one of the most serious complications of sepsis, acute kidney injury (AKI) is pathologically associated with excessive inflammation. 2,5-Dihydroxyacetophenone (DHAP) is isolated from Radix rehmanniae praeparataand exhibit potent anti-inflammatory property. This research aimed at determining the role of DHAP in sepsis-associated AKI (SA-AKI) and the underlying mechanism. Plasma creatinine (Cre), blood urea nitrogen (BUN), tumour necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) levels of SA-AKI patients were detected to evaluate their clinical characteristics. SA-AKI rat models were established by using caecum ligation puncture (CLP) surgery. CLP-induced rats were administered via oral gavage with 20 or 40 mg DHAP after 2 h of CLP surgery. Subsequently, survival rates, serum indexes, histopathological changes, inflammatory factors, renal function indexes and extracellular regulated protein kinases (ERK) and nuclear factor-κB (NF-κB) signalling pathways were detected. SA-AKI patients exhibited markedly higher levels of plasma Cre, BUN, TNF-α and IL-1β than healthy people. Compared with sham rats, CLP-induced septic rats showed significantly decreased survival rate, increased serum lactate dehydrogenase activity and serum lactate level, obvious renal histopathological injury, upregulated TNF-α, IL-1β and TGF-β1 levels, elevated serum creatinine, BUN and serum cystatin C concentrations, serum neutrophil gelatinase-associated lipocalin and kidney injury molecule-1 levels and reduced renal artery blood flow. All the above CLP-induced changes in septic rats were mitigated after DHAP administration. Additionally, CLP-induced elevation in phosphorylated-ERK1/2 and nuclear NF-κB p65 protein levels was inhibited by DHAP treatment. DHAP hinders SA-AKI progression in rat models by inhibiting ERK and NF-κB signalling pathways.

Therapeutic role of Arabic gum against nicotinamide/streptozotocin-induced diabetes and nephropathy in Wistar rats

Background Chronic kidney disease is mainly caused by diabetic nephropathy and also causes a lot of suffering and death for people with diabetes, as one of the worst long-term complications. Arabic gum (AG) has been reported to have antioxidant, hypolipidemic and hypoglycemic effects. Objective The goal of this study was to scrutinize the antioxidant and anti-inflammatory roles of AG against nicotinamide (NA)/streptozotocin (STZ)-induced diabetic nephropathy in Wistar rats. Materials and methods The experiment involved three groups of 18 adult male Wistar rats (six each). The normal control group received 0.9% NaCl orally for 8 weeks. The diabetic group received NA intraperitoneal injection (120 mg/kg b.w.) followed by 60 mg/kg body weight (bw) STZ in citrate buffer (pH 4.5) after 15 min. After confirming the induction of diabetes, animals received 0.9% NaCl orally for 8 weeks. The AG-treated diabetic group received 20 mg AG/kg bw/day orally for 8 weeks after diabetes induction. Results and conclusion Diabetic rats exhibited hyperglycemia which was confirmed by increased levels of serum fasting glucose and fructosamine. Elevated serum urea, creatinine, uric acid, cystatin c, and sodium levels were noticed in the serum of diabetic rats while potassium levels were markedly reduced reflecting nephropathy. Oxidative stress was evident in the diabetic kidney, as indicated by increased malondialdehyde (MDA) and decreased reduced glutathione (GSH), glutathione peroxidase (GPx) and superoxide dismutase (SOD). AG administration ameliorated elevated fasting blood glucose and serum fructosamine levels as well as the kidney function parameters in serum. AG also attenuated oxidative stress and increased antioxidant capacity in the diabetic kidney. Immune-inflammatory mediators, such as tumor necrosis factor-alpha (TNF-α), nuclear factor kappa B (NF-κB), and tumor suppressor protein (p53) expression were significantly upregulated in diabetic rats, but AG produced a downregulation of them. Thus, AG possesses an antidiabetic effect and has a nephropreventive effect that was manifested by a decrease of urea, creatinine, uric acid, cystatin c and sodium. AG also has anti-inflammatory and antioxidant effects and minimizes histopathological alterations in the kidneys of diabetic rats. Despite these ameliorative effects, the efficacy and safety of AG as an adjunct drug for diabetic kidney disease needs to be validated by more scientific research.

