PT - JOURNAL ARTICLE AU - Gisele Vajgel AU - Suelen Cristina Lima AU - Diego Jeronimo S. Santana AU - Camila B. L. Oliveira AU - Denise Maria N. Costa AU - Pamela J. Hicks AU - Maria Alina G. M. Cavalcante AU - Carl D. Langefeld AU - Lucila Maria Valente AU - Sergio Crovella AU - Gianna Mastroianni Kirsztajn AU - Barry I. Freedman AU - Paula Sandrin-Garcia TI - A single <em>APOL1</em> nephropathy variant increases risk of advanced lupus nephritis in Brazilians AID - 10.3899/jrheum.190684 DP - 2019 Nov 15 TA - The Journal of Rheumatology PG - jrheum.190684 4099 - http://www.jrheum.org/content/early/2019/11/08/jrheum.190684.short 4100 - http://www.jrheum.org/content/early/2019/11/08/jrheum.190684.full AB - Objective Apolipoprotein L1 gene (APOL1) G1 and G2 renal-risk alleles (RRAs) are associated with end-stage renal disease (ESRD) in blacks with lupus nephritis (LN). The present study determined frequencies of APOL1 RRAs in non-white Brazilian patients with LN and controls to assess association with renal outcomes. Methods APOL1 RRAs were genotyped in 222 healthy blood donors (controls) and 201 cases with LN from three outpatient clinics. Two single nucleotide polymorphisms in the G1 (rs73885319; rs60910145) and an indel for the G2 (rs71785313) variant were genotyped. Results The frequency of APOL1 RRAs in non-white Brazilian LN cases did not differ significantly from healthy controls, few participants had 2 RRAs. In the sample, 84.6% of LN cases and 82.9% of controls had 0 RRAs, 13.4% and 15.3% had 1 RRA, and 2.0% and 0.4% had 2 RRAs, respectively. LN cases with &gt;1 APOL1 RRAs had similar baseline characteristics and renal responses to treatment, yet faced higher risk for progressive chronic kidney disease (CKD) to an eGFR &lt;30 ml/min/1.732 compared to those with 0 RRAs (11.1% with 0, 29.6% with 1; 50% with 2 RRAs, p=0.005). Although glomerular lesions and activity scores on initial kidney biopsy did not differ significantly between individuals based on APOL1 genotype, chronicity scores, tubular atrophy and interstitial fibrosis were more severe in those with &gt;1 RRA. Conclusion Although initial kidney lesions and treatment responses were similar, a single APOL1 RRA in non-white Brazilians with LN was associated with increased risk of advanced CKD and possibly more tubulo-interstitial damage.