Serum cystatin C as an endogenous marker of renal function in patients with mild to moderate impairment of kidney function.

BACKGROUND: Estimation of the glomerular filtration rate (GFR) is essential for the evaluation of patients with chronic kidney disease (CKD). Recently, serum cystatin C was proposed as a new endogenous marker of GFR and in our study its diagnostic accuracy was compared with that of other markers of GFR. METHODS: In this study, 164 patients with CKD stages 2-3 (GFR 30-89 ml/min/1.73 m2), who had performed 51Cr-labelled ethylenediaminetetra-acetic acid clearance, were enrolled. In each patient, serum creatinine and serum cystatin C were determined. Creatinine clearance was calculated using the Cockcroft-Gault (C&G) and the modification of diet in renal disease (MDRD) formulas. RESULTS: The mean 51CrEDTA clearance was 57 ml/min/1.73 m2, the mean serum creatinine 149 micromol/l and the mean serum cystatin C 1.74 mg/l. We found significant correlation between 51CrEDTA clearance and serum creatinine (R = -0.666), serum cystatin C (R = -0.792), reciprocal of serum creatinine (R = 0.628), reciprocal of serum cystatin C (R = 0.753) and calculated creatinine clearance from the formulas C&G (R = 0.515) and MDRD formulas (R = 0.716). The receiver operating characteristic (ROC) curve analysis (cut-off for GFR 60 ml/min/1.73 m2) showed that serum cystatin C had a significantly higher diagnostic accuracy than serum creatinine (P = 0.04) and calculated creatinine clearance from the C&G formula (P < 0.0001), though only in female patients. No difference in diagnostic accuracy was found between serum cystatin C and creatinine clearance calculated from the MDRD formula. CONCLUSIONS: Our results indicate that serum cystatin C is a reliable marker of GFR in patients with mildly to moderately impaired kidney function and has a higher diagnostic accuracy than serum creatinine and calculated creatinine clearance from the C&G formula in female patients.     

Serum cystatin C as a reliable marker of changes in glomerular filtration rate in children with urinary tract malformations

PURPOSE: Cystatin C has been suggested as a simple method of estimating GFR more accurately than creatinine in children. We compared the diagnostic accuracy of cystatin C with serum creatinine and the Schwartz formula for estimating GFR in patients with UTMs. MATERIALS AND METHODS: We prospectively compared 72 patients with UTMs (20 days to 36 months old, 58 males and 14 females) with a group of 72 healthy controls (10 days to 48 months old, 53 males and 19 females). All patients underwent nuclear medicine clearance investigations with (99m)Tc DTPA. RESULTS: Serum concentration of cystatin C revealed a higher correlation with (99m)Tc DTPA (r = 0.62, p <0.001) than serum concentration of creatinine (r = 0.30, p <0.01) or Schwartz formula (r = 0.51, p <0.001). These results were more evident in patients with uropathy (19) with mild renal impairment. Agreement between methods was assessed using Bland Altman analysis. Mean differences between GFR calculated with (99m)Tc DTPA and cystatin C based GFR estimation or Schwartz formula were -2.6% +/- 46.7% and -73.4% +/- 53.6%, respectively. Diagnostic accuracy in identifying decreased GFR measured as AUC was always highest for cystatin C but hardly sufficient for the 3 variables. Cystatin C performed better in the 0 to 6-month-olds (0.70 +/- 0.08 for cystatin C, 0.58 +/- 0.07 for Schwartz estimate) and patients older than 12 months (0.82 +/- 0.09 for cystatin C, 0.65 +/- 0.11 for Schwartz estimate). CONCLUSIONS: Cystatin C proved to be a superior marker rate over serum creatinine in estimating glomerular filtration in children younger than 3 years with UTMs and mild renal impairment, thus, offering a more specific and practical measure for monitoring GFR.     

