Antineutrophilic cytoplasmic antibody-associated vasculitis with hypocomplementemia has a higher incidence of serious organ damage and a poor prognosis

Fukui, Shoichi; Iwamoto, Naoki; Umeda, Masataka; Nishino, Ayako; Nakashima, Yoshikazu; Koga, Tomohiro; Kawashiri, Shin‐ya; Ichinose, Kunihiro; Hirai, Yasuko; Tamai, Mami; Nakamura, Hideki; Origuchi, Tomoki; Sato, Shuntaro; Kawakami, Atsushi

doi:10.1097/md.0000000000004871

Cited by 37 publications

(40 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“… ANCA-associated vasculitis Mouse models suggest complement important in pathogenesis of AAV [ 244 , 245 ] and C5aR blockade protects against AAV [ 246 ]. Observational clinical data: Hypocomplementaemia in AAV associated with concurrent TMA and higher mortality [ 247 ] and poor renal prognosis [ 248 ]. Majority of AAV renal biopsies are negative for immune complexes but are positive for C3d, C4d and C5b-9 staining [ 249 ].…”

Section: Evidence For the Role Of Complement In The Tmasmentioning

confidence: 99%

“…Hypocomplementaemia in AAV associated with concurrent TMA and higher mortality [ 247 ] and poor renal prognosis [ 248 ].…”

Section: Evidence For the Role Of Complement In The Tmasmentioning

confidence: 99%

“…Mouse models suggest that complement is important in pathogenesis [ 244 , 245 ] and C5aR blockade is protective [ 246 ]. In humans, the majority of AAV biopsies show deposition of C3d, C4d and C5b-9 [ 249 ], and hypocomplementaemia is associated with higher mortality [ 247 ] and worse renal prognosis [ 248 ]. There are no published reports of complement-inhibiting therapy in patients with AAV and TMA.…”

Section: Evidence For the Role Of Complement In The Tmasmentioning

confidence: 99%

See 2 more Smart Citations

Complement C5-inhibiting therapy for the thrombotic microangiopathies: accumulating evidence, but not a panacea

Brocklebank

Kavanagh

2017

Clinical Kidney Journal

View full text Add to dashboard Cite

Thrombotic microangiopathy (TMA), characterized by organ injury occurring consequent to severe endothelial damage, can manifest in a diverse range of diseases. In complement-mediated atypical haemolytic uraemic syndrome (aHUS) a primary defect in complement, such as a mutation or autoantibody leading to over activation of the alternative pathway, predisposes to the development of disease, usually following exposure to an environmental trigger. The elucidation of the pathogenesis of aHUS resulted in the successful introduction of the complement inhibitor eculizumab into clinical practice. In other TMAs, although complement activation may be seen, its role in the pathogenesis remains to be confirmed by an interventional trial. Although many case reports in TMAs other than complement-mediated aHUS hint at efficacy, publication bias, concurrent therapies and in some cases the self-limiting nature of disease make broader interpretation difficult. In this article, we will review the evidence for the role of complement inhibition in complement-mediated aHUS and other TMAs.

show abstract

Section: Evidence For the Role Of Complement In The Tmasmentioning

confidence: 99%

“…Hypocomplementaemia in AAV associated with concurrent TMA and higher mortality [ 247 ] and poor renal prognosis [ 248 ].…”

Section: Evidence For the Role Of Complement In The Tmasmentioning

confidence: 99%

Section: Evidence For the Role Of Complement In The Tmasmentioning

confidence: 99%

See 1 more Smart Citation

Complement C5-inhibiting therapy for the thrombotic microangiopathies: accumulating evidence, but not a panacea

Brocklebank

Kavanagh

2017

Clinical Kidney Journal

View full text Add to dashboard Cite

show abstract

“…The final subject group thus consisted of 101 patients with AAV (Figure ). Seventy of the 101 patients had been included in our prior investigation of hypocomplementemia of AAV, and the other 31 patients were new patients.…”

Section: Methodsmentioning

confidence: 99%

Antineutrophilic cytoplasmic antibody‐associated vasculitis with and without renal involvement: C3 contributes to prognosis, but renal involvement does not

et al. 2018

Self Cite

View full text Add to dashboard Cite

Objectives:We investigated the impact of renal involvement at diagnosis on the prognosis of patients with antineutrophilic cytoplasmic antibody (ANCA)-associated vasculitis (AAV). Methods:The relationship between renal involvement at diagnosis, clinical variables at diagnosis, and prognosis (including relapse episodes, initiation of dialysis, and death) was examined in 101 Japanese patients with AAV.Results: Sixty-eight patients had renal involvement at diagnosis. The renal-involvement patients had significantly higher ages at diagnosis, significantly lower hemoglobin levels, and significantly lower platelet levels. They had significantly lower C3 levels, but showed no significant difference in C4 levels. Overall survival rate was significantly worse in patients with than in patients without renal involvement (P = 0.003, log-rank test). Multivariable analysis using a logistic regression model demonstrated that C3 contributed to dialysis initiation: odds ratio (per 10 mg/dL of C3): 0.68; range: 0.49-0.90; P = 0.007. A Cox proportional hazard model revealed that the C3 level and age at diagnosis contributed significantly to overall survival: hazard ratio (per 10 mg/dL of C3) 0.81, range 0.69-0.95, P = 0.011; 1.08, 1.02-1.15, P = 0.013, respectively. Renal involvement did not contribute significantly to overall survival. Patients with C3 levels ≥100 mg/dL had a better survival rate than patients with C3 levels <100 mg/dL. Conclusions:Although patients with renal involvement had higher ages, lower C3 levels at diagnosis, and poorer prognoses, multivariable analysis demonstrated that the C3 level and age at diagnosis, but not renal involvement, contributed significantly to overall survival. Our results demonstrate the relationship between C3 hidden behind renal involvement and AAV prognosis. K E Y W O R D Santineutrophilic cytoplasmic antibody, C3, complement, renal involvement, vasculitis

show abstract

“…В большинстве представленных исследований для оценки активности системы комплемента были использованы лабораторные и иммуногистохимические методы, которые до настоящего времени не вошли в повседневную практику. В обычной лечебной работе врачам доступно преимущественно определение уровня C3 и C4 компонентов системы комплемента или ее [36]. В другом исследовании снижение концентрации С3 компонента комплемента, выявленное у 20% пациентов с ААВ, также сопровождалось снижением почечной и общей выживаемости [37].…”

Section: активация системы комплемента при аав: клинические данныеunclassified

Complement in ANCA-associated vasculitis: from pathogenesis to treatment

Zykova¹,

Vinogradova²,

Shchegoleva³

et al. 2019

CPT

View full text Add to dashboard Cite

Antineutrophilic cytoplasmic antibody-associated vasculitis with hypocomplementemia has a higher incidence of serious organ damage and a poor prognosis

Abstract: Supplemental Digital Content is available in the text

Cited by 37 publications

References 27 publications

Complement C5-inhibiting therapy for the thrombotic microangiopathies: accumulating evidence, but not a panacea

Complement C5-inhibiting therapy for the thrombotic microangiopathies: accumulating evidence, but not a panacea

Antineutrophilic cytoplasmic antibody‐associated vasculitis with and without renal involvement: C3 contributes to prognosis, but renal involvement does not

Complement in ANCA-associated vasculitis: from pathogenesis to treatment

Contact Info

Product

Resources

About