Evaluation of Gentian cystatin C reagent on Abbott Ci8200 and calculation of glomerular filtration rate expressed in mL/min/1.73 m2 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?m², 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 (R² = 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.     

Performance evaluation of a particle-enhanced turbidimetric cystatin C assay on the Abbott ci8200 analyzer

Objectives

Glomerular filtration rate (GFR) is widely accepted as the best overall measure of kidney function. Cystatin C is a novel endogenous GFR marker that has been shown to be superior to creatinine for estimation of GFR in several studies. There is a need for cystatin C assays adapted to routine chemistry instrument to minimize turnaround times and allowing 24 h/day availability.

Materials and methods

We have evaluated a new cystatin C assay developed for Architect cSystem (Abbott Laboratories, Abbott Park, IL, USA).

Results

The cystatin C assay showed good agreement with the corresponding assay from Dade Behring (Deerfield, IL, USA). The assay has a very low total imprecision and a good linearity.

Conclusions

The new cystatin C assay is an interesting alternative to current cystatin C assays. On an Architect cSystem the assay can be performed with the same turnaround times and availability as creatinine.     

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.     

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.     

Particle enhanced turbidimetric immunoassay for the determination of urine cystatin C on Cobas c501

ObjectiveUrinary cystatin C has been reported to be a good marker for tubular damage and acute kidney injury. The aim of this study was to develop a high throughput assay for the quantification of urine cystatin C.MethodsAntigen-excess, imprecision, interference, linearity, recovery, sample stability and reference values were evaluated on Cobas c501.ResultsThe assay was linear over the dynamic range of the study (R² = 0.9994). The total assay imprecision was below 5%. The assay recovery was estimated at 87–100%. No tendency to antigen-excess (up to 35 mg/L), nor interference with haemoglobin (1.25–10 g/L) was observed. Cystatin C was stable for 1 day at ambient temperature (19–23 °C) but for 2 days at + 4 °C. The reference interval for cystatin C in urine was < 0.414 mg/L.ConclusionsThe urinary cystatin C assay verified to be a reliable assay with convenient performance characteristics, enabling routine testing on clinical chemistry platforms.     

ACE levels may affect cystatin C measurements

ObjectiveTo assess the relationship between angiotensin-converting enzyme (ACE) levels and cystatin C in a patient with the presumed diagnosis of sarcoidosis.Design and methodsCase report with correlation analysis between ACE levels and cystatin C concentrations while considering gold-standard nuclear medicine glomerular filtration rate (GFR) methods for the measurement of renal function.ResultsWe observed a strong correlation between ACE levels and cystatin C concentration in 12-year old with the presumed diagnosis of sarcoidosis in the absence of renal pathology and abnormal renal function.ConclusionElevated ACE levels may cause non-specific cystatin C elevation irrespective of GFR.     

Performance evaluation of the Roche Tina-quant Cystatin C assay and reference interval for cystatin C in healthy blood donors

Abstract

Objective. To evaluate the performance of the Roche Diagnostics Tina-quant Cystatin C particle enhanced immuno turbidimetric assay for the measurement of plasma and serum cystatin C, and to establish reference intervals for cystatin C in healthy blood donors. Methods and materials. The cystatin C measurements were performed on the Roche Modular Analytics P automated clinical chemistry analyzer. Results. The cystatin C assay was linear in the measuring range 0.40–7.00 mg/L. Within-run CVs ≤ 2.0%, between-run CVs ≤ 4.2%, and total CVs ≤ 5.5% in plasma pools and in commercial cystatin C control materials (range 1.0–4.7 mg/L). Recovery was 99.4–109.3%. No interference was detected from haemoglobin < 0.9 mmol/L, bilirubin < 330 μmol/L and Intralipid® < 20 g/L. Measurement of cystatin C in Li-heparin plasma did not differ significantly from cystatin C measured in serum. Forty patient samples run on the Modular Analytics P (y) were compared to the Siemens Cystatin C assay on the BN II (x): y = 0.817x + 0.270, Sy.x = 0.168 (Deming regression). The non-parametric reference interval for cystatin C was calculated to be 0.41–0.91 mg/L in females (n = 86), and 0.43–0.94 mg/L in males (n = 76). The Mann-Whitney U test showed a significant difference between the two genders (p = 0.015), but the difference was without clinical relevance. A common reference interval for both genders (n = 162) was calculated to be 0.41–0.92 mg/L. Conclusion. The performance of the Tina-quant Cystatin C assay was acceptable for clinical use.     