Glomerular filtration rate estimated by cystatin C among different clinical presentations

Glomerular filtration rate (GFR) estimates from serum creatinine has not been generalizable across all populations. Cystatin C has been proposed as an alternative marker for estimating GFR. The objective of this study was to compare cystatin C with serum creatinine for estimating GFR among different clinical presentations. Cystatin C and serum creatinine levels were obtained from adult patients (n=460) during an evaluation that included a GFR measurement by iothalamate clearance. Medical records were abstracted for clinical presentation (healthy, native chronic kidney disease or transplant recipient) at the time of GFR measurement. GFR was modeled using the following variables: cystatin C (or serum creatinine), age, gender and clinical presentation. The relationship between cystatin C and GFR differed across clinical presentations. At the same cystatin C level, GFR was 19% higher in transplant recipients than in patients with native kidney disease (P<0.001). The association between cystatin C and GFR was stronger among native kidney disease patients than in healthy persons (P<0.001 for statistical interaction). Thus, a cystatin C equation was derived using only patients with native kidney disease (n=204). The correlation with GFR (r(2)=0.853) was slightly higher than a serum creatinine equation using the same sample (r(2)=0.827), the Modification of Diet in Renal Disease equation (r(2)=0.825) or the Cockcroft-Gault equation (r(2)=0.796). Averaged estimates between cystatin C and serum creatinine equations further improved correlation (r(2)=0.891). Cystatin C should not be interpreted as purely a marker of GFR. Other factors, possibly inflammation or immunosuppression therapy, affect cystatin C levels. While recognizing this limitation, cystatin C may improve GFR estimates in chronic kidney disease patients.     

Serum cystatin C as a marker of the renal function in patients with spinal cord injury

OBJECTIVE: To investigate the relationship between serum cystatin C, serum creatinine, and (51)Cr-EDTA-clearance in patients with spinal cord injury. SETTING: The Spinal Cord Unit, Viborg-Kjellerup County Hospital. METHODS: Twenty-four men and seven women aged 20.3 to 68.0 years with motor complete spinal cord injury (ASIA A or B) were included. Serum cystatin C was measured by an automated particle-enhanced nephelometric immunoassay (Dade Behring), serum creatinine by an enzymatic method (Vitros 950), and (51)Cr-EDTA-clearance by a multiple plasma sample method. RESULTS: A linear relationship was found between (51)Cr-EDTA-clearance and the reciprocal values of cystatin C and creatinine. The correlation coefficient between (51)Cr-EDTA-clearance and 1/cystatin C was 0.72 compared to the correlation coefficient between (51)Cr-EDTA-clearance and 1/creatinine being 0.26. Comparison of the area under the curves in the non-parametric receiver operating characteristics (ROC) plots for serum cystatin C (area under the curve (AUC)=0.912; SE=0.065), and serum creatinine (AUC=0.507; SE=0.115) revealed significant differences (P-values=0.0005). CONCLUSION: In patients with spinal cord injury serum cystatin C is a better marker of the renal function compared to serum creatinine.     

Cystatin C as a marker of renal function in kidney transplant patients

INTRODUCTION: Serum creatinine (sCr) is the most commonly used biochemical parameter for gauging kidney function, but, due to its limitations, it is not the ideal marker for glomerular filtration rate (GFR). Cystatin C (sCyC) appears to be an endogenous marker of GFR. AIM: To assess the use of sCyC as a marker of renal function in kidney transplant patients, we compared it with sCr and with creatinine clearance either in a 24-hour urine or calculated using the Cockroft-Gault formula. METHODS: Among 78 patients (62.8% men, 37.2% women) undergoing kidney transplantation (average age 44.87 +/- 13.37 years) we determined at 2, 5, 7, 15, and 30 days, and 6, 12 and 18 months after kidney transplantation: sCr (using the Jaffé colorimetric method), sCyC (immunonephelometry), creatinine clearance with a 24-hour urine, creatinine clearance using the Cockroft-Gault formula. RESULTS: During the first 30 days following transplantation, there was a progressive decline in sCr levels. sCyC increased up to the fifth day, coinciding with the highest doses of steroids, and then decreased. At 6, 12, and 18 months, there was a correlation between sCyC and sCr, creatinine clearance in a 24-hour urine or calculated with the Cockroft-Gault formula (R = 0.859; R = -0.713, and R = -0.684, respectively, P < .001.) CONCLUSIONS: sCyC is an endogenous marker of GFR. Its limitations relate to its being affected by the high doses of steroids in the first days following transplantation. In the 18-month posttransplant period, it correlated with creatinine clearance in a 24-hour urine or calculated by the Cockroft-Gault formula.     