Association of serum cystatin C level with coronary atherosclerotic plaque burden: a comprehensive analysis of observational studies and genetic study

Background and AimsEpidemiological studies show that high circulating cystatin C is associated with risk of cardiovascular disease (CVD), independent of creatinine-based renal function measurements. However, the relationship between serum cystatin C level and coronary atherosclerotic plaque burden is limited. We aimed to evaluate the relationship between circulating cystatin C and coronary atherosclerotic plaque burden.MethodsThis study was a cross-sectional study based on China community population. Measurements of plaque burden were based on the segment-involvement score (SIS) and segment stenosis score (SSS), which derived from the Coronary Artery Tree Model Depicting Coronary Artery Plaque Scores. Logistic regression model was used to demonstrate the association between cystatin C level and coronary artery plaque burden. Mendelian randomization (MR) analyses were conducted to assess the causal effect of cystatin C level on coronary atherosclerosis risk.ResultsA total of 3,043 objects were included in the present study. The odds risks (OR) of severe plaque burden in the highest serum cystatin C levels (OR: 2.50; Cl:1.59–3.91; P < 0.001) and medium-level cystatin C levels (OR: 1.86; 95% Cl: 1.21–2.88; P = 0.005) were significantly higher after fulled adjusted confounders compared with the lowest levels of serum cystatin C by SSS. The MR analysis showed that genetic predicted cystatin C levels was associated with an increased risk of coronary atherosclerosis (OR, 1.004; 95% CI, 1.002–1.006, P < 0.001) .ConclusionElevated serum cystatin C levels were associated with coronary atherosclerotic plaque burden. Cystatin C levels had a causal effect on an increased risk of coronary atherosclerosis at the genetic level.What is already known on this topic?Coronary artery disease is currently the most common cardiovascular disease and the leading global cause of mortality. Previous studies reported that higher serum cystatin C levels were associated with an increased risk for future cardiovascular events, independent of the normal creatinine levels or estimated glomerular filtration rate (eGFR) values. The presence of high-risk coronary atherosclerotic plaque burden is associated with increased risk of cardiovascular events. However, the association between serum cystatin C and coronary atherosclerotic plaque burden is not very clear.What this study adds?Our study demonstrated that the elevated serum cystatin C levels were associated with coronary atherosclerotic plaque burden. In addition, we found that serum cystatin C levels had a causal effect on an increased risk of coronary atherosclerosis at the genetic level.How this study might affect research, practice or policy?Current research finds that serum cystatin C levels were associated with coronary atherosclerosis. The metabolic pathway of cystatin C could be a target for new therapies against CAD.

Increased serum cystatin C levels in patients with idiopathic epiretinal membrane

ABSTRACT Clinical relevance Increased serum cystatin C may play a role in the pathogenesis of idiopathic epiretinal membrane (IERM). Physicians should be aware of this relationship and should refer patients to the ophthalmology clinic for screening. Background To evaluate the serum cystatin C level in patients with IERM, and its associations with visual acuity. Methods Sixty-eight patients with IERM and sixty-nine controls were enrolled in this cross-sectional study. Based on the results of optical coherence tomography, patients with IERM were divided into four stages (I, II, III and IV). Serum cystatin C was measured in all participants. Serum cystatin C levels were compared between the control group and IERM group and between the IERM group with different optical coherence tomography stages. Multiple linear regression was used to evaluate the relationship between serum cystatin C and IERM stages and best corrected visual acuity. Results Serum cystatin C level was higher in the IERM group than in the control group (P < 0.001). There were statistically significant differences in serum cystatin C among different stages of IERM (P I vs II = 0.011, P I vs IV < 0.001 and P III vs IV = 0.040, respectively). There were significant differences in best corrected visual acuity among different stages of IERM (P I vs III = 0.018, P I vs IV < 0.001, P II vs IV < 0.001 and PIII vs IV < 0.001, respectively). Regression analysis showed a positive correlation between serum cystatin C and best corrected visual acuity (t = 2.238 P = 0.029). The cut-off value of receiver operation characteristic curve of serum cystatin C for IERM was 0.775. Conclusion This study revealed that serum cystatin C may be involved in the pathogenesis of IERM and can predict its occurrence. Elevated serum cystatin C appears to be associated with the severity of the disease and relatively poor vision acuity in IERM patients.

