Clinical value of serum cystatin C by ELISA for estimation of glomerular filtration rate

The search for whether endogenous markers of changes in glomerular filtration rate (GFR) by serum cystatin C assay and serum cystatin C compare with creatinine clearance by the Cockeroft-Gault formula and the evaluation of its clinical significance as a marker of GFR is important in clinical practice at present. Serum cystatin C was determined by sandwich enzyme immunoassay using a kit. Control blood samples were collected from 70 healthy subjects and 168 patients with various kidney diseases. Creatinine clearance (Cockeroft-Gault formula) as a measure of GFR, in 168 patients with various kidney diseases, depends on the creatinine clearance; GFR parameters were used to divide patients into two groups. The GFR was >80 mL/min in 38 patients (group A) and <80 mL/min in 130 patients (group B). The two groups were analyzed by correlation coefficient and diagnostic sensitivity and specificity were assessed by the receiver-operating characteristic (ROC) plots (area under the curve). Of the 70 healthy control individuals, the serum level of cystatin C was measured as normal value range and a reference interval of 1.05+/-0.18 micro g/mL (mean+/-1.96 SD, 95% confidence limits for the upper references limit is 1.4 microg/mL). In group A, serum cystatin C had no correlation to the creatinine clearance (r=0.171, P>0.05) and in group B, serum cystatin C was closely correlated to the creatinine clearance (r=-0.771, P<0.001). Diagnostic sensitivity and specificity were assessed by the ROC plots for serum cystatin C (area under the curve=0.8461, SE=0.057) and creatinine clearance (area under the curve=0.7642, SE=0.068). These data suggest that combined measurement of serum cystatin C is useful to estimate GFR, especially to detect the reduction of GFR. Further studies are required to evaluate the whether serum cystatin C as a more sensitive marker of early renal injury might be extremely useful, particularly in nonproteinuric or unapparent renal disease.     

Serum cystatin C assay for the detection of early renal impairment in diabetic patients

The ability to assess renal function in diabetes patients rapidly and early is of major importance. This study was designed to determine whether cystatin C can replace serum creatinine as the screening marker for reduced glomerular filtration rate (GFR) in type 2 diabetes patients. The study was performed on 51 type 2 diabetic patients. GFR was estimated by the plasma clearance of (99m)Tc-DTPA. The correlation between (99m)Tc-DTPA clearance and levels of serum cystatin C, serum creatinine, and creatinine clearance was determined. Sensitivity and specificity for the diagnosis of renal impairment (defined as GFR<68 ml/min) were calculated by a receiver operating characteristic (ROC) curve for serum cystatin C, serum creatinine, and creatinine clearance. The correlation coefficients with (99m)Tc-DTPA clearance were -0.744 for serum cystatin C, -0.658 for serum creatinine, and +0.625 for creatinine clearance (P<0.001). With a cutoff value of 68 mL/min, the area under the ROC curve (AUC) was 0.891 for cystatin C, 0.77 for creatinine, and 0.753 for creatinine clearance. The AUC was statistically different between serum cystatin C and creatinine clearance (P<0.05). The ROC plot indicates that cystatin C is superior to serum creatinine and creatinine clearance for detecting impaired GFR. Serum cystatin C appropriately reflects GFR in diabetes, and is more efficacious than serum creatinine and creatinine clearance in detecting reduced GFR in type 2 diabetes patients.     