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.     

Analytic and clinical validation of a standardized cystatin C particle enhanced turbidimetric assay (PETIA) to estimate glomerular filtration rate

Abstract Background: Cystatin C is an alternative biomarker for assessing glomerular filtration rate (GFR), yet lack of standardization could hinder its widespread use. In this study we analytically and clinically validated a newer cystatin C particle-enhanced turbidimetric assay (PETIA) traceable to a certified reference material and compared it to the more commonly used particle-enhanced nephelometric assay (PENIA). Methods: Samples from four patient cohorts at the Mayo Clinic were studied: 1) clinical convenience samples (n=50); 2) samples from patients undergoing iothalamate urinary clearance testing for clinical indications (n=101); 3) volunteers without kidney disease (n=292); 4) samples from 1999-2000 with previous cystatin C measurements. Results: The cystatin C PETIA was analytically robust between 0.15 mg/L and 8.36 mg/L. PETIA cystatin C values were 27.5% higher than PENIA results. Furthermore, PENIA results were 12.9% lower in 2010 than in 2000. PETIA cystatin C values and existing equations performed reasonably well to estimate GFR with an overall -7.4% bias for all patients analyzed. Age and gender specific reference intervals were established for the PETIA cystatin C. Conclusions: Cystatin C can be precisely measured by PETIA traceable to the international reference material, ERM-DA471/IFCC, using a routine chemistry autoanalyzer. There are important biases between this assay and the widely employed Siemens PENIA. This study highlights the importance of assay standardization if cystatin C is to be widely used to estimate GFR.     

Evaluation of the Roche COBAS AmpliPrep/COBAS TaqMan HCV Test

The performance of the Roche COBAS AmpliPrep/COBAS TaqMan HCV Test (CAP/CTM) was evaluated. The limit of detection was 9.5 IU/mL using the 3rd International Standard. Serial dilutions of each genotype demonstrated good reproducibility and linearity. Correlation with samples previously tested with the Roche Analyte Specific Reagent (ASR) was very good, with the CAP/CTM assay measuring 0.24 log IU/mL higher on average than ASR. Genotype inclusivity evaluated in the CAP/CTM, ASR, and Siemens Versant HCV RNA 3.0 Assay (bDNA) assay using a commercially available panel showed higher measurements than ASR or bDNA. The differences in observed CAP/CTM and ASR results for genotype 3 patient samples were significantly different (P < 0.05) from those for both genotype 1 and 2 samples. Common inhibitory substances had no more than a 0.25 log IU/mL affect. Overall, the automated CAP/CTM assay exhibits excellent sensitivity, reproducibility, and dynamic range. Its performance is compatible with its use in guiding therapy using direct acting antivirals such as boceprevir and telaprevir.     

Discrepancies between creatinine‐based and cystatin C‐based equations in estimating prevalence of stage 3 chronic kidney disease in an elderly population

Background. The prevalence of stage 3 chronic kidney disease (CKD) is increasing, calculated using the modification of diet in renal disease (MDRD) study equation for estimating glomerular filtration rate (GFR). Cystatin C‐based equations are also being used to estimate GFR. Using creatinine‐based and cystatin C‐based equations, the aim of our study was to measure the difference in prevalence of stage 3 CKD in a population. Methods. CKD screening is organized in the Province of Liège, Belgium. On a voluntary basis, people aged between 45 and 75 years are invited for screening. GFR is estimated using the MDRD study equation and by the three recent cystatin C‐based equations proposed by Levey's group. The Levey 1 equation is based on cystatin C only and the Levey 2 equation on cystatin C corrected for age and sex. The Levey 3 equation combines cystatin C, creatinine, age and sex. Results. The population screened comprised 754 people. Cystatin C is highly correlated with creatinine (r = 0.6196, p<0.0001). Prevalence of stage 3 CKD when GFR is estimated by the MDRD equation study is 17.2?%, which is significantly and much higher than the prevalence obtained when cystatin C‐based equations are used. Indeed, prevalence is 2?%, 3.3?% and 5.8?% with the Levey 1, 2 and 3 equations, respectively. Conclusions. The prevalence of stage 3 CKD varies strongly following the method used for estimating GFR, creatinine‐based or cystatin C‐based equations. Such discrepancies must be confirmed and explained in additional studies using GFR measured with a reference method.     

