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Increased renal damage in hypocomplementemic patients with ANCA-associated vasculitis: retrospective cohort study
L García1, C E Pena2, R Águila Maldonado2
1Department of Rheumatology, Hospital San Martín de La Plata, La Plata, Buenos Aires, Argentina. lucilagarciavar@hotmail.com.ar.
Insights
Hypocomplementemia, defined as low C3 or C4 levels, is linked to worse kidney outcomes in antineutrophilic cytoplasmic antibody-associated vasculitis (AAV). Patients with complement deposits in kidney biopsies show more aggressive disease and poorer prognosis.
Area of Science:
- Nephrology
- Immunology
- Rheumatology
Background:
- The complement system significantly contributes to the pathogenesis of antineutrophilic cytoplasmic antibody-associated vasculitis (AAV), particularly affecting the kidneys.
- Patients with complement deposits on the glomerular basal membrane exhibit more aggressive kidney disease than those with pauci-immune vasculitis.
Purpose of the Study:
- To investigate the association between hypocomplementemia and clinical/laboratory findings in AAV patients.
- To analyze the correlation of hypocomplementemia with renal histology, progression to renal insufficiency, and mortality in AAV.
Main Methods:
- A retrospective cohort study of 93 AAV patients (2000-2007).
- Hypocomplementemia defined as C3 < 80 mg/dL or C4 < 15 mg/dL.
- Comparison of demographic, clinical, laboratory, and histopathological data between hypocomplementemic and normocomplementemic patients using logistic regression analysis.
Main Results:
- Seven patients (11.1%) presented hypocomplementemia, showing greater kidney involvement.
- Four of 30 analyzed renal biopsies (13.3%) revealed immunocomplex (IC) or complement deposits.
- Non-pauci-immune AAV patients exhibited terminal chronic renal disease (TCRD).
Conclusions:
- Low complement levels are associated with increased renal damage in AAV patients.
- Renal biopsies confirming IC and/or complement deposits correlate with more aggressive kidney disease.
- Hypocomplementemia at disease onset indicates greater organ involvement, poorer prognosis, and higher mortality.
Introduction:
The complement system has an important role in the pathogenesis of vasculitis associated with antineutrophilic cytoplasmic antibody (AAV) mainly at the level of the kidneys because patients with complement deposits on the glomerular basal membrane present more aggressive disease compared with those with pauci-immune vasculitis.
Aim:
To analyze the association of hypocomplementemia with the clinical manifestations, laboratory data, renal histology, progress to renal insufficiency, and mortality of patients with AAV.
Methods:
Retrospective cohort study (2000-2007) included 93 patients with AAV. Hypocomplementemia is defined as having C3 values lower than 80 mg/dL or C4 values below 15 mg/dL. Demographic, statistical, clinical, hematological, serological, and histopathological characteristics of all the patients with and without diagnosis of hypocomplementemia were compared. In order to evaluate variable independence, a logistic regression analysis was used.
Results:
Ninety-three patients were studied of whom 63 (67.7%) had complement dosage at the moment of AAV diagnosis. Seven patients (11.1%) presented hypocomplementemia and a greater kidney involvement compared with normocomplementemic patients. Thirty renal biopsies were analyzed and 4 (13.3%) showed immunocomplex (IC) or complement deposits by an immunofluorescence test (IFT). Patients with "non-pauci-immune" AAV also presented terminal chronic renal disease (TCRD).
Conclusion:
There is an association between low complement and the degree of renal damage in patients with AAV. Patients with renal biopsies confirming IC and/or complement deposits showed more aggressive renal disease. Key Points • The complement system has an important role in the pathogenesis of vasculitis associated to antineutrophilic cytoplasmic antibody. • The studies in murine models confirming the complement activation by alternative pathway and particularly the receptor C5a (C5aR) is necessary for the development of glomerulonefritis. • Complement deposit observed in the renal biopsies of patients diagnosed with AAV was correlated to greater kidney damage, greater proteinuria and major disease activity compared to patients diagnosed with typical pauci-immune vasculitis. • The presence of hypocomplementemia at the onset of the disease was also associated with a greater organ involvement, poor prognosis and greater mortality.
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