THE PRACTICAL USE OF CYSTATIN C MEASUREMENT IN PATIENTS WITH VARIOUS RENAL DISEASES

Objective:To investigate the clinical usefulness in terms of estimation for glomerular filtration rate(GFR), we determined the serum cystatin C levels in 72 healthy adults , 63 children, and 109 patients with various renal diseases, and compared the serum cystatin C concentrations with serum creatinine levels. In addition, the renal function was evaluated in 5 adults receiving renal transplantations using cystatin C.Methods:Serum cystatin C levels were measured by a particle-enhanced nephelometric immunoassay on Dade Behring nephelometer system. Serum and urine creatinine concentrations were determined by use of Jaff’s kinetic assay.Results: The cystatin C concentration at birth was typically double that found in adults, then fell to a constant level after 1 year, a value that was maintained to about 60 years. The studies of cystatin C in the elderly showed that the circulation cystatin C levels rose gradually above 60 years. There was a significant positive correlation between serum cystatin C and creatinine level (r=0.921, P <0.01) in the patients with various renal diseases. Serum cystatin C was inversely and logarithmically correlated with creatinine clearance as shown in the equation lg cystatin C =-0.6061gCCr+1.209(r=-0.887, P <0.01). Serum cystatin C levels rose prior to creatinine concentrations and started to increase over normal range when creatinine clearance remained within normal range. After renal transplantation,cystatin C concentration significantly decreased during the first week(-43% vs -21% for creatinine) in patients without delayed graft function. In some cases of acute renal impairment, the increase in serum cystatin C values was more prominent than that of creatinine.Conclusion:Serum cystatin C is probably more attractive for estimation of renal function than serum creatinine and creatinine clearance especially for detection of the mild reduction of glomerular filtrate rate in patients with various kidney diseases. Serum cystatin C can also be used as an alternative marker of allograft function in adult transplant patients.

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

BACKGROUND Coronary heart disease(CHD)and heart failure(HF)are the major causes of morbidity and mortality worldwide.Early and accurate diagnoses of CHD and HF are essential for optimal management and prognosis.However,conventional diagnostic methods such as electrocardiography,echocardiography,and cardiac biomarkers have certain limitations,such as low sensitivity,specificity,availability,and cost-effectiveness.Therefore,there is a need for simple,noninvasive,and reliable biomarkers to diagnose CHD and HF.AIM To investigate serum cystatin C(Cys-C),monocyte/high-density lipoprotein cholesterol ratio(MHR),and uric acid(UA)diagnostic values for CHD and HF.METHODS We enrolled 80 patients with suspected CHD or HF who were admitted to our hospital between July 2022 and July 2023.The patients were divided into CHD(n=20),HF(n=20),CHD+HF(n=20),and control groups(n=20).The serum levels of Cys-C,MHR,and UA were measured using immunonephelometry and an enzymatic method,respectively,and the diagnostic values for CHD and HF were evaluated using receiver operating characteristic(ROC)curve analysis.RESULTS Serum levels of Cys-C,MHR,and UA were significantly higher in the CHD,HF,and CHD+HF groups than those in the control group.The serum levels of Cys-C,MHR,and UA were significantly higher in the CHD+HF group than those in the CHD or HF group.The ROC curve analysis showed that serum Cys-C,MHR,and UA had good diagnostic performance for CHD and HF,with areas under the curve ranging from 0.78 to 0.93.The optimal cutoff values of serum Cys-C,MHR,and UA for diagnosing CHD,HF,and CHD+HF were 1.2 mg/L,0.9×10^(9),and 389μmol/L;1.4 mg/L,1.0×10^(9),and 449μmol/L;and 1.6 mg/L,1.1×10^(9),and 508μmol/L,respectively.CONCLUSION Serum Cys-C,MHR,and UA are useful biomarkers for diagnosing CHD and HF,and CHD+HF.These can provide information for decision-making and risk stratification in patients with CHD and HF.

