Introduction
Methods
Results
Covariate | SDRNT1BIO (n = 859) | FinnDiane (n = 315) | p valuea | ||
---|---|---|---|---|---|
Frequency/Median (IQR) | MaR | Frequency/Median (IQR) | MaR | ||
Age (years) | 55.5 (46.1, 64.4) | 0 | 46.3 (36.6, 52.5) | 0 | <1 × 10−16 |
Sex (female) (%) | 56.8 | 0 | 44.8 | 0 | 2 × 10−4 |
Diabetes duration (years) | 26.5 (17.4, 37.5) | 0 | 31.9 (25.4, 37.9) | 0 | 2 × 10−12 |
Length of follow-up (years) | 5.2 (4.4, 5.7) | 0 | 8.8 (5.9, 12.2) | 0 | <1 × 10−16 |
Start of follow-up (calendar year) | 2012 (2011, 2012) | 0 | 1999 (1998, 2001) | 0 | – |
End of follow-up (calendar year) | 2017 (2017, 2017) | 0 | 2010 (2006, 2013) | 0 | – |
eGFR (ml min−1 [1.73 m]−2) | 72.0 (62.1, 84.5) | 0 | 58.6 (45.7, 67.0) | 0 | <1 × 10−16 |
Achieved eGFR (ml min−1 [1.73 m]−2) | 73.1 (58.6, 85.2) | 0 | 29.9 (10.0, 55.9) | 0 | <1 × 10−16 |
Weighted average of historical eGFR (ml min−1 [1.73 m]−2) | 81.2 (70.6, 91.4) | 32 | 64.8 (52.4, 76.7) | 108 | <1 × 10−16 |
ACR (mg/mmol) | 0.5 (0.3, 1.9) | 21 | 25.0 (7.6, 69.5) | 56 | 8 × 10−15 |
ACR category (normo/micro/macro)b (%) | 81.4/10.5/5.7 | 21 | 0/27.3/72.7 | 0 | <1 × 10−16 |
Prospective eGFR slope (ml min−1 [1.73 m]−2 year−1) | −0.8 (−2.8, 0.7) | 0 | −2.4 (−4.4, −1.0) | 0 | 3 × 10−13 |
Rapid progressors (slope < −3) (%) | 22.6 | 0 | 40.3 | 0 | 2 × 10−09 |
HbA1c (mmol/mol) | 68.0 (60.0, 79.0) | 0 | 71.6 (62.8, 82.5) | 2 | 1 × 10−02 |
HbA1c (%) | 8.4 (7.6, 9.4) | 0 | 8.7 (7.9, 9.7) | 2 | 1 × 10−02 |
BMI (kg/m2) | 27.2 (24.6, 30.5) | 3 | 25.7 (23.2, 28.2) | 2 | 1 × 10−09 |
HDL-cholesterol (mmol/l) | 1.6 (1.3, 1.9) | 19 | 0.9 (0.7, 1.1) | 0 | <1 × 10−16 |
Total cholesterol (mmol/l) | 4.5 (3.9, 5.1) | 6 | 5.1 (4.5, 5.7) | 0 | <1 × 10−16 |
SBP (mmHg) | 134.0 (122.0, 146.0) | 0 | 144.5 (131.0, 158.0) | 4 | 6 × 10−14 |
DBP (mmHg) | 74.0 (68.0, 80.0) | 0 | 80.0 (72.5, 89.0) | 4 | <1 × 10−16 |
Ever smoker (%) | 64.5 | 0 | 52.1 | 23 | 1 × 10−02 |
On any anti-hypertensive treatment (%) | 61.7 | 0 | 94.3 | 3 | <1 × 10−16 |
On ACE or ARB (%) | 56.5 | 0 | 86.0 | 3 | <1 × 10−16 |
Biomarker | SDRNT1BIO | FinnDiane | ||
---|---|---|---|---|
β coefficient (95% CI) | p value | β coefficient (95% CI) | p value | |
Luminex proteins | ||||