Variations in assay protocol for the Dako cystatin C method may change patient results by 50% without changing the results for controls.

BACKGROUND: Cystatin C is increasingly used as a glomerular filtration marker, but so far only a few companies produce most of the cystatin C reagents suited for turbidimetry or nephelometry use in clinical laboratories. METHODS: We studied different protocols for measuring cystatin C on an Architect ci8200 system using cystatin C reagents from Dako (Glostrup, Denmark). The results were compared with those obtained with Dade Behring reagents (Deerfield, IL, USA) on a BN ProSpec system. RESULTS: Differences in assay protocol on the same instrument with the Dako reagent yielded an up to 50% difference in glomerular filtration rate calculated from the cystatin C results when analyzing patient samples, but had no effect on the results for controls. There were also significant differences regarding linearity and kinetics between samples and controls/calibrators. CONCLUSIONS: The results indicate different reactivity of the Dako antibodies against calibrators and controls in comparison with patient samples, highlighting the importance of using controls and calibrators that do not differ from patient samples.     

Evaluation of NM-BAPTA method for plasma total calcium measurement on Cobas 8000®

ObjectivesA new method was developed by Roche for the measurement of plasma calcium using the chromophore 5-nitro-5′-methyl-(1,2-bis(o-aminophenoxy)ethan-N,N,N′,N′-tetraacetic acid (NM-BAPTA) which could have several advantages over the CPC method. The aim of our study was to evaluate the analytical performances of the NM-BAPTA assay from Roche on c701/Cobas 8000® and to perform a comparison study of calcium values with CPC and Arsenazo III methods.MethodsThe analytical performance including imprecision study, linearity, and stability of the NM-BAPTA assay was tested on the c701/Cobas 8000®analyzer. The most frequent interferences such as magnesium and gadolinium-based contrast agents (Gd-CAs) were examined with spiked human plasma on the selected method. The calcium Arsenazo III method from Horiba (Montpellier, France) installed on ABX Pentra 400® was used as a reference method. Linear regression analysis was performed to compare data from the different methods.ResultsThe CV of the NM-BAPTA assay showed good analytical performances with CV <1.5%, in agreement with the proposed and interim European biologic goals. We found no interference neither with gadobenate dimeglumine nor with gadoteric acid considering significant findings as interference greater than 5%. In the analytical range from 0.85 to 3.80 mmol/L, the NM-BAPTA method was closely correlated to the Arsenazo III method.ConclusionsOur data demonstrate that this new calcium NM-BAPTA method developed by Roche analyzers perform as well as the conventional method, especially for the outermost values. Thus, this new colorimetric assay could substitute the CPC method on Roche analyzers.     

Plasma cystatin C as a marker of renal function in patients with liver cirrhosis

Cystatin C is a low molecular weight protein and the plasma level of cystatin C is mainly determined by glomerular filtration, making cystatin C an endogenous marker of glomerular filtration rate. The aim of the study was to elucidate the applicability of plasma cystatin C as a marker of renal function in patients with liver cirrhosis. Serum cystatin C and creatinine concentrations were compared with creatinine clearance. Thirty-six patients (14 females and 22 males aged between 33 and 81 years) with liver cirrhosis with normal to severely impaired kidney function were included. Plasma cystatin C was measured by an automated particle-enhanced nephelometric immunoassay (Dade Behring Diagnostics) and plasma creatinine by an enzymatic method. Plasma levels of cystatin C and creatinine were found to increase with decreasing values of creatinine clearance. The reciprocal values of cystatin C and creatinine were compared with those for creatinine clearance revealing an r 2 of 0.37 and 0.18, respectively. Comparison of the areas under the curves (AUC ) of the non-parametric receiver-operating characteristic plots for plasma cystatin C (AUC = 0.7364; SE = 0.0929) and plasma creatinine (AUC = 0.6309; SE = 0.1028) revealed a significant difference between plasma cystatin C and plasma levels of creatinine (p-value = 0.03). The results demonstrate that the diagnostic accuracy of plasma cystatin C was better than plasma creatinine in identifying liver cirrhotic patients with reduced glomerular filtration rate.     

