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Journal of the American Society of Nephrology : JASN logoLink to Journal of the American Society of Nephrology : JASN
. 2024 May 21;35(7):980–983. doi: 10.1681/ASN.0000000000000381

Correction: Validation of eGFR for Detecting Associations between Serum Protein Biomarkers and Subsequent GFR Decline

PMCID: PMC11230707  PMID: 38625741

Enoksen, Inger T.T.; Rinde, Nikoline B.; Svistounov, Dmitri; Norvik, Jon V.; Solbu, Marit D.; Eriksen, Bjørn O.; Melsom, Toralf. Validation of eGFR for Detecting Associations Between Serum Protein Biomarkers and Subsequent GFR Decline. J Am Soc Nephrol. 2023;34(8): 1409–1420. doi:10.1681/ASN.0000000000000147

The authors identified an error in the software used for calculating iohexol clearance in the GFR measurements during the Renal Iohexol Clearance Survey 3 (RENIS-3).1 The error involved the calculation of the time from iohexol injection to sampling, which increased the random error in the iohexol clearance measurements. The iohexol clearances measured in RENIS-3, used for longitudinal analyses in the manuscript, initially reported a mean (SD) of 81.7 (14.9) ml/min per 1.73 m2. However, the corrected mean (SD) is 81.6 (14.3) ml/min per 1.73 m2.

After correcting the measured GFR (mGFR) values, most of the associations between proteins and outcomes and the differences between GFR methods remained unchanged. However, some proteins exhibited slight alterations in the magnitude of the differences between GFR methods, whereas the directions of the differences did not change. This primarily affected the results that were borderline significant or nonsignificant. When looking at differences between GFR methods, three protein associations shifted from nonsignificant to significant (of a total of eight associations), and six protein associations (of a total of seven associations) shifted from significant to nonsignificant.

Specifically, the following changes were observed using the corrected mGFR:

In the analysis of accelerated GFR decline, differences between mGFR and eGFRcyscre changed for three proteins: fatty acid binding protein 4 in the unadjusted model and model 1 (P values changed from 0.07 to 0.01 and from 0.12 to 0.02, respectively), TNF receptor 2 in model 2 (P values changed from 0.03 to 0.06), and galectin-3 (Gal-3) in the unadjusted model (P values changed from 0.04 to 0.09).

In the incident CKD analysis, three additional proteins exhibited significant different associations between mGFR and eGFR: TNF-related apoptosis-inducing ligand receptor 2 for eGFRcys and eGFRcyscre in model 2 (P value changed from 0.09 to 0.04 and from 0.05 to 0.02, respectively), Umod for eGFRcre in all models (P value changed from 0.09 to 0.04 in the unadjusted model, from 0.08 to 0.02 in model 1, and from 0.07 to 0.03 in model 2), and MMP2 for eGFRcre in the unadjusted model (P value changed from 0.09 to 0.04). In addition, three more proteins (monocyte chemoattractant protein-1, soluble urokinase-type plasminogen activator receptor, and Gal-3) showed nonsignificant differences between mGFR versus eGFR: monocyte chemoattractant protein-1 in unadjusted analysis (mGFR versus eGFRcys: P value changed from 0.04 to 0.10), soluble urokinase-type plasminogen activator receptor in unadjusted and model 1 (mGFR versus eGFRcre: P value changed from 0.04 to 0.07 and 0.04 to 0.08, respectively), and Gal-3 in unadjusted and model 1 (mGFR versus eGFRcyscre unadjusted: P value changed from 0.02 to 0.31 and mGFR versus eGFRcre model 1: P value changed from 0.03 to 0.14).

The corrected Tables 2 and 3 appear above.

Table 2.

Odds ratios for accelerated measured GFR and eGFR decline per doubling or SD increase in baseline protein concentration

