Creatinine EQA results: why they fail and what to check.
What is known to go wrong with creatinine in external quality assurance, how each problem shows itself in the results, and the checks to make, with every source listed. This is the creatinine monograph EQAWarden ships with. First check: Identify the method on the report (Crea_2 Jaffe vs ECre_2 enzymatic) and compare with that peer group, not the all-method mean.
The limits, units and methods behind every creatinine result.
| RCPAQAP APS, General Serum Chemistry (GSC) | ±8 µmol/L up to 100 µmol/L, ±8% above |
|---|---|
| RCPAQAP APS, Body Fluids | ±16 µmol/L up to 100 µmol/L, ±16% above |
| Units | µmol/L. 1 mg/dL = 88.402 µmol/L; 1 mmol/L = 1000 µmol/L; 1 mg/L = 8.8402 µmol/L. 88.4 is the conventional rounded factor (from M = 113.12 g/mol). |
| Methods | Kinetic Jaffe (alkaline picrate), rate-blanked, with fixed intercept correction (-0.3 mg/dL = -26.5 µmol/L for serum/plasma) - Atellica CH Crea_2 (confidence: High) Enzymatic (creatininase/creatinase/sarcosine oxidase/peroxidase-Trinder) - Atellica CH ECre_2 (principle per chart 'Enzymatic'; reaction scheme textbook) (confidence: High/Medium) IDMS (GC or LC) - reference methods (confidence: High) |
| Standardisation | Numerous JCTLM-listed IDMS RMPs (NIST, DGKC, Ghent, NIM, LGC) and serum CRMs (NIST SRM 967a-type, ERM-DA250a-253a, BCR-573/574/575, KRISS, HSA HRM-3007A, LNE CRM Bio 101a)[5]. Atellica Crea_2 is traceable to IDMS via patient-sample correlation and NIST SRM 967[1]. Jaffe methods remain non-specific: IDMS traceability of calibration does not remove sample-specific chromogen bias[4]. |
| Expected error mode | Mixed. Jaffe matrix/chromogen effects are constant (intercept); calibration errors are proportional. At low creatinine the constant component dominates relative %. |
| Biological variation | Within-subject CV 4.39% and between-subject CV 15.81%, from the EFLM database (meta-analysis, 17 studies). |
| Desirable performance | Imprecision 2.19%, bias 4.1%, total allowable error 7.72%, derived from biological variation (Fraser). |
Platform details are for the Siemens Atellica, the platform EQAWarden's first release covers. Other platforms differ: check your own instructions for use.
4 ways a creatinine result goes wrong in EQA, and how to tell them apart.
Jaffe fixed intercept correction does not match EQA matrix
Why it happens. Crea_2 subtracts 26.5 µmol/L from every serum/plasma result to offset the average protein-related pseudo-creatinine of native serum; processed/lyophilised material with different protein content or chromogen reactivity is over- or under-corrected.
Direction. either (often negative for low-protein or protein-altered material; positive where non-creatinine chromogens are added)
How it shows. Constant offset (non-zero intercept on result-vs-target regression) relative to enzymatic/IDMS targets; Jaffe peer groups separate from enzymatic groups; most important at low creatinine (50-100 µmol/L).
Check. Compare with the same-method (compensated kinetic Jaffe) peer group and the enzymatic group; regress the cycle for intercept vs slope; if an IDMS reference value is provided, interpret with the commutability caveat.
Non-commutability of processed material for creatinine
Why it happens. Jaffe and some enzymatic methods respond to matrix components of processed materials differently from native serum.
Direction. method-specific
How it shows. All-method mean biased relative to IDMS value; method-group differences not present in patient samples.
Check. Prefer peer-group assessment unless the material is documented as commutable.
Interferents co-spiked in multi-analyte material (bilirubin, glucose, ketoacids, pyruvate, cefoxitin)
Why it happens. Atellica Crea_2 IFU: unconjugated bilirubin 15-20 mg/dL decreases results 13-16%; glucose 332 mg/dL (18.4 mmol/L) +10.6%; pyruvate 10 mg/dL +17.6%; cefoxitin 5 mg/dL +17%; dopamine +13.7%. Enzymatic Trinder methods are depressed by bilirubin, NAC, NAPQI, dobutamine, calcium dobesilate.
Direction. negative (bilirubin); positive (glucose, pyruvate/ketoacids, cefoxitin for Jaffe)
How it shows. Sample-specific deviation matching the interferent-rich sample; absent in other samples of the cycle.
Check. Check the same sample's bilirubin, glucose (and any drug) targets; compare Jaffe vs enzymatic peer groups on that sample.
ECre_2 NAPQI interference (recall Z-2283-2020)
Why it happens. N-acetyl-p-benzoquinone imine (paracetamol metabolite) interferes with the peroxidase step of Trinder-based enzymatic creatinine.
Direction. negative (Trinder chemistry)
How it shows. Patient-sample issue; not expected in EQA material unless NAPQI is present (paracetamol itself is not NAPQI).
Check. Relevant to patient-result reviews; for EQA only if the provider documents such additives.
Confidence. Medium[3]
The checks, in order.
- Identify the method on the report (Crea_2 Jaffe vs ECre_2 enzymatic) and compare with that peer group, not the all-method mean.
