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 (eGFR_CystC) 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 eGFR_CystC using the formula eGFR (mL/min/1.73m²) = 79.901*(cystatin C value in mg/L)^?1.4389. Results. There was good correlation between eGFR_CystC 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 eGFR_CystC 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. eGFR_CystC is an efficient, practical and cost‐effective alternative to iohexol clearance in patients with reduced GFR.     

The values of estimated glomerular filtration rate calculated with creatinine and cystatin C based equations in healthy adults

The glomerular filtration rate (GFR) is widely accepted as the best overall index of kidney function. GFR can be measured as the clearance of exogenous or endogenous filtration markers or clinically estimated from serum concentrations of creatinine or cystatin C. Recently, it has been recommended that an estimated GFR (eGFR) should be reported in addition to the value of filtration markers. In this study, we determined the values of eGFR, based on creatinine and cystatin C equations, in 125 healthy volunteers aged 20-75 years. Creatinine was measured by a kinetic alkaline picrate method on an ARCHITECT ci8200 analyzer (Abbott Diagnostics, Wiesbaden, Germany). Cystatin C was determined by a latex particle-enhanced immunonephelometric assay (BNII, Dade Behring, Marburg, Germany). The eGFR values were calculated for creatinine using the Modification of Diet in Renal Disease (MDRD) study equation and Rule's quadratic equation and for cystatin C according to the equation published by Hoek et al. The reference intervals for eGFRs with MDRD, Rule's quadratic and Hoek's equations were calculated nonparametrically and were determined to be 63.5-124.6 mL/min/1.73 m2, 78.3-139.2 mL/min/1.73 m2 and 72.2-115.6 mL/min/1.73 m2, respectively. According to the US National Kidney Foundation, chronic kidney disease (CKD) can be defined as a GFR < 60 mL/min/1.73 m2. Our results showed that healthy adults had eGFR values > 63.5 mL/min/1.73 m2. However, it is important to note that these normal values overlap with values in stages 1 and 2 of CKD, thus an eGFR greater than 60 mL/min/1.73 m2 does not exclude kidney disease.     

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.     

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.     

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.     

Assessing glomerular filtration rate in renal transplant recipients by estimates derived from serum measurements of creatinine and cystatin C

BACKGROUND: Assessing glomerular filtration rate (GFR) is of importance in the surveillance of renal transplant recipients. As serum markers alone are inaccurate for estimating GFR, several equations have been developed with the aim of translating a serum value into a corresponding and more accurate GFR. The present study investigated the diagnostic characteristics of GFR estimates obtained by the simplified MDRD formula and the cystatin C based estimate described by Larsson et al. METHODS: Prospective study in 29 stable renal transplant recipients. GFR was assessed with (125)I-Iothalamate clearance, creatinine was measured with a modified Jaffe method on Dimension RxL (Dade-Behring, Dudingen, Switzerland), cystatin C was determined by particle enhanced turbidimetric immunassay (PETIA; Dako, Glostrup, Denmark). Bias, precision and diagnostic accuracy of the two GFR estimates were assessed with Bland-Altman method and receiver-operating characteristics (ROC) analysis. The latter was performed at a GFR cut-off of 60 ml/min/1.73 m2. RESULTS: The cystatin C based GFR estimate normalized to a body surface area of 1.73 m2 exhibited a bias of -4.7 ml/min/1.73 m2, the 95% limits of agreement were -25.5-16 ml/min/1.73 m2 with an AUC of 0.87. The MDRD estimates obtained from the original creatinine revealed biased results. Thus, non-constant recalibration of creatinine was done. Recalibrated creatinine gave an MDRD GFR estimate with a bias of 1.7 ml/min/1.73 m2. The limits of agreement were -23.1-26.4 ml/min/1.73 m2. ROC analysis revealed an AUC 0.8 and was not significantly different from the cystatin C based GFR estimate. CONCLUSIONS: In renal transplant recipients, the cystatin C based GFR estimate exhibits similar diagnostic characteristics like the simplified MDRD formula. In contrast to cystatin C measurement, recalibration of creatinine might be necessary before implementing the simplified MDRD formula into clinical routine.     

