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Patterns of Kidney Function Decline Associated with APOL1 Genotypes: Results from AASK
Adrienne Tin1,2, Morgan E Grams3, Michelle Estrella3
1Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
Summary
Patients with chronic kidney disease (CKD) and high-risk APOL1 genotypes are more likely to experience a steady decline in estimated glomerular filtration rate (eGFR). This suggests a persistent pathophysiologic process linked to APOL1 risk status in CKD progression.
Area of Science:
- Nephrology
- Genetics
- Chronic Kidney Disease Research
Background:
- Kidney function decline (eGFR) varies significantly among patients with chronic kidney disease (CKD).
- Identifying factors influencing eGFR trajectories is crucial for understanding CKD progression.
- APOL1 gene variants are associated with increased risk for CKD, particularly in individuals of African ancestry.
Purpose of the Study:
- To investigate if estimated glomerular filtration rate (eGFR) trajectory patterns differ based on APOL1 risk genotype.
- To determine the association between APOL1 high-risk status and specific patterns of eGFR decline in a longitudinal cohort.
Main Methods:
- A longitudinal observational study involving 622 participants from the African American Study of Kidney Disease and Hypertension.
- APOL1 genotyping was performed to classify participants into high-risk (two risk alleles) and low-risk (zero or one risk allele) groups.
- eGFR trajectories were estimated over a median follow-up of 9 years, categorizing them into steady decline, unsteady decline, steady stable, and unsteady stable patterns.
Main Results:
- Over 9 years, approximately 24.0% showed steady eGFR decline, 25.9% unsteady decline, 25.6% steady stable, and 24.6% unsteady stable.
- Participants with steady decline had lower baseline eGFR and higher urine protein-to-creatinine ratio.
- APOL1 high-risk individuals had significantly higher odds of experiencing a steady eGFR decline pattern compared to low-risk individuals, even after adjustments (adjusted OR, 1.59).
Conclusions:
- Among patients with hypertension-attributed CKD, high-risk APOL1 genotype is associated with a greater likelihood of steady eGFR decline.
- These findings suggest that APOL1 risk variants may drive a persistent pathophysiologic process contributing to CKD progression.
- Understanding the role of APOL1 in eGFR trajectories can inform personalized risk stratification and management strategies for CKD.