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03-02-2022 | Hemolytic Uremic Syndrome | Systematic Review/Meta-analysis

Systematic review of atypical hemolytic uremic syndrome biomarkers

Authors: Rupesh Raina, Sidharth K. Sethi, Marie-Agnès Dragon-Durey, Amrit Khooblall, Divya Sharma, Priyanka Khandelwal, Ron Shapiro, Olivia Boyer, Hui Kim Yap, Arvind Bagga, Christoph Licht

Published in: Pediatric Nephrology | Issue 7/2022

Abstract

Background and objectives

Observing biomarkers that affect alternative pathway dysregulation components may be effective in obtaining a new and more rapid diagnostic portrayal of atypical hemolytic uremic syndrome. We have conducted a systematic review on the aHUS biomarkers: C3, C5a, C5b-9, factor B, complement factor B, H, and I, CH50, AH50, d-dimer, as well as anti-CFH antibodies.

Methods

An exhaustive literature search was conducted for aHUS patient population plasma/serum, collected/reported at the onset of diagnosis. A total of 60 studies were included with the data on 837 aHUS subjects, with at least one biomarker reported.

Results

The biomarkers C3 [mean (SD): 72.1 (35.0), median: 70.5 vs. reference range: 75–175 mg/dl, n = 752]; CH50 [28.3 (32.1), 24.3 vs. 30–75 U/ml, n = 63]; AH50 [27.6% (30.2%), 10% vs. ≥ 46%, n = 23]; and CFB [13.1 (6.6), 12.4, vs. 15.2–42.3 mg/dl, n = 19] were lower among aHUS subjects as compared with the reference range.

The biomarkers including C4 [mean (SD): 20.4 (9.5), median: 20.5 vs. reference range: 14–40 mg/dl, n = 343]; C4d [7.2 (6.5), 4.8 vs. ≤ 9.8 μg/ml, n = 108]; CFH [40.2 (132.3), 24.5 vs. 23.6–43.1 mg/dl, n = 123 subjects]; and CFI [8.05 (5.01), 6.55 mg/dl vs. 4.4–18.1 mg/dl, n = 38] were all observed to be within the reference range among aHUS subjects.

The biomarkers C5a [mean (SD): 54.9 (32.9), median: 48.8 vs. reference range: 10.6–26.3 mg/dl, n = 117]; C5b-9 [466.0 (401.4), 317 (186–569.7) vs. ≤ 250 ng/ml, n = 174]; Bb [2.6 (2.1), 1.9 vs. ≤ 1.6 μg/ml, n = 77] and d-dimer [246 (65.05), 246 vs. < 2.2 ng/ml, 2, n = 2 subjects] were higher among patients with aHUS compared with the reference range.

Conclusion

If a comprehensive complement profile were built using our data, aHUS would be identified by low levels of C3, CH50, AH50, and CFB along with increased levels of C5a, C5b-9, Bb, anti-CFH autoantibodies, and d-dimer.

Graphical abstract

A higher resolution version of the Graphical abstract is available as Supplementary information.

Available only for authorised users

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Title: Systematic review of atypical hemolytic uremic syndrome biomarkers
Authors: Rupesh Raina
Sidharth K. Sethi
Marie-Agnès Dragon-Durey
Amrit Khooblall
Divya Sharma
Priyanka Khandelwal
Ron Shapiro
Olivia Boyer
Hui Kim Yap
Arvind Bagga
Christoph Licht
Publication date: 03-02-2022
Publisher: Springer Berlin Heidelberg
Keywords: Hemolytic Uremic Syndrome
Biomarkers
Published in: Pediatric Nephrology / Issue 7/2022
Print ISSN: 0931-041X
Electronic ISSN: 1432-198X
DOI: https://doi.org/10.1007/s00467-022-05451-2

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Systematic review of atypical hemolytic uremic syndrome biomarkers

Abstract

Background and objectives

Methods

Results

Conclusion

Graphical abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background and objectives

Methods

Results

Conclusion

Graphical abstract

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