Serum cystatin C level as a potentially good marker for impaired kidney function

OBJECTIVES: To evaluate the diagnostic significance of serum cystatin C levels in clinical practice. DESIGN AND METHODS: Serum (99m)Tc-DTPA clearance was compared with serum cystatin C, creatinine, beta(2)-microglobulin levels and creatinine clearance in a group of patients aged 42.61 +/- 7.55 years with glomerular filtration rates of 10-60 mL/min/1.73 m(2) (n = 52) and healthy controls aged 43.90 +/- 12.06 years (n = 52). RESULTS: No effect of sex on serum cystatin C levels was observed, but average levels increased with age. No significant difference was evident between the mean cystatin C levels of three blood samples taken at 1 month intervals from healthy subjects. Reference clearance was correlated with creatinine clearance (r = 0.957), cystatin C (r = 0.828), beta(2)-microglobulin (r = 0.767) and creatinine (r = 0.682). 60 mL/min/1.73 m(2) was chosen as the borderline for receiver-operating characteristics analysis. The values for the cut-off point, sensitivity, specificity and the area under curve were determined for cystatin C as 1.36 mg/L, 98%, 99% and 0.99 +/- 00.1, respectively; for creatinine, the values were 103 micromol/L, 80%, 100% and 0.97 +/- 0.01, respectively, and for beta(2)-microglobulin, the values were 2.51 mg/L, 86%, 92% and 0.94 +/- 0.02, respectively. CONCLUSION: Serum cystatin C level can be used as a marker for renal damage.     

Calculation of glomerular filtration rate expressed in mL/min from plasma cystatin C values in mg/L

The Cockcroft Gault formula is often used to calculate the glomerular filtration rate (GFR) from plasma creatinine results. In Sweden this calculation is not usually done in the laboratory, but locally in the wards. These manual calculations could cause erroneous results. In several studies plasma cystatin C has been shown to be superior to plasma creatinine for estimation of GFR. One limitation of using cystatin C as a GFR marker is that there is no conversion formula transforming cystatin C expressed as mg/L to GFR expressed as mL/min. In this study plasma creatinine and cystatin C were compared with iohexol clearance. A stronger correlation (p < 0.0001) was found between cystatin C and iohexol clearance (r2 = 0.91) than between creatinine and iohexol clearance (r2 = 0.84). From the correlation data a formula was calculated to convert cystatin C expressed as mg/L to GFR (mL/min). The formulas y = 77.24x(-1.2623) (Dade Behring cystatin C calibration) or y = 99.43x(-1.5837) (DakoCytomation cystatin C calibration) are used to calculate GFR expressed in mL/min from the cystatin C value in mg/L and both results are reported to the referral doctor. These formulas can provide the clinicians with reliable and readily available GFR data based on single measurements of cystatin C concentrations.     

Improved prediction of decreased creatinine clearance by serum cystatin C: use in cancer patients before and during chemotherapy

BACKGROUND: Serum cystatin C, a cysteine protease inhibitor, has been suggested as a new marker of glomerular filtration rate (GFR). This study explored the possibility of replacing the creatinine clearance (CrCl) estimation of GFR with cystatin C in early detection of renal impairment in cancer patients on chemotherapy. METHODS: Serum creatinine and cystatin C concentrations as well as 24-h CrCl were determined simultaneously in 72 cancer patients. Among them, 60 were treated with combined chemotherapy with cisplatin (CDDP). Creatinine was determined enzymatically with a spectrophotometric method. Serum cystatin C was determined by a particle-enhanced turbidimetric immunoassay. RESULTS: Cystatin C and creatinine correlated significantly (P = 0.001) with CrCl. The correlation was significantly better for cystatin C than creatinine (r = 0.84 vs 0.74; P = 0.01). Stepwise regression analysis identified no differences for the correlations between cystatin C and CrCl in patients with or without metastases (r = 0.82 and 0.84, respectively) as well as before treatment and before the fourth cycle of chemotherapy (r = 0.70 and 0.75, respectively). A cystatin C cutoff concentration of 1.33 mg/L had 87% sensitivity and 100% specificity for detecting CrCl <78 mL/min. ROC analysis indicated that cystatin C was superior to serum creatinine for predicting CrCl <78 mL/min (P <0.04). CONCLUSIONS: Serum cystatin C is superior to serum creatinine for detection of decreased CrCl and potentially for the estimation of GFR in cancer patients independent of the presence of metastases or chemotherapy.     

