胱抑素C对造影剂肾病早期的预测价值

<正>造影剂肾病(CIN)是指使用造影剂48 h内发生的排除其他原因的急性肾功能损害〔1〕。目前CIN的诊断仍以血肌酐(Scr)浓度升高作为评判标准,但Scr浓度容易受多种因素的影响,以该指标作为肾功能损害评判指标缺乏敏感性及特异性。目前,胱抑素(Cys)C在评价肾功能损害中具有良好的敏感性和特异性。本研究探讨Cys C对CIN的早期预测价值。1对象与方法     

血清胱抑素C在糖尿病肾病早期诊断方面的研究进展

糖尿病肾病(diabetic nephropathy)是糖尿病的主要慢性并发症之一,已成为终末期肾功能衰竭的首位原因.肾功能主要由肾小球滤过率(renal glomerular filtration rate,GFR)反映.近年来相关临床试验已证明,血清胱抑素C(cystatin C,Cys C)与GFR有良好相关性,可以将其作为GFR的替代指标用于糖尿病肾病的诊断.Cys C是一种低分子量蛋白质,相对分子量小,是半胱氨酸蛋白酶抑制物超家族的成员之一,可由机体所有有核细胞产生,产生率恒定.循环中的Cys C能够自由通过肾小球滤过膜,并在近曲小管几乎完全被重吸收,不再重新回到血液循环中,同时,肾小管也不分泌Cys C,因此它是一种反映肾小球滤过率变化的理想的内源性标志物.Cys C测定的方法学也在不断发展,使血清Cys C测定在糖尿病肾病早期诊断的临床应用和推广成为可能.     

血清胱抑素C与糖尿病肾病

血清胱抑素C是一种半胱氨酸蛋白酶抑制剂,由机体所有有核细胞以恒定的速率产生,其相对分子质量小,可被肾小球自由滤过,在近端肾小管被代谢.血清胱抑素C作为一种内源性标志物,可以较早的反映肾小球滤过率的变化,故其在糖尿病肾病早期诊断中有重要的价值.     

早期胱抑素C检测指导水化疗法预防造影剂肾病

目的:根据胱抑素C(Cys C)水平调整造影术后补液方案,观察其预防造影剂肾病(CIN)的效果。方法:280例冠状动脉造影患者随机分为常规水化组和指导水化组各140例,前者根据造影剂用量指导补液量,后者根据术后8h血清Cys C水平指导补液量,检测术前及术后8h、24h、48h血清Cys C及血清肌酐(SCr)水平,并进行比较分析。结果:常规水化组输液量较指导水化组多[(828.4±344.6)ml∶(746.6±308.2)ml,P<0.05];常规水化组有7例发生CIN,4例发生心力衰竭,而指导水化组无一例发生CIN及心力衰竭。结论:根据Cys C水平调整造影术后水化方案,能有效预防CIN的发生,并可避免过多输液加重心脏负担。     

血清胱抑素C在2型糖尿病肾病诊断中的应用

目的探讨血清胱抑素C(Cys-C)在2型糖尿病肾病诊断中的应用价值。方法选取昆明医科大学第一附属医院肾内科住院部2016年9月—2017年12月收治的2型糖尿病患者355例,其中按照尿白蛋白肌酐比值(ACR)不同,分为正常白蛋白尿组、微量白蛋白尿组、大量白蛋白尿组,分别检测3组患者血清胱抑素C(Cys-C)、尿素(Urea)、血肌酐(Scr)及肾小球滤过率(eGFR,以MDRD公式计算)。结果微量白蛋白尿组及大量白蛋白尿组Cys-C水平均明显高于正常白蛋白尿组(P<0.05)。糖尿病肾病组中Cys-C、Urea、Scr、eGFR阳性率分别为95%、71%、86%、96%,且Cys-C和eGFR检测阳性率结果明显高于Urea和Scr(P<0.05)。结论Cys-C更为准确地反映肾小球滤过功能,尤其在诊断糖尿病患者早期肾损伤中具有重要临床意义。     