Role of cystatin C and renal resistive index in assessment of renal function in patients with liver cirrhosis

AIM:To evaluate the clinical significance of cystatin C and renal resistive index for the determination of renal function in patients with liver cirrhosis.METHODS:We conducted a study of 63 patients with liver cirrhosis.A control group comprised of 30 age and gender-matched healthy persons.Serum cystatin C was determined in all study subjects and renal Doppler ultrasonography was made.Estimated glomerular filtration rate from serum creatinine(GFRCr)and cystatin C(GFRCys)was calculated.RESULTS:We confirmed significant differences in val-ues of cystatin C between patients with different stages of liver cirrhosis according to Child-Pugh(P=0.01),and a significant correlation with model of end stage liver disease(MELD)score(rs=0.527,P<0.001).More patients with decreased glomerular filtration rate were identified based on GFRCys than on GFRCr(P<0.001).Significantly higher renal resistive index was noted in Child-Pugh C than in A(P<0.001)and B stage(P=0.001).Also,a significant correlation between renal resistive index and MELD score was observed(rs=0.607,P<0.001).Renal resistive index correlated significantly with cystatin C(rs=0.283,P=0.028)and showed a negative correlation with GFRCys(rs=-0.31,P=0.016).CONCLUSION:Cystatin C may be a more reliable marker for assessment of liver insufficiency.Additionally,cystatin C and renal resistive index represent sensitive indicators of renal dysfunction in patients with liver cirrhosis.

Management of patients with hepatitis C infection and renal disease

Hepatitis C virus(HCV) infection in patients with end-stage renal disease(ESRD) is associated with more rapid liver disease progression and reduced renal graft and patients' survival following kidney transplantation. Evaluations and management of HCV in patients with renal disease are challenging. The pharmacokinetics of interferons(IFN), ribavirin(RBV) and some direct acting antiviral(DAA), such as sofosbuvir, are altered in patients with ESRD. With dose adjustment and careful monitoring, treatment of HCV in patients with ESRD can be associated with sustained virological response(SVR) rates nearly comparable to that of patients with normal renal function. DAA-based regimens, especially the IFNfree and RBV-free regimens, are theoretically preferred for patients with ESRD and KT in order to increase SVR rates and to reduce treatment side effects. However, based on the data for pharmacokinetics, dosing safety and efficacy of DAA for patients with severe renal impairment are lacking. This review will be focused on the evaluations, available pharmacologic data, and management of HCV in patients with severe renal impairment, patients who underwent KT, and those who suffered from HCV-related renal disease, according to the available treatment options, including DAA.

Clinical application of simultaneous detection of cystatin C,cathepsin S,and IL-1 in classification of coronary artery disease

Cystatin C,cathepsin S,and IL-1 are three important biomarkers of atherosclerosis.Previous studies emphasized the relationship between individual biomarkers in coronary artery disease（CAD） patients and severity of atherosclerostic lesions of the coronary arteries,while combined cystatin C,cathepsin S,and IL-1 have not been reported for clinical classification of CAD.We aimed to establish a link between cystatin C,cathepsin S,IL-1 and CAD in this cohort study.Totally 112 subjects were enrolled and divided into the stable angina pectoris group,the unstable angina pectoris group and the acute myocardial infarction（AMI） groups,and 50 healthy adults served as controls.The levels of the three biomarkers were detected by ELISA.The results showed that serum level of cystatin C（mg/L） was higher in CAD patients compared with those in the healthy controls（AMI vs.unstable angina pectoris vs.stable angina pectoris vs.controls：1.27±0.18 vs.1.09±0.19 vs.0.91±0.05 vs.0.78±0.07,all P〈0.01）.Cathepsin S（ng/mL） was also significantly different among the groups（AMI vs.unstable angina pectoris vs.stable angina pectoris vs.controls：67.30±8.36 vs.56.90±7.16 vs.49.8±2.72 vs.67.30±8.36,all P〈0.01）.IL-1（pg/mL） was significantly different among the groups as well（AMI vs.unstable angina pectoris vs.stable angina pectoris vs.controls：2.96±0.57 vs.2.46±0.24 vs.2.28±0.09 vs.2.02±0.13,all P〈0.01）.Spearman＇s correlation test revealed positive correlation between cystatin C,cathepsin S,IL-1 and Gensini score（r=0.451,0.491,0.397,respectively）.It is suggested that simultaneous detection of cystatin C,cathepsin S,and IL-1 in serum may be useful in clinical classification and assessment of severity of CAD.

