Guide
Jaffe or enzymatic creatinine: what a method change does at the decision lines
Creatinine is measured by two chemistries that agree on average and differ in what else they react to. This note sets out why, what calibration traceability does and does not fix, and how to count the results a change of method or device moves across a decision line.
Why the two chemistries differ
The Jaffe method measures the colour creatinine forms with alkaline picrate. Other substances in the sample react too, so the method is less specific. Enzymatic methods use a chain of enzyme reactions and are less prone to those interferences. In a comparison of both on the same analyser and samples, the authors describe the Jaffe method as less expensive but more susceptible to interferences [Schmidt et al., 2015]. The KDIGO 2024 guideline reinforces the use of enzymatic assays instead of the Jaffe method, given the interference of many drugs and substances with the latter, and asks laboratories to consider enzymatic assays consistently in children [KDIGO, 2024].
What IDMS traceability fixes, and what it does not
Creatinine calibration is standardised by making routine methods traceable to a reference measurement procedure; the laboratory Jaffe method in one of the comparisons below is traceable to isotope dilution mass spectrometry (IDMS) [Msilanga et al., 2025]. The US National Kidney Disease Education Program’s laboratory working group set out a plan for standardising creatinine measurement worldwide, and noted that measurement variability makes estimated GFR least accurate in the normal and slightly raised creatinine range, which is the range that matters for detecting chronic kidney disease [Myers et al., 2006].
The same report is clear on the limit: standardisation of calibration does not correct for analytical interferences [Myers et al., 2006]. Two methods traceable to the same reference can agree on a clean sample and still differ on a patient whose sample carries an interfering substance. That is why a method change is checked on patient samples, not only on calibrators.
How a small bias moves eGFR categories
eGFR is calculated from creatinine with age and sex, and rises as creatinine falls. A small creatinine bias therefore moves eGFR most where results are dense around a category boundary. In the outpatient comparison of the two methods, there was no overall mean bias, yet a small share of pairs fell into different eGFR categories, with the highest risk at the boundary that defines chronic kidney disease; the differences were not significant relative to biological variation, and the authors judged the risk low if results near that boundary are interpreted with caution [Schmidt et al., 2015].
That is the right shape of answer for a method change: not “is there a bias” but “how many results move across a line, and is that more than repeat testing would move anyway”. The house guide on bias at clinical decision limits sets out the counting method.
Five public comparisons
Public data
The explorer holds five paired creatinine comparisons from four open-access studies: one method change on a single laboratory analyser and four point-of-care devices against a laboratory. We re-analysed each with the same program and the same two creatinine lines. Devices are described generically. In all five, repeat-test imprecision is an assumed default, not measured in the study, so the expected counts are estimates under that assumption.
Same analyser, kinetic Jaffe creatinine against central lab analyser, enzymatic creatinine (Schmidt et al., 2015)
Crossed after the change: 23
Expected from repeat testing alone: about 41
Point of care creatinine meter against central lab analyser, Jaffe creatinine (Msilanga et al., 2025)
Crossed after the change: 29
Expected from repeat testing alone: about 19
Point of care device B against central lab chemistry analyser (Giachino et al., 2024)
Crossed after the change: 46
Expected from repeat testing alone: about 16
Point of care analyser, venous whole blood against central lab serum analyser, kinetic Jaffe (Krisher et al., 2024)
Crossed after the change: 1
Expected from repeat testing alone: about 1
Point of care creatinine meter, capillary against central lab serum analyser, kinetic Jaffe (Krisher et al., 2024)
Crossed after the change: 28
Expected from repeat testing alone: about 1
Fig. 1. The method change on one analyser moved fewer results across the lines than repeat testing alone would; 3 of the 4 point-of-care comparisons moved more.