糖尿病患者肾小球滤过率评估方法的临床应用研究

目的探讨适用于2型糖尿病患者肾脏功能评估的肾小球滤过率(GFR)估算公式,比较简化肾脏病膳食改善试验(MDRD)、推荐的肾脏病膳食改善试验(rMDRD)、慢性肾脏病流行病学协作组(CKD-EPI)和半胱氨酸蛋白酶抑制剂C(Cys C)相关GFR 4个GFR估算公式的实际应用。方法收集178例2型糖尿病患者的相关资料,检测血清肌酐(SCr)及Cys C浓度,同时行同位素99m锝-二乙三胺五乙酸(99mTc-DTPA)肾动态显像,得出同位素GFR(iGFR),并以此作为GFR的参考标准。依据美国糖尿病协会(ADA)标准将178例患者分成3个亚组[GFR 15～59、60～89、≥90 mL/(min·1.73 m2)],对各公式的GFR估算值(eGFR)与iGFR进行配对t检验、相关分析、Bland-Altman分析、受试者工作特征(ROC)曲线及15%、30%、50%符合率比较。结果 MDRD公式应用于GFR<60 mL/(min·1.73 m2)的患者,其eGFR与iGFR相关性较好,符合率较高,偏差无统计学意义;应用于GFR≥60 mL/(min·1.73 m2)的患者,其eGFR与iGFR差异有统计学意义(P<0.001)。rMDRD公式计算eGFR在准确性、诊断效能等方面与MDRD公式无明显差异。CKD-EPI公式应用于GFR≥90 mL/(min·1.73 m2)的患者,其eGFR与iGFR的符合率高于MDRD和rMDRD;应用于GFR 60～89 mL/(min·1.73 m2)的患者时,其符合率低于Cys C GFR公式。Cys C GFR公式得出的eGFR与iGFR的相关性、偏差、一致性及符合率均明显优于MDRD和rMDRD公式,尤其应用于GFR≥90 mL/(min·1.73 m2)的患者时,其eGFR与iGFR偏差无统计学意义,明显优于其他3个公式。结论 4个GFR估算公式均能准确估算GFR<60 mL/(min·1.73 m2)的2型糖尿病患者的肾功能水平。在GFR≥90 mL/(min·1.73 m2)时,Cys C GFR公式明显优于传统以SCr为基础的GFR估算公式。     

Kidney function estimating equations in patients with chronic kidney disease

Background: The current guidelines emphasise the need to assess kidney function using predictive equations rather than just serum creatinine. The present study compares serum cystatin C‐based equations and serum creatinine‐based equations in patients with chronic kidney disease (CKD). Methods: Seven hundred and sixty‐four adult patients with CKD were enrolled. In each patient serum creatinine and serum cystatin C were determined. Their glomerular filtration rate (GFR) was estimated using three serum creatinine‐based equations [Cockcroft–Gault (C&G), modification of diet in renal disease (MDRD) and the Chronic Kidney Disease Epidemiology Collaboration equation (CKD‐EPI)] and two serum cystatin C‐based equations [our own cystatin C formula (GFR = 90.63 × cystatin C^?1.192) and simple cystatin C formula (GFR = 100/cystatin C)]. The GFR was measured using ⁵¹CrEDTA clearance. Results: Statistically significant correlation between ⁵¹CrEDTA clearance with serum creatinine, serum cystatin C and all observed formulas was found. The receiver operating characteristic curve analysis (cut‐off for GFR 60 ml/min/1.73 m²) showed that serum cystatin C and both cystatin C formulas had a higher diagnostic accuracy than C&G formula. Bland and Altman analysis for the same cut‐off value showed that all formulas except simple cystatin C formula underestimated measured GFR. The accuracy within 30% of estimated ⁵¹CrEDTA clearance values differs according to stages of CKD. Analysis of ability to correctly predict patient’s GFR below or above 60 ml/min/1.73 m² showed statistically significant higher ability for both cystatin C formulas compared to MDRD formula. Conclusion: Our results indicate that serum cystatin C‐based equations are reliable markers of GFR comparable with creatinine‐based formulas.     