Clinical usefulness of serum cystatin C and the pertinent estimation of glomerular filtration rate based on cystatin C

Aim: Although cystatin C has been developed as an alternative marker for estimating glomerular filtration rate (GFR), its clinical use is as yet limited. The significance of cystatin C for differentiating chronic kidney disease (CKD) stages and established cystatin C‐based equations estimating GFR were evaluated. Methods: The fresh frozen serum samples from CKD (n = 119) and healthy volunteers (n = 22) were evaluated. Serum creatinine (sCr) was measured by the kinetic Jaffé method, and recalibrated to the isotope dilution mass spectrometry (IDMS). Cystatin C was measured using a particle‐enhanced nephelometric assay. Results: CKD stages were more sensitively differentiated by cystatin C compared to sCr, especially in moderate and severe kidney dysfunction. Sex and body mass index did not affect cystatin C level. Pearson's correlation coefficients of reciprocal of cystatin C, measured and recalibrated sCr compared to systemic inulin clearance (Cl_in) were 0.757, 0.734 and 0.709, respectively. We derived novel pertinent equations based on cystatin C (model 1: 1.404 × cystatin C^?0.895 × age^0.006 × weight^1.074 × height^?1.562 × (0.865; if female); model 2: 43.287 × cystatin C^?0.906 × age^0.101 × (0.762; if female)]. Models 1 and 2 showed superior performance in representing systemic Cl_in than the IDMS Modification of Diet in Renal Disease (MDRD) study equations did (adjusted r² = 0.76 and 0.72 for models 1 and 2, and 0.64 and 0.65 for 4 and 6 variable IDMS MDRD equations, respectively). Conclusion: Cystatin C reflects kidney dysfunction sensitively, and thus cystatin C‐based estimation of GFR could provide a reliable support for clinical practice.     

血半胱氨酸蛋白酶抑制剂C在筛查早期肾功能异常中的临床意义

目的探讨血半胱氨酸蛋白酶抑制剂C在健康体检中筛查早期肾功能异常的临床意义。方法选择在我院健康体检中心的体检者75名,根据半胱氨酸蛋白酶抑制剂C水平将研究对象分为实验组和对照组,比较2组血半胱氨酸蛋白酶抑制剂C、血肌酐、尿素氮和99mTc—DTPA清除率。结果实验组血清半胱氨酸蛋白酶抑制剂C浓度高于对照组（P〈0．01）,实验组肾小球滤过率低于对照组（P〈0．01）。2组血肌酐和尿素氮均在正常范围,组间无统计学差异（P〉0．05）。血清半胱氨酸蛋白酶抑制剂C浓度与肾小球滤过率呈负相关（r=-0．75,P〈0．01）。结论血半胱氨酸蛋白酶抑制剂C是反映肾小球滤过率灵敏指标,为在健康体检中筛查早期肾功能异常提供了一个优于其他的指标。     

Serum cystatin C--a superior marker of rapidly reduced glomerular filtration after uninephrectomy in kidney donors compared to creatinine

AIMS: Acute renal failure (ARF), defined by a rapid decrease of glomerular filtration rate (GFR), is associated with high mortality. Early and accurate detection of decreasing GFR is critical to prevent the progression of ARF and to potentially improve its outcome. Serum creatinine, the conventional GFR marker, has major limitations. We prospectively evaluated whether serum cystatin C detected a rapid GFR decrease earlier and more accurately than serum creatinine. METHODS: In ten patients undergoing nephrectomy for living related kidney transplantation, serum creatinine and cystatin C were determined daily. The decrease of GFR was quantitated preoperatively by creatinine clearance and MAG3 scintigraphy. The GFR decrease was defined by a 50-100% increase of cystatin C or creatinine from preoperative values. Ten patients without renal impairment served as controls. RESULTS: Initially, patients had a creatinine clearance of 105 +/- 14 ml/min/1.73 m2. Due to nephrectomy, patients lost 45 +/- 3% of their renal function. Serum cystatin C significantly increased already one, serum creatinine two days after nephrectomy. Cystatin C demonstrated an increase by 50-100% 1.4 +/- 0.9 days earlier than creatinine (p = 0.009). Serum cystatin C performed well detecting the GFR decrease with higher diagnostic values compared to creatinine. This was indicated by a sensitivity of 50, 70 and 80% of cystatin C to detect the GFR decrease on the three days following nephrectomy. CONCLUSIONS: Serum cystatin C detects rapid GFR decreases one to two days earlier than creatinine. Cystatin C is an early and accurate marker to detect rapid GFR decreases as in ARF.     

