Table 4.
Summary of key findings in patients with anti-factor H (FH) associated hemolytic uremic syndrome (HUS).
| Objective, N | Result | Conclusion |
|---|---|---|
| Demographic features, N = 436 | Of 781 patients < 18-years-old, 55.8% had anti-FH antibodies. Cases peak between December and April; prodrome: fever (54.6%), upper respiratory tract infection (10.3%), diarrhea (6.7%) | Seasonal predilection and prodromal symptoms indicate possible infectious trigger |
| Cohorts: 2007-12 (N = 119); 2013-18 (N = 317) | Earlier diagnosis and initiation of therapy in cohort of 2013-18; better outcomes at 3-months (33.3 vs. 18.3%) and at last follow-up (P = 0.022) in recent years | Prompt recognition and appropriate management improves outcomes |
| Anti-FH antibody titer and impact on course | Anti-FH titers at onset negatively correlate with serum C3, platelets and hemoglobin level; positive correlation with LDH levels and need for dialysis. Mean anti-FH titers 700-1164 AU/ml over 10-year follow up Anti-FH titers ≥1,330 AU/ml at 6-months predicts relapse (sensitivity 75%, specificity 81.4%; AUC 0.86); 15.8% patients in remission show antibody levels >1,330 AU/ml | Anti-FH antibody titer correlates with disease severity at onset. Titers high in remission; need biomarkers to predict relapse. Patients with anti-FH titers >1,330 AU/ml at risk of relapse—require careful clinical monitoring. |
| Functional characterization of antibodies, N = 44 | Circulating FH immune complexes (CIC) decline but correlate with anti-FH titers during remission. During remission, median soluble terminal complement complex (sC5b-9) levels were 329.9 ng/ml and 594 ng/ml in patients with high or low titers, respectively. | CIC and sC5b-9 elevated even during remission; unsatisfactory biomarkers of disease |
| Free FH ≤ 440 mg/l at 6-months predicts relapse (sensitivity 70%, specificity 100%; AUC 0.91). Presence of free FH ≤ 440 mg/l and antibody ≥1,330 AU/ml associated with 6.3-fold risk of relapse | Low levels of free FH predict relapse; requires examination in a larger cohort | |
| FH epitope specificity, N = 8 | Similar binding during onset, relapse, remission. Strong binding to SCR 17–20; also to others | Binding at multiple epitopes on FH |
| Outcome, N = 356 | Independent predictors of adverse outcome: Anti-FH ≥8,000 AU/ml, long time to begin PEX (>14 days from onset) and short duration PEX (< 14 days); combined PEX and immunosuppression were protective. Maintenance immunosuppression reduces risk of relapses. | Antibody titers at onset predict early mortality and outcomes. Adequate PEX with immunosuppression improve outcomes. |
| Outcomes at 4.4 ± 2.5 year from onset, N = 50 | eGFR 100.2 ± 21.1 ml/min/1.73 m2; proteinuria (58%), severe ambulatory hypertension (38%), masked (30%), prehypertension (18%), left ventricular hypertrophy (28%), and dyslipidemia (10%). | More than one-third patients show renal and cardiovascular sequelae |
| Renal reserve, N = 41 | Median renal reserve 15.9%. Inverse association with mean systolic pressure, number of relapses, urine protein-to-creatinine ratio, and increased left ventricular mass index. | Suggest long term assessment for proteinuria, ambulatory hypertension, cardiovascular outcomes |
AUC, area under the curve; eGFR, estimated glomerular filtration rate; FH, factor H; LDH, lactate dehydrogenase; PEX, plasma exchange; SCR, short consensus repeats; sC5b-9, soluble terminal complement complex.