Abstract
Objective G1 and G2 polymorphisms of APOL1 gene, exclusively found among patients of African ancestry, have been associated with chronic kidney disease (CKD) and collapsing glomerulopathy. We investigated their impact on lupus nephritis (LN).
Methods We included patients from 6 hospitals in Paris and Marseille in France, between January 2017 and March 2020, with biopsy-proven LN, African ancestry and age >18 years at the time of inclusion. We excluded those with HIV infection. The data were retrospectively collected at LN diagnosis, 1 year after diagnosis and at last follow-up. APOL1 genotyping was performed and we divided patients in 2 groups: the high-risk genotype (HRG) group with 2 risk alleles and the low-risk genotype (LRG) group with 1 or 0 risk allele. All patients signed a consent form for the genetic analysis and protocol approval was obtained from the ethic committee CERAPHP (Comité d’Ethique de la Recherche AP-HP Centre), registration number 00011928.
Results Ninety-nine patients were included, 13 in the HRG group and 86 in the LRG group. At LN diagnosis, clinical and biological characteristics were similar except for kidney function that was more impaired in the HRG group compared to the LRG group with a median serum creatinine of 131μmol/L [73–641] versus 66μmol/L [53–128] (p=0.01). Patients in the HRG group were more likely to have a serum creatinine above 200μmol/L compared to the LRG group (46% versus 11%, p=0.01, OR 7.1[1.8–28.6]), and required acute haemodialysis more frequently (31% versus 1% respectively, p = 0.001, OR 34.7[3.5–345.1]). Collapsing glomerulopathy was more frequent in the HRG group (46% of patients, versus 5%, OR 17.5[3.3–91.9], p=0.001). Patients in the HRG group were more likely to develop CKD at 1 year follow-up (33% versus 5%, OR 9.6[2.0–46.1]) (table 1). Survival without kidney failure was poorer in the HRG group with a hazard ratio (HR) of 4.6 [1.5–14.2], p=0.006, even after adjusting with the kidney response at 12 months (adjusted HR 6.24[1.8–21.6], p=0.004) (figure 1).
Conclusion APOL1 high risk genotype was associated to a worse kidney function at diagnosis, development of collapsing glomerulopathy and higher risk of subsequent kidney failure.
Patient survival without end-stage kidney disease. Legends: Data were censored at 15 years after LN diagnosis. Kaplan Meyer curve was analyzed with the log rank test. ESKD: End stage kidney disease; HRG: High risk genotype; LRG: Low risk genotype; HR: Hazard Ratio. *Hazard ratio was calculated based on the Cox regression, and was adjusted with the kidney response at 12 months (overall response versus none).