Evaluation of serum cystatin C and chromogranin A as markers of nephropathy in patients with type 2 diabetes mellitus

Nephropathy is a significant cause of morbidity and mortality in patients with diabetes mellitus (DM). The condition is characterized by persistent albuminuria and years of progressive renal structural changes associated with decline in the glomerular filtration rate (GFR). This study evaluates whether serum concentrations of the endogenous markers of GFR, cystatin C and chromogranin A could be used as indicators of nephropathy in 77 patients with Type 2 DM. On the basis of early morning urine microalbumin:creatinine ratio, patients were divided into patients without diabetic nephropathy (DN) who were normoalbuminuric (n = 27) and patients with DN who were microalbuminuric (n = 8) or macroalbuminuric (n = 42). Patients with reduced GFR or elevated serum cystatin C did not show the expected increase in serum chromogranin A. Twenty-six percent of the patients with normoalbuminuria and 6% of those with DN had serum chromogranin A below the detection limit of the assay (< 2 U/L). In patients with DN, serum chromogranin A showed significant correlation with serum cystatin C, but not with serum creatinine and creatinine clearance. Serum cystatin C and creatinine showed poor correlation with duration of DM and HbA1c. Serum cystatin C and creatinine were significantly higher in patients with DN than in normoalbuminuric patients. Serum cystatin C showed significant correlation with serum creatinine (rs = 0.45, p = 0.002), but not with creatinine clearance (rs = 0.23, p = 0.17) in patients with DN. Four of nine patients with creatinine clearance between 50 and 80 mL/min had increased (> or = 1.4 mg/L) serum cystatin C compared with only two patients with increased serum creatinine concentration. Twenty of 50 (40%) patients with DN had elevated serum cystatin C compared with 6 of 50 (12%) with elevated serum creatinine. If microalbuminuria is regarded as the "gold-standard" test, serum cystatin C has a sensitivity of 40% and specificity of 100% for the detection of DN. However, further studies are required to confirm the usefulness of serum cystatin C estimation as a screening test and as an early indicator and predictor of the development of DN.     

Relationships among serum cystatin C,serum creatinine,lean tissue mass and glomerular filtration rate in healthy adults

In an effort to increase our knowledge of the optimal use of serum cystatin C and creatinine as glomerular filtration rate (GFR) markers, these variables, as well as lean tissue mass and GFR, were determined in a population of 42 healthy young adults (men and women with normal GFR). Dual­energy X­ray absorptiometry and measurement of the plasma clearance of iohexol were used to measure lean tissue mass and GFR, respectively. Serum creatinine was significantly correlated to lean tissue mass (r=0.65; p&lt;0.0001) but not to GFR (1/creatinine vs. GFR: r=0.11; p=0.106). In contrast, serum cystatin C correlated with GFR (1/cystatin C vs. GFR: r=0.32; p=0.0387), especially in men (1/cystatin C vs. GFR: r=0.64; p=0.0055), but not to lean tissue mass. These results might explain previous observations that serum cystatin C seems to be a better marker for GFR than serum creatinine, particularly for individuals with small to moderate decreases in GFR. However, the results also show that the serum concentrations of both creatinine and cystatin C are determined not only by GFR, but also by other factors. Since these additional factors differ for cystatin C and creatinine, it seems justified to use serum creatinine and cystatin C in conjunction to estimate GFR, at least until it is known in what situations serum creatinine or cystatin C is the preferable marker.     