Protein Unadjusted P Value for Difference Model 1 P Value for Difference Model 2 P Value for Difference
OR 95% CI OR 95% CI OR 95% CI
MCP-1a
 mGFR 1.27 0.90 to 1.79 1.21 0.81 to 1.80 1.24 0.82 to 1.87
 eGFRcre 1.11 0.80 to 1.55 0.59 1.11 0.79 to 1.57 0.75 1.10 0.78 to 1.56 0.67
 eGFRcys 1.31 0.98 to 1.75 0.88 1.28 0.91 to 1.79 0.84 1.00 0.62 to 1.63 0.51
 eGFRcyscre 1.13 0.82 to 1.55 0.62 1.08 0.76 to 1.53 0.67 1.01 0.70 to 1.46 0.48
TRAIL-R2a
 mGFR 1.32b 1.02 to 1.70b 0.97 0.68 to 1.40 1.06 0.73 to 1.54
 eGFRcre 1.53b 1.18 to 1.97b 0.43 1.41b 1.07 to 1.86b 0.10 1.27 0.94 to 1.71 0.47
 eGFRcys 2.27b 1.50 to 3.44b 0.03b 2.18b 1.49 to 3.18b 0.002b 1.33 0.78 to 2.29 0.50
 eGFRcyscre 1.52b 1.17 to 1.97b 0.44 1.34 0.99 to 1.83 0.17 1.01 0.63 to 1.63 0.88
FABP4a
 mGFR 0.90 0.76 to 1.06 0.88 0.71 to 1.09 1.01 0.79 to 1.28
 eGFRcre 1.18 0.94 to 1.48 0.06 1.17 0.86 to 1.60 0.13 1.02 0.76 to 1.35 0.95
 eGFRcys 1.34b 1.08 to 1.66b 0.004b 1.74b 1.25 to 2.44b 0.001b 1.01 0.68 to 1.48 1.00
 eGFRcyscre 1.32b 1.04 to 1.68b 0.01b 1.44b 1.00 to 2.06b 0.02b 1.11 0.79 to 1.55 0.64
TNFR-2
 mGFR 1.31b 1.13 to 1.53b 1.09 0.91 to 1.32 1.25b 1.03 to 1.51b
 eGFRcre 1.24b 1.07 to 1.44b 0.62c 1.19b 1.02 to 1.39b 0.50d 1.07 0.91 to 1.26 0.23
 eGFRcys 2.57b 2.07 to 3.18b <0.001b 2.45b 1.93 to 3.12b <0.001b 1.10 0.82 to 1.47 0.47
 eGFRcyscre 1.44b 1.22 to 1.70b 0.43 1.31b 1.10 to 1.55b 0.17 0.95 0.77 to 1.17 0.06
CD40Lig
 mGFR 1.03 0.88 to 1.19 1.01 0.85 to 1.20 0.98 0.82 to 1.18
 eGFRcre 1.10 0.96 to 1.26 0.48 1.07 0.93 to 1.24 0.58 1.09 0.94 to 1.26 0.39
 eGFRcys 1.15 0.98 to 1.35 0.29 1.18 1.00 to 1.39 0.21 1.20 0.96 to 1.50 0.19
 eGFRcyscre 1.11 0.97 to 1.28 0.43 1.10 0.95 to 1.29 0.44 1.09 0.93 to 1.27 0.43
GDF-15
 mGFR 1.28 0.74 to 2.23 1.09 0.95 to 1.24 1.12b 1.01 to 1.26b
 eGFRcre 1.10 0.95 to 1.28 0.61 1.06 0.95 to 1.18 0.79 1.01 0.85 to 1.19 0.28
 eGFRcys 1.69 0.96 to 2.96 0.50 1.38 0.65 to 2.94 0.54 1.13 0.99 to 1.29 0.94
 eGFRcyscre 1.19 0.83 to 1.71 0.83 1.11 1.00 to 1.25 0.77 0.96 0.75 to 1.24 0.28
Tie2
 mGFR 1.02 0.87 to 1.20 0.88 0.74 to 1.04 0.90 0.76 to 1.07
 eGFRcre 0.89 0.74 to 1.08 0.28e 0.90 0.74 to 1.09 0.89 0.87 0.71 to 1.06 0.79
 eGFRcys 1.29b 1.09 to 1.52b 0.05 1.14 0.95 to 1.35 0.04b 1.12 0.89 to 1.41 0.13
 eGFRcyscre 1.04 0.88 to 1.23 0.88 0.99 0.83 to 1.17 0.37 0.94 0.78 to 1.12 0.76
MMP7
 mGFR 1.76b 1.49 to 2.08b 1.58b 1.32 to 1.90b 1.77b 1.44 to 2.16b
 eGFRcre 1.54b 1.31 to 1.81b 0.27 1.46b 1.23 to 1.72b 0.50 1.34b 1.13 to 1.59b 0.04b
 eGFRcys 1.90b 1.62 to 2.24b 0.50 1.86b 1.57 to 2.20b 0.21 1.75b 1.37 to 2.23b 0.94
 eGFRcyscre 1.83b 1.56 to 2.15b 0.74 1.71b 1.45 to 2.02b 0.55 1.52b 1.27 to 1.81b 0.27
suPAR
 mGFR 1.06 0.94 to 1.19 0.99 0.83 to 1.18 0.99 0.83 to 1.17
 eGFRcre 1.05 0.94 to 1.18 0.96 1.02 0.90 to 1.15 0.77 1.00 0.86 to 1.16 0.94
 eGFRcys 1.14 0.98 to 1.31 0.46 1.13 1.00 to 1.27 0.23 1.04 0.85 to 1.27 0.70
 eGFRcyscre 1.11 0.98 to 1.26 0.60 1.07 0.95 to 1.20 0.46 1.02 0.88 to 1.18 0.79
MMP2
 mGFR 1.00 0.85 to 1.19 1.03 0.87 to 1.21 1.03 0.88 to 1.22
 eGFRcre 1.03 0.88 to 1.21 0.83 1.02 0.88 to 1.19 0.96 0.99 0.84 to 1.17 0.72
 eGFRcys 0.98 0.82 to 1.17 0.82 0.95 0.79 to 1.14 0.51 0.84 0.66 to 1.07 0.17
 eGFRcyscre 1.03 0.88 to 1.20 0.84 1.01 0.87 to 1.18 0.87 1.00 0.85 to 1.17 0.75
Umod
 mGFR 0.80b 0.68 to 0.95b 0.99 0.83 to 1.18 0.94 0.78 to 1.13
 eGFRcre 0.81b 0.67 to 0.98b 0.93f 0.79b 0.65 to 0.97b 0.11 0.84 0.69 to 1.03 0.43
 eGFRcys 0.52b 0.43 to 0.63b <0.001b 0.61b 0.49 to 0.75b <0.001b 0.85 0.62 to 1.16 0.57
 eGFRcyscre 0.72b 0.60 to 0.87b 0.39 0.77b 0.63 to 0.94b 0.07 0.89 0.71 to 1.11 0.70
Gal-3
 mGFR 1.00 0.84 to 1.20 1.10 0.91 to 1.34 1.15 0.96 to 1.38
 eGFRcre 1.19b 1.04 to 1.37b 0.13 1.18 1.02 to 1.36 0.60 1.11 0.95 to 1.30 0.77
 eGFRcys 1.10 0.96 to 1.26 0.41 1.25 1.06 to 1.47 0.33 0.97 0.76 to 1.24 0.26
 eGFRcyscre 1.21b 1.06 to 1.38b 0.09 1.25 1.08 to 1.45 0.31 1.16 0.99 to 1.36 0.96