Plasma cystatin C as a marker of renal function in patients with liver cirrhosis

Cystatin C is a low molecular weight protein and the plasma level of cystatin C is mainly determined by glomerular filtration, making cystatin C an endogenous marker of glomerular filtration rate. The aim of the study was to elucidate the applicability of plasma cystatin C as a marker of renal function in patients with liver cirrhosis. Serum cystatin C and creatinine concentrations were compared with creatinine clearance. Thirty-six patients (14 females and 22 males aged between 33 and 81 years) with liver cirrhosis with normal to severely impaired kidney function were included. Plasma cystatin C was measured by an automated particle-enhanced nephelometric immunoassay (Dade Behring Diagnostics) and plasma creatinine by an enzymatic method. Plasma levels of cystatin C and creatinine were found to increase with decreasing values of creatinine clearance. The reciprocal values of cystatin C and creatinine were compared with those for creatinine clearance revealing an r2 of 0.37 and 0.18, respectively. Comparison of the areas under the curves (AUC) of the non-parametric receiver-operating characteristic plots for plasma cystatin C (AUC=0.7364; SE=0.0929) and plasma creatinine (AUC=0.6309: SF=0.1028) revealed a significant difference between plasma cystatin C and plasma levels of creatinine (p-value=0.03). The results demonstrate that the diagnostic accuracy of plasma cystatin C was better than plasma creatinine in identifying liver cirrhotic patients with reduced glomerular filtration rate.     

血清胱抑素C测定对糖尿病肾病早期诊断的临床意义

目的研究血清胱抑素C在2型糖尿病肾病早期诊断中的临床应用。方法收集115例2型糖尿病患者,根据24小时尿白蛋白排泄量,将患者分为单纯性糖尿病组、早期DN组、临床DN组。比较三组患者血清胱抑素C、血肌酐、肾小球滤过率、肌酐清除率检测出。肾功能异常的比例并分析血清胱抑素c与肾小球滤过率的相关性;根据肾小球滤过率的数值,将单纯性糖尿病组的患者分为eGFR％60ml／min／1．73m^2和eGFR≥60ml／min／1．73m^2组,对两组间血清胱抑素C等各项指标进行比较,进行统计学分析。结果 1.血清胱抑素C与肌酐清除率检出肾功能异常的比例相当,但均明显高于血肌酐及尿素氮。2．在24小时尿白蛋白排泄量〈30mg的患者中,eGFR〈60ml／min／1．73m^2组患者的胱抑素C的水平明显高于eGFR≥60ml／min／1．73m^2的患者。结论血清胱抑素C与肾小球滤过率有很好的相关性,且在正常蛋白尿的糖尿病患者中即可以提示早期肾小球滤过率的下降。     

Therapeutic drug monitoring on COBAS INTEGRA 400--evaluation results

The COBAS INTEGRA 400 (Roche Diagnostics GmbH) is a random access analyzer with a consolidated test menue for routine clinical chemistry, specific proteins, drugs of abuse screening and therapeutic drug monitoring (TDM) and different measuring technologies. It was the aim of the present study to evaluate the suitability of this instrument as dedicated analyzer for TDM. Eight assays based on three different technologies were included: Acetaminophen (enzymatic method), Amikacin/ Phenytoin/ Free Phenytoin/ Lidocaine (fluorescence polarization immunoassays; FPIA), Digitoxin/Digoxin (kinetic interaction of microparticles in solution; KIMS). The study comprised the determination of imprecision according to NCCLS EP-T protocol, method comparison and linearity studies. The assays were compared with the corresponding methods on AxSYM or TDx analyzers (Abbott Laboratories). For Acetaminophen and Amikacin COBAS INTEGRA 700 was used as additional comparison instrument. The results are summarized in a table (table 6). Precision results are well acceptable with within-run CVs < 5% and total CVs < 6% except for Digitoxin and Digoxin which show a somewhat higher imprecision at low concentrations. Results obtained for Acetaminophen and Amikacin on COBAS INTEGRA 400 and 700 show excellent agreement. A good comparability is also found between COBAS INTEGRA 400 and AxSYM or TDx methods with slight systematic deviations for Acetaminophen, Amikacin and Free Phenytoin. The lower correlation coefficient for the digoxin method comparison can be attributed to two discrepant samples. Linearity throughout the range studied which covered > 80% of the measuring range was confirmed for the five assays tested (Digitoxin, Digoxin, Lidocaine, Free Phenytoin, Phenytoin) based on the acceptance criteria of +/- 10% deviation of the measured values from the theoretical values. Based on the analytical performance of the TDM tests studied it can be concluded that the COBAS INTEGRA 400 is very well suited for routine TDM analysis.     