CD27 antigen | −0.31 (−0.36, −0.26) | 7 × 10−30 | −0.43 (−0.55, −0.32) | 1 × 10−13 |
KIM-1 | −0.26 (−0.31, −0.21) | 2 × 10−24 | −0.34 (−0.44, −0.25) | 2 × 10−11 |
β2-microglobulin | −0.28 (−0.34, −0.23) | 4 × 10−22 | −0.33 (−0.44, −0.21) | 9 × 10−08 |
α1-microglobulin | −0.28 (−0.33, −0.23) | 2 × 10−25 | −0.31 (−0.41, −0.20) | 1 × 10−08 |
Cystatin-C | −0.30 (−0.36, −0.24) | 1 × 10−21 | −0.24 (−0.36, −0.13) | 6 × 10−05 |
Thrombomodulin | −0.28 (−0.34, −0.23) | 3 × 10−24 | −0.30 (−0.41, −0.20) | 3 × 10−08 |
TNFR1 | −0.24 (−0.29, −0.19) | 5 × 10−19 | −0.29 (−0.39, −0.18) | 2 × 10−07 |
Osteopontin | −0.17 (−0.23, −0.12) | 3 × 10−11 | −0.24 (−0.34, −0.14) | 8 × 10−06 |
IL-2 receptor α | −0.22 (−0.27, −0.17) | 4 × 10−17 | −0.18 (−0.28, −0.08) | 3 × 10−04 |
Osteoprotegerin | −0.14 (−0.20, −0.09) | 8 × 10−07 | −0.22 (−0.32, −0.12) | 3 × 10−05 |
Fibroblast growth factor 21 | −0.15 (−0.20, −0.11) | 9 × 10−10 | −0.19 (−0.29, −0.09) | 1 × 10−04 |
IGF-binding protein 7 | −0.12 (−0.17, −0.07) | 8 × 10−06 | −0.18 (−0.28, −0.08) | 5 × 10−04 |
N-terminal prohormone of brain natriuretic peptide | −0.18 (−0.23, −0.12) | 3 × 10−10 | −0.02 (−0.12, 0.08) | 7 × 10−01 |
Tissue inhibitor of metalloproteinases 1 | −0.13 (−0.18, −0.08) | 4 × 10−07 | −0.18 (−0.27, −0.09) | 2 × 10−04 |
Tamm–Horsfall urinary glycoprotein | 0.15 (0.09, 0.20) | 8 × 10−08 | 0.17 (0.08, 0.27) | 6 × 10−04 |
Trefoil factor 3 | −0.15 (−0.20, −0.09) | 1 × 10−07 | Not tested | |
LC-MS/MS metabolites | ||||
Free sialic acid | −0.28 (−0.34, −0.23) | 1 × 10−21 | −0.32 (−0.44, −0.20) | 5 × 10−07 |
SDMA | −0.20 (−0.26, −0.14) | 1 × 10−10 | −0.30 (−0.42, −0.18) | 2 × 10−06 |
3-Methyl-histidine | −0.17 (−0.24, −0.11) | 7 × 10−08 | −0.24 (−0.36, −0.13) | 3 × 10−05 |
Tryptophan/kynurenine | 0.22 (0.17, 0.28) | 4 × 10−15 | 0.16 (0.05, 0.27) | 4 × 10−03 |
SDMA/ADMA | −0.12 (−0.18, −0.06) | 2 × 10−05 | −0.20 (−0.31, −0.09) | 6 × 10−04 |
Free cystine | −0.17 (−0.23, −0.11) | 2 × 10−09 | Not tested | |
TMAO | −0.15 (−0.20, −0.09) | 1 × 10−07 | −0.17 (−0.28, −0.07) | 1 × 10−03 |
C4DC methylmalonyl/C5OH | −0.15 (−0.21, −0.09) | 1 × 10−06 | −0.16 (−0.27, −0.05) | 4 × 10−03 |
Tryptophan | 0.16 (0.12, 0.21) | 7 × 10−11 | Not tested | |
C5DC (glutaryl) carnitine | −0.13 (−0.18, −0.07) | 6 × 10−06 | −0.14 (−0.25, −0.03) | 2× 10−02 |
