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Observational Study
. 2021 Apr;36(4):917-925.
doi: 10.1007/s00467-020-04751-9. Epub 2020 Oct 7.

Early relapse rate determines further relapse risk: results of a 5-year follow-up study on pediatric CFH-Ab HUS

Johannes Hofer  1   2   3 , Magdalena Riedl Khursigara  4   5 , Markus Perl  6 , Thomas Giner  4 , Alejandra Rosales  4 , Gerard Cortina  4 , Siegfied Waldegger  4 , Therese Jungraithmayr  4   7 , Reinhard Würzner  8
Affiliations
Observational Study

Early relapse rate determines further relapse risk: results of a 5-year follow-up study on pediatric CFH-Ab HUS

Johannes Hofer et al. Pediatr Nephrol. 2021 Apr.

Abstract

Background: The complement factor H antibody (CFH-Ab)-associated hemolytic uremic syndrome (HUS) forms a distinct subgroup within the complement-mediated HUS disease spectrum. The autoimmune nature of this HUS subgroup implies the potential benefit of a targeted immunosuppressive therapy. Data on long-term outcome are scarce.

Methods: This observational study evaluates the clinical outcome of 19 pediatric CFH-Ab HUS patients from disease onset until their 5-year follow-up.

Results: All but one relapse occurred during the first 2 years, and patients who had no relapse within the first 6 months were relapse-free until the end of the observation period. Kidney function at disease onset determines long-term kidney function: all individuals with normal kidney function at disease onset had normal kidney function after 5 years, and all patients with reduced kidney function at onset had impaired kidney function at the last follow-up. Level of CFH-Ab titer at disease onset was not correlated with a higher risk of recurrences or worse long-term outcome after 5 years. Resolution of CFH-Ab titers after 5 years was common.

Conclusions: CFH-Ab HUS patients have a varied overall long-term course. Early relapses are common, making close surveillance during the first years essential, regardless of the initial CFH-Ab titer.

Keywords: CFH-Ab; Hemolytic uremic syndrome; Immunosuppressive therapy.

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Conflict of interest statement

J.H., M.R. K., and R.W. have received honoraria from Alexion Pharmaceuticals Inc. and/or unrestricted educational grants and have served on various advisory boards.

Figures

Fig. 1
Fig. 1
Swimmer plot grouped according to the outcome. The outcome after the 5-year follow-up period determines the group assignment. In patients 1, 3, 4, 5, 7, 11, 15, 16, 17, and 18, CFH-Ab titers dropped and are negative at 5-year follow-up. In patients 2, 6, 9, 10, 12, 13, 14, and 19, CFH-Ab titers are still detectable at 5-year follow-up but in the low titer range (> 100 and < 600 AU/ml). X-axis: years of observation. Beginning of the bars refers to onset of disease, which was quasi identical to the timepoint of HUS diagnosis (maximum of 2-week difference). Y-axis: group assignment and patient ID. Complete remission: normalization of LDH, haptoglobin, hemoglobin, and platelets in combination with normal kidney function. Partial remission: normalization of LDH, haptoglobin, hemoglobin, and platelets but presence of chronic kidney disease and/or proteinuria [13]. AU arbitrary units, CFH-Ab complement factor H antibodies, CKD stage 5 chronic kidney disease, Ecu eculizumab, HUS hemolytic uremic syndrome, IS any kind of immunosuppressive therapy except eculizumab, PT plasma therapy (any kind)
Fig. 2
Fig. 2
Relapse-free survival curve. As further detailed in the text, all of the first relapses occurred within the first 6 months after disease onset. One patient is missing as the exact timepoint of the first relapse is not known (but was before 6 months after disease onset)
Fig. 3
Fig. 3
Evolution of CFH-Ab titers over 5-year follow-up period. Steady decrease of available CFH-Ab titers from disease onset up to 5-year follow-up (at 5 years, 55% of patients with CFH-Ab titers under cut-off of 100 AU/ml)
See this image and copyright information in PMC

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