Association Between Serum Cystatin C and Cognitive Decline Independently from Creatinine: Evidence from Two Nationally Representative Aging Cohorts.

Studies on the association between cystatin C based estimated glomerular filtration rate (eGFRcys) and cognitive outcomes yielded inconsistent results. The present study aimed to examine the potential association of eGFRcys with subsequent cognitive decline rate. A total of 11,503 community-based participants were involved in our analyses, including 5,837 (aged 72.9±6.3; 58.6% women) in the Health and Retirement Study (HRS) from the US and 5,666 (aged 58.1±9.2; 49.0% women) in the China Health and Retirement Longitudinal Study (CHARLS). The association of eGFRcys with subsequent cognitive decline rate was evaluated by linear mixed models. During 85,266 person-years of follow-up, both baseline elevated serum cystatin C (-0.048 standard deviation [SD]/year per mg/L; 95% confidence interval [CI], -0.060 to -0.036; p < 0.001) and decreased eGFRcys (0.026 SD/year per 30 mL/min/1.73m2; 95% CI, 0.020 to 0.032; p < 0.001) were associated with faster cognitive decline rate after full adjustment. Compared with those had eGFRcys ≥90 mL/min/1.73m2, participants with eGFRcys between 60 to 90 mL/min/1.73m2 (-0.012 SD/year; 95% CI, -0.020 to -0.004; p = 0.004) and those with eGFRcys <60 mL/min/1.73m2 (-0.048 SD/year; 95% CI, -0.058 to -0.039; p < 0.001) experienced statistically significantly faster cognitive decline after adjustment. The associations were independent from serum creatinine/eGFRcre (eGFR that was calculated from serum creatinine). Decreased eGFRcys are significantly associated with faster cognitive decline after full adjustment, independently from serum creatinine/eGFRcre. Serum cystatin C might be a risk factor or a prodromal biomarker of cognitive decline.

Сироватковий цистатин С як маркер ниркової дисфункції в дітей з ювенільним ідіопатичним артритом

An accurate assessment of the estimated glomerular filtration rate (eGFR) is important for early detection of chronic kidney disease, control of nephrotoxicity, and dose adjustment of drugs. To date, there has been only one cohort retrospective study of the prevalence of chronic kidney disease in children with juvenile idiopathic arthritis (JIA). Purpose - to determine the level of serum cystatin C and, on its basis, the state of eGFR depending on the form of the clinical course, degree of activity, methods of treatment of JIA in children. Materials and methods. 80 children with JIA were examined. The content of serum cystatin C was determined by enzyme-linked immunosorbent assay. The Hoek formula was used to calculate eGFR based on the level of cystatin C in blood serum. Results. A decrease in eGFR below 90 ml/min/1.73m2 to 63.08 ml/min/1.73m2 based on serum cystatin C was found in 41.3% of children with JIA. The variant of the clinical course of JIA does not affect the concentration of serum cystatin С and the level of eGFR. Meanwhile, a high degree of risk of developing a decrease in eGFR in children with polyarthritis was established - 72.7% versus 48.9% (OR=2.78; CI: 1.07-7.24; p&lt;0.04). Elevated serum cystatin С levels and decreased eGFR are associated with the degree of JIA activity and its duration. A decrease in eGFR is observed in all children with high activity of JIA, 71.4% - with low activity, 28.3% - in remission. A low risk of developing a decrease in eGFR in children in remission of JIA was established - 51.5% versus 91.5% (OR=0.10; CI: 0.03-0.34; p&lt;0.001). The duration of the active stage of JIA ≥4 years negatively affects the level of eGFR, which leads to a high risk of developing a decrease in eGFR - 39.4% versus 17% (OR=3.17; CI: 1.13-8.9; p&lt;0.04). A high risk of developing a decrease in eGFR was established in children with JIA who received non-steroidal anti-inflammatory drugs (NSAIDs) at the time of the examination - 54.5% versus 8.5% (OR=12.9; CI: 3.76-44.25; p&lt;0.001). The use of immunobiological therapy is associated with a low risk of developing a decrease in eGFR - 9.1% versus 46.8% (OR=0.11; CI: 0.03-0.42; p&lt;0.001). Conclusions. Renal dysfunction was found in 41.3% of children with JIA. Its development is affected by high activity of JIA, duration of the active stage of JIA ≥4 years, and treatment with NSAIDs. The study was carried out in accordance with the principles of the Helsinki Declaration. The study protocol was approved by the Local Ethics Committee of the institution specified in the work. Informed consent was obtained from the parents of the children for the research. No conflict of interests was declared by the authors. Key words: juvenile idiopathic arthritis, renal dysfunction.

