Thrombotic microangiopathy and poor renal outcome in lupus patients with or without antiphospholipid syndrome

To assess the presence of acute thrombotic microangiopathy (aTMA) and chronic vascular lesions (cTMA) in lupus nephropathy, and to evaluate their association with extrarrenal lupus features, aPL positivity, antiphospholipid syndrome (APS) and renal survival.

We studied lupus patients with renal biopsy, ≥1 year of post-biopsy follow-up and at least two aCL (IgG-IgM), anti-β2GP-I (IgG-IgM) and/or lupus anticoagulant (LAC) determinations. A blinded nephropathologist evaluated all biopsies. We retrospectively collected clinical, serological, treatment and renal survival data. We plotted survival curves and used Cox regression analysis.

A total of 90 biopsies were included with a median disease duration 5.9 years and median follow-up 2.4 years. Eleven patients (12.2%) had cTMA and 3 (3%) aTMA. There was no difference in age, lupus duration, hypertension, drugs, APS, non-renal lupus features, low C3 or C4 aCL IgG, anti-β2GP1-IgG or IgM and LAC between cTMA and non-cTMA groups. The cTMA group had aCL-IgM less frequently (27% vs. 66%, p=0.02), more class IV nephropathy (100% vs. 40%, p=0.01), higher activity index scores (7.5 vs. 2, p=0.03) and a tendency to need chronic dialysis (54.5% vs. 24% p=0.06). At four years of follow-up, 28% of the cTMA group and 62% of the non-cTMA group were free of dialysis (log rank p=0.03). cTMA was associated with chronic dialysis (RR 2.9, CI 95% 1.1-8.1, p=0.03).

cTMA conferred a poor renal outcome. We found a low frequency of TMA that was not associated with with APL positivity or APS, suggesting that other factors hitherto not studied are involved in its pathogenesis.