Introduction
Methods
Results
Characteristic | SDR (n = 227) | GoDARTS (n = 430) | CARDS (n = 183) |
---|---|---|---|
Age, years | 68.6 (61.6, 75.5) | 73.0 (68.0, 78.0) | 64.6 (60.8, 69.3) |
eGFR, ml min−1 [1.73 m]−2 | 52.6 (42.2, 58.5) | 53.4 (43.3, 63.8) | 62.1 (54.5, 68.7) |
HbA1c, mmol/mol | 61.2 (50.3, 74.9) | 54.1 (46.5, 62.6) | 58.5 (49.7, 71.6) |
HbA1c, % | 7.7 (6.8, 9.0) | 7.1 (6.4, 7.9) | 7.5 (6.7, 8.7) |
BMI, kg/m2 | 29.0 (26.0, 32.6) | 30.6 (27.1, 34.2) | 29.0 (26.4, 31.2) |
Diabetes duration, years | 10.0 (3.0, 15.9) | 7.9 (4.5, 13.0) | 8.0 (4.0, 11.5) |
Systolic blood pressure, mmHg | 147.2 (143.7, 151.0) | 143.0 (131.1, 155.5) | 147.0 (138.0, 160.0) |
Diastolic blood pressure, mmHg | 79.6 (76.1, 81.5) | 71.5 (65.0, 80.0) | 82.5 (76.5, 90.0) |
Weighted average of historic eGFR, ml min−1 [1.73 m]−2 | 53.4 (43.2, 61.3) | 60.8 (50.6, 71.8) | NA |
Annualised eGFR slope, ml min−1 [1.73 m]−2 year−1 | −1.3 (−2.8, 0.1) | −0.5 (−1.9, 0.8) | NA |
Year at baseline | 1997 (1997, 1998) | 2005 (2005, 2007) | 1999 (1998, 2000) |
Follow-up duration, years | 8.7 (4.8, 13.1) | 7.1 (5.3, 8.8) | 3.2 (2.9, 4.0) |
Male sex | 83 (36.6) | 194 (45.1) | 121 (66.1) |
Albuminuria, yes | 84 (37.0) | 133 (30.9) | 27 (14.8) |
ACEi/ARB use | NA | 313 (72.8) | 107 (58.5) |
Insulin use | 88 (38.8) | 122 (28.4) | 42 (23.0) |
Current smoking | 10 (4.4) | 42 (9.8) | 35 (19.1) |
Biomarker | Method | SDR | GoDARTS | CARDS | |||
---|---|---|---|---|---|---|---|
OR (95% CI) | p value | OR (95% CI) | p value | OR (95% CI) | p value | ||
Adrenomedullin (ng/ml)a | Luminex | – | – | 1.47 (1.26, 1.72) | 1.11 × 10−6 | 1.58 (1.09, 2.34) | 1.90 × 10−2 |
ADMA (nmol/l) | MSMS | 1.46 (1.18, 1.81) | 4.60 × 10−4 | 1.04 (0.90, 1.21) | 5.97 × 10−1 | Not measured | – |
B2M (μg/ml) | Luminex | 1.98 (1.54, 2.56) | 1.28 × 10−7 | 1.59 (1.34, 1.89) | 1.37 × 10−7 | 2.92 (1.79, 5.06) | 4.93 × 10−5 |
Cystatin C (ng/ml) | Luminex | 1.83 (1.40, 2.38) | 8.08 × 10−6 | 1.64 (1.36, 1.97) | 2.03 × 10−7 | 1.84 (1.22, 2.84) | 4.31 × 10−3 |
Fibroblast growth factor 23 (ng/ml) | Luminex | 1.12 (0.89, 1.41) | 3.20 × 10−1 | 1.37 (1.17, 1.59) | 7.67 × 10−5 | 1.51 (1.07, 2.15) | 2.00 × 10−2 |
IL-2Ra (pg/ml) | Luminex | 1.62 (1.28, 2.07) | 8.00 × 10−5 | 1.20 (1.02, 1.41) | 2.38 × 10−2 | 2.06 (1.42, 3.11) | 2.89 × 10−4 |
KIM-1 (ng/ml) | Luminex | 1.66 (1.32, 2.09) | 1.85 × 10−5 | 1.48 (1.25, 1.76) | 6.65 × 10−6 | 1.94 (1.37, 2.81) | 2.52 × 10−4 |
