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Albumin Creatinine Ratio
Albumin Creatinine Ratio
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ABSTRACT
Background Urine albumin-to-creatinine ratio (ACR) and protein-to-creatinine ratio (PCR) are used to
measure urine protein. Recent guidelines endorse ACR use, and equations have been developed incor-
porating ACR to predict risk of kidney failure. For situations in which PCR only is available, having a method
to estimate ACR from PCR as accurately as possible would be useful.
Methods We used data from a population-based cohort of 47,714 adults in Alberta, Canada, who had
simultaneous assessments of urine ACR and PCR. After log-transforming ACR and PCR, we used cubic
splines and quantile regression to estimate the median ACR from a PCR, allowing for modification by
specified covariates. On the basis of the cubic splines, we created models using linear splines to develop
equations to estimate ACR from PCR. In a subcohort with eGFR,60 ml/min per 1.73 m2, we then used the
kidney failure risk equation to compare kidney failure risk using measured ACR as well as estimated ACR
that had been derived from PCR.
Results We found a nonlinear association between log(ACR) and log(PCR), with the implied albumin-to-
protein ratio increasing from ,30% in normal to mild proteinuria to about 70% in severe proteinuria, and
with wider prediction intervals at lower levels. Sex was the most important modifier of the relationship
between ACR and PCR, with men generally having a higher albumin-to-protein ratio. Estimates of kidney
failure risk were similar using measured ACR and ACR estimated from PCR.
CLINICAL RESEARCH
Conclusions We developed equations to estimate the median ACR from a PCR, optionally including spec-
ified covariates. These equations may prove useful in certain retrospective clinical or research applications
where only PCR is available.
Table 1. Patient characteristics in the full cohort, the subcohort used for application of the KFRE, and the subcohort used for
the repeated measures analysis
% of Patientsa
Characteristic Full Cohort Subcohort for Application of the Subcohort for Repeated Measures Analysis
(N547,714) KFRE (n59998) (n517,259) (74,341 Pairs)b
Age in yr, median (IQR) 59.3 (47.2–70.4) 71.3 (61.9–79.1) 58.9 (49.0–70.1)
Age category, yr
18–49 29.8 8.3 26.9
50–69 44.5 37.6 47.9
$70 25.7 54.1 25.2
Women 46.6 46.4 43.9
KDIGO CKD PCR category, mg/gc
A1: ,150 (normal/mild) 65.8 45.3 59.4
A2: 150–500 (moderate) 19.0 25.4 20.9
A3: .500 (severe) 15.2 29.3 19.7
KDIGO CKD ACR category, mg/gc
A1: ,30 (normal/mild) 61.9 42.4 54.7
A2: 30–300 (moderate) 23.8 31.0 26.4
A3: .300 (severe) 14.3 26.6 18.9
KDIGO CKD eGFR category, ml/
min per 1.73 m2
G1: eGFR$90 35.0 — 32.1
G2: eGFR560–89 33.3 — 33.4
G3A: eGFR545–59 12.3 38.9 13.2
G3B: eGFR530–44 11.1 34.5 13.5
G4: eGFR515–29 7.1 22.9 7.1
G5: eGFR,15 1.1 3.7 0.7
Hypertension 62.4 87.7 66.8
Diabetes 47.1 56.7 54.9
Year of ACR/PCR test pair
2002–2006 11.9 16.0 16.2
2007–2011 29.3 40.4 39.8
2012–2016 58.8 43.6 44.0
Laboratory locationd
Edmonton 66.5 62.7 67.5
Calgary 17.8 24.9 16.4
Other 15.8 12.4 16.1
a
Unless otherwise indicated.
b
Percents in this column are calculated on the basis of the number of patients, using characteristics on the date of the earliest pair.
c
To convert ACR or PCR from milligrams per gram to milligrams per millimole, multiply by 0.113.
d
In Edmonton, most urine albumin measurements were made using a Siemens Advia 1800 analyzer, with an immunoturbidimetric method. Urine protein was
measured using a colorimetric method (pyrogallol red) on a Protein Pointe Scientific analyzer (from September 2013 to December 2016), a Wako analyzer (July 2011
to September 2013), and a Genzyme analyzer (before July 2011). In Calgary, most measurements were made with a Roche Integra analyzer, with albumin measured
with an immunoturbidimetric method and protein with a turbidimetric method (benzethonium chloride). Testing at other sites was done using various analyzers and
methods, which we were unable to determine in all cases.
[i.e., variation in log(ACR) changes with log(PCR)]. 24 using a Wald test for the groups of variables that correspon-
Through this process we created models for median lo- ded to each covariate.
g(ACR) with no covariates, specified covariates, and all
covariates. In addition, to better describe the prediction in- Alternative Approaches
terval for estimated log(ACR), we fit quantile regression Because models incorporating restricted cubic splines do not
models for the 25th and 75th percentiles. Because the coef- easily allow the estimation of predicted values from the coef-
ficients from models with cubic splines with interactions are ficients alone, we created models with log(PCR) transformed
difficult to interpret, we assessed the effect of each covariate with a linear spline, with knots on the basis of inflections of the
graphically by plotting the predicted median ACR versus the cubic spline. We created four models: one with only the linear
measured PCR, including 95% confidence intervals (95% spline of log(PCR); one with sex and linear spline interactions
CIs), for each covariate value using models that contained added; one with age, sex, diabetes, hypertension, GFR cate-
the spline, the covariate, and interactions. We also tested the gory, and linear spline interactions added; and one with all
statistical significance of each covariate in a full model by covariates, including laboratory location.