改良MDRD公式、血清肌酐、肌酐清除率、胱抑素C及尿微量白蛋白在慢性肾病早期诊断中的应用

目的采用估算的肾小球滤过率（eGFR）在慢性肾病（CKD）患者中分期,用于比较各期血清肌酐（Scr）、肌酐清除率（Ccr）、胱抑素C（CystatinC）及尿微量白蛋白（mAlb）的异常率,分析该五项指标在慢性肾病早期诊断中的应用。方法Scr和尿肌酐采用苦味酸动力学法测定,血清Cystatinc采用胶乳增强免疫比浊法,尿mAlb采用速率散射比浊法,eGFR主要基于Scr及年龄而采用简化的肾病膳食改良试验（MDRD）方程进行计算。结果CKD患者随着eGFR的降低,Nor、Ccr、CystatinC三指标平均水平在各期间的差异有统计学意义（P〈0．05）。而尿mAlb在各期内离散度很大,各水平间差异无统计学意义（P〉0．05）。当eGFR≥90mL／min时,Ccr、CystatinC、尿mAlb与Scr的异常率分别为18．42％、22．37％、25．0％、0,前三者与Scr比较差异均有统计学意义（P〈0．05）,而三者间异常率比较差异无统计学意义（P〉0．05）;当eGFR在60-89mL／min时,异常率分别为28．89％、46．67％、22．22％、2。22％,前三者与Scr比较差异同样有统计学意义（P〈0．05）;当eGFR在30～59mL／min时,异常率分别为90．48％、76．19％、57．14％、52．38％,Ccr及CystatinC异常率与Scr比较差异有统计学意义（P〈0．05）,Ccr异常率最为显著;在eGFR≤29mL／min时,Scr、Ccr、CystatinC、尿mAlb四项指标的异常率均为100％。结论当eGFR〉60mL／min,Scr不能反映GFR的下降,eGFR高估了实际的GFR,而应增加CystatinC和Ccr来评价肾脏功能;当eGFR在30-59mL／min,Scr、CystatmC、Ccr及mAlb能检出一半以上的病例异常,其中CystatinC及Ccr能检出3／4GFR下降的病例,因此对于此期Scr正常,应增加CystatinC和Ccr检验来评价肾脏功能,必要时应检测^99mTc—DTPA清除率来检测GFR值;当eGFR％29mL／min,各指标都反映肾脏功能受损。对于出现尿mAlb的患者,说明肾脏早期受到损伤,24h尿mAlb量的多少不反映GFR的降低,应增加Cysta—tinC、Ccr及eGFR来判断CKD分期,必要时应检测^99mTc-DTPA清除率来检测GFR值。     

Evaluation of renal function in intensive care: plasma cystatin C vs. creatinine and derived glomerular filtration rate estimates.

Plasma cystatin C, a new marker of glomerular filtration rate (GFR), was prospectively evaluated in surgical intensive care. Cystatin C was measured (immunonephelometry, Dade-Behring) in 10 patients selected to cover a full range of GFR (phase I) and in 28 unselected consecutive patients followed for 5 days post-admission (phase II). Results were compared with (51)Cr-EDTA clearance (phase I only), plasma creatinine (kinetic Jaffe, Roche), 24-h or estimated by Cockcroft and Gault (CG) creatinine clearance (CrCl), and modified diet in renal disease (MDRD)-estimated GFR. In phase I, the highest correlation with(51)Cr-EDTA clearance (22-198 mL/min) was noted for CG CrCl (r(2): 0.883, p<0.001). During phase II follow-up, 24-h CrCl could not be calculated in 25% of daily evaluations. Cystatin C correlated with creatinine (0.856, p<0.0001) and CG CrCl with MDRD GFR (0.926, p<0.0001) in renal failure (10-78 mL/min, n=60). There was a +40% (p<0.001) median difference between cystatin C and creatinine (as a % of upper normal cut-off). Sensitivity/specificity to detect a <80 mL/min CG CrCl was 88/97% for cystatin C vs. 48/100% for creatinine (laboratory cut-off). In patients with normal and stable renal function (n=14), day-to-day intra-individual variation was 7.4% for cystatin C (vs. 10.6% for creatinine). In intensive care unit surgical adult patients, CG CrCl provides an easy and cost-effective estimate of GFR. Superior to creatinine, plasma cystatin C can be measured in selected patients where CG CrCl is known to be inaccurate.     

Beta-trace protein, cystatin C, beta(2)-microglobulin, and creatinine compared for detecting impaired glomerular filtration rates in children