The age related association is more pronounced for cystatin C estimated GFR than for creatinine estimated GFR in primary care patients

ObjectivesThere is an age associated change in GFR but this association may be influenced by the method used. The aims of the present study were to assess the association between age and cystatin C and creatinine based glomerular filtration rate estimates in primary care patients, and to determine the proportion of patients with clinically important renal impairment.Materials and methods1552 samples with simultaneous requests for creatinine and cystatin C from 1552 primary care patients in the county of Uppsala, Sweden were analysed. MDRD, CKD-EPI and cystatin C equations were used to calculate glomerular filtration rate (GFR) and the associations between GFR and age were explored.ResultsThe yearly change in cystatin C estimated GFR was 1.24 mL/min/1.73 m² while the corresponding decline for creatinine estimated GFR was 0.76 mL/min/1.73 m² for MDRD and 0.99 mL/min/1.73 m² for CKD-EPI.ConclusionsThe age related association with GFR estimates is smaller for creatinine estimates than for cystatin C estimates. This leads to differences in the number of patients with reduced eGFR detected with the three estimates and the patient treatment will depend on the estimate used. This is not coherent with a good patient care and we thus need to develop new eGFR equations with better agreement between the estimates.     

Clinical usefulness of cystatin C for the estimation of glomerular filtration rate in type 1 diabetes: reproducibility and accuracy compared with standard measures and iohexol clearance

OBJECTIVE-Assessment and follow-up of early renal dysfunction is important in diabetic nephropathy. Plasma creatinine is insensitive for a glomerular filtration rate (GFR) >50 ml/min and creatinine clearance is unwieldy and subject to collection inaccuracies. We aimed to assess the reproducibility, reliability, and accuracy of plasma cystatin C as a measure of GFR ranging from normal to moderate impairment due to type 1 diabetes in the presence of a normal plasma creatinine concentration. RESEARCH DESIGN AND METHODS-A sensitive immunoturbidimetric cystatin C assay was examined in 29 subjects with type 1 diabetes and 11 nondiabetic subjects. Duplicate measurements of the following were collected from each subject, 2 weeks apart: cystatin C, enzymatic plasma creatinine, 24-h creatinine clearance, GFR estimated from plasma creatinine by the Cockcroft-Gault equation, and iohexol clearance as a gold standard. RESULTS-Iohexol clearance ranged from 35 to 132 ml. min(-1). 1.73 m(-2). Plasma cystatin C compared well with the other clinically used tests. The reliability of cystatin C, as assessed by the discriminant ratio, was superior to creatinine clearance (3.4 vs. 1.5, P < 0.001) and the correlation of cystatin C with iohexol clearance (Rs -0.80) was similar to that of creatinine clearance (Rs -0.74) and superior to that of plasma creatinine and the Cockcroft-Gault estimate (Rs -0.54 and 0.66, respectively). Duplicate estimations were used to provide an unbiased equation to convert plasma cystatin C to GFR. CONCLUSIONS-Based on this study, cystatin C is a more reliable measure of GFR than creatinine clearance, is more highly correlated with iohexol clearance than plasma creatinine, and is worthy of further investigation as a clinical measure of GFR in type 1 diabetes.     

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.     

Evaluation of Gentian cystatin C reagent on Abbott Ci8200 and calculation of glomerular filtration rate expressed in mL/min/1.73 m(2) from the cystatin C values in mg/L

OBJECTIVE: Estimation of the glomerular filtration rate (GFR) is essential when evaluating patients with kidney disease and treating patients with drugs eliminated from the circulation by the kidneys. Cystatin C has been shown in several studies to be superior to creatinine in the estimation of GFR. At our hospitals, there is an increasing demand for cystatin C and at present we perform approximately 1500 cystatin C analyses a month. We thus need the assay available 24 h/day and to have it on our routine chemistry instrument to minimize handling time per test and time to reported test results. MATERIAL AND METHODS: We have evaluated a new cystatin C immunoassay from Gentian (Gentian, Moss, Norway) on Architect ci8200 (Abbott Laboratories, Abbott Park, Ill., USA). A prerequisite at our hospital is that cystatin C results are reported as a calculated GFR in mL/min/1.73 m(2), so we also made a comparison with iohexol clearance. RESULTS: The Gentian cystatin C assay showed good agreement with the corresponding assay from Dade Behring (Deerfield, Ill., USA) and good inter-laboratory concordance. The assay has very low total imprecision, good linearity and strong correlation with iohexol clearance (R (2) = 0.956). The equation for the correlation curve is: y = 79.901x(-1.4389). CONCLUSIONS: There was low inter-laboratory variation between the three laboratories involved in the cystatin C evaluation, and thus all three laboratories can use the same equation for calculating the estimated GFR.     

