Histological antiphospholipid-associated nephropathy versus lupus nephritis in patients with systemic lupus erythematosus: An observational cross-sectional study with longitudinal follow-up

Abstract

Introduction: Renal involvement is a severe complication in systemic lupus erythematosus (SLE). Moreover, a subset of SLE patients develop the anti-phospholipid syndrome (APS), characterised by the occurrence of anti-phospholipid antibodies in combination with macro- and microvascular thrombotic manifestations, including acute and chronic antiphospholipid-associated nephropathy (APLN). Clinical presentations of lupus nephritis and APLN are similar and a renal biopsy is necessary to differentiate between the conditions. Our aim with this study was to investigate the occurrence of histopathological findings consistent with APLN (hAPLN) in renal biopsies from SLE patients and to investigate associations with anti-phospholipid antibody specificities, clinical manifestations, HLA-DRB1 alleles, and long-term renal outcome. Method: Consecutive renal biopsies from 112 SLE patients with renal involvement were investigated and evaluated for findings of hAPLN; in all there were 236 renal biopsies. Data from biopsy reports and clinical information were collected. Autoantibodies against cardiolipin and β2-glycoprotein-1 were measured by enzyme-linked immunosorbent assay. A lupus anticoagulant test was determined with a modified Dilute Russel Viper Venom method. HLA genotyping was performed by sequence-specific primer PCR. Renal outcome was determined at study end. Results: The prevalence of hAPLN was 14.3% among SLE patients with renal involvement. Compared to patients with pure lupus nephritis, occurrence of hAPLN was associated with intima changes (odds ratio (OR) = 24; 95% confidence interval (CI), 3.0 to 189.8; P < 0.0001), hypertensive vascular changes (OR = 7.8; 95% CI, 1.6 to 39.4; P = 0.01), inflammatory infiltrates (OR = 6.5; 95% CI, 1.7 to 25.1; P = 0.007) and tubular atrophy (OR = 13.1; 95% CI, 1.7 to 103.6; P = 0.002). hAPLN was associated with the presence of cardiolipin antibodies (OR = 3.3; 95% CI, 1.0 to 10.8; P = 0.05) and triple anti-phospholipid antibody positivity (OR = 4.2; 95% CI, 1.3 to 13.7; P = 0.02). Patients with hAPLN were more hypertensive (OR = 3.8; 95% CI, 1.2 to 12.3; P = 0.03) and had higher levels of creatinine as compared to lupus nephritis patients (median 116 versus 75 μmol/L; P < 0.0001). We found significantly higher frequency of HLA-DRB1*13 (OR = 5.1; 95% CI, 1.7 to 15.4; P = 0.03) and development of end-stage renal disease (OR = 5.8; 95% CI, 1.7 to 19.7; P = 0.008) in hAPLN compared with lupus nephritis. Conclusion: hAPLN is a severe and often unrecognized condition in SLE patients with renal involvement. We have demonstrated an increased risk for development of renal impairment and a genetic predisposition in hAPLN patients compared to lupus nephritis patients.