Diagnostic Utility of Complement Serology for Atypical Hemolytic Uremic Syndrome

Meera Sridharan, Ronald S. Go, Roshini S. Abraham, Fernando Custodio Fervenza, Sanjeev M Sethi, Sandra C. Bryant, Grant M. Spears, David L. Murray, Maria A.V. Willrich

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Objective: To investigate the clinical utility of a 9-analyte complement serology panel (COMS) covering complement function (CH50 and AH50), components (C3, C4), factor B (CFB), factor H, and activation markers (C4d, Bb, and soluble membrane attack complex) for the diagnosis of atypical hemolytic uremic syndrome (aHUS). Methods: Physician orders for COMS from January 19, 2015, through November 4, 2016, were reviewed. Demographic characteristics, patient diagnosis, and laboratory parameters were recorded. Results: There were 177 COMS orders for 147 patients. The median patient age was 44.9 years (range, 0.9-88.0 years). Common reasons for ordering COMS included monitoring and diagnosis of C3 glomerulopathy and renal dysfunction and differentiation of aHUS from other thrombotic microangiopathies (TMAs). Forty-four patients had COMS ordered for TMAs: 8 had aHUS and all had 1 or more abnormalities within the alternative pathway of complement. Although the sensitivity of this finding for the diagnosis of aHUS is 100%, the specificity is only 28%, with a positive likelihood ratio of 1.39. Patients with aHUS had lower CH50, C3, and CFB than did those with secondary non-aHUS TMA (all P<.01). A combined CFB of 20.9 mg/dL or less and CH50 of 56% or less led to sensitivity of 75% with increased specificity of 88.9% and a diagnostic odds ratio of 24. Conclusion: A COMS abnormality should not be interpreted in isolation. In conjunction with clinical presentation, a decrease in both CFB and CH50 may be an important clue to support the diagnosis of aHUS.

Original languageEnglish (US)
Pages (from-to)1351-1362
Number of pages12
JournalMayo Clinic Proceedings
Volume93
Issue number10
DOIs
StatePublished - Oct 1 2018

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Serology
Complement Factor B
Thrombotic Microangiopathies
Complement C9
Alternative Complement Pathway
Complement Membrane Attack Complex
Complement Factor H
Hemolytic-Uremic Syndrome
Clinical Laboratory Techniques
Atypical Hemolytic Uremic Syndrome
Odds Ratio
Demography
Physicians
Kidney

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Diagnostic Utility of Complement Serology for Atypical Hemolytic Uremic Syndrome. / Sridharan, Meera; Go, Ronald S.; Abraham, Roshini S.; Fervenza, Fernando Custodio; Sethi, Sanjeev M; Bryant, Sandra C.; Spears, Grant M.; Murray, David L.; Willrich, Maria A.V.

In: Mayo Clinic Proceedings, Vol. 93, No. 10, 01.10.2018, p. 1351-1362.

Research output: Contribution to journalArticle

Sridharan, M, Go, RS, Abraham, RS, Fervenza, FC, Sethi, SM, Bryant, SC, Spears, GM, Murray, DL & Willrich, MAV 2018, 'Diagnostic Utility of Complement Serology for Atypical Hemolytic Uremic Syndrome', Mayo Clinic Proceedings, vol. 93, no. 10, pp. 1351-1362. https://doi.org/10.1016/j.mayocp.2018.07.008
Sridharan, Meera ; Go, Ronald S. ; Abraham, Roshini S. ; Fervenza, Fernando Custodio ; Sethi, Sanjeev M ; Bryant, Sandra C. ; Spears, Grant M. ; Murray, David L. ; Willrich, Maria A.V. / Diagnostic Utility of Complement Serology for Atypical Hemolytic Uremic Syndrome. In: Mayo Clinic Proceedings. 2018 ; Vol. 93, No. 10. pp. 1351-1362.
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AU - Go, Ronald S.

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AU - Sethi, Sanjeev M

AU - Bryant, Sandra C.

AU - Spears, Grant M.

AU - Murray, David L.

AU - Willrich, Maria A.V.

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N2 - Objective: To investigate the clinical utility of a 9-analyte complement serology panel (COMS) covering complement function (CH50 and AH50), components (C3, C4), factor B (CFB), factor H, and activation markers (C4d, Bb, and soluble membrane attack complex) for the diagnosis of atypical hemolytic uremic syndrome (aHUS). Methods: Physician orders for COMS from January 19, 2015, through November 4, 2016, were reviewed. Demographic characteristics, patient diagnosis, and laboratory parameters were recorded. Results: There were 177 COMS orders for 147 patients. The median patient age was 44.9 years (range, 0.9-88.0 years). Common reasons for ordering COMS included monitoring and diagnosis of C3 glomerulopathy and renal dysfunction and differentiation of aHUS from other thrombotic microangiopathies (TMAs). Forty-four patients had COMS ordered for TMAs: 8 had aHUS and all had 1 or more abnormalities within the alternative pathway of complement. Although the sensitivity of this finding for the diagnosis of aHUS is 100%, the specificity is only 28%, with a positive likelihood ratio of 1.39. Patients with aHUS had lower CH50, C3, and CFB than did those with secondary non-aHUS TMA (all P<.01). A combined CFB of 20.9 mg/dL or less and CH50 of 56% or less led to sensitivity of 75% with increased specificity of 88.9% and a diagnostic odds ratio of 24. Conclusion: A COMS abnormality should not be interpreted in isolation. In conjunction with clinical presentation, a decrease in both CFB and CH50 may be an important clue to support the diagnosis of aHUS.

AB - Objective: To investigate the clinical utility of a 9-analyte complement serology panel (COMS) covering complement function (CH50 and AH50), components (C3, C4), factor B (CFB), factor H, and activation markers (C4d, Bb, and soluble membrane attack complex) for the diagnosis of atypical hemolytic uremic syndrome (aHUS). Methods: Physician orders for COMS from January 19, 2015, through November 4, 2016, were reviewed. Demographic characteristics, patient diagnosis, and laboratory parameters were recorded. Results: There were 177 COMS orders for 147 patients. The median patient age was 44.9 years (range, 0.9-88.0 years). Common reasons for ordering COMS included monitoring and diagnosis of C3 glomerulopathy and renal dysfunction and differentiation of aHUS from other thrombotic microangiopathies (TMAs). Forty-four patients had COMS ordered for TMAs: 8 had aHUS and all had 1 or more abnormalities within the alternative pathway of complement. Although the sensitivity of this finding for the diagnosis of aHUS is 100%, the specificity is only 28%, with a positive likelihood ratio of 1.39. Patients with aHUS had lower CH50, C3, and CFB than did those with secondary non-aHUS TMA (all P<.01). A combined CFB of 20.9 mg/dL or less and CH50 of 56% or less led to sensitivity of 75% with increased specificity of 88.9% and a diagnostic odds ratio of 24. Conclusion: A COMS abnormality should not be interpreted in isolation. In conjunction with clinical presentation, a decrease in both CFB and CH50 may be an important clue to support the diagnosis of aHUS.

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