Simple cystatin C-based prediction equations for glomerular filtration rate compared with the modification of diet in renal disease prediction equation for adults and the Schwartz and the Counahan-Barratt prediction equations for children

BACKGROUND: Serum creatinine is the most commonly used marker for estimation of glomerular filtration rate (GFR). To compensate for its drawbacks as a GFR marker, several prediction equations including several parameters are being used, with the Modification of Diet in Renal Disease (MDRD), Schwartz, and Counahan-Barratt equations being the ones most widely accepted for estimation of relative GFR in mL x min(-1) x (1.73 m(2))(-1). The present study analyzes whether these GFR prediction equations for adults and children might be replaced by simple prediction equations based on plasma concentrations of cystatin C. METHODS: Data from 536 patients (0.3-93 years), consecutively referred for determination of GFR by an invasive gold standard procedure, were used for the analysis. Calculations of bias (median percentage of error), correlation (adjusted R(2)), and percentage of estimates within 30% and 50% of measured GFR were used in the comparisons. RESULTS: A cystatin C-based prediction equation using only concentration in mg/L and a prepubertal factor: GFR [mL x min(-1) x (1.73 m(2))(-1)] = 84.69 x cystatin C (mg/L)(-1.680) x 1.384 (if a child <14 years) assessed GFR equally well or better than the simplified MDRD, the Schwartz, and the Counahan-Barratt prediction equations for the adult (> or =18 years) and juvenile groups of the investigated cohort. Age did not influence the cystatin C-based prediction equation for adults, whereas gender did, but with a factor close to unity (0.948 for females). CONCLUSION: A GFR prediction equation based solely on cystatin C (in mg/L) and a prepubertal factor might replace the simplified MDRD prediction equation for adults and the Schwartz and Counahan-Barratt prediction equations for children.     

Validation of a new standardized cystatin C turbidimetric assay: Evaluation of the three novel CKD-EPI equations in hypertensive patients

Objectives

Analytical and clinical performances of the new standardized cystatin C particle-enhanced turbidimetric immunoassay (PETIA) using DiaSys reagents on Olympus AU2700® analyzer were evaluated.

Design and methods

We have studied imprecision, linearity, limit of detection and limit of quantification of this new immunoassay. Method comparison was assessed in relation to results generated by the standardized Siemens-particle-enhanced nephelometric immunoassay (PENIA). In order to evaluate the clinical relevance of this assay, estimated glomerular filtration rate (GFR) was calculated using MDRD, CKD-EPI creatinine, CKD-EPI cystatin C 2012 and CKD-EPI creatinine–cystatin C 2012 equations and compared to GFR measured using urinary clearance of ^99mTc-DTPA in 100 hypertensive patients.

Results

Cystatin C measurements using DiaSys reagents have reliable analytical performances and are comparable to the standardized Siemens-PENIA method (bias of 0.01 mg/L). The mean measured GFR was 90.0 ± 29.7 mL/min/1.73 m². Bias and accuracy of the three CKD-EPI equations were better than the MDRD. Both CKD-EPI creatinine-based and cystatin C-based formulae had similar bias, precision and accuracy. The combined creatinine–cystatin C equation was significantly more accurate and precise than the CKD-EPI creatinine equation in patients with GFR above 60 mL/min/1.73 m².

Conclusions

The use of cystatin C in a combined equation with creatinine could improve the accuracy of eGFR in the reference interval.     