Multicenter analytical evaluation of a high-sensitivity troponin T assay

BackgroundHigh-sensitivity cardiac troponin assays are being introduced clinically for earlier diagnosis of acute myocardial infarction (AMI). We evaluated the analytical performance of a high-sensitivity cardiac troponin T assay (hscTnT, Roche Diagnostics) in a multicenter, international trial.MethodsThree US and 5 European sites evaluated hscTnT on the Modular® Analytics E170, cobas® 6000, Elecsys 2010, and cobas® e 411. Precision, accuracy, reportable range, an inter-laboratory comparison trial, and the 99th percentile of a reference population were assessed.ResultsTotal imprecision (CVs) were 4.6–36.8% between 3.4 and 10.3 ng/L hscTnT. Assay linearity was up to 10,000 ng/L and the limit of blank and detection were 3 and 5 ng/L, respectively. The 99th percentile reference limit was 14.2 ng/L (n = 533). No significant differences between specimen types, assay incubation time, or reagent lots existed. A substantial positive bias (76%) exists between the 4th generation and hscTnT assays at the low end of the measuring range (< 50 ng/L). hscTnT serum pool concentrations were within 2SD limits of the mean of means in the comparison trial, indicating comparable results across multiple platforms and laboratories.ConclusionThe Roche hscTnT assay conforms to guideline precision requirements and will likely identify additional patients with myocardial injury suspicious for AMI.     

Plasmatic cystatin C for the estimation of glomerular filtration rate in intensive care units

Objective To compare the sensitivity of cystatin C and creatinine in detecting decreased glomerular filtration rate.Design Prospective observational study.Setting Medical intensive care unit at a university hospital.Patients and participants Fourteen patients hospitalised in a medical intensive care unit.Interventions Cystatin C and creatinine plasmatic levels were measured in 40 blood samples taken with an interval of at least 24 h.Measurements and results Glomerular filtration rate was estimated by creatinine clearance using 24-h urine collection and the classical Cockcroft-Gault equation. The ability of cystatin C to detect a glomerular filtration rate under 80 ml/min per 1.73 m² was significantly better than that of creatinine (p<0.05).Conclusions Cystatin C, a new plasmatic marker of renal function, could be used to detect renal failure in intensive care in the future.     

The blood serum concentration of cystatin C (gamma-trace) as a measure of the glomerular filtration rate

The blood serum concentrations of creatinine and the low molecular weight proteins cystatin C, beta 2-microglobulin and retinol-binding protein were measured in 106 patients whose glomerular filtration rates were assessed by Cr-ethylenediaminetetraacetate (EDTA)-clearance determinations. The reciprocals of the serum concentrations of creatinine, cystatin C and beta 2-microglobulin were closely correlated to the Cr-EDTA-clearance (r = 0.73, 0.75 and 0.70, respectively) in contrast to the corresponding values for retinol-binding protein (r = 0.39). The calculated values of the glomerular elimination rate for creatinine and cystatin C were normally distributed in contrast to those for beta 2-microglobulin. The calculated glomerular elimination rate of cystatin C was not correlated to age, sex, type of disorder or disease activity. The results demonstrate that the serum level of cystatin C is a better measure of the glomerular filtration rate than the serum level of beta 2-microglobulin.