造影剂肾病患者尿胱抑素C及血尿酸水平变化的临床意义

目的 探讨尿胱抑素C及血尿酸水平变化诊断造影剂肾病的临床意义.方法 将确诊发生造影剂肾病患者48例分为重型造影剂肾病组（达到造影剂肾病诊断标准后72 h内血肌酐未恢复到造影前基础水平）17例和轻型造影剂肾病组（达到造影剂肾病诊断标准后72 h内血肌酐恢复到造影前基础水平）31例.造影检查前后留取患者6h尿及空腹晨血,检测其血肌酐、尿肌酐、血胱抑素C、尿胱抑素C及血尿酸水平.结果 造影后与造影前比较,两组血肌酐、血胱抑素C、血尿酸水平明显增高（P均＜0.05）.造影后重型造影剂肾病组与轻型造影剂肾病组比较,尿胱抑素C、血尿酸水平明显升高（P均＜0.05）.结论 尿胱抑素C及血尿酸可以作为早期预测严重造影剂肾病的指标.     

胱抑素C在糖尿病肾病肾功能评估中的地位

临床上多应用内源性滤过标志物及其相关公式进行肾小球滤过率的估算。通过与其它。肾功能指标的比较,胱抑素C在糖尿病肾病患者肾小球滤过率估算方面具有优势,尤其在肾功能损伤早期诊断中有较高的灵敏度。     

血清胱抑素C在糖尿病肾病早期诊断中的意义

目的探讨血清胱抑素(Cys)C早期诊断糖尿病肾病(DN)的意义。方法 2型糖尿病患者140例按照尿清蛋白排泄率(UAER)分为糖尿病组(UAER30 mg/24 h,n=94)和DN组(UAER≥30 mg/24 h,n=46),并选取同期体检的健康者60例作为对照组。比较三组空腹血糖(FPG)、餐后2 h血糖(2 h PG)、糖化血红蛋白(Hb A1c)及尿微量清蛋白(m Alb)、肾功能相关指标及Cys C水平。结果 DN组和糖尿病组FPG、2 h PG、Hb A1c、m Alb、尿素氮(BUN)、血肌酐(Scr)、尿β2微球蛋白(MG)及Cys C水平均显著高于对照组,DN组FPG、2 h PG、Hb A1c、m Alb、BUN、Scr、β2-MG及Cys C水平显著高于糖尿病组(P0.05)。DN组BUN、Scr、β2-MG及Cys C阳性率显著高于糖尿病组和对照组,DN组Cys C阳性率显著高于同组的BUN、Scr、β2-MG阳性率(P0.05)。Cys C对DN早期诊断的灵敏度、特异度和准确度分别为86.96%、90.26%和85.24%,灵敏度显著高于BUN、Scr和β2-MG(P0.05),特异度显著高于β2-MG(P0.05),准确度显著高于BUN、Scr和β2-MG(P0.05)。结论血清Cys C早期诊断DN具有较高的灵敏度、特异度及准确度。     

胱抑素C的检测方法及临床应用进展

胱抑素C（CysC）为半胱氨酸蛋白酶抑制剂,亦称γ-微量蛋白及γ-后球蛋白,是一种低相对分子质量（13kD）的碱性非糖化蛋白质。近年来,CysC成为反映肾小球滤过率（GFR）的理想内源性标志物,广泛用于肾功能早期损伤判定、肿瘤及脑部病变诊断、肾移植术等领域。现将其检测方法及临床应用进展综述如下。     

胱抑素与老年肌酐正常肾损害患者肾小球滤过率的相关性研究

目的探讨在血清肌酐正常的老年肾损害患者中,胱抑素(cystatinC,Cys-C)对肾小球滤过率(GFR)评价的意义。方法对2002-11~2003-12泸州医学院附属医院86例有肾损害但血清肌酐(Scr)正常的老年患者,应用乳胶颗粒增强比浊法测定血清中Cys-C浓度,并采用CockCroft-Cault公式计算内生肌酐清除率(Ccr)。分别比较Cys-C与Scr和Ccr的相关性。结果56例Cys-C升高超过正常,占56.1%;比较Ccr≤59mL/min和Ccr>59mL/min两组间的Cys-C质量浓度发现,当Ccr≤50mL/min时,97.1%的患者Cys-C超过正常,在Ccr>59mL/min时,已有44.2%患者Cys-C超过正常。血清Cys-C与Scr存在高度的正直线相关(r=0.89,P<0.01);Cys-C与Ccr存在高度的负直线相关(r=-0.87,P<0.01)。结论在老年患者中,Cys-C比Scr和Ccr更敏感地反映早期肾小球滤过率的下降。     

