Apolipoprotein L1 risk variants associate with systemic lupus erythematosus-associated collapsing glomerulopathy

Abstract

Collapsing glomerulopathy is a devastating renal disease that primarily affects African Americans and associates with numerous etiologies, such as HIV and autoimmune disease. The presence of APOL1 risk alleles associates with HIV-associated collapsing glomerulopathy, but it is unknown whether these risk alleles also associate with systemic lupus erythematosus (SLE) -associated collapsing glomerulopathy. Here, re-examination of 546 renal biopsies from African-American patients with SLE identified 26 cases of collapsing glomerulopathy, which we genotyped for APOL1 risk alleles using DNA extracted from archived biopsy tissue. APOL1 strongly associated with SLE-associated collapsing glomerulopathy (P<0.001). In a recessive model, two APOL1 risk alleles conferred 5.4-fold (95% CI=2.4 to 12.1) higher odds of developing SLE-associated collapsing glomerulopathy (P<0.001). In conclusion, APOL1 genotyping of African-American patients with SLE might help identify patients at risk for collapsing glomerulopathy, an entity with a poor prognosis that is often resistant to treatment.

Figure 1.

Morphology of SLE-associated collapsing glomerulopathy. (A) Glomerular tuft collapse with overlying epithelial hypertrophy and hyperplasia in Bowman’s space (Jones methenamine silver). Original magnification, ×400. (B) Characteristic tubulointerstitial changes are evident from lower power, including focal tubular dilatation with large intraluminal hyaline casts and proximal tubules stuffed with protein droplets (periodic acid–Schiff). Original magnification, ×100. (C) Positive staining for IgG is present in glomeruli and tubular nuclei (direct immunofluorescence). Original magnification, ×200. (D) Transmission electron photomicrograph showing diffuse foot process effacement as well as mesangial and subepithelial deposits (unstained). Original magnification, ×3000.