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Table 2. Summary statistics for selected median regression models on the basis of cubic and linear splines, and specified
covariates
Models with Log(PCR) Models with Log(PCR)
Transformed with a Five-Knot Transformed with a Four-Knot Correlation Coefficient
Variables included Restricted Cubic Spline Linear Spline between Estimates from
No. of Pseudo No. of Pseudo Model Pairs
Model Model
Coefficients R2 Coefficients R2
Spline of log(PCR) only C1 5 0.624 L1 6 0.623 .0.99
Spline of log(PCR), sex, and interactions C2 10 0.629 L2 12 0.628 .0.99
Spline of log(PCR), sex, age, diabetes, C3 40 0.637 L3 48 0.635 .0.99
hypertension and eGFR category, and
interactions
Spline of log(PCR) sex, age, diabetes, C4 50 0.642 L4 60 0.641 .0.99
hypertension, eGFR category,
laboratory location, and interactions
The knots for the restricted cubic spline were at percentiles 5, 27.5, 50, 72.5, and 95 of log(PCR) (3.4668, 4.0625, 4.5664, 5.3992, and 7.7333, corresponding to PCR
values of 32.0, 58.1, 96.2, 221, and 2283 mg/g). Knots for the linear spline were at values of log(PCR) of 3.689, 4.094, 5.521, and 6.908, corresponding to PCR values
of 40, 60, 250, and 1000 mg/g. The number of coefficients includes the constant. The interactions are between the covariate and the spline terms. Pseudo R2 is the
proportion of the sum of absolute deviations from the median that is explained by the model.
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Table 3. Equations to estimate median and 25th and 75th percentiles of ACR from a PCR measurement, on the basis of
quantile regression models for log(ACR) containing only the linear spline terms for log(PCR)
Range of PCR, Equation to Estimate Median Equation to Estimate 25th Percentile Equation to Estimate 75th Percentile
mg/g Log(ACR) Log(ACR) Log(ACR)
PCR,40 0.951810.12643log(PCR) 0.552810.12973log(PCR) 1.452010.10743log(PCR)
PCR 40 to ,60 21.256810.72513log(PCR) 20.141610.31793log(PCR) 23.719311.50923log(PCR)
PCR 60 to ,250 26.783712.07513log(PCR) 26.246711.80923log(PCR) 24.957111.81163log(PCR)
PCR 250 to 22.964911.38343log(PCR) 27.183311.97883log(PCR) 21.447711.17603log(PCR)
,1000
PCR$1000 20.023910.95773log(PCR) 20.086710.92643log(PCR) 20.190210.99393log(PCR)
Log refers to the natural logarithm, so ACR5exp[log(ACR)]52.71828log(ACR). Median predicted ACR5exp[median of predicted log(ACR)]. ACR and PCR are in
milligrams per gram.
and 75th percentiles, whereas the estimates themselves are spline model, and 705 patients (7.1%; 95% CI, 6.6 to 7.6) using
shown in Supplemental Table 3. Overall, the median ACR the model with the linear spline and sex (Table 5). For 10% 2-
corresponding to a PCR of 150 mg/g was 35.5 mg/g (95% year risk of RRT, sensitivity was slightly higher but specificity
CI, 34.9 to 36.1), with an IQR of 16.0–65.8 mg/g, whereas the slightly lower for predictions on the basis of PCR; the overall
median ACR corresponding to a PCR of 500 mg/g was 301 mg/g correct classification was similar using measured ACR (87.7%;
(95% CI, 298 to 304), with an IQR of 213–357 mg/g. Being a 95% CI, 87.0 to 88.3) versus ACR predicted from the full cubic
man, younger, and having higher eGFR were associated with a spline model (87.2%; 95% CI, 86.6 to 87.9) and ACR predicted
higher median ACR for a PCR of 150 and 500 mg/g, whereas from the model with the linear spline and sex (87.0%; 95% CI,
diabetes and hypertension were associated with a higher me- 86.3 to 87.7). C-statistics were almost identical.
dian ACR only for a PCR of 150 mg/g. Laboratory testing in
Calgary was associated with a higher median ACR for a PCR of Assessment of Within-Person Correlation of ACR/PCR
500 mg/g, but with a lower median ACR for a PCR of 150 mg/g, Ratio
compared with laboratory testing in Edmonton. Supplemental Finally, in a cohort including 74,341 ACR/PCR pairs for
Table 3 also provides the estimated PCR corresponding to the 17,259 individuals, we fit a mixed linear regression model
KDIGO ACR category thresholds of 30 and 300 mg/g. For exam- for log(ACR) and found the intraclass correlation coefficient
ple, the PCR associated with a predicted median ACR of 30 mg/g to be 0.64, indicating that 64% of the variance that was not
was 139 mg/g (123 mg/g for men and 155 mg/g for women).
10000
ACR Classification Accuracy from PCR
The sensitivity, specificity, PPV, NPV, and overall agreement 3000
for measured ACR category versus measured PCR category,
and measured ACR category versus ACR category estimated 1000
Measured ACR (mg/g)
from PCR using the full cubic spline model are provided in
Table 4 for the A1/A2 and A2/A3 thresholds. The sensitivity 300
for identifying A2 versus A1 albuminuria improved when us-
ing the ACR category imputed from the full model compared 100
with using the measured PCR category (from 79.1% to
30
83.2%), but at the loss of some specificity. The overall agree-
ment using the ACR category imputed from the model was 10
slightly higher than it was using the PCR category at the A1/A2
threshold (88.8% versus 87.9%) and marginally higher at the 3
A2/A3 threshold (97.8% versus 97.6%).
Application of the Kidney Failure Risk Equation 3 10 30 100 300 1000 3000 10000
We identified 9998 patients with eGFR,60 ml/min per Predicted ACR (mg/g)
1.73 m2 and 2 years of follow-up to estimate the risk of kidney
Figure 3. This scatterplot of measured ACR versus predicted
failure using the KFRE (for baseline characteristics see Ta-
median ACR from the full cubic spline model (C4), for a 20%
ble 1). Among these, 484 (4.8%; 95% CI, 4.4 to 5.3) were random sample shows a relatively symmetrical distribution
observed to commence RRT within 2 years; using predictions around the line of identity (the diagonal line) indicating unbiased
on the basis of the KFRE, the corresponding estimates were prediction. The blue dots represent men and the red dots rep-
665 patients (6.7%; 95% CI, 6.2 to 7.2) using measured ACR, resent women. To convert ACR or PCR from milligrams per gram
694 patients (6.9%; 95% CI, 6.5 to 7.5) using the full cubic to milligrams per millimole, multiply by 0.113.