Use of cystatin C-based estimations of glomerular filtration rate in patients with type 2 diabetes

Aims/hypothesis  The Modification of Diet in Renal Disease (MDRD) equation has recognised limitations when using estimated GFR in persons at risk of chronic kidney disease. Equations based on cystatin C provide an alternative method. We compared performance of the MDRD equation with a selection of cystatin C-based formulae for estimation of GFR in normoalbuminuric patients with type 2 diabetes. Methods  Estimated GFR was calculated using the MDRD equation and the cystatin C formulae proposed by several investigator teams. Isotopic GFR was measured using plasma clearance of ⁵¹Cr-EDTA. Results  We studied 106 participants, of whom 83 (78%) were men with the following characteristics, mean (SD): age 61 (9) years, HbA_1c 7.10 (1.27)%, creatinine 89.0 (12.7) μmol/l, cystatin C 0.859 (0.234) mg/l and isotopic GFR 104.5 (20.1) ml min⁻¹ 1.73 m⁻². MDRD estimated GFR was 77.4 (13.6) ml min⁻¹ 1.73 m⁻² (p < 0.05 for difference from isotopic GFR). Cystatin C-based calculations of estimated GFR were: Perkins 124.5 (31.8), Rule 90.0 (30.0), Stevens (age) 96.0 (30.4) and Stevens (creatinine) 85.6 (19.0) ml min⁻¹ 1.73 m⁻² (p < 0.05 for difference with isotopic GFR). For Arnal’s, MacIsaac’s and Tan’s formulae cystatin-C estimated GFR were 101.7 (34.8), 102.1 (27.0) and 101.6 (27.8) ml min⁻¹ 1.73 m⁻², respectively (p = NS for difference with isotopic GFR). Cystatin C-based formulae were less biased and, with the exception of Perkins’ formula, more accurate to within 10% of isotopic GFR than MDRD. Conclusions/interpretation  Performance of cystatin C equations was superior to MDRD in normoalbuminuric patients with type 2 diabetes. These results support further evaluation of cystatin C for estimation of GFR in persons at risk of chronic kidney disease.     

Serum cystatin C versus serum creatinine in the estimation of glomerular filtration rate in rhabdomyolysis

Cystatin C has emerged as a possible, usable surrogate marker of renal function. We present a case that illustrates the clinical utility of cystatin C in the setting of acute kidney injury secondary to rhabdomyolysis. An African American male whose baseline cystatin C and serum creatinine levels taken a month prior to admission were compared against their daily values during his admission and at follow up. On admission, the patient's reduction in glomerular filtration rate (GFR) from baseline was much less when calculated with cystatin C than with serum creatinine. His clinical recovery was more reflective of the higher GFR with cystatin C than what would be assumed with his serum creatinine, which at its worst was 5 ml/min/1.73 m(2). The patient was eventually discharged from the hospital with a GFR of 40 ml/min by cystatin C despite his GFR by the MDRD equation being 12. Cystatin C may be a more accurate marker of the both the amount of injury and the rate of resolution of acute kidney injury than serum creatinine in rhabdomyolysis.     

