Baseline levels of markers of complement activation, vascular inflammation, endothelial activation and damage, coagulation, and renal injury in HV and in patients with aHUS
| Disease process and biomarker . | Range (minimum-maximum) observed in HV* . | Median baseline level in patients with aHUS (range, P value†) . | n/N (%) with elevated baseline level‡ . | Median fold increase over HV at baseline . |
|---|---|---|---|---|
| Complement activity | ||||
| AP activation | ||||
| Plasma Ba | 388.0-588.0 ng/mL | 2676.4 (935.0-3668.0; <.0001) | 35/35 (100) | 5.5 |
| Terminal complement | ||||
| U-C5a¶ | 0.0-0.7 ng/mg U-creatinine | 9.0 (0.3-76.6; .0001) | 26/29 (89.7) | 45.0 |
| Terminal complement | ||||
| U-sC5b-9¶ | 0.0-0.6 ng/mg U-creatinine | 30.5 (0.2-665.7; <.0001) | 23/27 (85.2) | 305.0 |
| Vascular inflammation/damage and coagulation | ||||
| Inflammation | ||||
| sTNFR1 | 407.3-1391.3 pg/mL | 17 616.9 (4008.5-54 158.2; <.0001) | 38/38 (100) | 18.7 |
| Endothelial activation | ||||
| sVCAM-1 | 159.2-444.7 ng/mL | 659.8 (375.4-1865.5; <.0001) | 36/38 (94.7) | 2.0 |
| Endothelial cell damage | ||||
| Thrombomodulin | 2.0-3.6 ng/mL | 10 (3.4-24.1; <.0001) | 33/34 (97.1) | 3.6 |
| Coagulation | ||||
| Prothrombin fragment 1+2 (F1+2) | 82.9-305.5 pmol/L | 1017.6 (217.7-5774.0; <.0001) | 36/38 (94.7) | 5.5 |
| d-dimer | 157.0-395.9 µg/L | 2735.0 (330.0-44 100.0; <.0001) | 34/36 (94.4) | 9.8 |
| Renal | ||||
| Renal injury | ||||
| U-clusterin | 5.7-437.1 ng/mg U-creatinine | 1232.3 (129.9-6091.2; <.0001) | 24/29 (82.8) | 8.6 |
| U-TIMP-1 | 0.0-5.4 ng/mg U-creatinine | 23.8 (1.4-230.4; <.0001) | 22/29 (75.9) | 39.7 |
| U-L-FABP-1 | 0.0-16.9 ng/mg U-creatinine | 58.0 (3.7-1309.8; <.0001) | 22/29 (75.9) | 48.3 |
| β2-microglobulin | 0.0-2.7 µg/mg U-creatinine | 18.4 (0.4-127.7; .0002) | 20/28 (71.4) | 46 |
| U-cystatin C | 0.3-301.3 ng/mg U-creatinine | 1256.9 (14.3-7189.6; .0005) | 18/26 (69.2) | 23.9 |
| Disease process and biomarker . | Range (minimum-maximum) observed in HV* . | Median baseline level in patients with aHUS (range, P value†) . | n/N (%) with elevated baseline level‡ . | Median fold increase over HV at baseline . |
|---|---|---|---|---|
| Complement activity | ||||
| AP activation | ||||
| Plasma Ba | 388.0-588.0 ng/mL | 2676.4 (935.0-3668.0; <.0001) | 35/35 (100) | 5.5 |
| Terminal complement | ||||
| U-C5a¶ | 0.0-0.7 ng/mg U-creatinine | 9.0 (0.3-76.6; .0001) | 26/29 (89.7) | 45.0 |
| Terminal complement | ||||
| U-sC5b-9¶ | 0.0-0.6 ng/mg U-creatinine | 30.5 (0.2-665.7; <.0001) | 23/27 (85.2) | 305.0 |
| Vascular inflammation/damage and coagulation | ||||
| Inflammation | ||||
| sTNFR1 | 407.3-1391.3 pg/mL | 17 616.9 (4008.5-54 158.2; <.0001) | 38/38 (100) | 18.7 |
| Endothelial activation | ||||
| sVCAM-1 | 159.2-444.7 ng/mL | 659.8 (375.4-1865.5; <.0001) | 36/38 (94.7) | 2.0 |
| Endothelial cell damage | ||||
| Thrombomodulin | 2.0-3.6 ng/mL | 10 (3.4-24.1; <.0001) | 33/34 (97.1) | 3.6 |
| Coagulation | ||||
| Prothrombin fragment 1+2 (F1+2) | 82.9-305.5 pmol/L | 1017.6 (217.7-5774.0; <.0001) | 36/38 (94.7) | 5.5 |
| d-dimer | 157.0-395.9 µg/L | 2735.0 (330.0-44 100.0; <.0001) | 34/36 (94.4) | 9.8 |
| Renal | ||||
| Renal injury | ||||
| U-clusterin | 5.7-437.1 ng/mg U-creatinine | 1232.3 (129.9-6091.2; <.0001) | 24/29 (82.8) | 8.6 |
| U-TIMP-1 | 0.0-5.4 ng/mg U-creatinine | 23.8 (1.4-230.4; <.0001) | 22/29 (75.9) | 39.7 |
| U-L-FABP-1 | 0.0-16.9 ng/mg U-creatinine | 58.0 (3.7-1309.8; <.0001) | 22/29 (75.9) | 48.3 |
| β2-microglobulin | 0.0-2.7 µg/mg U-creatinine | 18.4 (0.4-127.7; .0002) | 20/28 (71.4) | 46 |
| U-cystatin C | 0.3-301.3 ng/mg U-creatinine | 1256.9 (14.3-7189.6; .0005) | 18/26 (69.2) | 23.9 |
Normal ranges were evaluated in healthy volunteers (HV; n = 20 for serum analytes, n = 10 for plasma analytes, and n = 9 for urine analytes).
Baseline biomarker levels between groups were compared using the Wilcoxon rank sum test. Units are as indicated for HV levels.
Proportion of patients out of the total available samples evaluated showing levels higher than 95th percentile of HV levels.
Plasma C5a and sC5b-9 samples were not obtained under complement-preserving conditions and could not be assessed.