NT-ProBNP (pg/ml) | Luminex | 1.18 (0.96, 1.45) | 1.10 × 10−1 | 1.44 (1.21, 1.71) | 3.73 × 10−5 | 1.26 (0.88, 1.82) | 2.15 × 10−1 |
SDMA (nmol/l) | MSMS | 1.80 (1.33, 2.43) | 1.24 × 10−4 | 1.20 (0.98, 1.47) | 7.51 × 10−2 | Not measured | – |
Tamm–Horsfall urinary glycoprotein (μg/ml) | Luminex | 0.64 (0.50, 0.83) | 7.09 × 10−4 | 0.65 (0.53, 0.78) | 1.20 × 10−5 | 0.75 (0.54, 1.04) | 8.61 × 10−2 |
Troponin T (high sensitivity) (pg/ml) | ELISA | 1.66 (1.32, 2.11) | 2.33 × 10−5 | 1.05 (0.88, 1.26) | 5.63 × 10−1 | Not measured | – |
TNF receptor 1 (pg/ml) | Luminex | 1.63 (1.26, 2.13) | 2.30 × 10−4 | 1.32 (1.11, 1.56) | 1.69 × 10−3 | 1.85 (1.26, 2.82) | 2.62 × 10−3 |
Biomarker | ADM | ADMA | B2M | CysC | FGF23 | FRTN | IL2Ra | KIM-1 | MB | NT-proBNP | SDMA | THP | TnT | TNFR1 |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
eGFR | ||||||||||||||
SDR | – | −0.24 | −0.66 | −0.66 | −0.44 | 0.10 | −0.51 | −0.30 | −0.55 | −0.35 | −0.70 | 0.42 | −0.44 | −0.64 |
GoDARTS | −0.49 | −0.21 | −0.64 | −0.67 | −0.27 | −0.07 | −0.38 | −0.14 | −0.39 | −0.33 | −0.64 | 0.41 | −0.33 | −0.48 |
CARDS | 0.03 | – | −0.49 | −0.57 | −0.05 | 0.10 | −0.37 | −0.20 | −0.31 | −0.13 | – | 0.12 | – | −0.48 |
ADMa | ||||||||||||||
Go-DARTS | 1 | 0.26 | 0.70 | 0.69 | 0.52 | −0.03 | 0.52 | 0.21 | 0.27 | 0.54 | 0.48 | −0.47 | 0.42 | 0.51 |
CARDS | 1 | – | 0.38 | 0.05 | 0.62 | 0.01 | 0.25 | 0.13 | −0.09 | 0.67 | – | −0.04 | – | 0.10 |
ADMAb | ||||||||||||||
SDR | 1 | 0.35 | 0.41 | 0.19 | −0.09 | 0.27 | 0.07 | 0.07 | 0.16 | 0.48 | −0.24 | 0.19 | 0.34 | |
Go-DARTS | 1 | 0.31 | 0.26 | 0.15 | 0.04 | 0.30 | 0.01 | 0.06 | 0.22 | 0.37 | −0.13 | 0.13 | 0.18 | |
B2M | ||||||||||||||
SDR | 1 | 0.89 | 0.46 | 0.00 | 0.62 | 0.43 | 0.52 | 0.43 | 0.69 | −0.49 | 0.56 | 0.70 | ||
Go-DARTS | 1 | 0.87 | 0.38 | 0.05 | 0.62 | 0.27 | 0.34 | 0.41 | 0.61 | −0.54 | 0.42 | 0.65 | ||
CARDS | 1 | 0.67 | 0.36 | 0.07 | 0.61 | 0.25 | 0.27 | 0.45 | – | −0.27 | – | 0.57 | ||
CysC | ||||||||||||||
SDR | 1 | 0.48 | 0.00 | 0.59 | 0.42 | 0.60 | 0.38 | 0.71 | −0.48 | 0.53 | 0.69 | |||
Go-DARTS | 1 | 0.37 | 0.12 | 0.56 | 0.25 | 0.41 | 0.41 | 0.60 | −0.51 | 0.42 | 0.66 | |||
CARDS | 1 | 0.15 | 0.06 | 0.52 | 0.18 | 0.42 | 0.17 | – | −0.21 | – | 0.46 | |||
FGF23 | ||||||||||||||
SDR | 1 | −0.13 | 0.28 | 0.23 | 0.32 | 0.37 | 0.39 | −0.29 | 0.33 | 0.43 | ||||
Go-DARTS | 1 | −0.23 | 0.29 | 0.20 | 0.10 | 0.37 | 0.24 | −0.23 | 0.21 | 0.31 | ||||
CARDS | 1 | −0.17 | 0.24 | 0.25 | −0.01 | 0.53 | – | −0.02 | – | 0.19 | ||||
FRTN | ||||||||||||||