Contribution of lysosomal cysteine proteases in cardiac and renal diseases

Cardiac and renal diseases(CRDs) are characterized by extensive remodeling of the extracellular matrix(ECM)architecture of the cardiorenal system. Among the many extracellular proteolytic enzymes present in cardiorenal cells and involved in ECM remodeling, members of the matrix metalloproteinase family and serine protease family have received the most attention. However, recent findings from laboratory and clinical studies have indicated that cysteine protease cathepsins also participate in pathogenesis of the heart and kidney.Deficiency and pharmacological inhibition of cathepsins have allowed their in vivo evaluation in the setting of pathological conditions. Furthermore, recent studiesevaluating the feasibility of cathepsins as a diagnostic tool have suggested that the serum levels of cathepsins L, S and K and their endogenous inhibitor cystatin C have predictive value as biomarkers in patients with coronary artery disease and heart and renal failure. The goal of this review is to highlight recent discoveries regarding the contributions of cathepsins in CRDs, particularly hypertensive heart failure and proteinuric kidney disease.

Serum cystatin C can be used as a marker of renal function even in patients with intestinal urinary diversion

Objective:Recently,serum cystatin C(CysC)has been used as a novel marker of renal function.However,there is a lack of data on CysC levels in patients with intestinal urinary diversion(UD).Here we report CysC levels in such patients.Methods:We prospectively observed 38 patients who were diagnosed with bladder cancer and subsequently treated with radical cystectomy and UD at our institution in 2012 and 2013.Serum creatinine(sCr)and CysC were obtained optionally at the same time at least 1 month after radical cystectomy and UD.Results:The median CysC and sCr concentrations were 1.12 mg/L(range 0.75-2.47 mg/L)and 0.99 mg/dL(range 0.61-2.22 mg/dL),respectively.The median estimated concentrations of glomerular filtration rate(GFR)based on CysC(eGFRcys)and GFR based on creatinine(eGFRcreat)were 61.08 mL/min/1.73 m^2(range 22.64e99.89 mL/min/1.73 m^2)and 58.01 mL/min/1.73 m^2(range 23.48e91.82 mL/min/1.73 m2),respectively.CysC had a significant correlation with sCr(r=0.8607,p<0.0001)and eGFRcreat(r=-0.8993,p<0.0001).eGFRcys also had a significant correlation with eGFRcreat(r=0.8104,p<0.0001).Conclusion:The correlation between CysC and sCr was strong and the correlation coefficient was equivalent to that in patients without UD.The results suggest that CysC is not affected by UD and can be used as a marker of renal function similarly to sCr in patients with UD.

Assessment of Cystatin C-Based GFR Estimating Equations as a Novel Reliable Biomarker for Renal Pathology Diagnosis in Patients with Mild to Severe Tubular Affection

Background and Objective: Serum creatinine, a commonly used biomarker in determining glomerular filtration rate (GFR) and chronic kidney disease (CKD) stage, is highly variable biologically and does not rise until > 50% of renal function (RF) impairment occurs. Also, its production is not constant & is affected by many factors as muscle mass, age, inflammation. On the other hand, Cystatin C shows more stable production making it more suitable for assessment of kidney function. Also, It has been shown that the progression of CKD to renal failure, even in glomerular diseases, correlated better with the degree of tubular damage and interstitial fibrosis. So, our aim was to investigate the relation between kidney function assessed by different cystatin (Cys-C)-based estimated glomerular filtration rate (eGFR) in comparison to the gold standard Iohexol (Ioh) based measured (m)GFR in relation to the pathological degree of tubular damage in renal biopsy. To our knowledge, this is the first study that evaluates the relation of (Cys-C)-based eGFR to tubulointerstitial fibrosis in renal biopsy. Methods: This cross-sectional study was performed on 20 CKD cases who attended the Nephrology Department at Ain Shams University, where a renal biopsy was obtained, and individuals were allocated into two groups: group A (GA) with mild tubular affection (TA) and group B (GB) with moderate to severe TA. All participants were referred for measure-ment of GFR using Iohexol (Ioh) together with serum Cys-C level and eGFR was calculated using different Cys-C-based GFR estimating equations, which were further compared using Multivariate Linear Regression and Bland-Altman analyses. Results: Our results revealed a substantial statistical difference among the two studied groups regarding Hb, s creatinine, urea. GB had significantly lower levels for both eGFR and mGFR (82, 93, 115, or 115) ml/min/1.73m2, Vs. GA (200, 123, 162 or 124) ml/min/1.73m2, according to GFR_iohexol, Stevens, Grubb, and CKD_EPI_CYST equations, respectively, p 0.05. A significant correlation between CKD-EPI CYST and mGFR_Iohexol (Ioh) for GA was found (R = 0.601, p = 0.030), where there was a non-substantial relation between any of the used equations and the mGFR in category B (p > 0.05). There was no independent association between the eGFR results and Iohexol clearance. Stevens eGFR had the highest-level bias 33.9 compared with CKD_EPI_CYST (28) and Grubb eGFR (22.85). Conclusion: eGFR by CysC-based equations underestimate GFR in comparison to GFR-iohexol. There is significant correlation between eGFR by CysC-based equations and the gold standard GFR-iohexol only in mild degree of tubular affection and only with CKD-EPI-CYST equation. Stevens equation showed the highest bias while Grubb equation showed the least bias. Although cystatin-based equations have demonstrated a high level of correlation with measured GFR, they are still regarded as imprecise and cannot be established as equal to measured GFR or as a gold standard for GFR estimate.