Accelerated GFR decline defined as the 10% with the steepest annual GFR decline slope for the corresponding GFR method. CD40Lig, CD40 ligand receptor; CI, confidence interval; cre, creatinine; cys, cystatin C; FABP4, fatty acid binding protein 4; Gal-3, galectin-3; GDF-15, growth/differentiation factor 15; MCP-1, monocyte chemoattractant protein-1; mGFR, measured GFR; MMP2, matrix metalloproteinase 2; MMP7, matrix metalloproteinase 7; OR, odds ratio; suPAR, soluble urokinase-type plasminogen activator receptor; Tie2, TEK tyrosine kinase; TNFR-2, TNF receptor 2; TRAIL-R2, TNF-related apoptosis-inducing ligand receptor 2; Umod, uromodulin.

Model 1: Sex, age, body mass index, smoke (now, previously, newer).

Model 2: model 1+baseline GFR.

P value for statistically significant differences between measured GFR and the respective eGFR from creatinine, cystatin C, or both.

a

Log2 transformed.

b

Statistically significant association between protein and accelerated GFR decline or statistically significant difference between mGFR and eGFR.

A statistically significant difference between eGFRcre and eGFRcys:

c

P value: <0.001.

d

P value: <0.001.

e

P value: 0.004.

f

P value: 0.001.

Table 3.

Hazard ratios for incident CKD (<60 ml/min per 1.73 m2) per doubling or SD increase in baseline protein concentration

