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Kidney Disease Progression in Membranous Nephropathy among Black Participants with High-Risk APOL1 Genotype
Dhruti P Chen1, Candace D Henderson1, Jaeline Anguiano1
1UNC Kidney Center, Department of Medicine, University of North Carolina, Chapel Hill, North Carolina.
Insights
High-risk apolipoprotein L1 (APOL1) gene variants in Black individuals with membranous nephropathy are linked to faster kidney function decline and quicker progression to kidney failure. This finding highlights APOL1
Area of Science:
- Nephrology
- Genetics
- Chronic Kidney Disease Research
Background:
- Disparities in chronic kidney disease (CKD) progression persist among Black individuals.
- Genetic variants in the apolipoprotein L1 (APOL1) gene are implicated in kidney disease in the Black population.
- The specific influence of APOL1 variants in membranous nephropathy (MN) has remained unclear.
Purpose of the Study:
- To investigate the association between APOL1 gene variants and the progression of membranous nephropathy.
- To compare kidney disease progression rates in Black individuals with high-risk versus low-risk APOL1 genotypes and non-Black individuals with MN.
Main Methods:
- Analysis of longitudinally followed participants with available APOL1 genotyping data.
- Estimation of estimated glomerular filtration rate (eGFR) slopes using linear mixed-effects models.
- Comparison of groups using Fisher exact test, Kruskal-Wallis test, and Kaplan-Meier curves.
Main Results:
- Among Black participants with MN, 14% had a high-risk APOL1 genotype.
- Participants with high-risk APOL1 genotype showed a steeper eGFR decline (-16 ml/min/1.73 m²/year) compared to low-risk (-4 ml/min/1.73 m²/year) and non-Black participants (-2.0 ml/min/1.73 m²/year).
- High-risk APOL1 genotype was associated with younger age at onset and faster progression to kidney failure.
Conclusions:
- The prevalence of high-risk APOL1 variants in Black individuals with MN is similar to the general Black population.
- High-risk APOL1 genotype significantly accelerates eGFR decline and time to kidney failure in MN.
- APOL1 genotype is a critical factor influencing CKD progression in Black patients with membranous nephropathy.
Background:
Disparity in CKD progression among Black individuals persists in glomerular diseases. Genetic variants in the apolipoprotein L1 ( APOL1 ) gene in the Black population contribute to kidney disease, but the influence in membranous nephropathy remains unknown.
Methods:
Longitudinally followed participants enrolled in the Glomerular Disease Collaborative Network or Cure Glomerulonephropathy Network were included if they had DNA or genotyping available for APOL1 (Black participants with membranous nephropathy) or had membranous nephropathy but were not Black. eGFR slopes were estimated using linear mixed-effects models with random effects and adjusting for covariates and interaction terms of covariates. Fisher exact test, Kruskal-Wallis test, and Kaplan-Meier curves with log-rank tests were used to compare groups.
Results:
Among 118 Black membranous nephropathy participants, 16 (14%) had high-risk APOL1 genotype (two risk alleles) and 102 (86%) had low-risk APOL1 genotype (zero or one risk alleles, n =53 and n =49, respectively). High-risk APOL1 membranous nephropathy participants were notably younger at disease onset than low-risk APOL1 and membranous nephropathy participants that were not Black ( n =572). eGFR at disease onset was not different between groups, although eGFR decline (slope) was steeper in participants with high-risk APOL1 genotype (-16±2 [±SE] ml/min per 1.73 m 2 per year) compared with low-risk APOL1 genotype (-4±0.8 ml/min per 1.73 m 2 per year) or membranous nephropathy participants that did not identify themselves as Black (-2.0±0.4 ml/min per 1.73 m 2 per year) ( P <0.0001). Time to kidney failure was faster in the high-risk APOL1 genotype than low-risk APOL1 genotype or membranous nephropathy participants that were not Black.
Conclusions:
The prevalence of high-risk APOL1 variant among Black membranous nephropathy participants is comparable with the general Black population (10%-15%), yet the high-risk genotype was associated with worse eGFR decline and faster time to kidney failure compared with low-risk genotype and participants that were not Black.
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