BACKGROUND: Because of the limitations of serum creatinine as a marker of glomerular filtration rate (GFR) in children, we assessed the diagnostic accuracy of the novel marker beta-trace protein (BTP) in comparison with cystatin C (Cys-C), beta(2)-microglobulin (beta(2)-MG), and creatinine as conventional indicators of reduced GFR. METHODS: We obtained serum samples from 225 children (age range, 0.2-18 years) with various renal pathologies who were referred for nuclear medicine clearance investigations (technetium-diethylenetriamine pentaacetic acid or chromium-EDTA). We measured Cys-C, BTP (nephelometric tests; Dade Behring), beta(2)-MG (Tinaquant; Roche), and creatinine (enzymatic assay; Creatinine-PAP; Roche). RESULTS: Seventy-five children had reduced GFR (<90 mL x min(-1) x 1.73 m(-2)). One hundred fifty children (independent of gender and age) with values >90 mL x min(-1) x 1.73 m(-2) comprised the control group with gaussian distributions of BTP and Cys-C concentrations. The upper reference limits (97.5 percentile) were 1.01 mg/L for BTP and 1.20 mg/L for Cys-C. The correlations of nuclear medicine clearance with the reciprocals of BTP, Cys-C, and the Schwartz GFR estimate were significantly higher (r = 0.653, 0.765, and 0.706, respectively; P <0.05) than with the reciprocal of creatinine or beta(2)-MG (r = 0.500 and 0.557, respectively). ROC analysis showed a significantly higher diagnostic accuracy of BTP, Cys-C, and the GFR estimate for the detection of impaired GFR than serum creatinine (P <0.05). Compared to creatinine, BTP increased the diagnostic sensitivity by approximately 30%, but it was not more sensitive than Cys-C or the Schwartz GFR estimate. CONCLUSIONS: BTP is superior to serum creatinine and an alternative for Cys-C to detect mildly reduced GFR in children, but it is not better than the Schwartz GFR estimate.     

Estimated glomerular filtration rate (eGFRCystC) from serum cystatin C shows strong agreement with iohexol clearance in patients with low GFR

OBJECTIVE: Estimation of glomerular filtration rate (eGFR) is essential in the diagnosis and monitoring of patients with kidney disease and for correct dosage of drugs eliminated from the circulation by the kidneys. Cystatin C has been shown in several studies to be superior to creatinine in estimating eGFR. However, there are few studies on the performance of cystatin C estimated eGFR (eGFRCystC) in patients with advanced kidney disease and low GFR. MATERIAL AND METHODS: We measured serum cystatin C, together with serum creatinine, during iohexol clearance in patients with iohexol clearance below 30 mL/min/1.73 m2. The cystatin C values were used to calculate eGFRCystC using the formula eGFR (mL/min/1.73 m2) = 79.901*(cystatin C value in mg/L)-1.4389. RESULTS: There was good correlation between eGFRCystC and iohexol clearance (r = 0.88) in patients with iohexol clearance <30 mL/min/1.73 m2 and none of the patients had a difference between eGFRCystC and iohexol clearance exceeding 50 %. The Modification of Diet in Renal Disease (MDRD) equation and corrected MDRD eGFR showed a positive bias and weaker correlations with iohexol eGFR (MDRD = 5.32+1.22*iohexol clearance; corrected MDRD = 4.76+1.10*iohexol clearance; r = 0.59). For MDRD eGFR, 42 of 94 (44.7%) samples showed more than 50% difference to iohexol clearance. CONCLUSIONS: eGFRCystC is an efficient, practical and cost-effective alternative to iohexol clearance in patients with reduced GFR.     

Age- and sex-specific reference limits for creatinine, cystatin C and the estimated glomerular filtration rate

Abstract Background: Early detection of patients with chronic kidney disease is of great importance. This study developed reference limits for serum creatinine and serum cystatin C concentrations and for the estimated glomerular filtration rate (eGFR) in healthy subjects from the general population aged 25-65 years. Methods: This study defined a reference population including 985 subjects from the first follow-up of the Study of Health in Pomerania. Serum creatinine was measured with a modified kinetic Jaffé method. Serum cystatin C was measured with a nephelometric assay. The eGFR was calculated from serum creatinine according to the Cockcroft-Gault (eGFRCG) and the Modification of Diet in Renal Disease (eGFRMDRD) equation, respectively, as well as from serum cystatin C according to the formula by Larsson (eGFRLarsson). Non-parametric quantile regression was used to estimate the reference limits. For serum creatinine and serum cystatin C the 95th percentile and for eGFRCG, eGFRMDRD and eGFRLarsson the 5th percentile were selected as reference limits. All data was weighted to reflect the age- and sex-structure of the German population in 2008. Results: The reference limits for serum creatinine (men: 1.11-1.23 mg/dL; women: 0.93-1.00 mg/dL) and serum cystatin C levels (men: 0.92-1.04 mg/L; women: 0.84-1.02 mg/L) increased with advancing age. The reference limits for eGFR decreased with increasing age (eGFRCG men: 106.0-64.7 mL/min, women 84.4-57.9 mL/min; eGFRMDRD men: 82.5-62.2 mL/min/1.73 m2, women 75.0-58.2 mL/min/1.73 m2; eGFRLarsson men: 85.5-72.9 mL/min, women 94.5-75.7 mL/min). Conclusions: This study presents age- and sex-specific reference limits for five measures of renal function based on quantile regression models.     