200
150
100
60
40
30
20
10
Overall
Female
Male
18-49
50-69
70+
No diabetes
Diabetes
No hypertension
Hypertension
eGFR >=30
eGFR 15-29
eGFR <15
Edmonton
Calgary
Other
PCR = 150 mg/g PCR = 500 mg/g
Figure 4. The estimated median and 95% CIs of ACR at the KDIGO A1/A2 and A2/A3 PCR thresholds of 150 and 500 mg/g, vary by
covariate. To convert ACR or PCR from milligrams per gram to milligrams per millimole, multiply by 0.113. Age is in years and eGFR is
in ml/min per 1.73 m2, The estimates are on the basis of quantile regression models for the 50th percentile of log (ACR), with log(PCR)
transformed with a restricted cubic spline, and with each model containing only the specified covariate, the spline terms, and the
interactions between the specified covariate and the spline terms.
explained by the fixed effects was explained by between- PCR. Sex was the most important modifier of the relationship
person variability, and that there was moderately strong between ACR and PCR, with men generally having a higher
within-person correlation of the ACR/PCR ratio. albumin-to-protein ratio than women. The sex difference in
the median albumin-to-protein ratio varied substantially by
level of proteinuria, with the greatest difference occurring
DISCUSSION from 100 to 200 mg/g, where the median proportion for
women was 0.6 times that for men (e.g., for PCR of 150 mg/g,
We used a large, population-based cohort of same-day urine the median proportion was 30% for men and 18% for women;
ACR/PCR pairs to examine the relationship between the ACR median predicted ACR was 45 mg/g for men and 28 mg/g
and PCR for a wide range of proteinuria levels and clinically for women). At higher ranges, the difference was attenuated
relevant covariates. Consistent with prior research, we found (e.g., female/male ratio of 0.87 at PCR of 500 mg/g), and for
substantial variation in the median albumin-to-protein ratio PCR,45 mg/g the proportion was slightly higher for women
with the level of proteinuria, with the median ratio approaching than men. Our findings were generally consistent with
70% in severe (A3) proteinuria, but dropping to below 30% in those of Fisher et al.,10 who used urine samples from 3481
normal/mild (A1) proteinuria. Using splines to represent PCR patients and fit a multivariable regression equation for the
measurements, we developed equations to allow the estimation log(ACR)/log(PCR) ratio. They found a female/male ratio
of ACR from PCR, accounting for the nonlinear association be- of 0.75, with no allowance for variation with level of protein-
tween ACR and PCR measurements. These equations allow the uria, and excluding the highest 2.5% of ACR measurements.
accurate estimation of the median expected ACR from a PCR Our findings are also consistent with studies that found
measurement, for a wide range of PCR values. To describe the higher rates of albuminuria among men than women, but
range of probable ACR values corresponding to a PCR measure- higher rates of nonalbumin proteinuria among women than
ment, we also developed equations to estimate the 25th and 75th men.15,25,26 Our results contradict, however, the method used
percentiles of the expected ACR. Although we used advanced by Tangri et al.16 to convert PCR to ACR, which implies a
methods, the final equations are relatively simple to use. constant albumin/protein ratio of 38% for men and 57%
All covariates significantly modified the ACR–PCR associ- for women (i.e., female/male ratio of 1.5).
ation; however, the effect of these covariates on predicted me- Laboratory location was also an important modifier. In
dian PCR was small compared with the IQR for predicted Calgary and Edmonton, urine albumin was measured by an
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Values except ROC statistic are reported in percent. A1/A2 threshold: ACR530 mg/g, PCR5150 mg/g. A2/A3 threshold: ACR5300 mg/g, PCR5500 mg/g. Positive cases are above the threshold. ROC, receiver
0.86 (0.86 to 0.87)
0.95 (0.95 to 0.96)
(95% CI)
red) in Edmonton. Given that urine protein measurement is
known to vary by method, it is likely that the differences
between the sites were largely related to differences in protein
measurement. McTaggart et al.15 found that the pyrogallol red
method gave significantly lower protein measurements than
87.9 (87.6 to 88.2)
88.8 (88.5 to 89.1)
protein ratio for pyrogallol red, but only for PCR under ap-
proximately 300 mg/g; above this range, measurement with
pyrogallol red was associated with a lower albumin-to-
protein ratio.
79.1 (78.5 to 79.7) 93.3 (93.1 to 93.6) 88.0 (87.4 to 88.4) 87.9 (87.5 to 88.3)
83.2 (82.6 to 83.7) 92.3 (92.0 to 92.6) 86.9 (86.4 to 87.4) 89.9 (89.6 to 90.3)
94.7 (94.1 to 95.2) 98.0 (97.9 to 98.2) 89.0 (88.3 to 89.7) 99.1 (99.0 to 99.2)
95.4 (94.8 to 95.8) 98.2 (98.0 to 98.3) 89.7 (89.0 to 90.4) 99.2 (99.1 to 99.3)
A2/A3
Table 5. Comparisons of predicted versus observed cases of RRT commencement within 2 years among those with
eGFR,60 ml/min per 1.73 m2, on the basis of the KFRE, and estimates of classification accuracy at 10% risk, using measured
ACR versus ACR estimated from the PCR
Prediction using Prediction using Median ACR Prediction using Median ACR
Observed RRT within
RRT Cases Measured ACR Estimated from PCR with Estimated from PCR with
2 yr (95% CI)
(95% CI)a Model C4 (95% CI)a Model L2 (95% CI) a
improved estimation; in other applications this may not be The use of the KFRE to compare 2-year expected and ob-
the case. served RRT found little difference between using measured
Although the models provide precise estimates of the ex- ACR and ACR estimated from PCR. In our cohort, both mea-
pected median ACR (narrow 95% CIs), there was substantial sured ACR and ACR predicted from PCR overestimated the
unexplained variability in the ACR–PCR relationship, espe- risk of kidney failure by a small but similar amount. However,
cially at lower levels of proteinuria, resulting in wide predic- most cases of RRT (both expected and observed) were in peo-
tion intervals (Supplemental Figure 2). The greater variability ple with A3 albuminuria, and the ACR-to-PCR conversion is
at lower ranges of PCR was likely partly related to greater in- more accurate in this range; very few had A1 albuminuria,
dividual variability in disease states at lower ranges, as the where the conversion is less accurate. Its use with the KFRE
albumin-to-protein ratio is associated with the location of in people with A1 albuminuria has therefore not been ade-
kidney damage.6,27 This is supported by the moderately strong quately tested.