SDR | 1 | 0.01 | 0.27 | 0.13 | −0.04 | 0.03 | 0.03 | 0.13 | −0.04 | |||||
Go-DARTS | 1 | 0.01 | −0.05 | 0.18 | −0.11 | 0.08 | 0.04 | 0.02 | 0.03 | |||||
CARDS | 1 | −0.08 | 0.00 | 0.21 | 0.01 | – | 0.00 | – | −0.01 | |||||
IL2Ra | ||||||||||||||
SDR | 1 | 0.40 | 0.35 | 0.18 | 0.43 | −0.24 | 0.33 | 0.65 | ||||||
Go-DARTS | 1 | 0.24 | 0.24 | 0.26 | 0.41 | −0.30 | 0.25 | 0.60 | ||||||
CARDS | 1 | 0.28 | 0.09 | 0.30 | – | −0.26 | – | 0.51 | ||||||
KIM-1 | ||||||||||||||
SDR | 1 | 0.31 | 0.22 | 0.31 | −0.18 | 0.46 | 0.42 | |||||||
G-DARTS | 1 | 0.05 | 0.14 | 0.12 | −0.15 | 0.14 | 0.22 | |||||||
CARDS | 1 | 0.13 | 0.11 | – | −0.09 | – | 0.36 | |||||||
MB | ||||||||||||||
SDR | 1 | 0.20 | 0.56 | −0.29 | 0.59 | 0.47 | ||||||||
GoDARTS | 1 | 0.20 | 0.35 | −0.20 | 0.40 | 0.26 | ||||||||
CARDS | 1 | 0.13 | – | −0.13 | – | 0.18 | ||||||||
NT-proBNP | ||||||||||||||
SDR | 1 | 0.37 | −0.27 | 0.49 | 0.27 | |||||||||
GoDARTS | 1 | 0.39 | −0.30 | 0.41 | 0.30 | |||||||||
CARDS | 1 | – | −0.08 | – | 0.12 | |||||||||
SDMAb | ||||||||||||||
SDR | 1 | −0.47 | 0.56 | 0.61 | ||||||||||
Go-DARTS | 1 | −0.43 | 0.42 | 0.45 | ||||||||||
THP | ||||||||||||||
SDR | 1 | −0.38 | −0.40 | |||||||||||
GoDARTS | 1 | −0.40 | −0.39 | |||||||||||
CARDS | 1 | – | −0.29 | |||||||||||
TnTb | ||||||||||||||
SDR | 1 | 0.50 | ||||||||||||
Go-DARTS | 1 | 0.28 |
Biomarker panel | SDR | GoDARTS | CARDS | |||
---|---|---|---|---|---|---|
AUROC (95% CI) | Difference in test loge likelihood | AUROC (95% CI) | Difference in test loge likelihood | AUROC (95% CI) | Difference in test loge likelihood | |
Clinical covariates only | 0.628 (0.576, 0.679) | – | 0.552 (0.509, 0.595) | – | 0.457 (0.371, 0.542) | – |
Covariates + B2M | 0.690 (0.642, 0.738) | 11.6 | 0.604 (0.563, 0.645) | 12.1 | 0.655 (0.576, 0.735) | 11.6 |
Covariates + B2M + KIM-1 | 0.707 (0.661, 0.752) | 14.2 | 0.625 (0.584, 0.666) | 17.4 | 0.696 (0.620, 0.773) | 12.6 |
Covariates + B2M + KIM-1+ MB | 0.697 (0.651, 0.744) | 12.4 | 0.633 (0.593, 0.673) | 19.2 | 0.695 (0.619, 0.772) | 11.9 |
Covariates + B2M + KIM-1+ MB + NT-proBNP | 0.691 (0.643, 0.738) | 10.6 | 0.644 (0.605, 0.682) | 21.9 | 0.690 (0.613, 0.767) | 10.6 |
Covariates + B2M + KIM-1+ MB + NT-proBNP + ferritin | 0.689 (0.641, 0.737) | 10.5 | 0.644 (0.606, 0.681) | 21.2 | 0.684 (0.607, 0.762) | 10.0 |
Covariates + top five mass spectrometry biomarkers (SDMA–ADMA ratio, α1-antitrypsin 2, C16 acylcarnitine, proline and tryptophan)a | 0.623 (0.573, 0.672) | <0 | 0.554 (0.511, 0.596) | <0 | – | – |