Serum cystatin C levels are negatively correlated with post-stroke cognitive dysfunction

Stroke is the leading cause of death and long-term disability worldwide,and cognitive impairment and dementia are major complications of ischemic stroke.Cystatin C (CysC) has been found to be a neuroprotective factor in animal studies.However,the relationship between CysC levels and cognitive dysfunction in previous studies has revealed different results.This prospective observational study investigated the correlation between serum CysC levels and post-stroke cognitive dysfunction at 3 months.Data from 638 patients were obtained from the China Antihypertensive Trial in Acute Ischemic Stroke (CATIS).Cognitive dysfunction was assessed using the Mini-Mental State Examination (MMSE) at 3 months after stroke.According to the MMSE score,308 patients (52.9%) had post-stroke cognitive dysfunction.After adjusting for potential confounding factors,the odds ratio (95% CI) of post-stroke cognitive dysfunction for the highest quartile of serum CysC levels was 0.54 (0.30–0.98),compared with the lowest quartile.The correlation between serum CysC and cognitive dysfunction was modified by renal function status.We observed a negative linear dose-response correlation between CysC and cognitive dysfunction in patients with normal renal function (Plinearity = 0.044),but not in those with abnormal renal function.Elevated serum CysC levels were correlated with a low risk of 3-month cognitive dysfunction in patients with acute ischemic stroke,especially in those with normal renal function.The current results suggest that CysC is a protective factor for post-stroke cognitive dysfunction,and could be used to treat post-stroke cognitive dysfunction.The CATIS study was approved by the Institutional Review Boards at Soochow University from China (approval No.2012-02) on December 30,2012,and was registered at ClinicalTrials.gov (identifier No.NCT01840072) on April 25,2013.

The Relationship of Cystatin C,Creatinine,Estimated GFR,and Cardiovascular Events

This study examined the predictive value of plasma cystatin C,creatinine and estimated glomerular filtration rate (eGFR) as risk factors for cardiovascular disease in Chinese.Plasma cystatin C and creatinine were measured in 466 coronary heart disease (CHD) patients recruited from 4 hospitals and 349 healthy controls from local communities in Wuhan,China.Cockroft-Gault formula was used to estimate the glomerular filtration rate (GFR) after adjusting for body surface area.With each measure,the study population was divided into quintiles.The results showed that the patients had significantly higher levels of plasma cystatin C,creatinine,and lower level of eGFR than controls.Lower eGFR was associated with a higher risk of cardiovascular events.As compared with the first (highest) quintile,the hazard ratios (and 95% CIs) after multivariate adjustment for CHD were as follows:third quintile,2.98 (1.54-5.78);fourth quintile,3.34 (1.58-7.09);fifth quintile,4.37(1.84-10.35).With higher cystatin C quintiles (≥1.00 mg/L and ≥1.17 mg/L),the hazard ratios for CHD were 2.16 (1.23-3.81) and 2.34 (1.25-4.38),similar to those of creatinine 2.21 (1.21-4.03) and 2.03 (1.07-3.84).However,it was plasma cystatin C not eGFR or creatinine had stronger association with ischemic stroke.The highest quintile had the hazard ratio of 4.51 (1.45-14.08) after multivariate adjustment.It was concluded that plasma cystatin C,associated with renal function,is not an independent risk factor for cardiovascular disease.eGFR is a better risk predictor for CHD than plasma cystatin C and creatinine.But for ischemic stroke,plasma cystatin C is a better risk factor than creatinine and estimated GFR.