within-person correlation of the ACR/PCR ratio, seen in the Because of the wide prediction intervals for ACR, particu-
mixed model. It was also likely related to greater variability in larly at lower levels, the equations should only be used in
the reactivity of different total protein assays at these levels.8 specific situations. Table 6 summarizes potential clinical and
Table 6. Potential applications for PCR to ACR conversion equations, with recommendations and limitations
Potential Application Recommendation and Limitations
Clinical: Current use (e.g., is it acceptable to test with a PCR and use the Not recommended. ACR is the preferred test to assess albuminuria.6
equations to estimate ACR for CKD staging or kidney failure risk
prediction?)
Clinical: Retrospective/historical use (e.g., when there is a prior PCR Obtain an ACR when possible. If not feasible, one can use the equations to
result but no ACR is available) calculate the median, 25th and 75th percentiles of ACR, to estimate the
likely range. Estimation is more accurate in A3 proteinuria (.500 mg/g).
Research: Prospective use (e.g., collect data on PCR and convert to Not recommended. ACR is the preferred test to assess albuminuria.6
ACR)
Research: Retrospective use (e.g., to estimate ACR from historical PCR One can use the PCR and available covariates to estimate the median
data when no ACR available) expected ACR. One can also estimate the 25th and 75th percentiles of
ACR to estimate the likely range. Estimation is more accurate in A3
proteinuria (.500 mg/g).
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research applications, whether they are recommended, and fees from B. Braun and grants from Merck, outside the submitted work. All of the
associated limitations. We emphasize that the equations should remaining authors have nothing to disclose.
not be used in clinical care to justify measuring PCR rather than
ACR; ACR is the recommended test for albuminuria.6 The equa-
tions are most suited for retrospective applications (clinical or FUNDING
research) where PCR results are available but not ACR. We rec-
ommend estimating 25th and 75th percentiles of ACR in addition The study received funding from the Interdisciplinary Chronic Disease
Collaboration (ICDC); the ICDC is funded through an Alberta Innovates
to the median, to estimate an approximate range of ACR. Collaborative Research & Innovation Opportunity Team Grant. Dr. Hemmel-
Our study’s strengths include the large number of same-day garn, Dr. James, Dr. Manns, Dr. Quinn, Dr. Ravani, and Dr. Tonelli are sup-
ACR/PCR pairs, and linkage with other sources of data to de- ported by grants from the Canadian Institutes of Health Research. Dr. Tonelli
fine relevant covariates. Importantly, our regression models was supported by the David Freeze Chair in Health Services Research, Dr.
included methods that addressed the nonlinear relationship Manns was supported by the Svare Chair in Health Economics, and Dr. Hem-
melgarn was supported by the Roy and Vi Baay Chair in Kidney Disease, all at
between ACR and PCR, their skewed distributions, heterosce- the University of Calgary. The funding agencies had no role in the design and
dasticity, and covariate effects that varied with PCR. conduct of the study; in the collection, analysis, and interpretation of the data;
The study also had limitations. Our results may have been or in the preparation, review, or approval of the manuscript.
influenced by the type of patients who were tested with both
ACR and PCR, although by adjusting for several patient char-
acteristics we believe we substantially addressed this. We were SUPPLEMENTAL MATERIAL
not, however, able to account for the underlying cause of CKD
or race as potential modifiers. Additionally, we were unable to This article contains the following supplemental material online at
identify the analyzers and methods used in approximately http://jasn.asnjournals.org/lookup/suppl/doi:10.1681/ASN.2019060605/-/
20% of tests, and the overall results reflect the particular com- DCSupplemental.
bination of analyzers and methods in use in Alberta during the Supplemental Table 1. Equations to estimate the median and 25th
study period. However, the results presented here are appro- and 75th percentiles of ACR from a PCR measurement, by sex.
priate for the primary intended purpose of estimating ACR Supplemental Table 2. Regression coefficients for four models for me-
from PCR in large samples where several analyzers/methods dian log (ACR), with log (PCR) represented by a four-knot linear spline.
may have been used. Finally, the equations presented here Supplemental Table 3. Estimated median and IQR for ACR, at the
should be validated in other cohorts. KDIGO PCR category thresholds of 150 and 500 mg/g, for the overall
Our findings provide an improved method to estimate ACR cohort and for groups specified by covariates, and estimated PCR
from PCR, which can be used in specific retrospective clinical giving predicted median ACR at KDIGO ACR category thresholds.
or research applications, where ACR is unavailable. Supplemental Figure 1. Median and 25th and 75th percentiles of
predicted albumin-to-protein percent, by PCR value.
Supplemental Figure 2. Median and 25th and 75th percentiles of
predicted ACR by PCR value.
ACKNOWLEDGMENTS
Supplemental Figure 3. Effect of sex on predicted median ACR,
log scale.
Mr. R. Weaver and Dr. Hemmelgarn conceived and designed the
Supplemental Figure 4. Predicted median and 25th and 75th
study and drafted the manuscript. Mr. R. Weaver analyzed the data,
percentiles of ACR for men and women, by PCR value.
and Dr. James, Dr. Ravani, and Mr. C. Weaver provided additional
Supplemental Figure 5. Effect of sex on predicted median ACR,
guidance for the analysis. All authors revised the manuscript critically
linear scale, PCR,600 mg/g.
for important intellectual content and gave final approval of the
Supplemental Figure 6. Effect of sex on predicted median albu-
version to be published.
min-to-protein percent.