血清半胱氨酸蛋白酶抑制剂C在各期慢性肾脏病诊断中的应用价值

目的：探讨血清半胱氨酸蛋白酶抑制剂c（CystatinC）与血清肌酐（Scr）在不同时期慢性肾脏病（chronic kidney disease，CKD）患者肾功能检测中的敏感性，评价血清Cystatin C在各期CKD患者中的临床应用价值。方法：对129例不同时期CKD患者检测CystatinC，以^99mTc—DTPA清除率测得的肾小球滤过率（GFR）作为诊断评价的金指标，乳胶颗粒增强免疫透射比浊法检测血清CystatinC浓度，用全自动生化分析仪检测血清Scr。结果：与正常对照组比较，各期CKD组CystatinC值均有统计学差异，而各期CKD组Scr值与正常组比较，CKD1、CKD2期无统计学差异，CKD3～5期才有统计学差异；各期CKD组间比较显示CystatinC值均有统计学差异，而Scr值差异仅局限于CKD3～5期。并且血清CystatinC，Scr与^99mTc-DTPA清除率呈显著相关，尤其CystatinC相关性更好。结论：血清CystatinC在各期CKD中均能准确反映肾小球滤过功能，尤其能敏感提示早期肾功能损害，可成为判断肾功能损害程度的敏感指标，而且方法简便、敏感。     

Association of cystatin C and estimated GFR with inflammatory biomarkers: the Heart and Soul Study.

BACKGROUND: Cystatin C is a marker of kidney function that may also be associated with inflammation. In this study, we compared the relative strengths of association of cystatin C and estimated glomerular filtration rate (eGFR) with inflammatory biomarkers. METHODS: We measured serum cystatin C and creatinine in 990 outpatients with coronary artery disease enrolled in the Heart and Soul Study. GFR was estimated (eGFR) by the abbreviated Modification of Diet in Renal Disease (MDRD) equation. We compared the associations of serum cystatin C and eGFR with C-reactive protein (CRP) and fibrinogen, after adjustment for 24 h creatinine clearance. RESULTS: Cystatin C concentrations had moderate correlations with CRP (r=0.15, P<0.001) and fibrinogen (r=0.26, P<0.0001); eGFR had similar correlations with CRP (r=-0.17, P=0.01) and fibrinogen (r=-0.25, P<0.001) among persons with eGFR60 ml/min (r=0.04, P=0.32; r=-0.03, P=0.38). Quartiles of cystatin C were strongly and directly associated with CRP (P=0.02) and fibrinogen (P<0.007) after multivariate adjustment. However, these associations disappeared after adjustment for creatinine clearance (P=0.26 and 0.23, respectively). CONCLUSIONS: Cystatin C concentrations have moderate associations with CRP and fibrinogen that are not independent of creatinine clearance. Although a gold standard of kidney function is lacking, this analysis suggests that cystatin C captures an association of mildly impaired kidney function with increased inflammation.     

Cystatin C--a marker for assessment of the glomerular filtration rate in patients with cisplatin chemotherapy

BACKGROUND: Cystatin C has recently been proposed as an ideal marker for glomerular filtration rate (GFR). In this study, cystatin C serum levels were evaluated in comparison to serum creatinine concentrations and inulin clearances in patients with normal kidney function receiving cisplatin-based chemotherapy to assess the validity of cystatin C as an alternative endogenous marker of GFR. METHODS: Blood samples for the assessment of cystatin C, creatinine and inulin clearances were collected in patients before and after application of cisplatin in a clinical trial. Overall, 41 patients were included in the study, 35 of them were eligible receiving cisplatin in two different cisplatin-based chemotherapy schedules. RESULTS: A 21% increase of cystatin C serum levels was demonstrated in the placebo group after application of cisplatin. Analysis of inulin clearances revealed a 23% loss of inulin clearance in patients of the placebo arm. In contrast, significant changes could not be detected by analysis of serum creatinine levels. CONCLUSIONS: Cystatin C represents a more sensitive clinical marker than serum creatinine for the early assessment of GFR damage caused by cisplatin. Changes in cystatin C serum concentrations correlate well to GFR decrease as measured by inulin clearance.     