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。     

Different equations to combine creatinine and cystatin C to predict GFR. Arithmetic mean of existing equations performs as well as complex combinations

Abstract

Purpose: To test various ways of combining creatinine and cystatin C in equations to predict glomerular filtration rate (GFR). Material and methods: Performance of the following expressions to predict GFR was compared with measured GFR (iohexol clearance, mL/min/1.73 m²) in 857 patients: (i) Lund-Malmö creatinine equation, (ii) Grubb cystatin C equation, (iii) arithmetic mean of (1) and (2), (iv) geometric mean of (1) and (2), (v) linear regression on (1) and (2), (vi) regression on (1) and cystatin C, and (vii) regression on creatinine, cystatin C, age and gender. Results: For the entire cohort median percent error (bias) was <5% for all expressions, though all expressions tended to underestimate (?8.3 to 15.8%) GFR at levels ≥90 mL/min/1.73 m². The five expressions combining creatinine and cystatin C significantly improved correlation and accuracy (p<0.001) within 15 and 30% of measured GFR compared with the equations based on the separate analytes and with no significant difference between the five expressions. In a subgroup of patients with neurological disease and muscle atrophy the cystatin C equation performed better than the expressions combining creatinine and cystatin C. Conclusion: Simply calculating the arithmetic mean of predicted GFR based on separate creatinine and cystatin C equations performs equally well as more complex equations. Reporting GFR based on separate creatinine and cystatin C equations, and their arithmetic mean also has the definite advantage that the physician can choose the estimated GFR, most appropriate depending on the clinical setting and patient characteristics.     

Evaluation of creatinine, cystatin C and eGFR by different equations in professional cyclists during the Giro d'Italia 3-weeks stage race

Abstract In this study, creatinine-based equations to evaluate glomerular filtration rate (eGFR) were proposed to more accurately assess kidney function, and cystatin C, a parameter not dependent on muscular mass, was introduced to improve GFR calculation in professional cyclists during a long-lasting race. Nine cyclists participating in the 2011 Giro d'Italia were recruited. Blood and anthropometrical data were collected the day before (T-1) the race, on the 12th day (T 12) and on the 22nd day (T 22) of the race. Haemoglobin and haematocrit were registered. Haemodilution was observed at T 12, whilst stabilization was evident at T 22. Creatinine, cystatin C concentrations and eGFR values were not modified during the observed period; only GFR evaluated with the Cockcroft-Gault (CG) formula and expressed as ml/min/1.73 m(2) significantly decreased (p < 0.05) at T 22 in comparison with T-1, probably as a consequence of weight decrease. Cystatin C levels were in the reference range, while creatinine concentrations were lower. The lowest eGFR values were observed with CG normalized and the Modification of Diet in Renal Disease (MDRD) formulas. A good correlation was observed between the MDRD and the Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI) equations and between CG normalized and both CKD-EPI and MDRD formulas. The worst correlation was registered between CKD-EPI creatinine and cystatin C and all the other equations. In conclusion, adaptive mechanisms of renal function allow athletes to maintain stable creatinine, cystatin C and eGFR values during a long-lasting race. The use of GFR equations to evaluate general health status of sportsmen should be recommended with caution, considering also weight modification during competition.     

Prediction of relative glomerular filtration rate in adults: new improved equations based on Swedish Caucasians and standardized plasma-creatinine assays