This study is based in part on data provided by Alberta Health and
Supplemental Figure 7. Effect of age on predicted median ACR,
Alberta Health Services. The interpretation and conclusions con-
log scale.
tained herein are those of the researchers and do not represent the
Supplemental Figure 8. Effect of age on predicted median ACR,
views of the Government of Alberta or Alberta Health Services.
linear scale.
Neither the Government of Alberta, Alberta Health, nor Alberta
Supplemental Figure 9. Effect of age on predicted median albu-
Health Services express any opinion in relation to this study.
min-to-protein percent.
Supplemental Figure 10. Effect of eGFR category on predicted
median ACR, log scale.
DISCLOSURES
Supplemental Figure 11. Effect of eGFR category on predicted
median ACR, linear scale.
Dr. James and Dr. Hemmelgarn report grants from Amgen Canada, outside the
submitted work. Dr. Jun reports grants from VentureWise (a wholly owned com- Supplemental Figure 12. Effect of eGFR category on predicted
mercial subsidiary of NPS MedicineWise) to conduct a commissioned project median albumin-to-protein percent.
funded by AstraZeneca, outside the submitted work. Dr. Tonelli reports personal Supplemental Figure 13. Effect of diabetes on median ACR, log scale.
Supplemental Figure 14. Effect of diabetes on median ACR, 9. Atkins RC, Briganti EM, Zimmet PZ, Chadban SJ: Association between
linear scale. albuminuria and proteinuria in the general population: The AusDiab
study. Nephrol Dial Transplant 18: 2170–2174, 2003
Supplemental Figure 15. Effect of diabetes on albumin-to-protein
10. Fisher H, Hsu CY, Vittinghoff E, Lin F, Bansal N: Comparison of asso-
percent. ciations of urine protein-creatinine ratio versus albumin-creatinine ratio
Supplemental Figure 16. Effect of hypertension on median ACR, with complications of CKD: A cross-sectional analysis. Am J Kidney Dis
log scale. 62: 1102–1108, 2013
Supplemental Figure 17. Effect of hypertension on median ACR, 11. Methven S, MacGregor MS, Traynor JP, Hair M, O’Reilly DS, Deighan
CJ: Comparison of urinary albumin and urinary total protein as pre-
linear scale.
dictors of patient outcomes in CKD. Am J Kidney Dis 57: 21–28, 2011
Supplemental Figure 18. Effect of hypertension on albumin-to- 12. Wu MT, Lam KK, Lee WC, Hsu KT, Wu CH, Cheng BC, et al.: Albu-
protein percent. minuria, proteinuria, and urinary albumin to protein ratio in chronic
Supplemental Figure 19. Effect of laboratory location (proxy for kidney disease. J Clin Lab Anal 26: 82–92, 2012
analyzer and method) on median ACR, log scale. 13. Collier G, Greenan MC, Brady JJ, Murray B, Cunningham SK: A study of
the relationship between albuminuria, proteinuria and urinary reagent
Supplemental Figure 20. Effect of laboratory location (proxy for
strips. Ann Clin Biochem 46: 247–249, 2009
analyzer and method) on median ACR, linear scale. 14. Kim SM, Lee CH, Lee JP, Oh YK, Kim YS, Kim S, et al.: The association
Supplemental Figure 21. Effect of laboratory location (proxy for between albumin to creatinine ratio and total protein to creatinine ratio
analyzer and method) on albumin-to-protein percent. in patients with chronic kidney disease. Clin Nephrol 78: 346–352, 2012
Supplemental Figure 22. Comparison of predicted median ACR 15. McTaggart MP, Stevens PE, Price CP, Newall RG, Pinnock RG, Lamb EJ:
Investigation of apparent non-albuminuric proteinuria in a primary care
on the basis of models with PCR transformed with a restricted cubic
population. Clin Chem Lab Med 51: 1961–1969, 2013
spline (C1), and with PCR transformed with a linear spline (L1). 16. Tangri N, Grams ME, Levey AS, Coresh J, Appel LJ, Astor BC, et al.; CKD
Supplemental Figure 23. Scatterplot of measured ACR and median Prognosis Consortium: Multinational assessment of accuracy of equations for
ACR predicted from the linear spline model (L2). predicting risk of kidney failure: A meta-analysis. JAMA 315: 164–174, 2016
Supplemental Figure 24. Scatterplot of measured ACR versus ACR 17. Hemmelgarn BR, Clement F, Manns BJ, Klarenbach S, James MT,
Ravani P, et al.: Overview of the Alberta kidney disease network. BMC
estimated from PCR measurements using the equations of Tangri et al.16
Nephrol 10: 30, 2009
Supplemental Figure 25. Scatterplot showing measured ACR versus ACR 18. Hux JE, Ivis F, Flintoft V, Bica A: Diabetes in Ontario: Determination of
estimated from PCR measurements using the equation of Collier et al.13 prevalence and incidence using a validated administrative data algo-
Supplemental Figure 26. Estimated median, 25th and 75th per- rithm. Diabetes Care 25: 512–516, 2002
centiles of ACR at the KDIGO A1/A2 and A2/A3 PCR thresholds of 19. Quan H, Khan N, Hemmelgarn BR, Tu K, Chen G, Campbell N, et al.; Hy-
pertension Outcome and Surveillance Team of the Canadian Hypertension
150 and 500 mg/g, overall and by specified covariate.