Predictive value of serum cystatin C for risk of mortality in severe and critically ill patients with COVID-19

BACKGROUND The outbreak of coronavirus disease 2019(COVID-19)has rapidly evolved into a global pandemic.COVID-19 is clinically categorized into mild,moderate,severe,and critical illness.Acute kidney injury is an independent risk factor for poor prognosis in patients with.Serum cystatin C(s Cys C)is considered a more sensitive biomarker for early renal insufficiency than conventional indicators of renal function.Early detection of risk factors that affect the prognosis of severe and critically ill patients while using active and effective treatment measures is very important and can effectively reduce the potential mortality rate.AIM To determine the predictive value of s Cys C for the prognosis of patients with COVID-19.METHODS The clinical data of 101 severe and critically ill patients with COVID-19 at a designated hospital in Wuhan,Hubei Province,China were analyzed retrospectively.According to the clinical outcome,the patients were divided into a discharge group(64 cases)and a death group(37 cases).The general information,underlying diseases,and laboratory examination indexes of the two groups were compared.Multivariate Cox regression was used to explore the relationship between s Cys C and prognosis.The receiver operating characteristic(ROC)curve was used to demonstrate the sensitivity and specificity of s Cys C and its optimal cut-off value for predicting death.RESULTS There were significant differences in age,s Cys C,creatinine,C-reactive protein,serum albumin,creatine kinase-MB,alkaline phosphatase,lactate dehydrogenase,neutrophil count,and lymphocyte count between the two groups(P<0.001).Multivariate logistic regression analysis showed that s Cys C was an independent risk factor for death in patients with COVID-19(Odds ratio=1.812,95%confidence interval[CI]:1.300-2.527,P<0.001).The area under the ROC curve was 0.755(95%CI:1.300-2.527),the cut-off value was 0.80,the specificity was 0.562,and the sensitivity was 0.865.CONCLUSION s Cys C is an independent risk factor for death in patients with COVID-19.Patients with a s Cys C level of 0.80 mg/L or greater are at a high risk of death.

Comparison between Cystatin C and Traditional GFR Endogenous Markers

During the tests of glomerular filtration function,serum creatinine,urea and endogenous creatinine clearance rate are the most commonly used indicators,which possess many disadvantages.Currently,a large number of studies have been conducted on investigating new indicators reflecting changes in glomerular filtration rate.As a low-molecular weight protein,cystatin C is a member of cysteine protease inhibitor superfamily,which can be produced by all the nucleated cells in vivo with a stable generation rate.In the circulation process in vivo,cystatin C can only be removed via glomerular filtration,which is an ideal endogenous marker reflecting changes in glomerular filtration rate.Serum cystatin C concentration is superior to serum creatinine concentration in renal function tests.

Two-Hour Creatinine Clearance and Glomerular Filtration Rate Estimated from Serum Cystatin C and Creatinine in the Elderly to Preoperative Period

Introduction: The utility of estimates of glomerular filtration rate based on creatinine and cystatin C serum levels to assess renal function in older surgical patients remains to be determined. Objective: To determine whether 2h-creatinine clearance (CrCl-2h) can be an adequate substitute for glomerular filtration rate estimates obtained by measuring serum cystatin C and creatinine in the elderly at preoperation. Methods: A total of 102 consecutive elder patients undergoing pre-anesthesia evaluation for routine surgeries were included. Study subjects were allocated into three groups: Group 1 (G1)—hypertensive diabetic patients, Group 2 (G2)—hypertensive patients, and Group 3 (G3)—non-hypertensive and non-diabetic patients. Two-hour urine collection was performed and CrCl-2h adjusted for ultrasonic residual bladder volume was estimated. GFR was estimated based on creatinine and cystatin C serum levels. Bland-Altman analysis was used to compare methods. Results: The mean difference between the evaluated methods and CrCl-2h was &middotmin-1&middot1.73 m-2 for Cys-GFR, and >20 mL&middotmin-1&middot1.73 m-2 for Cr-GFR in all groups. CrCl-2h adjusted for ultrasonic residual bladder volume did not differ from non-adjusted CrCl-2h in none of the groups. Conclusion: Two-hour creatinine clearance was not an adequate substitute for GFR estimates based on creatinine and cystatin C serum levels in older patients at preoperation. The ultrasonic assessment of residual bladder volume had no significant influence on the calculation of two-hour creatinine clearance.