Elevated Serum Cystatin C and Decreased Cathepsin S/Cystatin C Ratio Are Associated with Severe Peripheral Arterial Disease and Polyvascular Involvement.

Peripheral arterial disease (PAD) is frequently associated with atherosclerotic manifestations of the carotids and coronaries. Polyvascular involvement and low ankle–brachial index predict major cardiovascular events and high mortality. Cathepsin S (Cat S) promotes the inflammatory pathways of the arterial wall, while Cystatin C (Cys C) functions as its inhibitor; therefore, Cys C was proposed to be a biomarker of progression in PAD. In a single-center observational study, we investigated the correlations of serum Cys C and Cat S/Cys C ratio in a group of 90 PAD patients, predominantly with polyvascular involvement. Cys C and Cat S/Cys C were associated with ankle–brachial index (ABI) scores <0.4 in univariate and multiple regression models. Furthermore, both markers correlated positively with the plasma Von Willebrand Factor Antigen (VWF: Ag) and Von Willebrand Factor collagen-binding activity (VWF: CB). In addition, Cat S/Cys C was significantly decreased, whereas Cys C increased in subjects with three-bed atherosclerotic involvement. According to our results, high serum Cys C and low Cat S/Cys C ratios may indicate severe peripheral arterial disease and polyvascular atherosclerotic involvement.

Evaluation of kidney dysfunction in childhood cancer survivors

BackgroundThe major increase in the survival rate among children with cancer is due to improvement in the diagnosis and treatment. Despite this increase, childhood cancer survivors (CCS) are at high risk of developing late complications such as nephrotoxicity due to chemotherapy. So, we aimed to detect early subclinical kidney dysfunction among CCS.MethodsThis cross-sectional study was implemented on 52 survivors of childhood cancer recruited from Pediatric Oncology Unit, Menoufia University. Laboratory evaluations for each participant, including complete blood count, serum urea, creatinine, urinary protein, urinary calcium, uric acid, and serum cystatin C and urinary Neutrophil Gelatinase Associated Lipocalin (UrNGAL) by ELISA were obtained.ResultsEstimated GFR was decreased in 23.1% of cases, with elevated serum cystatin C, UrNGAL and UrNGAL/Cr. There was a significant increase of Uprotein/Cr, UCa/Cr, UACR (p = 0.02), UrNGAL and UrNGAL/Cr (P < 0.001) in patients with tubular dysfunction compared without tubular dysfunction. There was a significant difference between two groups regarding cisplatin (P = 0.03) and high-dose methotrexate chemotherapy (p = 0.04). The AUCs for detecting kidney tubular dysfunction by UrNGAL and UrNGAL/Cr were 0.807 and 0.747.ConclusionA significant tubular dysfunction among childhood cancer survivors receiving chemotherapy as cisplatin and high-dose methotrexate.ImpactDetection of kidney dysfunction mainly tubular in childhood cancer survivors after finishing chemotherapy.Urinary NGAL is a good predictor for detection of tubular dysfunction in childhood cancer survivors after finishing chemotherapy.

Cystatin C and mortality risk in the general population: systematic review and dose response meta-analysis

