Background/Purpose: The pauci-immune nature of typical lesions in ANCA associated vasculitis (AAV) has led to the belief that complement does not play a role in the pathogenesis of this disease. Activation of the alternative complement pathway is necessary for the development of glomerulonephritis in murine models. The complement deposition in renal biopsies of patients with AAV was correlated with increased renal damage.

We hypothesized that there is greater morbidity, mortality and worse renal outcomes in hypocomplementemic patients with AAV compared to those who have normal complement values at the onset of the disease.

Our purpose was to compare clinical manifestations, laboratory values, histological type, renal prognosis and mortality in normal and hypocomplementemic patients with AAV.

Methods: Retrospective, observational, analytical study. Data from the medical records of patients over the age of 18 were evaluated between the years 2000-2017. Patients with diagnosis of AAV who met the criteria of ACR 1990 Classification or Chapel Hill Concensus Conference 2012 were included. Hypocomplementemia was defined as C3 values below 80 mg/dl or C4 below 15 mg/dl. Chi-square or Fisher’s exact test was used for dichotomous variables as appropriate. P-value <0.05 was considered statistically significant. Logistic regression analysis was used to identify predictors of survival.

Results: We analyzed 87 patients with AAV (female 56.2%, mean follow-up 24 months, mean age at onset of the disease 49 years ± 14.9 SD). Most frequent type of vasculitis was Granulomatosis with polyangeitis (49.4%).

Hypocomplementemia was determined in 7/57 patients (12.28%) and was significantly associated with renal damage (p: 0.034 OR 12.8 CI95% 0.69-236) particularly with decreased glomerular filtrate (p: 0.045 OR: 8.2 CI 95% 0.92-74.0). A higher prevalence of proteinuria greater than 1 gr/24 hs was observed in hypocomplementemic patients 57% vs 25% (p: 0.068).

All renal biopsies were classified as pauci-immune glomerulonephritis. Average number of glomeruli affected was 13 [IQR 25-75% (7-17)], predominating the sclerosing type (44%). The degree of interstitial fibrosis, tubular atrophy (52%) and vascular damage (57%) was mild. In 3 samples we observed deposits of immunocomplexes (IgG+), complement (C3+) or fibrinogen by immunofluorescence. These patients showed creatinine values above 4 mg/dl. There were no statistically significant differences in renal histology between groups (p: 0.091).

There was no association between hypocomplementemia and other organic damage or laboratory values.

Mortality rate was 18% (16/87), without differences between groups (p: 0.300).

Conclusion: Hypocomplementemia was associated with increased renal damage: decreased glomerular filtrate and greater values of proteinuria; as reported in the literature. We did not find any other statistically significant difference between groups.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/increased-renal-damage-in-hypocomplementemic-patients-with-anca-associated-vasculitis/