Methionine | 0.14 (0.09, 0.19) | 1 × 10−08 | Not tested | |
C4 carnitine | −0.13 (−0.18, −0.08) | 3 × 10−06 | Not tested | |
C2 carnitine | −0.12 (−0.17, −0.07) | 8 × 10−06 | Not tested | |
C3DC malonyl/3OHB | −0.12 (−0.17, −0.07) | 4 × 10−06 | −0.10 (−0.19, −0.01) | 3 × 10−02 |
Citrulline | −0.11 (−0.16, −0.05) | 7 × 10−05 | −0.10 (−0.20, 0.00) | 5 × 10−02 |
Threonine | 0.11 (0.06, 0.16) | 2 × 10−05 | 0.06 (−0.03, 0.15) | 2 × 10−01 |
Hydroxyproline | −0.10 (−0.15, −0.05) | 9 × 10−05 | −0.09 (−0.19, 0.00) | 6 × 10−02 |
Neopterin | −0.10 (−0.15, −0.05) | 9 × 10−05 | −0.10 (−0.19, −0.00) | 5 × 10−02 |
LC-MS/MS tryptic peptides | ||||
Retinal-binding protein 2 (575.8/695.3) | 0.09 (0.03, 0.14) | 1 × 10−03 | 0.20 (0.11, 0.29) | 2 × 10−05 |
Hyaluronan-binding protein 2 (575.2/901.5) | 0.04 (−0.02, 0.09) | 2 × 10−01 | 0.19 (0.10, 0.28) | 5 × 10−05 |
Extracellular glycoprotein lacritin (481.3/501.3) | 0.13 (0.08, 0.18) | 1 × 10−07 | 0.16 (0.07, 0.25) | 9 × 10−04 |
Albumin T70 (501.2/587.5) | 0.14 (0.09, 0.19) | 1 × 10−08 | 0.04 (−0.06, 0.13) | 4 × 10−01 |
Angiotensin II (349.8/136.1) | 0.14 (0.09, 0.19) | 1 × 10−07 | 0.04 (−0.05, 0.14) | 4 × 10−01 |
Cellular repressor of E1A-stimulated genes 1 (575.8/704.4) | 0.10 (0.05, 0.15) | 4 × 10−05 | 0.14 (0.04, 0.23) | 4 × 10−03 |
Chromogranin A (488.2/775.4) | −0.14 (−0.19, −0.09) | 2 × 10−08 | −0.02 (−0.12, 0.07) | 6 × 10−01 |
Albumin T6 (575.4/937.4) | 0.13 (0.08, 0.18) | 2 × 10−07 | 0.12 (0.03, 0.22) | 1 × 10−02 |
ApoC-III (598.8/854.4) | −0.12 (−0.17, −0.07) | 2 × 10−06 | −0.07 (−0.17, 0.03) | 2 × 10−01 |
Complement C3 (673.4/646.4) | −0.12 (−0.17, −0.07) | 4 × 10−06 | 0.04 (−0.05, 0.13) | 4 × 10−01 |
Albumin T34 (441.0/680.5) | 0.11 (0.06, 0.16) | 7 × 10−06 | 0.06 (−0.03, 0.16) | 2 × 10−01 |
Haptoglobin (490.5/562.6) | −0.11 (−0.16, −0.06) | 2 × 10−05 | 0.01 (−0.09, 0.10) | 9 × 10−01 |
Heparin cofactor II (514.8/814.4) | −0.10 (−0.15, −0.05) | 6 × 10−05 | −0.07 (−0.16, 0.03) | 2 × 10−01 |
Peroxidase (492.6/703.3) | −0.10 (−0.15, −0.05) | 4 × 10−05 | −0.03 (−0.12, 0.06) | 5 × 10−01 |
Biomarker | SDRNT1BIO | FinnDiane | ||
---|---|---|---|---|
OR (95% CI) | p value | OR (95% CI) | p value | |
Luminex proteins | ||||