Introduction Cystatin C has been identified as an independent predictor of all-cause and cardiovascular mortality in the general population. This meta-analysis to evaluate the association between serum cystatin C level and all-cause and cardiovascular mortality. We additionally conducted a dose-response analysis to examine a linear association between cystatin C and cardiovascular mortality. Methods PudMed and Embase databases were searched until January, 2021. All prospective cohort studies that reported a multivariate-adjusted risk estimated of all-cause and cardiovascular mortality for the highest compared with lowest cystatin C level were included. Results 13 prospective cohort studies, a total of 57,214 participants were included in this analysis. Meta-analysis indicated that the highest compared with lowest cystatin C level was associated with an increase of all-cause mortality (hazard ratio [HR]: 2.01; 95% confidence intervals [CI]: 1.60–2.53; I 2=89%) and cardiovascular mortality (2.62 [1.96–3.51]; I 2=52%). We found a significant log-linear dose-response association between cystatin C and cardiovascular mortality (p < 0.01). Every 0.1 mg/L increase in cystatin C level was associated with a 7.3% increased cardiovascular mortality. Conclusions Elevated serum cystatin C is associated with an increased risk of all-cause and cardiovascular mortality in the general populations. Particularly, cystatin C level and cardiovascular mortality showed linear correlation.

Altered kidney function induced by SARS-CoV-2 infection and acute kidney damage markers predict survival outcomes of COVID-19 patients: a prospective pilot study

Background Literature with regard to coronavirus disease 2019 (COVID-19) associated morbidities and the risk factors for death are still emerging. In this study, we investigated the presence of kidney damage markers and their predictive value for survival among hospitalized subjects with COVID-19. Methods Forty-seven participants was included and grouped as: ‘COVID-19 patients before treatment’, ‘COVID-19 patients after treatment’, ‘COVID-19 patients under treatment in intensive care unit (ICU)’, and ‘controls’. Kidney function tests and several kidney injury biomarkers were compared between the groups. Cumulative rates of death from COVID-19 were determined using the Kaplan–Meier method. The associations between covariates including kidney injury markers and death from COVID-19 were examined, as well. Results Serum creatinine and cystatin C levels, urine Kidney Injury Molecule-1 (KIM-1)/creatinine ratio, and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI), CKD-EPI cystatin C, and CKD-EPI creatinine–cystatin C levels demonstrated significant difference among the groups. The most significant difference was noted between the groups ‘COVID-19 patients before treatment’ and ‘COVID-19 patients under treatment in ICU’. Advancing age, proteinuria, elevated serum cystatin C, and urine KIM-1/creatinine ratio were all significant univariate correlates of death (p < 0.05, for all). However, only elevated urine KIM-1/creatinine ratio retained significance in an age, sex, and comorbidities adjusted multivariable Cox regression (OR 6.11; 95% CI: 1.22–30.53; p = 0.02), whereas serum cystatin C showing only a statistically non-significant trend (OR 1.42; 95% CI: 0.00–2.52; p = 0.09). Conclusions Our findings clearly demonstrated the acute kidney injury related to COVID-19. Moreover, urine KIM-1/creatinine ratio was associated with COVID-19 specific death.

Early detection of kidney diseases in diabetic patients with serum cystatin-C

Background: Prevalence of chronic kidney disease (CKD) is increased worldwide. According to Kidney Disease Improving Global Outcomes guidelines, CKD is defined as abnormalities of kidney structure or function, present for >3 months with implications for health. In individuals with Type-2 diabetes, assessment of kidney function is mandatory, as diabetic nephropathy constitutes the major cause of CKD which leads to end-stage renal disease in diabetic patients. Cystatin-“C”, an alternative biomarker of kidney function, is a better predictor of CKD and is less affected by age, race, or muscle mass. Hence, the presence of elevated serum cystatin C is directly linked with risk of developing a progressive form of CKD. Aim and Objectives: This study aims to evaluate the importance of serum cystatin C as a marker for early detection of CKD in diabetic and non-diabetic patients. Materials and Methods: A total of 25 non-diabetics with CKD (Group-I) and 25 diabetics with CKD (Group-II) were included in the study. Cystatin C and glucose were estimated in the serum sample. Latex-enhanced immunoturbidimetric assay method was used for the estimation of serum cystatin-C. Random blood glucose was estimated using glucose oxidase-peroxidase method. Student’s t-test was used for comparison between CKD with non-diabetics and CKD with diabetics by SPSS statistical package version 20.0. “P” < 0.05 was considered as statistically significant. The results of the two groups are expressed as Mean ± SD. Results: Serum cystatin-C levels were significantly increased (P < 0.001) in Group-I when compared to Group-II. There was a significant negative correlation (r = –0.447, P < 0.001) between serum cystatin C and estimating glomerular filtration rate was observed, which indicates that there is a possibility of renal damage in non-diabetic subjects. Conclusion: Cystatin C can be used as a good alternative marker compared to creatinine for assessing severe kidney damage.