Source Schmidt RL, Straseski JA, Raphael KL, Adams AH, Lehman CM (2015). A Risk Assessment of the Jaffe vs Enzymatic Method for Creatinine Measurement in an Outpatient Population. PLoS One. doi:10.1371/journal.pone.0143205 (opens in a new tab); PMC4657986 (opens in a new tab). Licence: CC BY 4.0 (opens in a new tab). Msilanga D, Muiru A, Msangi E, Shoo J, Mngumi J, Komba E, Balandya E, Ruggajo P, Bhimma R, Liu K (2025). PLoS One. doi:10.1371/journal.pone.0331969 (opens in a new tab); PMC12425315 (opens in a new tab) (title on the source page; it names the instruments). Licence: CC0 1.0 (opens in a new tab). Giachino M, Vetter B, Perone SA, Correia JC, Erkosar B, Heller O, Khanal VK, Lab B, Pataky Z, Poudel S, Rai M, Sharma SK (2024). Performance and usability of cardiometabolic point of care devices in Nepal: A prospective, quantitative, accuracy study. PLOS Glob Public Health. doi:10.1371/journal.pgph.0003760 (opens in a new tab); PMC11449279 (opens in a new tab). Licence: CC BY 4.0 (opens in a new tab). Krisher L, Jaramillo D, Dye-Robinson A, Dally M, Butler-Dawson J, Brindley S, Pilloni D, Cruz A, Villarreal Hernandez K, Schaeffer J, Adgate JL, Newman LS (2024). Application and comparison of point-of-care devices for field evaluation of underlying health status of Guatemalan sugarcane workers. PLOS Glob Public Health. doi:10.1371/journal.pgph.0003380 (opens in a new tab); PMC11265697 (opens in a new tab). Licence: CC BY 4.0 (opens in a new tab). Changes: Paired results re-analysed by NakedSignal's program; instruments described generically; only derived results are shown. Repeat-test imprecision assumed, not measured.
Show the numbers
| Comparison | Pairs | Slope | Lines | Changed category | Expected from repeat testing | Re-test band |
|---|---|---|---|---|---|---|
| Same analyser, kinetic Jaffe creatinine against central lab analyser, enzymatic creatinine (Schmidt et al., 2015) | 529 | 0.94 (95% interval 0.91 to 0.96) | 1.2 and 1.5 mg/dL | 23 | about 41 | Full |
| Point of care creatinine meter against central lab analyser, Jaffe creatinine (Msilanga et al., 2025) | 358 | 1.08 (95% interval 1.03 to 1.14) | 106.08 and 132.6 µmol/L | 29 | about 19 | Full |
| Point of care device B against central lab chemistry analyser (Giachino et al., 2024) | 345 | 1.11 (95% interval 0.98 to 1.24) | 1.2 and 1.5 mg/dL | 46 | about 16 | Full |
| Point of care analyser, venous whole blood against central lab serum analyser, kinetic Jaffe (Krisher et al., 2024) | 89 | 1.43 (95% interval 1.25 to 1.67) | 1.2 and 1.5 mg/dL | 1 | about 1 | Indicative |
| Point of care creatinine meter, capillary against central lab serum analyser, kinetic Jaffe (Krisher et al., 2024) | 89 | 4.33 (95% interval 3.14 to 6.25) | 1.2 and 1.5 mg/dL | 28 | about 1 | Indicative |
A method change on one analyser: nothing extra to manage
In the outpatient study, both chemistries ran on the same samples on the same analyser [Schmidt et al., 2015]. Our run treats the enzymatic method as the current one and the Jaffe method as the new one. Across 529 pairs, 23 results changed category, against about 41 expected from repeat testing alone. The change moved fewer results across the lines than measuring again on the same method would. That is a real outcome of this kind of report: sometimes the honest count is that there is nothing extra to manage. The comparison line (Fig. 2) has a slope of 0.94 (95% interval 0.91 to 0.96), so the difference is small at the lines but not zero, which matches the published finding of no overall mean bias.
Comparison line with slope 0.939 (95% interval 0.911 to 0.964) and intercept 0.053, drawn against the line of no change. Decision limits drawn at 1.2, 1.5 mg/dL. Where the comparison line sits above the line of no change, the new system reads higher; below, lower.
Fig. 2. Enzymatic and Jaffe creatinine on the same analyser: slope 0.94, close to the line of no change across the range of the two creatinine lines.