- Regress the cycle's results on targets: intercept (constant) error points to Jaffe matrix/chromogen or blanking issues; slope error to calibration.
- Check same-sample bilirubin, glucose and drug targets for interference-driven sample-specific outliers.
- Check units (µmol/L vs mg/dL vs mmol/L) - ratios 88.4 or 1000.
- Review calibration (CHEM CAL lot), QC and reagent lot changes; the 26.5 µmol/L correction is fixed and cannot be adjusted by the user.
- If the lab reports eGFR from EQA creatinine, remember constant creatinine errors have the greatest eGFR impact at low creatinine.
Unit traps
- Ratio ~88.4 (or 0.0113) = mg/dL vs µmol/L confusion.
- Ratio 1000 = mmol/L vs µmol/L (common in eGFR-related LIS fields).
EQAWarden runs these checks as rules on every survey, ranks the likely causes with their evidence, and the reviewer decides. All analytes · The 58 rules · The whole knowledge base · How an EQA investigation runs
Questions about creatinine EQA.
What is the RCPAQAP allowable performance specification for creatinine?
In the General Serum Chemistry (GSC) programme it is ±8 µmol/L up to 100 µmol/L, ±8% above, evaluated at the target. RCPAQAP can change its specifications, so confirm the current table at each enrolment year.
What is a common cause of a failed creatinine EQA result?
Jaffe fixed intercept correction does not match EQA matrix. Crea_2 subtracts 26.5 µmol/L from every serum/plasma result to offset the average protein-related pseudo-creatinine of native serum; processed/lyophilised material with different protein content or chromogen reactivity is over- or under-corrected.
What should be checked first when a creatinine EQA result fails?
Identify the method on the report (Crea_2 Jaffe vs ECre_2 enzymatic) and compare with that peer group, not the all-method mean.
How are creatinine units converted?
1 mg/dL = 88.402 µmol/L; 1 mmol/L = 1000 µmol/L; 1 mg/L = 8.8402 µmol/L.
Where every fact on this page came from.
- Siemens Healthineers. Atellica CH Creatinine_2 (Crea_2) - Instructions for Use, 11110159_EN Rev. 05, 2024-09. Siemens Document Library document-id 1156188: https://content.doclib.siemens-healthineers.com/rest/v1/view?document-id=1156188 (downloaded 2026-09-28; English, Australia filter)
- US FDA 510(k) K161494 decision summary - Atellica CH Creatinine_2 (Crea_2): modified kinetic Jaffe with rate blanking and intercept correction. https://www.accessdata.fda.gov/cdrh_docs/reviews/K161494.pdf
- US FDA Class 2 recall Z-2283-2020 (2020-05-04): Atellica CH Enzymatic Creatinine_2 (ECre_2) - interference from N-acetyl-p-benzoquinone imine (NAPQI, paracetamol metabolite). https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfRes/res.cfm?id=181443
- Myers GL, Miller WG, Coresh J, et al. Recommendations for improving serum creatinine measurement: a report from the Laboratory Working Group of the National Kidney Disease Education Program. Clin Chem 2006;52:5-18. doi:10.1373/clinchem.2005.0525144
- JCTLM Database of higher-order reference materials, measurement methods/procedures and services. https://www.jctlmdb.org/ (queried 2026-09-28 via the public search API https://www.jctlmdb.org/backend/api/jctlm/searchRmp|searchRm|searchRms)
- Siemens Healthineers. Atellica CH Analyzer Assay Chart, 11484427 Rev. 01, 2020-11 (based on Atellica SW 1.23). https://cdn0.scrvt.com/39b415fb07de4d9656c7b516d8e2d907/6f443342fd9db5ed/8508a28d54b7/Atellica_CH_Analyzer_Assay_Chart-_11484427_Rev_01_DXDCM_09017fe9804f1df2-1606323973050.pdf
- IUPAC standard atomic weights (abridged, CIAAW) used to compute molar masses: H 1.008, C 12.011, N 14.007, O 15.999, Na 22.990, Mg 24.305, P 30.974, Cl 35.45, K 39.098, Ca 40.078, Fe 55.845, I 126.904, Li 6.94 (https://www.ciaaw.org/atomic-weights.htm; textbook values)
- Miller WG, Jones GRD, Horowitz GL, Weykamp C. Proficiency testing/external quality assessment: current challenges and future directions. Clin Chem 2011;57:1670-80. doi:10.1373/clinchem.2011.168641
- EFLM Biological Variation Database (Aarsand AK et al., EFLM WG-BV). https://biologicalvariation.eu/ - meta-analysis values read from https://biologicalvariation.eu/api/meta_calculations and individual studies from https://biologicalvariation.eu/api/bv_specifications, retrieved 2026-09-28
- Fraser CG. Biological Variation: From Principles to Practice. Washington DC: AACC Press; 2001 (textbook; formulae desirable CVa<=0.5CVi, bias<=0.25*sqrt(CVi^2+CVg^2), TEa=1.65*CVa+bias)
- RCPAQAP. Chemical Pathology Analytical Performance Specifications (web page; dateModified 2025-03-05). https://rcpaqap.com.au/resources/chemical-pathology-analytical-performance-specifications/
See EQAWarden review a creatinine result.
Twenty minutes on a video call, on a fictional demo year: the score, the findings, the ranked causes and the signed review.