Education Programs: Validation of a case definition to define hypertension
using administrative data. Hypertension 54: 1423–1428, 2009
20. Levey AS, Stevens LA, Schmid CH, Zhang YL, Castro AF 3rd, Feldman
HI, et al.; CKD-EPI (Chronic Kidney Disease Epidemiology Collabora-
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JASN 31: 591–601, 2020 Equations to Estimate ACR from PCR 601
Erratum
Table 3. Equations to estimate the median and 25th and 75th percentiles of ACR from a PCR measurement, based on quantile
regression models for log(ACR) containing only the linear spline terms for log(PCR)
Equation to Estimate Equation to Estimate Equation to Estimate
Range of PCR (mg/g)
Median log(ACR) 25th Percentile log(ACR) 75th Percentile log(ACR)
PCR ,40 0.951810.12643log(PCR) 0.552810.12973log(PCR) 1.452010.10743log(PCR)
PCR 40 to ,60 21.256810.72513log(PCR) 20.141610.31793log(PCR) 23.719311.50923log(PCR)
PCR 60 to ,250 26.783712.07513log(PCR) 26.246711.80923log(PCR) 24.957111.81163log(PCR)
PCR 250 to ,1000 22.964911.38343log(PCR) 27.183311.97883log(PCR) 21.447711.17603log(PCR)
PCR $1000 20.023910.95773log(PCR) 0.086710.92643log(PCR) 20.190210.99393log(PCR)
Log refers to the natural logarithm, so ACR5exp(log[ACR])52.71828log(ACR). Median-predicted ACR5exp(median of predicted log[ACR]). ACR and PCR are in
mg/g.
Supplementary material
Table of contents
Table S1. Equations to estimate the median, 25th and 75th percentiles of ACR from a PCR measurement,
by sex
Table S2. Regression coefficients for 4 models for median log(ACR), with log(PCR) represented by a 4-
knot linear spline
Table S3. Estimated median and interquartile range for ACR, at the KDIGO PCR category thresholds of
150 and 500 mg/g, for the overall cohort and for groups specified by covariates, and estimated PCR
giving predicted median ACR at KDIGO ACR category thresholds.
Figure S1. Median, 25th and 75th percentiles of predicted albumin:protein percent, by PCR value
Figure S2. Median, 25th and 75th percentiles of predicted ACR by PCR value
Figure S3. Effect of sex on predicted median ACR, log scale
Figure S4. Predicted median, 25th, and 75th percentiles of ACR for males and females, by PCR value
Figure S5. Effect of sex on predicted median ACR, linear scale, PCR < 600 mg/g
Figure S6. Effect of sex on predicted median albumin:protein percent
Figure S7. Effect of age on predicted median ACR, log scale
Figure S8. Effect of age on predicted median ACR, linear scale
Figure S9. Effect of age on predicted median albumin:protein percent
Figure S10. Effect of eGFR category on predicted median ACR, log scale
Figure S11. Effect of eGFR category on predicted median ACR, linear scale
Figure S12. Effect of eGFR category on predicted median albumin:protein percent
Figure S13. Effect of diabetes on median ACR, log scale
Figure S14. Effect of diabetes on median ACR, linear scale
Figure S15. Effect of diabetes on albumin:protein percent
Figure S16. Effect of hypertension on median ACR, log scale
Figure S17. Effect of hypertension on median ACR, linear scale
Figure S18. Effect of hypertension on albumin:protein percent
Figure S19. Effect of lab location (proxy for analyzer and method) on median ACR, log scale
Figure S20. Effect of lab location (proxy for analyzer and method) on median ACR, linear scale
Figure S21. Effect of lab location (proxy for analyzer and method) on albumin:protein percent
Figure S22. Comparison of predicted median ACR based on models with PCR transformed with a
restricted cubic spline (C1), and with PCR transformed with a linear spline (L1).
Figure S23. Scatterplot of measured ACR and median ACR predicted from the linear spline model (L2).
Figure S24: Scatterplot of measured ACR versus ACR estimated from PCR measurements using the
equations of Tangri et al. (2016).
Figure S25. Scatterplot showing measured ACR versus ACR estimated from PCR measurements using the
equation of Collier et al. (2009).
Figure S26. Estimated median, 25th and 75th percentiles of ACR at the KDIGO A1/A2 and A2/A3 PCR
thresholds of 150 and 500 mg/g, overall and by specified covariate.
1
Table S1. Equations to estimate the median, 25th and 75th percentiles of ACR from a PCR measurement,
by sex, based on quantile regression models for log(ACR) containing the linear spline terms for log(PCR),
sex, and interactions between sex and the spline terms.
Range of PCR Equation to estimate Equation to estimate 25th Equation to estimate 75th
(mg/g) median of log(ACR) percentile of log(ACR) percentile of log(ACR)
Females:
<40 1.7060 – 0.0572*log(PCR) 1.2796 – 0.0386*log(PCR) 1.6731 + 0.0642*log(PCR)
40 to <60 0.2183 + 0.3460*log(PCR) 0.7094 + 0.1159*log(PCR) -1.4845 + 0.9202*log(PCR)
60 to <250 -6.2539 +1.9269*log(PCR) -5.0158 + 1.5144*log(PCR) -5.3268 + 1.8587*log(PCR)
250 to <1000 -4.4287 + 1.5963*log(PCR) -9.0693 + 2.2486*log(PCR) -1.9764 + 1.2519*log(PCR)
≥1000 0.0445 + 0.9488*log(PCR) -0.0479 + 0.9426*log(PCR) -0.1429 + 0.9864*log(PCR)
Males:
<40 0.7373 + 0.1697*log(PCR) 0.5589 + 0.1083*log(PCR) 1.2593 + 0.1460*log(PCR)
40 to <60 -2.7625 + 1.1184*log(PCR) -0.7944 + 0.4751*log(PCR) -5.9091 + 2.0891*log(PCR)
60 to <250 -6.9212 + 2.1342*log(PCR) -7.6388 + 2.1469*log(PCR) -4.4236 + 1.7263*log(PCR)
250 to <1000 -1.9690 + 1.2372*log(PCR) -4.8345 + 1.6390*log(PCR) -1.1395 + 1.1315*log(PCR)
≥1000 -0.1522 + 0.9742*log(PCR) 0.0862 + 0.9267*log(PCR) -0.2425 + 1.0016*log(PCR)
Log refers to the natural logarithm, so ACR = exp(log(ACR)) = 2.71828log(ACR). Median predicted ACR =
exp(median of predicted log(ACR)). ACR and PCR are in mg/g.