Protein Unadjusted P Value for Difference Model 1 P Value for Difference Model 2 P Value for Difference
HR 95% CI HR 95% CI HR 95% CI
MCP-1a
 mGFR 0.89 0.58 to 1.37 0.89 0.55 to 1.37 0.80 0.47 to 1.36
 eGFRcre 1.00 0.58 to 1.73 0.56 0.95 0.53 to 1.70 0.74 0.93 0.54 to 1.59 0.69
 eGFRcys 1.24 0.86 to 1.78 0.10 1.17 0.78 to 1.75 0.28 1.06 0.74 to 1.51 0.44
 eGFRcyscre 1.06 0.64 to 1.75 0.40 1.00 0.59 to 1.68 0.64 0.87 0.51 to 1.46 0.85
TRAIL-R2a
 mGFR 1.72b 1.37 to 1.96b 1.62b 1.27 to 1.87b 1.59b 1.20 to 2.11b
 eGFRcre 1.67b 1.20 to 2.31b 0.61 1.58b 1.08 to 2.31b 0.80 1.37 0.81 to 2.30 0.31
 eGFRcys 1.62b 1.44 to 1.83b 0.69 1.44b 1.25 to 1.67b 0.46 1.00 0.63 to 1.58 0.04b
 eGFRcyscre 1.57b 1.26 to 1.96b 0.42 1.39b 1.08 to 1.80b 0.27 0.82 0.46 to 1.44 0.02b
FABP4a
 mGFR 2.11b 1.58 to 2.53b 1.72b 1.28 to 2.23b 1.08 0.79 to 1.48
 eGFRcre 1.91b 1.39 to 2.64b 0.65 1.86b 1.27 to 2.73b 0.72 1.19 0.77 to 1.83 0.69
 eGFRcys 2.37b 1.87 to 3.01b 0.40 1.70b 1.28 to 2.26b 0.93 0.98 0.72 to 1.34 0.45
 eGFRcyscre 2.31b 1.75 to 3.06b 0.53 1.89b 1.37 to 2.61b 0.49 0.99 0.67 to 1.46 0.53
TNFR-2
 mGFR 1.53b 1.37 to 1.57b 1.40b 1.25 to 1.42b 1.22b 1.11 to 1.34b
 eGFRcre 1.37b 1.20 to 1.57b 0.11c 1.27b 1.12 to 1.44b 0.19d 1.09 0.88 to 1.36 0.40
 eGFRcys 1.69b 1.63 to 1.75b 0.005b 1.63b 1.55 to 1.72b 0.002b 1.01 0.85 to 1.21 0.19
 eGFRcyscre 1.58b 1.47 to 1.71b 0.36 1.46b 1.34 to 1.58b 0.50 0.95 0.80 to 1.14 0.06
CD40Lig
 mGFR 1.07 0.91 to 1.29 1.02 0.89 to 1.24 1.00 0.81 to 1.23
 eGFRcre 0.97 0.72 to 1.32 0.36 0.95 0.70 to 1.29 0.53 0.93 0.96 to 1.27 0.64
 eGFRcys 1.08 0.89 to 1.31 0.88 0.99 0.86 to 1.15 0.78 0.91 0.77 to 1.08 0.36
 eGFRcyscre 1.04 0.82 to 1.32 0.67 0.97 0.78 to 1.20 0.44 0.96 0.75 to 1.22 0.57
GDF-15a
 mGFR 1.65b 1.23 to 2.22b 1.48b 1.03 to 2.13b 1.18 0.82 to 1.70
 eGFRcre 1.27 0.91 to 1.76 0.33 1.07 0.71 to 1.62 0.34e 0.76 0.48 to 1.19 0.11
 eGFRcys 2.18b 1.72 to 2.77b 0.048b 2.14b 1.55 to 2.96b 0.07 1.11 0.74 to 1.65 0.78
 eGFRcyscre 2.07b 1.47 to 2.91b 0.15 1.79b 1.19 to 2.69b 0.29 0.96 0.58 to 1.58 0.38
Tie2
 mGFR 0.92 0.85 to 1.25 0.95 0.87 to 1.29 0.84 0.66 to 1.06
 eGFRcre 1.12 0.87 to 1.46 0.05 1.14 0.85 to 1.53 0.08 1.08 0.82 to 1.42 0.10
 eGFRcys 1.11 0.93 to 1.33 0.06 1.05 0.88 to 1.27 0.33 1.12 0.92 to 1.36 0.09
 eGFRcyscre 1.09 0.87 to 1.37 0.05 1.09 0.86 to 1.40 0.16 1.00 0.79 to 1.26 0.30
MMP7
 mGFR 1.71b 1.62 to 2.11b 1.59b 1.53 to 1.99b 1.36b 1.16 to 1.60b
 eGFRcre 1.71b 1.47 to 1.99b 0.99 1.65b 1.39 to 1.96b 0.74 1.42b 1.13 to 1.79b 0.81
 eGFRcys 1.88b 1.69 to 2.09b 0.09 1.80b 1.58 to 2.06b 0.08 1.65b 1.35 to 2.02b 0.07
 eGFRcyscre 1.89b 1.67 to 2.14b 0.11 1.75b 1.51 to 2.03b 0.15 1.48b 1.23 to 1.80b 0.42
suPAR
 mGFR 1.10b 1.06 to 1.15b 1.05 0.94 to 1.24 1.06 0.84 to 1.33
 eGFRcre 0.95 0.67 to 1.35 0.07f 0.81 0.54 to 1.23 0.08g 0.61b 0.41 to 0.90b 0.02b,h
 eGFRcys 1.14b 1.10 to 1.17b 0.13 1.13b 1.04 to 1.22b 0.15 1.08 0.90 to 1.30 0.83
 eGFRcyscre 1.11b 1.04 to 1.19b 0.60 1.06 0.85 to 1.33 0.83 0.81 0.61 to 1.10 0.17
MMP2
 mGFR 1.14 0.93 to 1.35 1.06 0.87 to 1.24 1.10 0.87 to 1.38
 eGFRcre 1.27 1.02 to 1.60 0.04b 1.19 0.95 to 1.48 0.07 1.20 0.88 to 1.64 0.33
 eGFRcys 1.18 1.01 to 1.38 0.66 1.12 0.98 to 1.27 0.47 1.24b 1.03 to 1.49b 0.30
 eGFRcyscre 1.18 0.93 to 1.48 0.62 1.09 0.89 to 1.35 0.62 1.01 0.81 to 1.27 0.69
Umod
 mGFR 0.72b 0.58 to 0.94b 0.69b 0.56 to 0.93b 0.80 0.59 to 1.07
 eGFRcre 0.91 0.66 to 1.26 0.04b,i 0.92 0.65 to 1.30 0.02b,j 1.13 0.84 to 1.52 0.03b
 eGFRcys 0.67b 0.50 to 0.89b 0.43 0.71b 0.53 to 0.95b 0.87 0.98 0.70 to 1.37 0.17
 eGFRcyscre 0.74 0.53 to 1.05 0.83 0.75 0.53 to 1.07 0.49 1.04 0.73 to 1.48 0.12
Gal-3
 mGFR 1.33b 1.07 to 1.45b 1.22 0.97 to 1.35 1.19 0.99 to 1.44
 eGFRcre 1.38b 1.15 to 1.64b 0.44 1.32b 1.09 to 1.60b 0.14 1.18 0.98 to 1.43 0.87
 eGFRcys 1.30b 1.13 to 1.50b 0.59 1.18b 1.01 to 1.38b 0.56 1.09 0.97 to 1.22 0.34
 eGFRcyscre 1.38b 1.18 to 1.63b 0.31 1.28b 1.07 to 1.52b 0.38 1.12 0.96 to 1.32 0.64