中青年高血压病患者肱动脉脉压与肾小球滤过率的相关性研究

目的:探讨原发性高血压患者肱动脉脉压与肾小球滤过率(glomerular filtration rate,GFR)的相关性关系。方法:连续入选初诊的中青年(30~65岁)原发性高血压病患者318例,平均年龄(47.9±7.1)岁,测量右上臂肱动脉的收缩压和舒张压并计算肱动脉脉压作为观察组,同期选择年龄匹配的430例血压正常人群,平均年龄(47.9±8.5)岁,作为对照组,收集两组患者的临床和实验室检查资料。根据MDRD公式计算患者的GFR(e GFR),按照数值分布的三分位点分别将观察组患者分为A、B、C三组,同法将对照组患者分为a、b、c三组。结果:随着分组e GFR的降低,观察组患者的年龄、肱动脉脉压及血清肌酐均呈明显增高趋势(P0.05);而舒张压在组间比较呈明显降低趋势(P0.05)。对照组患者的年龄、肱动脉收缩压、平均动脉压、TG、TC、SCr均呈明显增高趋势(P0.05);而肱动脉脉压在组间比较差异无统计学意义。针对观察组和对照组分别做相关和多元线性回归分析,结果显示:e GFR与观察组患者年龄、肱动脉脉压、SCr、UA呈显著负相关(r=-0.124,-0.150,-0.753,-0.131,P0.05),而与肱动脉舒张压、HDL-C呈显著正相关(r=0.125,0.097,P0.05);e GFR与对照组患者年龄、SCr、TC、TG、ALT呈显著负相关(r=-0.440,-0.749,-0.226,-0.178,-0.121,P0.05),与肱动脉脉压无相关性。结论:相对于血压正常人群,中青年高血压病患者肱动脉脉压与e GFR呈负相关,是e GFR的独立影响因素。     

血清肌酐、胱抑素C及肾小球滤过率与支架内再狭窄的相关性

目的探讨血清肌酐、血清胱抑素C(Cys C)及肾小球滤过率(GFR)与冠状动脉内置入药物洗脱支架后发生支架内再狭窄的相关性。方法回顾性分析624例患者,均于冠状动脉内植入药物洗脱支架且于中国医科大学附属盛京医院复查冠状动脉造影,按复查造影结果分为再狭窄组(147例)及非再狭窄组(477例),统计并分析所有患者的临床资料、生化指标、介入靶血管、再狭窄等数据。结果无论是PCI术前、术后以及复查造影时,再狭窄组患者的血清肌酐、血清Cys C水平均高于非再狭窄组(P0.05);GFR均低于非再狭窄组(P0.05);通过多因素Cox回归分析示,血清肌酐及血清Cys C水平升高、GFR下降是预测药物洗脱支架内再狭窄的独立危险因子。结论肾功能水平与支架内再狭窄的发生密切相关,血清肌酐及Cys C升高、GFR下降是冠状动脉内药物洗脱支架术后发生再狭窄的独立危险因素。     

Serum cystatin C as an early marker of nephropathy among type 2 diabetics: A meta-analysis

AimThe varying views as to the usefulness of serum cystatin C (CysC) as an early marker of diabetic nephropathy (DN) prompted us to investigate existing literature to determine whether serum CysC can be used as an early marker of DN using a meta-analysis approach.Materials and methodsTwelve studies written in English were retrieved from PubMed using various key search terms. Data were extracted from the included studies by two of the authors and was subjected to statistical analysis using Review Manager 5.3 and Meta-Essentials. Levels of serum CysC were compared between the study groups using the standardized mean difference (SMD) and 95% confidence interval (CI).ResultsOverall outcomes indicate that serum CysC levels are higher among those with microalbuminuria (MI) and macroalbuminuria (MA) than those in the control group (CN) and those with normoalbuminuria (NO). However, these findings were heterogeneous, which warranted an investigation using the Galbraith plot. Heterogeneity was either reduced or lost in the post-outlier outcomes indicating combinability of the studies.ConclusionSerum CysC is shown to be a superior biomarker in the early diagnosis of DN. However, further studies are still needed to verify our claims.     

Inverse association of estimated cystatin C- and creatinine-based glomerular filtration rate with left ventricular mass: Results from the Study of Health in Pomerania

Background

Left ventricular hypertrophy (LVH) is an independent predictor of cardiovascular disease in the general population and in patients with chronic kidney disease. The objective of this study was to investigate the association of estimated glomerular filtration rate (eGFR) with left ventricular mass index (LVMI), LVH and left ventricular geometry. A question of clinical relevance is whether estimated glomerular filtration rate based on cystatin C (eGFR_cystatinC) is a better marker for cardiovascular risk than estimated glomerular filtration rate based on creatinine (eGFR_creatinine).

Methods

The study sample included 2830 individuals from the population-based Study of Health in Pomerania (SHIP). LVH was defined as echocardiographic LVMI > 48 g/m^2.7 in men and > 44 g/m^2.7 in women. Kidney function, as assessed by eGFR, was determined from established equations: the creatinine-based Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation and a cystatin-based multivariable equation.

