P0351IMPACT OF APOL1 POLYMORPHISM ON LUPUS NEPHRITIS

Abstract

Abstract Background and Aims African ancestry is associated with more severe kidney involvement and end stage renal disease (ESRD) in lupus nephritis (LN). Two polymorphisms of the apolipoprotein L1 gene (APOL1), defining the risk allels (RA) G1 and G2, particularly frequent among subjects of African ancestry, markedly increase the risk of ESRD and the occurrence of collapsing glomerulopathy (CG) in the general population. The aim of this study was to assess the impact of ApoL1 RA on clinical, biological, and histological presentation of LN, and its prognosis. Method Patients of African ancestry with biopsy-proven LN were included between January 2017 and September 2018. Clinical, laboratory and pathology datas were retrospectively collected and ApoL1 genotyping was performed. Results Among the 53 included patients, 31 had no RA, 16 were heterozygous with only one RA and 6 had 2 RA (G1/G1 or G2/G2 or G1/G2). The population was divided in 2 groups: low risk polymorphism (LRP) group defined by the presence of 0 or 1 RA, and high risk polymorphism (HRP) group with 2 RA. At presentation, hypertension (OR 25,4 [1,3-510,3]) and acute renal failure (OR: 9,3 [1,3-65,2]), were more frequent in the HRP group when compared to the LRP group. Initial median serum creatinine was respectively 363 μmol/l (IQR 119-594) vs 64 μmol/l (IQR 55-127). After 2-year follow-up, median eGFR was 59mL/min (IQR 41-91) in the HRP group and 117mL/min (IQR 92-124mL/min) in the LRP group. Patients in the HRP group were more likely to have an impaired renal function with an estimated glomerular filtration rate (eGFR) <60mL/min compared to patients in the LRP group (OR: 13,5 [2,1-86,5]). Moreover, ESRD-free survival was worse in the HRP group (Hazard ratio: 78,8 [5,3-1124,0]) despite similar chronicity indexes on initial kidney biopsy and comparable therapeutic strategies. As for histological findings, CG was observed in 67% of patient’s kidney biopsy in the HRP group whereas it only concerned 12% of patient’s kidney biopsy in the LRP group (OR: 14,8 [2,4-84,8]). Conclusion The ApoL1 polymorphism strongly affects LN prognosis in patients with African ancestry, resulting in more severe inaugural presentation, higher risk of subsequent severe chronic kidney disease and development of collapsing glomerulopathy for subjects with 2 RA.