2
Table S2. Regression coefficients for 4 models for median log(ACR), with log(PCR) represented by a 4-
knot linear splinea
Model L3: spline of Model L4: Spline of
Model L2:
log(PCR), sex, age, log(PCR), sex, age,
Model L1: spline of
diabetes, diabetes,
Coefficient spline of log(PCR), sex,
hypertension, eGFR hypertension, eGFR
log(PCR) only and spline
category and spline category, lab location
interactions
interactions and spline interactions
Constant 0.9518 1.7060 1.3364 1.3150
S1 0.1264 -0.0572 0.0000 0.0065
S2 0.7251 0.3460 0.4057 0.6304
S3 2.0751 1.9269 2.0689 2.0960
S4 1.3834 1.5963 1.6078 1.4437
S5 0.9577 0.9488 0.8924 0.9078
Male -0.9687 -0.4602 -0.3977
S1*male 0.2269 0.0769 0.0592
S2*male 0.7724 0.8306 0.8919
S3*male 0.2073 0.2046 0.1567
S4*male -0.3591 -0.3364 -0.2948
S5*male 0.0255 0.0253 0.0188
Age2 (50-69)‡ -0.3893 -0.2468
Age3 (70+) -0.8035 -0.8066
S1*age2 0.1315 0.0890
S2*age2 -0.5499 -0.5153
S3*age2 -0.0916 -0.0812
S4*age2 0.1495 0.1504
S5*age2 0.0443 0.0308
S1*age3 0.2864 0.2902
S2*age3 -0.7594 -0.8201
S3*age3 -0.2584 -0.2447
S4*age3 0.2392 0.2450
S5*age3 0.0734 0.0600
Diabetes 0.7794 0.7336
S1*Diabetes -0.1576 -0.1446
S2*Diabetes 0.0269 -0.0305
S3*Diabetes -0.0954 -0.0806
S4*Diabetes -0.0842 -0.0614
S5*Diabetes 0.0318 0.0104
Hypertension 0.4015 0.4172
S1*Hypertension -0.0750 -0.0806
S2*Hypertension 0.2104 0.2475
S3*Hypertension 0.0059 -0.0040
S4*Hypertension -0.1450 -0.1496
S5*Hypertension -0.0069 0.0110
eGFR2 (G4) b
0.9382 2.4382
3
Model L3: spline of Model L4: Spline of
Model L2:
log(PCR), sex, age, log(PCR), sex, age,
Model L1: spline of
diabetes, diabetes,
Coefficient spline of log(PCR), sex,
hypertension, eGFR hypertension, eGFR
log(PCR) only and spline
category and spline category, lab location
interactions
interactions and spline interactions
eGFR3 (G5) 0.0246 0.1705
S1*eGFR2 -0.2607 -0.6650
S2*eGFR2 0.5950 0.5470
S3*eGFR2 -0.2955 -0.2693
S4*eGFR2 0.0847 0.0718
S5*eGFR2 0.0343 0.0209
S1*eGFR3 0.0000 0.0000
S2*eGFR3 1.2408 1.1727
S3*eGFR3 -0.8760 -0.9144
S4*eGFR3 0.3702 0.3366
S5*eGFR3 0.0549 0.0600
Calgary labb
-0.1802
Other lab -0.0483
S1*Calgary lab 0.0073
S2*Calgary lab -0.1450
S3*Calgary lab 0.1180
S4*Calgary lab 0.1904
S5*Calgary lab -0.0079
S1*Other lab 0.0330
S2*Other lab -0.8841
S3*Other lab -0.1720
S4*Other lab 0.4166
S5*Other lab 0.0318
a
The knots for the linear spline were at log(PCR) = 3.689, 4.094, 5.521 and 6.908, corresponding to PCR
values of 40, 60, 250, 1000 mg/g. S1 to S5 represent the variables for the 5 linear spline segments.
b
The reference age category was 18 to 59, the reference eGFR category was G1 to G3, and the reference
lab location was Edmonton.
4
Table S3. Estimated median and interquartile range for ACR, at the KDIGO PCR category thresholds of
150 and 500 mg/g, for the overall cohort and for groups specified by covariates, and estimated PCR
giving predicted median ACR at KDIGO ACR category thresholds.
PCR = 150 mg/g PCR = 500 mg/g PCR (mg/g) PCR (mg/g)
Estimated Estimated Estimated Estimated giving predicted giving predicted
Covariate median IQR for median IQR for median ACR of median ACR of
ACR ACR ACR ACR 30 mg/g 300 mg/g
None (Overall estimates) 35.5 16.0, 65.8 301 213, 357 139 498
Sex
Female 28.0 13.1, 54.5 277 176, 346 155 528
Male 45.5 21.2, 75.9 315 243, 362 123 481
Age, years
18-49 41.0 15.9, 76.6 336 248, 381 130 460
50-69 35.6 15.7, 66.4 308 220, 359 139 491
≥70 32.2 16.5, 56.4 271 182, 331 145 538
No diabetes 31.4 13.8, 63.4 307 195, 368 147 492
Diabetes 39.2 18.4, 66.6 300 222, 348 132 500
No hypertension 31.0 12.6, 64.5 306 171, 366 148 493
Hypertension 36.9 17.8, 66.0 301 221, 354 136 499
eGFR category
≥30 ml/min/1.73m2 35.9 16.2, 66.6 310 227, 361 138 488
15-29 ml/min/1.73m2 31.6 15.1, 53.7 257 175, 321 146 559
<15 ml/min/1.73m2 19.3 7.9, 41.6 205 121, 282 184 647
Laboratory location
Edmonton 42.3 17.3, 75.2 302 221, 348 127 497
Calgary 34.5 18.0, 58.7 341 258, 390 142 460
Other 22.8 11.9, 45.9 251 153, 316 169 564
The overall estimates are from quantile regression models containing only the cubic spline terms, while
estimates for the effect of each covariate are from quantile regression models containing the cubic
spline terms, the covariate(s), and interactions between the covariate(s) and the spline terms. Estimates
of the median ACR are transformed from quantile regression models for the 50th percentile of log(ACR);
estimates of the IQR of ACR are transformed from quantile regression models for the 25th and 75th
percentiles of log(ACR). Estimates of PCR that give predicted median ACR at the KDIGO ACR category
thresholds are from the 50th percentile models. IQR = interquartile range.