Sofosbuvir Use in the Setting of End-stage Renal Disease:A Single Center Experience

Background and Aims:Patients with chronic hepatitis C (CHC) and end-stage renal disease (ESRD) who are dialysisdependent form a unique group,in which safety,tolerability and efficacy of sofosbuvir (SOF)-based direct-acting antivirals (DAAs) need further evaluation.Methods:We performed a retrospective analysis of 14 patients with CHC and ESRD on dialysis who received 15 courses of SOF-based therapy.We evaluated dose escalation to standard-dose SOF in this proof-of-principle experience.Results:Sustained virological response (defined as undetectable viral load at 12 weeks,SVR-12) was achieved in 13 out of the 15 (86.7%) treatment courses.Seven (46.6%) patients received reduced half dose as conservative proof-of-principal to mitigate potential toxicity.In 13 out of 15 treatment courses,patients completed the designated treatment duration.One patient was treated twice and developed SVR-12 with the retreatment.One patient was lost to follow-up and counted as a non-responder.Premature discontinuations were not due to DAA-related adverse effects.There were no reports of severe adverse effects or drug interactions.Conclusion:We treated CHC patients with ESRD using dose escalation to standard-dose SOF in this proof-of-principle experience and achieved SVR rates comparable to general population.

Prognostic values of serum cystatin C and β2 microglobulin, urinary β2 microglobulin and N-acetyl-β-D-glucosaminidase in early acute renal failure after liver transplantation

Background Acute renal failure （ARF） after liver transplantation is associated with high mortality and morbidity. Early therapeutic or preventive intervention is hampered by the lack of early effective prognostic factors. Recent studies indicated that serum levels of cystatin C and β2-microglobulin （β2 MG） as well as urinary β2 MG and N-acetyI-β-D- glucosaminidase （NAG） would increase in patients with early and mild renal impairment. In this study, these factors were detected during the different stages in patients who accepted orthotopic liver transplantation （OLT）, and their feasibilities to predict early ARF after OLT were also analyzed. Methods Sixty patients with normal blood urea nitrogen （BUN） and serum creatinine （SCr） who received modified piggyback liver transplantation without veno-venous bypass were prospectively studied. Blood samples were drawn from patients for the determination of serum β2 MG（n=60）, SCr （n=60） and serum Cystatin C （n=39） at following 5 intervals： before operation （TO）, 20 minutes before anhepatic phase （T1）, 25 minutes in anhepatic （T2）, 60 minutes after reperfusion （T3） and at the end of operation（T4）. Urinary B2 MG （n=60） and NAG （n=60） were also examined at following 3 intervals： before operation （TO）, 60 minutes after reperfusion （T3） and at the end of operation （T4）. According to the Rimola A criteria of ARF in 24 hours after operation, all the patients were divided into two groups： ARF group and non-ARF group. The data were statistically analyzed to evaluate the feasibiliy of regarding these factors as prognostic factors for early ARF after liver transplantation in patients with normal SCr and BUN before operation. Results Ten of sixty cases showed ARF（16.7%）. The Logistic regression analysis showed that the levels of serum and urinary β2 MG as well as serum cystatin C before operation were correlated with early ARF after liver transplantation （P 〈0.05）, while only serum levels of cystatin C and Cr at the end of operation correlated with early ARF （P〈0.05, P〈0.01） after liver transplantation. The serum β2 MG, Cystatin C, SCr and urinary β2 MG levels in ARF group were much more higher than that in non-ARF group（P 〈0.05, P 〈0.01）. There were significant differences between the correct and false predictive positive ratios of serum cystatin C, serum and urinary β2 MG levels before operation （P 〈0.05, P 〈0.01）, while only SCr showed significant difference between these groups at the end of operation （P 〈0.01）. Conclusions The results revealed that there was potential renal damage among those patients who demonstrated normal SCr and BUN before operation, and that liver transplantation could aggravate this damage and causing ARF. Here we provided the prognostic values of serum Cystatin C, β2 MG, urinary β2 MG and NAG in patients with early acute renal failure after liver transplantation.