English

BACKGROUND Increased levels of urinary biomarkers can be detected in type 2 diabetic patients before the onset of significant albuminuria and may be used as an early marker of renal injury in diabetic nephropathy (DN) which would play a significant role for the effective management and treatment approaches in diabetic care. We wanted to evaluate cystatin C and microalbumin as effective early biomarkers in assessing nephropathy in patients with type 2 diabetes mellitus in this study. METHODS A cross-sectional study was conducted among 180 subjects grouped into healthy controls, clinically proven T2DM without nephropathy and type 2 DM with nephropathy comprising 60 participants in each group. Fasting and postprandial blood samples and urine samples were collected and analysed by standard methods. eGFR was calculated using CKD-EPI 2012 equation. IBM - SPSS version 20 was used for statistical analysis. RESULTS Diabetic nephropathy patients had significantly elevated serum cystatin C and microalbumin (2.43 ± 0.59, 700.5 ± 591.8 mg / L, respectively), compared to T2DM (0.98 ± 0.26, 63.7 ± 102.9 mg / L, respectively), and the control study subjects (0.81 ± 0.16, 11.15 ± 8.9 mg / L, respectively). Serum cystatin C showed AUC of 0.994 (95 % CI, 0.986 - 1.00) whereas microalbumin showed 0.944 (95 % CI, 0.907 - 0.981). Serum cystatin C showed a sensitivity of 96.7 % and a specificity of 91.7 % at a cutoff point of 1.34 mg / L whereas at a cut-off point of 138.5 mg / L for microalbumin, the sensitivity and specificity were 90 % and 83.3 % respectively. CONCLUSIONS Serum cystatin C and microalbumin both could be considered as markers for early detection of nephropathy in T2DM patients. The more prominent rise in serum cystatin C values provide an earlier diagnosis of diabetic nephropathy among T2DM patients. KEY WORDS Biomarker, Type 2 Diabetes Mellitus, Cystatin C, Diabetic Nephropathy, Microalbumin

Higher serum level of Cystatin C: An additional risk factor of CAD.

Cystatin C has been proposed as a useful biomarker of early impaired kidney function and a predictor of mortality risk. The present study is to investigate the association between serum Cystatin C and the severity of coronary artery lesions, Gensini score (GS), and the risk of coronary artery disease (CAD).A total of 682 CAD patients (230 females, 452 males; mean age 62.6 ± 10.7 years, range from 31 to 86 years) and 135 controls (41 females, 94 males; mean age 58.0 ± 10.3 years, range from 38 to 84 years) were recruited in the present study. Enzyme-linked immunosorbent assay was applied to measure serum cystatin C levels and other serum indexes. The estimated glomerular filtration rate and GS were calculated.Serum low-density lipoprotein cholesterol (LDL-C), uric acid, Cystatin C, and homocysteine (HCY) were significantly elevated in CAD patients compared to controls. There were significant differences regarding total cholesterol, triglyceride, high-density lipoprotein, low-density lipoprotein, cystatin C, eGFR and GS among stable angina pectoris (SAP), unstable angina group (UAP), and acute myocardial infarction (AMI) patients. AMI group had an elevated serum Cystatin C, LDL-C, HCY, and GS than SAP and UAP patients. When stratified patient groups by the quartiles of Cystatin C, we found age, the proportion of male and patients with diabetes, HCY, and GS were increased in Q4 than in other quartile groups. Spearman correlation test revealed a positive relationship between Cystatin C, HCY, and GS. Multivariate logistic regression analysis revealed that serum Cystatin C level, presence of hypertension and diabetes, HCY, age, and male were the risk factors for coronary artery lesions.In summary, our results suggested that cystatin C is a promising clinical biomarker that provides complementary information to the established risk determinants. The serum Cystatin C level is strongly associated with GS and could be used to evaluate the severity of coronary artery lesions.

Cystatin C, Vitamin D and Thyroid Function Test Profile in Chronic Kidney Disease Patients.