Incident CKD is defined as new-onset GFR <60 ml/min per 1.73 m2 during follow-up. CD40Lig, CD40 ligand receptor; CI, confidence interval; cre, creatinine; cys, cystatin C; FABP4, fatty acid binding protein 4; Gal-3, galectin-3; GDF-15, growth/differentiation factor 15; HR, hazard ratio; MCP-1, monocyte chemoattractant protein-1; mGFR, measured GFR; MMP2, matrix metalloproteinase 2; MMP7, matrix metalloproteinase 7; suPAR, soluble urokinase-type plasminogen activator receptor; Tie2, TEK tyrosine kinase; TNFR-2, TNF receptor 2; TRAIL-R2, TNF-related apoptosis-inducing ligand receptor 2; Umod, uromodulin.

A total of 1409 individuals are included in the analysis; the respective numbers of baseline CKD and incident CKD for the GFR methods are: measured GFR; n=8 and n=95. eGFRcre; n=4 and n=51. eGFRcys; n=5 and n=96. eGFRcyscr; n=3 and n=62.

Model 1: sex, age, body mass index, smoke (now, previously, newer).

Model 2: model 1+baseline GFR.

a

Log2 transformed.

b

Statistically significant association between protein and incident CKD or statistically significant difference between mGFR and eGFR.

Difference between eGFRcre and eGFRcys:

c

P value: <0.001.

d

P value: <0.001.

e

P value: 0.04.

f

P value: 0.004.

g

P value: 0.002.

h

P value: 0.004.

i

P value: 0.008.

j

P value: 0.03.

None of the changes have any consequences for the discussion or conclusions of the article.

Reference

  • 1.Enoksen ITT Rinde NB Svistounov D, et al. Validation of eGFR for detecting associations between serum protein biomarkers and subsequent GFR decline. J Am Soc Nephrol. 2023;34(8):1409–1420. doi: 10.1681/ASN.0000000000000147 [DOI] [PMC free article] [PubMed] [Google Scholar]

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