Increased Serum Cystatin C in Early Parkinson’s Disease with Objective Sleep Disturbances

Background：Sleep disturbance is one of the major non-motor symptoms which cause the disability of Parkinson’s disease （PD） patients. Cystatin C （CysC） is a more sensitive biomarker than serum creatinine or estimated glomerular filtration rate. Previous studies have reported altered CysC levels in neurodegenerative disorders and sleep disorders. This study aimed to explore the correlations of serum CysC levels and objective sleep disturbances in early PD.Methods：We recruited 106 early PD patients and 146 age- and sex-matched controls. All participants underwent clinical investigation and video-polysomnography. Sleep parameters and serum levels of CysC were measured. Then, we investigated the relationships between CysC and clinical variables and objective sleep disturbances in early PD patients.Results：The mean serum level of CysC was significantly higher in patients with early PD （1.03 ± 0.19 mg/L） compared to controls （0.96 ± 0.15 mg/L, P = 0.009）. There were significantly positive correlations between serum CysC levels and age （r = 0.334, P 〈 0.001）, gender （r = 0.264, P = 0.013）, and creatinine levels （r = 0.302, P = 0.018） in early PD patients. Increased serum CysC levels in early PD patients were significantly associated with higher apnea and hypopnea index （AHI） （r = 0.231, P = 0.017）, especially hypopnea index （r = 0.333, P 〈 0.001）. In early PD patients, elevated serum CysC levels were positively correlated with oxygen desaturation index （r = 0.223, P = 0.021）, percentage of time spent at oxygen saturation （SaO2） 〈90% （r = 0.644, P 〈 0.001）, arousal with respiratory event during sleep （r = 0.247, P = 0.013）. On the contrary, the elevated serum CysC levels were negatively correlated with mean and minimal SaO2 （r = ？0.323, ？0.315, both P = 0.001） in PD patients.Conclusions：The level of serum CysC was higher in early PD patients. PD patients with elevated serum CysC levels had more respiratory events and more severe oxygen desaturation. Therefore, the serum CysC levels may predict the severities of sleep-disordered breathing problems in early PD patients.

Association of cystatin C level and cardiovascular prognosis for patients with preexisting coronary heart disease:a meta-analysis

The association of circulating levels of cystatin C(CysC)and risk of recurrent cardiovascular events in patients with preexisting coronary heart disease are uncertain.To qualitatively and quantitatively address this issue,we performed a random meta-analysis of results from prospective studies on the topic.We searched electronic and printed sources(up to 16 October 2011)using keywords and retrieved articles for seven prospective studies according to the selection criteria.Data were abstracted and meta-analysis was performed using the random-effects model(RevMan 5.0.23 software).The cohorts involved 4,576 patients with preexisting coronary heart disease(CHD)and normal or mild chronic kidney disease,and follow-up ranged from 5.6 to 40.6 months.Highest versus lowest baseline CysC level was significantly associated with increased risk of cardiovascular events(OR 2.30,95%CI 1.80–2.94),all-cause mortality(OR 5.69,95%CI 3.70–8.74),but not with recurrent MI(OR 1.75,95%CI 0.77–4.00).In heterogeneity testing for studies reporting cardiovascular events and all-cause mortality,no significant heterogeneity was found,and exclusion of any single study did not alter the overall finding.For risk of recurrent MI,significant heterogeneity was found among the five trials(v2=13.16,P=0.01,I2=70%)and exclusion of the Taglieri et al.[12]study from the analysis resulted in a rise in relative risk(OR 2.36,95%CI 1.09–5.15).In conclusion,for patients with established CHD,high baseline level of CysC is associated with increased risk of cardiovascular events and all-cause death during long-term follow-up.