5
Figure S1. Median, 25th and 75th percentiles of predicted albumin:protein percent, by value of PCR, from
quantile regression cubic spline models for log(ACR) including only the spline terms for log(PCR)
Figure S2. Median, 25th and 75th percentiles of predicted ACR by PCR value, log scale, from quantile
regression cubic spline models of log(ACR) containing only the spline terms of log(PCR)
6
Figure S3. Effect of sex on predicted median ACR, log scale (from a model containing the cubic spline,
sex, and spline interactions).
Figure S4. Predicted median, 25th and 75th percentiles of ACR for males and females, log scale (from
quantile regression models containing the cubic spline, sex and spline interactions).
7
Figure S5. Effect of sex on predicted median ACR, linear scale, PCR < 600 mg/g (from a model containing
the cubic spline, sex, and spline interactions).
Figure S6. Effect of sex on predicted median albumin:protein percent (from a model containing the
cubic spline, sex, and spline interactions).
8
Figure S7. Effect of age on predicted median ACR, log scale (from a model containing the cubic spline,
age, and spline interactions).
Figure S8. Effect of age on predicted median ACR, linear scale (from a model containing the cubic spline,
age, and spline interactions).
9
Figure S9. Effect of age on predicted median albumin:protein percent (from a model containing the
cubic spline, age, and spline interactions).
Figure S10. Effect of eGFR category on predicted median ACR, log scale (from a model containing the
cubic spline, eGFR category, and spline interactions).
10
Figure S11. Effect of eGFR category on predicted median ACR, linear scale (from a model containing the
cubic spline, eGFR category, and spline interactions).
Figure S12. Effect of eGFR category on predicted median albumin to protein percent (from a model
containing the cubic spline, eGFR category, and spline interactions).
11
Figure S13. Effect of diabetes on median ACR, log scale (from a model containing the cubic spline,
diabetes, and spline interactions).
Figure S14. Effect of diabetes on median ACR, linear scale (from a model containing the cubic spline,
diabetes, and spline interactions).
12
Figure S15. Effect of diabetes on percent albumin (from a model containing the cubic spline, diabetes,
and spline interactions).
Figure S15. Effect of hypertension on median ACR, log scale (from a model containing the cubic spline,
hypertension, and spline interactions).
13
Figure S17. Effect of hypertension on median ACR, linear scale (from a model containing the cubic
spline, hypertension, and spline interactions).
Figure S18. Effect of hypertension on percent albumin (from a model containing the cubic spline,
hypertension, and spline interactions).
14
Figure S19. Effect of lab location (proxy for analyzer and method) on median ACR, log scale (from a
model containing the cubic spline, lab location, and spline interactions).
Figure S20. Effect of lab location (proxy for analyzer & method) on median ACR, linear scale (from a
model containing the cubic spline, lab location, and spline interactions).
15
Figure S21. Effect of lab location (proxy for analyzer and method) on percent albumin (from a model
containing the cubic spline, lab location, and spline interactions).
16
Figure S22. Comparison of predicted median ACR based on models with PCR transformed with a
restricted cubic spline (C1), and with PCR transformed with a linear spline (L1). The knots for the
restricted cubic spline were at percentiles 5, 27.5, 50, 72.5 and 95 of log(PCR) (3.4668, 4.0625, 4.5664,
5.3992 and 7.7333, corresponding to PCR values of 32.0, 58.1, 96.2, 221 and 2283 mg/g). Knots for the
linear spline were at values of log(PCR) of 3.689, 4.094, 5.521 and 6.908, corresponding to PCR values of
40, 60, 250 and 1000 mg/g.
17
Figure S23. Scatterplot of measured ACR and median ACR predicted from the linear spline model (L2) for
a 20% random sample. The blue dots represent males and the red dots females. To convert ACR or PCR
from mg/g to mg/mmol, multiply by 0.113.
18
Figure S24. Scatterplot of measured ACR versus ACR estimated from PCR measurements for a 20%
random sample, using the equations of Tangri et al.1 The equations are: ACR = PCR/1.7566 if female;
ACR = PCR/2.655 if male. Blue dots represent males, red dots females.
19
Figure S25. Scatterplot showing measured ACR versus ACR estimated from PCR measurements for a
20% random sample, using the equation of Collier et al.2 Note that the lowest 22% of PCR values could
not be shown as the predicted ACR was negative if the PCR was <52 mg/g. The equation is: ACR = (-4 +
0.68*PCR)/0.113. Blue dots represent males, red dots females.
20
Figure S26. Estimated median, 25th and 75th percentiles of ACR at the KDIGO A1/A2 and A2/A3 PCR
thresholds of 150 and 500 mg/g, overall and by specified covariate. To convert ACR or PCR from mg/g to
mg/mmol, multiply by 0.113. The estimates are based on quantile regression models for the 25th, 50th
and 75th percentiles of log(ACR), with log(PCR) transformed with a restricted cubic spline, and with each
model containing only the specified covariate, the spline terms, and the interactions between the
specified covariate and the spline terms.
References:
1. Tangri, N, Grams, ME, Levey, AS, Coresh, J, Appel, LJ, Astor, BC, et al., C. K. D. Prognosis Consortium:
Multinational Assessment of Accuracy of Equations for Predicting Risk of Kidney Failure: A Meta-
analysis. JAMA, 315: 164-174, 2016.
2. Collier, G, Greenan, MC, Brady, JJ, Murray, B, Cunningham, SK: A study of the relationship between
albuminuria, proteinuria and urinary reagent strips. Ann Clin Biochem, 46: 247-249, 2009.
21