Results

We found an inverse association between eGFR and LVMI. This association was stronger in models with eGFR_cystatinC than in models with eGFR_creatinine. Subjects with moderately-to-severely decreased kidney function (defined as eGFR 15–< 60 mL/min per 1.73 m²) had higher odds for abnormal geometric patterns of the left ventricle than subjects with normal eGFR when eGFR_cystatinC was used.

Conclusions

The findings suggest that eGFR_cystatinC is superior to eGFR_creatinine for assessing the risk of cardiovascular disease.     

Serum cystatin C as an indicator for early detection of diabetic nephropathy in type 2 diabetes mellitus

BackgroundDiabetes mellitus (DM) refers to a group of common metabolic disorders that share the phenotype of hyperglycemia. The metabolic dysregulations associated with DM causes secondary pathophysiological changes in multiple organ systems which result in various complications, responsible for the morbidity and mortality associated with the disease.MethodsThe present study was carried out on 40 patients with type 2 diabetes mellitus, who were recruited from those attending outpatient clinic and inpatient of Internal Medicine Department at The National Institute of Diabetes and Endocrinology from January 2017 to june 2017.ResultsThe mean Cystatin C values in Group I were 0.74, group II were 1.07. and in Group III were 3.25, The results show that the Cystatin C values were raised even in the patients with Normoalbuminuria with GFR ≥90 whom clinical albuminuria had not yet started.Conclusionsserum Cystatin C may be considered as an early marker, than microalbuminuria and serum creatinine, the commonly used marker for nephropathy, for declining renal function, in diabetic subjects. Further studies in larger population are needed to confirm this result.     

Accurate measurement of individual glomerular filtration rate in cancer patients: an ongoing challenge

A narrow therapeutic index is a characteristic feature of cytotoxic agents. Some of these agents are almost entirely eliminated renally in unchanged active form. As a consequence, assessment of the individual glomerular filtration rate (GFR) may help to predict the pharmacokinetic behaviour of cytotoxic agents in plasma more precisely. In addition, GFR-adapted individualization of cancer chemotherapy may have an enormous impact on the severity of side effects. Several methods are available to determine GFR or creatinine clearance (CrCl). GFR-measurement based on experimental methods with radiolabelled isotopes, contrast media or inulin helps to reflect the real situation very closely. In addition, 24-h urine collection is a convenient and feasible method to measure creatinine clearance. Finally, several mathematical equations exist to estimate GFR or CrCl based on serum creatinine and other parameters. Only a few of these equations have been developed in oncologic patients. However, some of these equations are routinely used in clinical practice, because they allow a rapid estimation of GFR. Based on the fact that clinically relevant differences have been assessed between calculated values and the real situation, mathematical calculation of GFR or CrCl does not seem to be appropriate to assess individual renal function precisely enough over a broad range of individual GFR or CrCl. Whether the measurement of low-molecular-weight proteins, such as cystatin C and ss-trace protein, may help to reflect the real situation more precisely is a matter of controversial debate.     

肾小球滤过率和肾有效血浆流量"分离现象"对诊断早期糖尿病肾病的意义

目的探讨肾小球滤过率(GFR)和肾有效血浆流量(ERPF)的变化对诊断早期糖尿病肾病(DN)的意义。方法根据尿白蛋白排泄率(UAER)将105例2型糖尿病(T2DM)患者分为3组:无DN(NDN)组,早期DN(EDN)组,临床DN(CDN)组。用SPECT测定GFR、ERPF值,并测定尿白蛋白(UAlb)、尿免疫球蛋白G(UIgG)、α1微球蛋白(Uα1-MG)、β2微球蛋白(Uβ2-MG)、血清肌酐(SCr)和尿素氮(BUN)。结果NDN组GFR和ERPF值增高,与UAlb负相关;EDN组GFR增高与UAlb正相关,ERPF低于正常对照组,与UAlb负相关,出现GFR和ERPF"分离现象";CDN组GFR和ERPF明显降低,与UAlb负相关。UAlb、UIgG、Uα1-MG、Uβ2-MG与SCr、BUN正相关。结论核素显像测定GFR、ERPF"分离现象"能够及时反映糖尿病的早期肾脏损害,与UAlb联合检测有助于了解DN的病变程度。