Table 2.
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 |
*
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.