Determination of the production rate and non-renal clearance of cystatin C and estimation of the glomerular filtration rate from the serum concentration of cystatin C in humans

Cystatin C has been proposed as an endogenous marker for measuring glomerular filtration rate (GFR) and is regarded as being equivalent to or better than creatinine. However, there are no published data on the production rate (Cys(pr)) or on the non-renal clearance of cystatin C (CL(nr)) in humans, which are essential parameters for GFR calculation. GFR was determined by measuring the plasma clearance of iohexol. Cystatin C, creatinine, urea and albumin were determined on the same serum samples as iohexol; 381 patients with a GFR range of 12-151 ml/min/1.73 m2, and 70 patients on haemodialysis were evaluated. Renal clearance of cystatin C (CLr) equals GFR * S (the sieving coefficient). Plasma clearance (CL) = CLr + CLnr. The relationship between Cys(pr) and the elimination rate (CL * serum-cystatin C) can be expressed as Cys(pr) = (S * GFR+CLnr) * serum-cystatin C. Assuming that the unknown values of Cys(pr) and CLnr are independent of GFR, the equation can be solved from GFR (iohexol clearance) and serum cystatin C (s-Cys) patient data. For S=1, we found Cys(pr) = 0.124 +/- 0.023 mg/min/1.73 m2 and Cl(nr)=22.3 ml/min/1.73 m2. For S = 0.94, found in rats, the values will be Cys(pr) = 0.117 mg/min/1.73 m2 and Cl(nr) = 21 ml/min/1.73 m2 and S-Cys in 70 patients on chronic haemodialysis was found to be 5.74 +/- 1.15 mg/l, in agreement with a calculated value of 5.56 mg/l (s-Cys=124/22.3) for GFR=zero. The mean value of the calculated Cl(nr) for the 70 patients was 22.7 +/- 6.6 ml/min/1.73 m2, which confirms the calculated level and indicates its biological variation. We thus propose the following formula for calculating GFR using the values found for CLnr and Cys(pr) in this study: GFR=124/s - Cys - 22.3 ml/min/1.73 m2, where serum cystatin C concentration is given as mg/l.     

血清胱抑素C：一种简便测定肾小球滤过率的标志物

目的 :评价测定肾小球滤过率 (GFR)的一种简便方法—血清胱抑素C检测的临床意义。方法 :对 5 0例不同肾病患者及70名正常人同时测定血清胱抑素C及内生肌酐清除率、血肌酐值 ,并对两组结果进行相关分析。结果 :血清胱抑素C与内生肌酐清除率及血肌酐值有高度相关性 (r值分别为r =- 0 .83 4 ,p <0 .0 0 1和r =0 .867,p <0 .0 0 1)。结论 :血清胱抑素C检测是一种简便、可靠测定GFR的标志物     

Comparison of estimated glomerular filtration rates from serum creatinine and cystatin C in patients with impaired creatinine production

Determination of the glomerular filtration rate (GFR) is important for the drug dosage adjustment and clinical management of patients. The aim of our study was the comparison of estimated GFR values from serum creatinine (eGFRcreatinine) and cystatin C (eGFRcystatin C) in patients with impaired creatinine production. A total of 564 serum samples from patients with kidney disease (n=179), liver (n=71) and kidney (n=182) transplants, critically ill patients (n=82) and healthy subjects (n=50) were analyzed for serum creatinine and cystatin C. The creatinine production rate (CPR) was significantly lower in the different groups of patients than in the control group (p<0.001). A negative correlation was found between the eGFRcreatinine/eGFRcystatin C ratio and CPR (r= -0.964, p<0.001). For CPR higher than 800 mg/24h both procedures for estimating the GFR classified values higher and lower than 60 mL/min with an acceptable agreement; however, for CPR less than 800 mg/24h the eGFRcreatinine led to false negatives in a high number of cases with eGFRcystatin C <60 mL/min.     