Rapid and accurate assessment of glomerular filtration rate in patients with renal transplants using serum cystatin C.

BACKGROUND: Assessment of renal function in patients with renal transplants is of great importance. Various studies have reported cystatin C as an easily and rapidly assessable marker that can be used for accurate information on renal function impairment. To date, no study is available to define the role of cystatin C in patients with renal transplants. METHODS: Thirty steady-state patients (50% male/50% female) with status post-kidney transplantation were studied. To assess renal function, cystatin C, creatinine clearance, serum creatinine, beta2-microglobulin (beta2M), and [125I]iothalamate clearance were determined. Correlations and non-parametric ROC curves for accuracy, using a cut-off glomerular filtration rate (GFR) of 60 ml/min, were obtained for the different markers allowing for calculations of positive predictive values (PPV), positive likelihood ratios (PLR), specificity and sensitivity, respectively. Further, to evaluate the usefulness of these markers for monitoring, intraindividual coefficients of variation (CVs) for cystatin C and creatinine measurements were compared in 85 renal transplant patients. Measurements consisted of at least six pairs of results, which were obtained at different time points during routine follow-up. RESULTS: Cystatin C correlated best with GFR (r=0.83), whereas serum creatinine (r=0.67), creatinine clearance (r=0.57) and beta2M (r=0.58) all had lower correlation coefficients. The diagnostic accuracy of cystatin C was significantly better than serum creatinine (P=0.025), but did not differ significantly from creatinine clearance (P=0.76) and beta2M (P=0.43). At a cut-off of 1.64 mg/l, cystatin C has a PPV of 93%, PLR of 6.4, specificity 89% and sensitivity 70%, respectively. For beta2M, PPV 83%, PLR 1.7, specificity 67% and sensitivity 75% was seen at a cut-off of 3.57 mg/l. Accordingly, at a cut-off of 125 micromol/l for serum creatinine, a PPV 76%, PLR 1.4, specificity 44% and sensitivity 80% was revealed. Finally, at a cut-off of 66 ml/min/1.73 m2 for creatinine clearance, the following characteristics were found: PPV 94%, PLR 7.7, specificity 89% and sensitivity 85%. The intraindividual variation of creatinine was significantly lower than that of cystatin C (P<0.001). With increasing concentrations, their ratios of CV tended towards a value of 1, demonstrating identical variability at low GFR. CONCLUSION: Together, our data show that in patients with renal transplants, cystatin C, in terms of PPV and PLR, has a similar diagnostic value as creatinine clearance. However, it is superior to serum determinations of creatinine and beta2M. The intraindividual variation of cystatin C is greater than that of creatinine. This might be due to the better ability of cystatin C to reflect temporary changes especially in mildly impaired GFR, most critical for early detection of rejection and other function impairment. Thus, cystatin C allows for rapid and accurate assessment of renal function (GFR) in renal transplants and is clearly superior to the commonly used serum creatinine.     

Estimating the glomerular filtration rate using serum cystatin C levels in patients with spinal cord injuries