Urinary cystatin C:pediatric reference intervals and comparative assessment as a biomarker of renal injury among children in the regions with high burden of CKDu in Sri Lanka

Background Cystatin C(Cys-C)is an emerging biomarker of renal diseases and its clinical use,particularly for screening the communities affected by chronic kidney disease of unknown etiology(CKDu),is hindered due to the lack of reference intervals(RIs)for diverse ethnic and age groups.The present study aimed to define RIs for urinary Cys-C(uCys-C)for a healthy pediatric population in Sri Lanka and in turn compare the renal function of the residential children in CKDu endemic and non-endemic regions in Sri Lanka.Methods A cross-sectional study was conducted with 850 healthy children(10-17 years)from selected locations for reference interval establishment,while a total of 892 children were recruited for the comparative study.Urine samples were collected and analyzed for Cys-C,creatinine(Cr)and albumin.Cr-adjusted uCys-C levels were partitioned by age,and RIs were determined with quantile regression(2.5th,50th and 97.5th quantiles)at 90%confidence interval.Results The range of median RIs for uCys-C in healthy children was 45.94-64.44 ng/mg Cr for boys and 53.58-69.97 ng/mg Cr for girls.The median(interquartile range)uCys-C levels of children in the CKDu endemic and non-endemic regions were 58.18(21.8-141.9)and 58.31(23.9-155.3)ng/mg Cr with no significant difference(P=0.781).A significant variation of uCys-C was noted in the children across age.Conclusions Notably high uCys-C levels were observed in children with elevated proteinuria.Thus,uCys-C could be a potential biomarker in identifying communities at high risk of CKDu susceptibility.

Anti-hepatitis C virus therapy in chronic kidney disease patients improves long-term renal and patient survivals

BACKGROUND Hepatitis C virus (HCV) infection is a documented risk factor for chronic kidney disease (CKD) and progression to end-stage renal disease (ESRD). However, to date there are no reports on the long-term hard endpoints (ESRD and death) of anti-HCV therapy [interferon-based therapy (IBT) or new direct-acting antivirals] in CKD patients. Direct-acting antivirals are not available in Taiwan’s singlepayer national health insurance database currently released for research. Therefore, we hypothesized that a retrospective analysis of the long-term outcomes of IBT in CKD patients will serve as a proxy for direct-acting antivirals to increase our understanding of progression to ESRD following HCV infection. AIM To evaluate the long-term outcomes (ESRD and death) of anti-HCV therapy, especially IBT, in HCV-infected patients with stage 1-5 CKD. METHODS We analyzed 93894 Taiwan Residents adults diagnosed with CKD and without HBV infection. Of these, 4.9% were infected with HCV. Of the 4582 HCV-infected CKD patients, 482 (10.5%) received IBT (treated cohort). They were matched 1:4 with 1928 untreated HCV-infected CKD patients (untreated cohort) by propensity scores and year, which further matched 1:2 by propensity scores with 3856 CKD patients without HCV infection (uninfected cohort). All participants were followed until the occurrence of ESRD, death, or the end of 2012. The association between HCV infection, IBT use, and risks of ESRD and death was analyzed using competing risk analysis. RESULTS Taking the uninfected cohort as a reference, the adjusted hazard ratios for ESRD, after adjusting for competing mortality, were 0.34 (0.14-0.84, P = 0.019) and 1.28 (1.03-1.60, P = 0.029) in the treated and untreated cohorts, respectively. The treated cohort had a 29%(0.54-0.92, P = 0.011) decrease in mortality compared to the untreated cohort, in which the mortality was 31%(1.18-1.45, P < 0.001) higher than in the uninfected cohort. The reduced risks of ESRD (0.14, 0.03–0.58, P = 0.007) and death (0.57, 0.41-0.79, P = 0.001) were greatest in HCV-infected CKD patients who received at least 4 mo of IBT, which accounted for 74% of the treated cohort.CONCLUSION Adequate anti-HCV therapy in CKD patients improves long-term renal and patient survival.

Intermediate conductance, Ca^2＋-activated K^＋ channels： a novel target for chronic renal diseases

Renal failure is a medical condition in which the kidneys are not working properly. There are two types of kidney failure： 1） acute kidney failure, which is sudden and often reversible with adequate treatment; and 2） chronic renal failure, which develops slowly and often is not reversible. The last stage of chronic renal failure is fatal without dialysis or kidney transplant. The treatment for chronic renal failure is focusing on slowing the progression of kidney damage. Several reports have described a promising approach to slow the loss of renal function through inhibition of the basolateral membrane, Ca^2＋-activated K^＋ （KCa3.1） channel with a selective and nontoxic blocker TRAM-34. This review summarizes pathophysiological studies that describe the role of KCa3.1 in kidney diseases.