Cystatin C and estimates of renal function: searching for a better measure of kidney function in diabetic patients

BACKGROUND: Early identification of impairment in renal function is crucial in diabetic patients. Serum cystatin C may be the most sensitive indicator of glomerular filtration rate (GFR) in the clinical setting. METHODS: We compared cystatin C with creatinine, the Cockcroft-Gault (C-G) formula, and the Modification of Diet in Renal Disease (MDRD) study equation for the assessment of early decreased renal function in 288 diabetic patients (125 type 1, 163 type 2) with renal impairment [GFR: 4-222 mL x min(-1) x (1.73 m(2))(-1)]. Relationships of cystatin C, creatinine, and iohexol clearance were linearized by plotting their reciprocals in a simple regression model. Diagnostic efficiency was calculated from ROC curves. RESULTS: In this study population, cystatin C (P = 0.0013) was better correlated with GFR (r = 0.857) than were creatinine (r = 0.772), C-G (r = 0.750), and MDRD (r = 0.806), a result replicated in patients with normal renal function (P = 0.023, type 1; P = 0.011, type 2), but not in those with decreased GFR. Mean cystatin C concentrations showed step-by-step statistically significant increases as GFR decreased, allowing very early detection of reduction in renal function. At 90 mL x min(-1) x (1.73 m(2))(-1) and 75 mL x min(-1) x (1.73 m(2))(-1) cut-points, diagnostic efficiencies of cystatin C (89% and 92%) were better than those of the other variables (79%-82% and 85%-86%, respectively; P = 0.01). CONCLUSIONS: All data supported the value of serum cystatin C compared with conventional estimates based on serum creatinine measurement for detecting very early reduction of renal function. Use of cystatin C to measure renal function will optimize early detection, prevention, and treatment strategies for diabetic nephropathy.     

Relationships among serum cystatin C, serum creatinine, lean tissue mass and glomerular filtration rate in healthy adults

In an effort to increase our knowledge of the optimal use of serum cystatin C and creatinine as glomerular filtration rate (GFR) markers, these variables, as well as lean tissue mass and GFR, were determined in a population of 42 healthy young adults (men and women with normal GFR). Dual-energy X-ray absorptiometry and measurement of the plasma clearance of iohexol were used to measure lean tissue mass and GFR, respectively. Serum creatinine was significantly correlated to lean tissue mass (r=0.65; p < 0.0001) but not to GFR (1/creatinine vs. GFR: r=0.11; p=0.106). In contrast, serum cystatin C correlated with GFR (1/cystatin C vs. GFR: r=0.32; p=0.0387), especially in men (1/cystatin C vs. GFR: r=0.64; p=0.0055), but not to lean tissue mass. These results might explain previous observations that serum cystatin C seems to be a better marker for GFR than serum creatinine, particularly for individuals with small to moderate decreases in GFR. However, the results also show that the serum concentrations of both creatinine and cystatin C are determined not only by GFR, but also by other factors. Since these additional factors differ for cystatin C and creatinine, it seems justified to use serum creatinine and cystatin C in conjunction to estimate GFR, at least until it is known in what situations serum creatinine or cystatin C is the preferable marker.     

肾病患者内源性肾小球滤过率的实验室评价

目的 :评估肾病患者内源性肾小球滤过率 (GFR)。方法 :测定了 5 7例肾病患者和 39例健康对照血中CystatinC(CysC )、尿素、肌酐和肌酐清除率浓度。结果 :患者尿素、肌酐、肌酐清除率和CysC浓度与健康对照组间均存在明显差异 (P <0 .0 0 1 ) ;相关分析表明CysC和肌酐清除率之间 (P <0 .0 1 )、CysC和肌酐之间 (P <0 .0 1 )存在明显的相关关系。而肌酐和尿素之间 (P >0 .0 5 ) ,以及肌酐和肌酐清除率之间 (P >0 .0 5 )无明显相关关系存在。结论 :肾病患者血中CysC浓度增高 ,对GFR功能早期受损的评估优于尿素、肌酐和肌酐清除率。     