Study design:Prospective cohort study.Objectives:To investigate the relationship between (51)chromium-ethylene-diamine-tetra-acetate ((51)Cr-EDTA) clearance, serum cystatin C (CysC), serum creatinine, creatinine clearance and estimated glomerular filtration rate (eGFR(MDRD), MDRD stands for modification of diet in renal disease) based on the serum creatinine in patients with complete or incomplete spinal cord injury (SCI) and to develop and evaluate a GFR-estimating equation using serum CysC.Settings:Spinal Cord Injury Unit, Viborg Regional Hospital, Viborg, Denmark.Methods:Ninety-eight men and 47 women with SCI were included in the study. Serum CysC levels were measured by an automated particle-enhanced nephelometric immunoassay, serum and urine creatinine levels were measured by an enzymatic method traceable to the IDMS creatinine reference method, and (51)Cr-EDTA clearance was measured by a multiple plasma sample method.Results:The area under the curves (AUCs) in the non-parametric receiver operating characteristics (ROC) plots for serum CysC were compared with serum creatinine and to eGFR(MDRD) and revealed a significant difference (P-value<0.05) for all SCI patients. There was no significant difference between the AUC for serum CysC compared with the AUC for creatinine clearance. GFR (ml?min(-1) per 1.73?m(2)) can be calculated from serum CysC values (mg?l(-1)) using the equation eGFR(CysC)=212·exp(0.914·CysC). The model accurately predicted the GFR of 88% of patients within ±30% of the measured GFR, and it was able to predict the GFR of 50% of patients within ±10% of the measured GFR.Conclusion:In patients with SCI, GFR can be estimated independent of age, sex and muscle mass by a newly developed equation based on a single serum CysC value.     

动态监测血清胱抑素 C 评价肾移植术后肾功能的改变

目的 监测肾移植受者血清胱抑素C(Cys C)浓度以评估移植肾功能的改变. 方法 监测58例肾移植成功受者术前及术后不同时间的血清Cys C、肌酐(SCr)、β2-微球蛋白(β2-MG)和尿素氮(BUN)水平;并于术后第7天使用99mTc-DTPA测定受者肾小球虑过滤(GFR),比较其与上述四项指标的相关性.以GFR=1.5 ml/s为临界值,绘制ROC曲线,比较各项检测指标鉴别轻度与中重度肾功能损伤的诊断性能.计算受者不同时间段血清Cys C及SCr变异系数及其比值(R值). 结果 Cys C于术后第1天下降达48.1%,明显大于其他指标的下降幅度.血清Cys C、SCr、β2-MG和BUN与GFR相关系数依次为0.876、0.691、0.589和0.516.血清Cys C、SCr、β2-MG和BUN的诊断性能:敏感性分别为91.3%、87.2%、82.6%和87.0%;特异性分别为80.0%、69.2%、71.4%和42.9%;阳性预期值分别为82.0%、73.7%、74.3%和60.4%;阳性似然比分别为4.81、2.83、2.87和1.53;ROC曲线下面积(AUC)分别为0.914、0.828、0.803和0.765.SCr的变异系数显著小于Cys C(P＜0.01),Cys C＜2 mg/L的受者R值大多＜1,Cys C＞2 mg/L的受者,伴随Cys C水平升高,R值趋近于1. 结论 Cys C与GFR相关性最好;Cys C的诊断性能及准确性均优于其他指标,即使肾功能有微小损伤,Cys C也会有显著改变.因此,肾移植术后动态监测Cys C对于及时判断移植肾存活及肾微小损伤时肾功能的改变优于其他指标.     

Glomerular filtration rate estimated from the uptake phase of 99mTc-DTPA renography in chronic renal failure.

BACKGROUND: The purpose of the study was to compare the estimation of glomerular filtration rate (GFR) from 99mTc-DTPA renography with that estimated from the renal clearance of 51Cr-EDTA, creatinine and urea. METHODS: Fifty patients with reduced renal function (serum creatinine between 150 and 600 micromol/l) were enrolled in the study. GFR was estimated from the uptake phase of 99mTc-DTPA renography (GFR(DTPA)). The renal clearance of 51Cr-EDTA (GFR(EDTA)) was used as the reference method. Creatinine clearance (C(Cr)), urea clearance (C(Ur)) and the mean of urea and creatinine clearance (C(Cr+Ur)/2) were also calculated from urine collected during a period of 24 h. Limits of agreement were used for method comparison. RESULTS: The limit of agreement between GFR(DTPA) and GFR(EDTA) was 2 +/- 17 ml/min. The mean difference did not deviate significantly from zero. The other clearance techniques had larger limits of agreement and a mean difference significantly different from zero. Furthermore, C(Ur) and C(Cr+Ur)/2 had systematic deviations of the differences, indicating that C(Ur) and C(Cr+Ur)/2 are poor estimates of GFR. CONCLUSION: The limit of agreement between GFR(DTPA) and GFR(EDTA) are acceptable and, therefore, GFR estimated from 99mTc-DTPA renography is acceptable for clinical use in patients with reduced renal function. Furthermore, the method is simple and less time consuming compared with renal clearance techniques.     

