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Published on: June 8, 2022
Effect of a Single Apolipoprotein L1 Gene Nephropathy Variant on the Risk of Advanced Lupus Nephritis in Brazilians
Gisele Vajgel1,2, Suelen Cristina Lima3,4, Diego Jeronimo S Santana3,4
1From the Division of Nephrology, Hospital das Clinicas, Federal University of Pernambuco (UFPE); Molecular Biology Laboratory, Keizo Asami Immunopathology Laboratory (LIKA), UFPE; Division of Nephrology, Instituto de Medicina Integral Prof. Fernando Figueira (IMIP), Recife, Pernambuco, Brazil; Division of Public Health Sciences, Department of Biostatistical Sciences, and Center for Diabetes Research, and Department of Internal Medicine, Section on Nephrology, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA; Division of Nephrology, Department of Medicine, Federal University of São Paulo (UNIFESP), São Paulo, Brazil. giselevajgel@hotmail.com.
Objective:
Apolipoprotein L1 gene (APOL1) G1 and G2 renal risk alleles (RRA) are associated with endstage renal disease in blacks with lupus nephritis (LN). The present study determined frequencies of APOL1 RRA in nonwhite Brazilian patients with LN and controls to assess association with renal outcomes.
Methods:
APOL1 RRA were genotyped in 222 healthy blood donors (controls) and 201 cases with LN from 3 outpatient clinics. Two single-nucleotide polymorphisms in the G1 (rs73885319 and rs60910145) and an indel for the G2 (rs71785313) variant were genotyped.
Results:
The frequency of APOL1 RRA in nonwhite Brazilian LN cases did not differ significantly from healthy controls, and few participants had 2 RRA. In the sample, 84.6% of LN cases and 84.2% of controls had 0 RRA, 13.4% and 15.3% had 1 RRA, and 2.0% and 0.4% had 2 RRA, respectively. LN cases with ≥ 1 APOL1 RRA had similar baseline characteristics and renal responses to treatment, yet faced higher risk for progressive chronic kidney disease (CKD) to an estimated glomerular filtration rate < 30 ml/min/1.73 m2 compared to those with 0 RRA (11.2% with 0, 29.6% with 1; 50% with 2 RRA, 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 ≥ 1 RRA (p = 0.011, p = 0.002, p = 0.018, respectively).
Conclusion:
Although initial kidney lesions and treatment responses were similar, a single APOL1 RRA in nonwhite Brazilians with LN was associated with increased risk of advanced CKD and possibly more tubulointerstitial damage.
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