KIM-1 | 1.82 (1.52, 2.17) | 4 × 10−11 | 2.11 (1.52, 3.00) | 2 × 10−05 |
CD27 antigen | 1.65 (1.38, 1.99) | 9 × 10−08 | 1.89 (1.33, 2.71) | 4 × 10−04 |
TNFR1 | 1.89 (1.54, 2.33) | 2 × 10−09 | 1.26 (0.93, 1.73) | 1 × 10−01 |
α1-microglobulin | 1.86 (1.51, 2.31) | 1 × 10−08 | 1.76 (1.28, 2.47) | 7 × 10−04 |
Thrombomodulin | 1.82 (1.50, 2.22) | 2 × 10−09 | 1.72 (1.26, 2.38) | 7 × 10−04 |
β2-microglobulin | 1.51 (1.25, 1.85) | 3 × 10−05 | 1.73 (1.20, 2.56) | 4 × 10−03 |
Cystatin-C | 1.70 (1.37, 2.14) | 3 × 10−06 | 1.44 (1.02, 2.05) | 4 × 10−02 |
IL-2 receptor α | 1.60 (1.34, 1.91) | 2 × 10−07 | 1.27 (0.95, 1.70) | 1 × 10−01 |
N-terminal prohormone of brain natriuretic peptide | 1.50 (1.24, 1.82) | 4 × 10−05 | 1.09 (0.83, 1.43) | 5 × 10−01 |
LC-MS/MS metabolites | ||||
Free sialic acid | 1.63 (1.33, 2.00) | 4 × 10−06 | 1.51 (1.05, 2.20) | 3 × 10−02 |
Tryptophan/kynurenine | 0.67 (0.55, 0.82) | 7 × 10−05 | 0.93 (0.68, 1.26) | 6 × 10−01 |
Threonine | 0.68 (0.57, 0.80) | 8 × 10−06 | 0.80 (0.61, 1.03) | 8 × 10−02 |
Methionine | 0.69 (0.58, 0.82) | 4 × 10−05 | Not tested | |
Tryptophan | 0.69 (0.58, 0.82) | 4 × 10−05 | Not tested |
SDRNT1BIO | FinnDiane | |||||||
---|---|---|---|---|---|---|---|---|
Basic covariates | Full covariates | Basic covariates | Full covariates | |||||
Platform | Diff. logLik |
r
2
| Diff. logLik |
r
2
| Diff. logLik |
r
2
| Diff. logLik |
r
2
|
Baseline | – | 0.47 | – | 0.63 | – | 0.33 | – | 0.45 |
Luminex | 86.3 | 0.58 | 24.1 | 0.65 | 34.5 | 0.48 | 14.7 | 0.50 |
LC-MS/MS | 91.8 | 0.58 | 24.7 | 0.65 | 23.5 | 0.43 | 8.4 | 0.47 |
Both platforms | 103.2 | 0.60 | 29.4 | 0.65 | 36.3 | 0.48 | 16.5 | 0.50 |
Platform | SDRNT1BIO | FinnDiane | ||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
Basic covariates | Full covariates | Basic covariates | Full covariates | |||||||||
Diff. logLik | AUC |
Λ
| Diff. logLik | AUC |
Λ
| Diff. logLik | AUC |
Λ
| Diff. logLik | AUC |
Λ
| |
Baseline | – | 0.51 | 0 | – | 0.61 | 0.3 | – | 0.70 | 0.6 | – | 0.78 | 1.3 |
Luminex | 25.4 | 0.65 | 0.3 | 6.2 | 0.64 | 0.4 | 8.8 | 0.74 | 0.9 | 0.3 | 0.78 | 1.4 |
LC-MS/MS | 12.2 | 0.60 | 0.2 | 1.2 | 0.62 | 0.3 | 5.2 | 0.72 | 0.9 | −0.6 | 0.78 | 1.6 |
Both platforms | 22.1 | 0.63 | 0.3 | 3.8 | 0.63 | 0.4 | 7.8 | 0.73 | 1 | −0.1 | 0.78 | 1.8 |