Cystatin C does not detect acute changes in glomerular filtration rate in early diabetic nephropathy

BACKGROUND: The measurement of renal functional reserve (acute change in glomerular filtration rate [GFR] after protein load) allows the detection of sub-clinical renal dysfunction and has prognostic implications in diabetes. Our aim was to test cystatin C as an index of GFR and renal functional reserve. METHODS: GFR was measured by C(Sinistrin) at baseline and after protein load in 28 diabetic patients with serum creatinine <1.2 mg/dL. The C(Sinistrin) was compared with cystatin C, serum creatinine, creatinine clearance, and Cockcroft-Gault formula. RESULTS: Baseline C(Sinistrin) ranged from 67-172 mL/min. Regression analysis showed an overall low relationship between C(Sinistrin) and the indirect markers of GFR. The highest correlation with C(Sinistrin) was obtained for cystatin C clearance (R(2) = 0.58, r = 0.76, p < 0.001), the 1/serum cystatin C (R(2) = 0.58, r = 0.76, p < 0.001), and serum cystatin C (R(2) = 0.52, r = 0.72, p < 0.001). Renal functional reserve was preserved in 6 of 28 patients. There was no significant change in cystatin C in response to protein load. CONCLUSION: Wide variation in baseline GFR emphasizes the need for the early detection of renal dysfunction. Cystatin C correlated best with C(Sinistrin) at baseline, but did not detect renal functional reserve.     

Cystatin C is a more sensitive marker than creatinine for the estimation of GFR in type 2 diabetic patients

BACKGROUND: Glomerular filtration rate (GFR) is the best overall index of renal function in health and disease. Inulin and 51Cr-EDTA plasma clearances are considered the gold standard methods for estimating GFR. Unfortunately, these methods require specialized technical personnel over a period of several hours and high costs. In clinical practice, serum creatinine is the most widely used index for the noninvasive assessment of GFR. Despite its specificity, serum creatinine demonstrates an inadequate sensitivity, particularly in the early stages of renal impairment. Recently, cystatin C, a low molecular mass plasma protein freely filtered through the glomerulus and almost completely reabsorbed and catabolized by tubular cells, has been proposed as a new and very sensitive serum marker of changes in GFR. This study was designed to test whether serum cystatin C can replace serum creatinine for the early assessment of nephropathy in patients with type 2 diabetes. METHODS: The study was performed on 52 Caucasian type 2 diabetic patients. Patients with an abnormal albumin excretion rate (AER) were carefully examined to rule out non-diabetic renal diseases by ultrasonography, urine bacteriology, microscopic urine analysis, and kidney biopsy. Serum creatinine, serum cystatin C, AER, serum lipids, and glycosylated hemoglobin (HbA1c) were measured. GFR was estimated by the plasma clearance of 51Cr-EDTA. In addition the Cockcroft and Gault formula (Cockcroft and Gault estimated GFR) was calculated. RESULTS: Cystatin C serum concentration progressively increased as GFR decreased. The overall relationship between the reciprocal cystatin C and GFR was significantly stronger (r = 0.84) than those between serum creatinine and GFR (r = 0.65) and between Cockcroft and Gault estimated GFR and GFR (r = 0.70). As GFR decreased from 120 to 20 mL/min/1.73 m2, cystatin C increased more significantly that serum creatinine, giving a stronger signal in comparison to that of creatinine over the range of the measured GFR. The maximum diagnostic accuracy of serum cystatin C (90%) was significantly better than those of serum creatinine (77%) and Cockcroft and Gault estimated GFR (85%) in discriminating between type 2 diabetic patients with normal GFR (>80 mL/min per 1.73 m2) and those with reduced GFR (<80 mL/min/1.73 m2). In particular, the cystatin C cut-off limit of 0.93 mg/L corresponded to a false-positive rate of 7.7% and to a false-negative rate of 1.9%; the serum creatinine cut-off limit of 87.5 micromol/L corresponded to a false-positive rate of 5.8% and to a false-negative rate of 17.0%. CONCLUSIONS: Cystatin C may be considered as an alternative and more accurate serum marker than serum creatinine or the Cockcroft and Gault estimated GFR in discriminating type 2 diabetic patients with reduced GFR from those with normal GFR.     