OBJECTIVE: To evaluate newly developed equations predicting relative glomerular filtration rate(GFR) in adult Swedish Caucasians and to compare with the Modification of Diet in Renal Disease(MDRD) and Mayo Clinic equations using enzymatic and zero-calibrated plasma creatinine assays. MATERIAL AND METHODS: GFR was measured with iohexol clearance adjusted to 1.73 m(2). One population sample (n=436/Lund) was used to derive an equation based on plasma-creatinine/age/gender, and a second with the addition of lean body mass (LBM). Both equations were validated in a separate sample (n=414/Malm?). The coefficients of the equations were eventually fine-tuned using all 850 patients and yielding Lund-Malm? equations without (LM) and with LBM-term (LM(LBM)).Their performance was compared with the MDRD(CC) (conventional creatinine calibration), MDRD(IDMS) (isotope dilution mass spectroscopy traceable calibration) and Mayo Clinic equations. RESULTS: The Lund equations performed similarly in both samples. In the combined set, the Mayo Clinic/MDRD(CC) resulted in +19.0/+10.2 % median bias, while bias for the other equations was < 10 %. LM(LBM) had the highest accuracy (86 % of estimates within 30 % of measured GFR), significantly (p < 0.001) better than for MDRD(IDMS) (80 %). In men with BMI < 20 kg/m(2), MDRD(IDMS)/LM had +46 %/+19 % median bias. MDRD(IDMS) also overestimated GFR by 22 %/14 % in men/women above 80 years of age. The LM(LBM) equation had < 10 % bias irrespective of BMI, age or GFR except for a 15 % negative bias at GFR > 90 mL/min/1.73 m(2). CONCLUSION: The newly developed Lund-Malm? equations for GFR estimation performed better than the MDRD(IDMS) and Mayo Clinic equations in a Swedish Caucasian sample. Inclusion of an LBM term improved performance markedly in certain subgroups.     

Decentralized glomerular filtration rate (GFR) estimates in healthy kidney donors show poor correlation and demonstrate the need for improvement in quality and standardization of GFR measurements in Sweden

OBJECTIVE: Glomerular filtration rate (GFR) is generally accepted as the best overall index of renal function. Thus, all potential live kidney donors are tested to ensure that they have a normal GFR before they are eligible for kidney transplantation. The choice of GFR test is very much dependent on local traditions and may include iohexol, 51Cr-EDTA, inulin, or creatinine clearance based on urine collection, and creatinine clearance calculated from the Cockcroft-Gault or Modification of Diet in Renal Disease (MDRD) equation as well as cystatin C. The aim of this study was to compare the results of GFR measurements performed in all actual live kidney donors who have undergone live donor nephrectomy at the University Hospital in Uppsala, Sweden, between the years 2000 and 2004. MATERIAL AND METHODS: The patients were selected from all parts of Sweden and the measurements were performed at their local hospital. RESULTS: We found large discrepancies between repeated iohexol measurements in these presumably healthy individuals. There was also a poor correlation between iohexol clearance and calculated creatinine clearance using the Cockcroft-Gault (R2=0.046) or MDRD formula (R2=0.045). CONCLUSIONS: The study shows that the standardization and quality of GFR measurements in Sweden have to be improved.     

Variation of serum creatinine, cystatin C, and creatinine clearance tests in persons with normal renal function

BACKGROUND: To determine the potential sensitivity of several renal function tests for detecting early changes in renal function, we compared the within-individual (W-I) variation over 5 months of serum creatinine, serum cystatin C, and creatinine clearance. METHODS: On 31 healthy subjects, blood and timed urine specimens were collected once each month to get 6 collections. Creatinine (enzymatic) in serum and urine and cystatin C (immunonephelometric) in serum were measured and glomerular filtration rate (GFR) by creatinine clearance and the Modification of Diet in Renal Disease (MDRD) equation were calculated. To compare W-I variations between different creatinine methods, we also measured creatinine by both enzymatic and kinetic alkaline picrate methods on 15 sets of frozen samples. RESULTS: For the 31 volunteers, the mean W-I variations for serum creatinine (5.8%) and cystatin C (5.4%) were both much lower than the W-I variation of creatinine clearance (18.7%). As expected, the MDRD GFR had a similar W-I variation (6.7%) to that of serum creatinine and its values were markedly different than GFR by creatinine clearance. On the 15 sets of frozen samples, the W-I variation of creatinine measured by the enzymatic method (CV 5.2%) was slightly less than by the picrate method (CV 6.2%). CONCLUSIONS: The low W-I variation of both serum cystatin C and serum creatinine suggests that serial measurements of either would detect a changes in renal function earlier than would GFR by creatinine clearance or MDRD equation, which allows reporting only for GFRs<60 ml/min/1.7 m(2). While we measured only creatinine clearance, the large variability, difficulty, and cost of all clearance measurements make them impractical for routine monitoring of patients.