APOL1 Risk Variants in Collapsing Lupus Glomerulopathy
Christopher Larsen, Marjorie Beggs, Mohammad Saeed, Patrick Walker. Nephropath, Little Rock, AR; University of Arkansas for Medical Sciences, Little Rock, AR
Background: Collapsing glomerulopathy (CG) is a devastating renal disease affecting African Americans (AA) which has been reported in association with numerous etiologies, the most well known being HIV (HIVAN). Recently, an association was found between the presence of APOL1 risk alleles and HIVAN. CG also occurs in the setting of systemic lupus erythematosus (SLE) as a part of the spectrum of so-called lupus podocytopathy. We sought to determine if Collapsing Lupus Glomerulopathy (CLG) was also associated with the presence of APOL1 risk alleles.
Design: A total of 546 renal biopsies were identified in the case file of our institution from AA patients with SLE. Two renal pathologists confirmed the diagnosis of CG. Additional features examined include the ISN/RPS Classification, activity score, chronicity score and the presence of microcystic tubular dilatation and arteriosclerosis. DNA was extracted from archived biopsy tissue and genotyped for APOL1 risk alleles using TaqMan assays. The pathologists were blinded to the APOL1 genotype at the time of evaluation.
Results: A total of 26 cases of CLG were identified. APOL1 strongly associated with CLG (c2=24.8, P<0.001). In a recessive model, APOL1 risk alleles conferred 5.4 fold higher odds of developing CLG (c2=20.6, P<0.001, Odds ratio CI95=2.4 – 12.1). APOL1 risk alleles were also found to be associated with non-necrotizing crescents (c2=7.1, P=0.008, OR= 1.6, CI95=1.2 – 2.3) and microcystic dilatation (c2=12, P=0.001, OR= 2.2, CI95=1.4 – 2.3). Other morphologic features were not found to be associated with APOL1.
Conclusions: We found that CLG is strongly associated with the presence of APOL1 risk alleles and we suspect that this initial study actually under represents the strength of the association. There is extensive morphologic overlap between CLG and proliferative lupus nephritis (PLN) resulting from the morphologic similarity between a florid collapsing lesion and cellular crescent formation. Given this overlap and the higher incidence of “crescents” in biopsies from patients with 2 APOL1 risk alleles, it is plausible that some of the cases categorized as PLN might actually represent CLG. APOL1 genotyping of AA patients with SLE might prove helpful in the future to identify patients at risk for CLG, an entity with a poor prognosis which is often resistant to treatment.
Category: Kidney (does not include tumors)
Tuesday, March 5, 2013 8:00 AM
Proffered Papers: Section H, Tuesday Morning