Background: The progression of chronic kidney disease (CKD) is concomitant with complications, including thyroid dysfunction, dyslipidemia and cardiovascular diseases. The aim of this study is to determine serum cystatin C levels, and the prevalence of vitamin D deficiency and thyroid dysfunction in CKD patients. Methods: A cross-sectional study was conducted involving 140 CKD patients (stages 1–5) that were referred to a renal clinic. Demographic data was collected and thyroid function tests, serum 25-OH-vitamin D, cystatin C levels, and routine biochemistry tests were determined using cobas 6000 analyzer. Results: 129 (92.1%) of CKD patients had elevated serum cystatin C levels and there was a stepwise increase from stage 1–5. Overt hypothyroidism was present in one patient and nine had subclinical hypothyroidism. There was a stepwise reduction in serum 25-OH-vitamin D levels from stage 2–5, 31 (22.1%) had vitamin D insufficiency and 31 (22.1%) presented with deficiency. Conclusions: 25-OH-vitamin D deficiency and thyroid disorders are exhibited in chronic kidney disease patients and the severity of the former rises with disease progression, as indicated by elevated cystatin C levels. Routine screening and timely intervention is recommended so as to reduce the risk of cardiovascular diseases.

Cystatin C is a potential predictor of unfavorable outcomes for cerebral ischemia with intravenous tissue plasminogen activator treatment: A multicenter prospective nested case–control study

The aim of this study was to explore whether cystatin C (CysC) could be used as a potential predictor of clinical outcomes in acute ischemic stroke (AIS) patients treated with intravenous tissue plasminogen activator (IV-tPA). We performed an observational study including a retrospective analysis of data from 125 AIS patients with intravenous thrombolysis. General linear models were applied to compare CysC levels between groups with different outcomes; logistic regression analysis and receiver-operating characteristic curves were adopted to identify the association between CysC and the therapeutic effects. Compared with the "good and sustained benefit" (GSB) outcome group (defined as ≥4-point reduction in National Institutes of Health Stroke Scale or a score of 0-1 at 24h and 7days) and the "good functional outcome" (GFO) group (modified Rankin Scale score 0-2 at 90days), serum CysC baseline levels were increased in the non-GSB and non-GFO groups. Logistic regression analysis found that CysC was an independent negative prognostic factor for GSB (odds ratio[OR]0.010; p=0.005) and GFO (OR 0.011; p=0.021) after adjustment for potential influencing factors. Receiver-operating characteristic curves showed the CysC-involved combined models provided credible efficacy for predicting post-90-day favorable clinical outcome (area under the curve0.86; p<0.001). Elevated serum CysC is independently associated with unfavorable clinical outcomes after IV-tPA therapy in AIS. Our findings provide new insights into discovering potential mediators for neuropathological process or treatment in stroke.

Risk factors and long-term outcomes of acute kidney injury complication after type A acute aortic dissection surgery in young patients

ObjectiveTo identify risk factors and long-term outcomes of acute kidney injury (AKI) in young patients who underwent type A acute aortic dissection (TA-AAD) emergency surgeries.MethodsThis retrospective study enrolled 121 consecutive patients less than 40 years old who received TA-AAD emergency surgeries between January 2014 to December 2018 in Nanjing Drum Tower hospital. The diagnosis of AKI was made based on the KDIGO criteria. Multivariable regression analysis was performed to identify risk factors for postoperative AKI. Kaplan–Meier curves were generated to compare long-term outcomes between patients with and without AKI complication after TA-AAD surgeries.ResultsAmong all enrolled patients, AKI occurred in 51 patients (42.1%) and renal replacement therapy (RRT) was required in 15 patients (12.4%). The development of postoperative AKI was associated with increased 30-day mortality (P = 0.041), longer ICU stay time (P < 0.001) and hospital stay time (P = 0.006). Multivariable analysis indicated that elevated preoperative serum cystatin C (sCyC) (OR = 6.506, 95% CI: 1.852–22.855, P = 0.003) was the only independent risk factor for developing AKI. The areas under the receiver-operating characteristic curve (AUC) of preoperative sCyC was 0.800 (95% CI: 0.719, 0.882). Preoperative sCyC had a sensitivity of 64.7% and a specificity of 83.8% in diagnosing postoperative AKI with a cut-off value of 0.895 mg/L. In addition, our data suggested there was no difference discovered regarding long-term cumulative survival rate between patients with and without AKI during a median 29 months follow-up period.ConclusionsPostoperative AKI after TA-AAD surgeries was relatively common in young patients and associated with increased short-term mortality. Elevated preoperative sCyC was identified as an independent risk factor for AKI with potential diagnostic merit.

