Accuracy of GFR estimating equations combining standardized cystatin C and creatinine assays: a cross-sectional study in Sweden
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Jonas Björk
Abstract
Background: The recently established international cystatin C calibrator makes it possible to develop non-laboratory specific glomerular filtration rate (GFR) estimating (eGFR) equations. This study compares the performance of the arithmetic mean of the revised Lund-Malmö creatinine and CAPA cystatin C equations (MEANLM-REV+CAPA), the arithmetic mean of the Chronic Kidney Disease Epidemiology Collaboration equation (CKD-EPI) creatinine and cystatin C equations (MEANCKD-EPI), and the composite CKD-EPI equation (CKD-EPICREA+CYSC) with the corresponding single marker equations using internationally standardized calibrators for both cystatin C and creatinine.
Methods: The study included 1200 examinations in 1112 adult Swedish patients referred for measurement of GFR (mGFR) 2008–2010 by plasma clearance of iohexol (median 51 mL/min/1.73 m2). Bias, precision (interquartile range, IQR) and accuracy (percentage of estimates ±30% of mGFR; P30) were compared.
Results: Combined marker equations were unbiased and had higher precision and accuracy than single marker equations. Overall results of MEANLM-REV+CAPA/MEANCKD-EPI/CKD-EPICREA+CYSC were: median bias –2.2%/–0.5%/–1.6%, IQR 9.2/9.2/8.8 mL/min/1.73 m2, and P30 91.3%/91.0%/91.1%. The P30 figures were about 7–14 percentage points higher than the single marker equations. The combined equations also had a more stable performance across mGFR, age and BMI intervals, generally with P30 ≥90% and never <80%. Combined equations reached P30 of 95% when the difference between eGFRCREA and eGFRCYSC was <10% but decreased to 82% at a difference of ≥40%.
Conclusions: Combining cystatin C and creatinine assays improves GFR estimations with P30 ≥90% in adults. Reporting estimates of both single and combined marker equations in clinical settings makes it possible to assess the validity of the combined equation based on the agreement between the single marker equations.
Acknowledgments
Librarian Elisabeth Sassersson for excellent service regarding literature references.
Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.
Financial support: None declared.
Employment or leadership: None declared.
Honorarium: None declared.
Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.
Appendix
Calculation of iohexol clearance (=measured GFR)
GFR was calculated from the iohexol concentration with corrections for lack of complete uniform distribution and non-immediate mixing and using Bröchner-Mortensen’s correction [15] to achieve results corresponding to multi-compartment kinetics of iohexol. Initial GFR was calculated as follows:
where t=time interval between injection and sampling (min). ln=natural logarithm. Qtot=injected amount of iohexol (mg). Ct=iohexol concentration (mg/mL) at time (t) after injection and V=distribution volume (mL) calculated as a function of body weight (kilogram) [44]:
To correct for lack of complete uniform distribution of iohexol the correction factor (m) for distribution volume was calculated [20]:
The corrected distribution volume (V*=V/m) was used calculate the final GFR:
Body surface area equation of DuBois and DuBois [21].
Equations for estimating GFR
In all GFR estimating equations below plasma (serum) creatinine (pCr) is expressed in μmol/L (to convert pCr from μmol/L to mg/dL, divide by 88.4), cystatin C (pCysC) in mg/L, age in years and estimated GFR in mL/min/1.73 m2 body surface area. ln=natural logarithm.
The revised Lund-Malmö creatinine equation (LM-REVCREA) [1]
The final CAPA cystatin C equation (CAPACYSC) [13]
CKD-EPI creatinine equation for Caucasians (CKD-EPICREA) [2]
CKD-EPI cystatin C equation (CKD-EPICYSC) [12]
CKD-EPI creatinine-cystatin C equation for Caucasians (CKD-EPICREA+CYSC) [12]
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Supplemental Material
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Artikel in diesem Heft
- Frontmatter
- Editorials
- Variable accuracy of home pregnancy tests: truth in advertising?
- The highs and lows of tumor biomarkers: lost illusions
- Mini Review
- Matrix metalloproteinases as biomarkers of disease: updates and new insights
- Opinion Papers
- Preanalytical quality improvement. In pursuit of harmony, on behalf of European Federation for Clinical Chemistry and Laboratory Medicine (EFLM) Working group for Preanalytical Phase (WG-PRE)
- Colour coding for blood collection tube closures – a call for harmonisation
- Harmonization protocols for thyroid stimulating hormone (TSH) immunoassays: different approaches based on the consensus mean value
- Genetics and Molecular Diagnostics
- Detection of HLA-B*58:01 with TaqMan assay and its association with allopurinol-induced sCADR
- General Clinical Chemistry and Laboratory Medicine
- Comparison of analytical sensitivity and women’s interpretation of home pregnancy tests
- Accuracy of GFR estimating equations combining standardized cystatin C and creatinine assays: a cross-sectional study in Sweden
- Immunoassay of thyroid peroxidase autoantibodies: diagnostic performance in automated third generation methods. A multicentre evaluation
- Urinary prevalence, metabolite detection rates, temporal patterns and evaluation of suitable LC-MS/MS targets to document synthetic cannabinoid intake in US military urine specimens
- Development and validation of a HPLC-UV method for the quantification of antiepileptic drugs in dried plasma spots
- One year B-vitamins increases serum and whole blood folate forms and lowers plasma homocysteine in older Germans
- Role of cerebrospinal fluid biomarkers to predict conversion to dementia in patients with mild cognitive impairment: a clinical cohort study
- Reference Values and Biological Variations
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- The baseline serum value of α-amylase is a significant predictor of distance running performance
- Cancer Diagnostics
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- Clinical utility of determining tumor markers in patients with signs and symptoms of cancer
- Uric acid levels in blood are associated with clinical outcome in soft-tissue sarcoma patients
- The lymphocyte to monocyte ratio in peripheral blood represents a novel prognostic marker in patients with pancreatic cancer
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- Predictive value for death and rehospitalization of 30-day postdischarge B-type natriuretic peptide (BNP) in elderly patients with heart failure. Sub-analysis of Italian RED Study
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