Source Schmidt RL, Straseski JA, Raphael KL, Adams AH, Lehman CM (2015). A Risk Assessment of the Jaffe vs Enzymatic Method for Creatinine Measurement in an Outpatient Population. PLoS One. doi:10.1371/journal.pone.0143205 (opens in a new tab); PMC4657986 (opens in a new tab). Licence: CC BY 4.0 (opens in a new tab). Changes: Paired results re-analysed by NakedSignal's program; instruments described generically; only derived results are shown.
Point of care against the laboratory: more to manage
The point-of-care comparisons are a different kind of change: a device outside the laboratory, often on capillary blood, against a laboratory method. KDIGO supports point-of-care creatinine where laboratory access is limited, provided the same quality criteria, including external quality assessment, apply [KDIGO, 2024].
- A point-of-care meter against a laboratory Jaffe method in people living with HIV: the authors report substantial agreement and a small eGFR bias that changes direction across the range [Msilanga et al., 2025]. Here 29 results changed category against about 19 expected, at 106.08 and 132.6 µmol/L (the same two lines in SI units).
- A point-of-care device against a central laboratory analyser: the authors report a small negative average bias within recommended limits [Giachino et al., 2024]. Here 46 results changed category against about 16 expected.
- Two devices against a laboratory kinetic Jaffe method in field conditions: the authors found the venous analyser agreed well and the capillary meter read higher, especially at higher values [Krisher et al., 2024]. The venous analyser moved 1 result against about 1 expected; the capillary meter moved 28 against about 1. Both comparisons are small, so their re-test bands are graded indicative.
Each comparison has its own page with its comparison line, re-test band and full numbers (links in the table under Fig. 1), and all of them sit side by side in the change explorer.
Where our lines come from
The creatinine lines in these comparisons (1.2 and 1.5 mg/dL) were set for the public run so that every series could be read the same way. They are configured, not taken from a guideline. Clinical guidelines work in eGFR categories, which need age and sex with each result; a laboratory running its own comparison names the lines its clinicians use, for creatinine, eGFR or both, before the results are opened.
What this does not cover
- Paediatrics. Children have low creatinine, where non-creatinine chromogens weigh most in the Jaffe method [KDIGO, 2024]. None of these comparisons is paediatric.
- Choice of eGFR equation. The equation changes eGFR categories independently of the creatinine method. It is outside this note.
- Specific interferents. Which drugs or substances affect which method is a question for interference studies, not for paired patient comparisons.
- Individual patients. Counts describe a population of results. They are not advice about any one patient.
Sources
- Schmidt RL, Straseski JA, Raphael KL, Adams AH, Lehman CM (2015). A Risk Assessment of the Jaffe vs Enzymatic Method for Creatinine Measurement in an Outpatient Population. PLoS ONE. pmc.ncbi.nlm.nih.gov/articles/PMC4657986/
- Myers GL, Miller WG, Coresh J, et al. (2006). Recommendations for improving serum creatinine measurement: a report from the Laboratory Working Group of the National Kidney Disease Education Program. Clinical Chemistry. doi.org/10.1373/clinchem.2005.0525144
- Levin A, Ahmed SB, Carrero JJ, et al. (2024). Executive summary of the KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease: known knowns and known unknowns. Kidney International. kdigo.org/wp-content/uploads/2017/02/KDIGO-2024-CKD-Guideline-Executive-Summary.pdf
- Giachino M, Vetter B, Perone SA, et al. (2024). Performance and usability of cardiometabolic point of care devices in Nepal: A prospective, quantitative, accuracy study. PLOS Global Public Health. pmc.ncbi.nlm.nih.gov/articles/PMC11449279/
- Msilanga D, Muiru A, Msangi E, et al. (2025). PLoS ONE. pmc.ncbi.nlm.nih.gov/articles/PMC12425315/
- Krisher L, Jaramillo D, Dye-Robinson A, et al. (2024). Application and comparison of point-of-care devices for field evaluation of underlying health status of Guatemalan sugarcane workers. PLOS Global Public Health. pmc.ncbi.nlm.nih.gov/articles/PMC11265697/
Each link was opened and checked on 26 September 2026. One deposit is cited without its title because the title names a device maker; the link gives it in full.