Repeated Administration of Clinical Doses of Tramadol and Tapentadol Causes Hepato- and Nephrotoxic Effects in Wistar Rats

Tramadol and tapentadol are fully synthetic and extensively used analgesic opioids, presenting enhanced therapeutic and safety profiles as compared with their peers. However, reports of adverse reactions, intoxications and fatalities have been increasing. Information regarding the molecular, biochemical, and histological alterations underlying their toxicological potential is missing, particularly for tapentadol, owing to its more recent market authorization. Considering the paramount importance of liver and kidney for the metabolism and excretion of both opioids, these organs are especially susceptible to toxicological damage. In the present study, we aimed to characterize the putative hepatic and renal deleterious effects of repeated exposure to therapeutic doses of tramadol and tapentadol, using an in vivo animal model. Male Wistar rats were randomly divided into six experimental groups, composed of six animals each, which received daily single intraperitoneal injections of 10, 25 or 50 mg/kg tramadol or tapentadol (a low, standard analgesic dose, an intermediate dose and the maximum recommended daily dose, respectively). An additional control group was injected with normal saline. Following 14 consecutive days of administration, serum, urine and liver and kidney tissue samples were processed for biochemical, metabolic and histological analysis. Repeated administration of therapeutic doses of both opioids led to: (i) increased lipid and protein oxidation in liver and kidney, as well as to decreased total liver antioxidant capacity; (ii) decreased serum albumin, urea, butyrylcholinesterase and complement C3 and C4 levels, denoting liver synthesis impairment; (iii) elevated serum activity of liver enzymes, such as alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase and γ-glutamyl transpeptidase, as well as lipid profile alterations, also reflecting hepatobiliary commitment; (iv) derangement of iron metabolism, as shown through increases in serum iron, ferritin, haptoglobin and heme oxygenase-1 levels. In turn, elevated serum cystatin C, decreased urine creatinine output and increased urine microalbumin levels were detected upon exposure to tapentadol only, while increased serum amylase and urine N-acetyl-β-D-glucosaminidase activities were observed for both opioids. Collectively, these results are compatible with kidney injury. Changes were also found in the expression levels of liver- and kidney-specific toxicity biomarker genes, upon exposure to tramadol and tapentadol, correlating well with alterations in lipid profile, iron metabolism and glomerular and tubular function. Histopathological analysis evidenced sinusoidal dilatation, microsteatosis, mononuclear cell infiltrates, glomerular and tubular disorganization, and increased Bowman’s spaces. Although some findings are more pronounced upon tapentadol exposure, our study shows that, when compared with acute exposure, prolonged administration of both opioids smooths the differences between their toxicological effects, and that these occur at lower doses within the therapeutic range.

Antiretroviral Therapy and Bone Health

Abstract Objective: To determine the incidence of osteopenia and osteoporosis in Bulgarian human immunodeficiency virus (HIV)-infected patients. Methods: Bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry in 41 Bulgarian HIV-infected patients. Results: Overall, 27% of patients had reduced BMD (7% osteoporosis and 20% osteopenia). There was a significant correlation between low BMD and increasing age and between low BMD and duration of antiretroviral therapy (ART) but no correlation with gender, therapy regimen or serum calcium or phosphate levels. Seventy-one percent had elevated serum cystatin C levels but there was no correlation between BMD and cystatin C levels. Serum calcium, phosphate, cystatin C and creatinine levels and the T- and Z-scores were tested for dependence on duration of therapy. Dependence was found for T- and Z-scores, (p = 0.048 and p = 0.038) but not for calcium, phosphate, cystatin C or creatinine levels. These variables were subsequently tested by means of cross-tabulation tables for correlations between pairs of parameters; no significant correlation was found between any pairs (R &gt; 0.5 for all comparisons). Conclusions: Significant correlations were observed between low BMD and increasing age and longer duration of ART but no relationship was observed with gender or therapy regimen.