Estimating glomerular filtration rate in kidney transplantation: a comparison between serum creatinine and cystatin C-based methods

Accurate measurement of GFR is critical for the evaluation of new therapies and the care of renal transplant recipients. Although not accurate in renal transplantation, GFR is often estimated using creatinine-based equations. Cystatin C is a marker of GFR that seems to be more accurate than creatinine. Equations to predict GFR based on the serum cystatin C concentration have been developed, but their accuracy in transplantation is unknown. GFR was estimated using four equations (Filler, Le Bricon, Larsson, and Hoek) that are based on serum cystatin C and seven equations that are based on serum creatinine in 117 adult renal transplant recipients. GFR was measured using radiolabeled diethylenetriaminepentaacetic acid (99mTc-DTPA), and the bias, precision, and accuracy of each equation were determined. The mean (99m)Tc-DTPA GFR was 58 +/- 23 ml/min per 1.73 m(2). The cystatin C-based equations of Filler and Le Bricon had the lowest bias (-1.7 and -3.8 ml/min per 1.73 m2), greatest precision (11.4 and 11.8 ml/min per 1.73 m2), and highest accuracy (87 and 89% within 30% of measured GFR, respectively). The cystatin C equations remained accurate even when the measured GFR was >60 ml/min per 1.73 m2. The creatinine-based equations were not as accurate, with only 53 to 80% of estimates within 30% of measured GFR. Cystatin C-based equations are more accurate at predicting GFR in renal transplant recipients than traditional creatinine-based equations. Further prospective studies with repetitive measurement of cystatin C are needed to determine whether cystatin C-based estimates of GFR will be sufficiently accurate to monitor long-term allograft function.     

Evaluation of cystatin C with iohexol clearance in cardiac surgery

Background: Post‐operative renal dysfunction after cardiac surgery is not uncommon and can lead to adverse outcome. The ability to accurately monitor renal function is therefore important. Cystatin C is known to be a sensitive marker of the glomerular filtration rate (GFR), but it has not been fully evaluated in cardiac surgery. Iohexol clearance is considered a reliable reference method for the determination of GFR. The aim of this study is to, for the first time, evaluate the diagnostic accuracy of plasma cystatin C compared with iohexol clearance in cardiac surgery. Methods: Twenty‐one patients scheduled for elective coronary artery bypass grafting were prospectively enrolled in the study. Before surgery and on the second post‐operative day, an iohexol clearance was performed. Plasma cystatin C, plasma creatinine and plasma C‐reactive protein were determined before surgery and on the first, second, third and fifth post‐operative day. Estimated creatinine and cystatin C clearances were determined. Results: Post‐operative cystatin C and 1/cystatin C correlated strongly to iohexol clearance (r=?0.90 and 0.86) and so did creatinine and 1/creatinine (r=?0.83 and 0.78). Estimated creatinine clearance differed from iohexol clearance (P<0.01), whereas estimated cystatin C clearance did not differ from iohexol clearance (P=0.81). No correlation was found between C‐reactive protein and cystatin C. Conclusion: This study indicates that clearance estimations based on cystatin C are more accurate compared with estimations based on creatinine in determining GFR in cardiac surgery. Cystatin C has, in this study population, a stronger correlation to iohexol clearance than creatinine.     

Serum cystatin C as an endogenous marker of renal function in patients with chronic kidney disease

The estimation of the glomerular filtration rate (GFR) is an essential part of the evaluation of patients with chronic kidney disease (CKD). Recently, serum cystatin C has been proposed as a new endogenous marker of GFR. Authors compared serum creatinine, creatinine clearance calculated from Cockcroft and Gault formula and serum cystatin C against (51)CrEDTA clearance in 252 patients with CKD and GFR <90 mL/min/1.73 m(2). Analysis of correlations and diagnostic accuracy (receiver operating characteristic curves) of different GFR markers indicate that serum cystatin C is a more reliable marker of GFR in patients with CKD than serum creatinine.