Evaluation of the clinical application of cystatin C, a new marker of the glomerular filtration rate, for the initial dose-setting of arbekacin

Objective:  Recent studies have shown that serum cystatin C is a better marker for measuring the glomerular filtration rate (GFR) than the conventional method, using serum creatinine concentration. The purpose of this study is to evaluate the clinical application of serum cystatin C as a marker of GFR to determine the initial dosage of arbekacin, an antibiotic primarily excreted via the kidneys. In this study, the predictability of serum arbekacin peak and trough concentrations were assessed using estimated population mean GFR values calculated from either serum creatinine (Cockcroft–Gault equation) or cystatin C (Sjöström equation) concentrations. Method:  Ninety‐five patients treated with arbekacin for methicillin‐resistant Staphylococcus aureus infection were divided into three groups according to their GFR values estimated by the serum cystatin C concentration as follows: normal to mild (GFR > 70 mL/min, n = 40), moderate (30 ≤ GFR ≤ 70 mL/min, n = 41) and severe (GFR < 30 mL/min, n = 14) renal impairment. Result:  The mean GFR (±SD) of 95 patients predicted by serum cystatin C concentration (64·6 ± 30·6 mL/min) was significantly lower (P < 0·001) than predicted by serum creatinine concentration (77·4 ± 43·9 mL/min). Prediction (difference of mean prediction error, ΔME) of the serum arbekacin concentration using the estimated GFR based on the serum cystatin C concentration was significantly less biased at the peak and trough concentrations than those determined using serum creatinine concentration. The accuracy of prediction (difference of the mean absolute error, ΔMAE) using serum cystatin C concentration was significantly better than with serum creatinine for both serum peak and trough concentrations in patients with moderately decreased GFR. However, there were no significant differences in the ΔMAE of normal to mild and severe renally impaired patients. Conclusion:  These results suggest that serum cystatin C is a useful marker of GFR for determining the initial dosage of arbekacin, especially in patients with moderate impairment of renal function.     

Diagnostic value of serum cystatin C for evaluation of hepatorenal syndrome

BACKGROUND: The evaluation of renal function in patients with decompensated cirrhosis is important for prognosis, dosage assessment of potentially nephrotoxic drugs and recognition of changes in glomerular filtration rate (GFR) to decide paracentesis and diuretic therapy. Patients with many different disorders of hepatic function can present with various abnormalities of renal function in the absence of other known causes of renal failure which has been called hepatorenal syndrome (HRS). Some reports have pointed out that serum creatinine levels frequently failed to rise above normal levels even when glomerular filtration rate (GFR) is very low in cirrhotic patients with hepatorenal syndrome. The aim of this study was to determine if estimation of serum cystatin C could replace creatinine clearance in routine GFR determinations for patients with cirrhosis. METHODS: Serum cystatin C, creatinine clearance (Clcr), and 99mTc-DTPA clearance were determined in 26 patients with cirrhosis. According to Child-Pugh's classification, 21 patients were in group C and 5 were in Group B. RESULTS: Pearson correlation analyses showed that correlation between serum cystatin C and 99mTc-DTPA clearance was r=-0.522, p=0.006, between serum creatinine and 99mTc-DTPA was r=-0.373, p=0.06. The results of our study demonstrated that neither serum creatinine nor creatinine clearance (Clcr) were good indicators of hepatorenal syndrome because the mean value for Clcr was found to be higher than Tc-DTPA clearance, and there was no correlation between these two parameters (r=0.059). Additionally, the mean value of serum creatinine was found to be within the normal range, whereas the mean DTPA clearance level was lower than normal range. CONCLUSIONS: This finding could be explained by the fact that cirrhotic patients with poor nutrition may have decreased protein intake, low muscle mass and lack of converting capacity of creatine to creatinine. Thus, we suggest that serum cystatin C assay, which has good analytical performance, could replace or at least be added to creatinine measurement for GFR assessment in patients with cirrhosis.