Related Experiment Video
Updated: Apr 30, 2026
Use of Ultra-high Field MRI in Small Rodent Models of Polycystic Kidney Disease for In Vivo Phenotyping and Drug Monitoring
Published on: June 23, 2015
APOL1 risk variants, race, and progression of chronic kidney disease
Afshin Parsa1, W H Linda Kao, Dawei Xie
1The authors' affiliations are listed in the Appendix.
Insights
High-risk APOL1 gene variants increase the risk of chronic kidney disease progression and end-stage renal disease in black patients. These APOL1 variants are associated with worse kidney outcomes compared to white patients, irrespective of diabetes.
Area of Science:
- Nephrology
- Genetics
- Epidemiology
Background:
- Black patients face a higher risk of end-stage renal disease (ESRD) compared to white patients in the U.S.
- Chronic kidney disease (CKD) progression varies significantly across racial groups.
Purpose of the Study:
- To investigate the impact of apolipoprotein L1 (APOL1) gene variants on CKD progression.
- To determine if APOL1 risk variants explain the disparity in CKD outcomes between black and white patients.
Main Methods:
- Two cohorts, the African American Study of Kidney Disease and Hypertension (AASK) and the Chronic Renal Insufficiency Cohort (CRIC) study, were analyzed.
- Patients were categorized into APOL1 high-risk (2 copies) and low-risk (0-1 copy) groups.
- Primary outcomes included ESRD, doubling of serum creatinine, and estimated glomerular filtration rate (eGFR) decline.
Main Results:
- In AASK, APOL1 high-risk patients had a significantly higher rate of the primary outcome (58.1% vs. 36.6%).
- In CRIC, black patients with APOL1 high-risk variants showed a faster eGFR decline and increased risk of renal outcomes compared to white patients.
- These associations persisted in both diabetic and non-diabetic participants.
Conclusions:
- APOL1 renal risk variants are linked to increased rates of ESRD and CKD progression in black patients.
- The findings suggest APOL1 genotype contributes to observed racial disparities in kidney disease.
- APOL1's role in CKD progression is independent of diabetes status.
Background:
Among patients in the United States with chronic kidney disease, black patients are at increased risk for end-stage renal disease, as compared with white patients.
Methods:
In two studies, we examined the effects of variants in the gene encoding apolipoprotein L1 (APOL1) on the progression of chronic kidney disease. In the African American Study of Kidney Disease and Hypertension (AASK), we evaluated 693 black patients with chronic kidney disease attributed to hypertension. In the Chronic Renal Insufficiency Cohort (CRIC) study, we evaluated 2955 white patients and black patients with chronic kidney disease (46% of whom had diabetes) according to whether they had 2 copies of high-risk APOL1 variants (APOL1 high-risk group) or 0 or 1 copy (APOL1 low-risk group). In the AASK study, the primary outcome was a composite of end-stage renal disease or a doubling of the serum creatinine level. In the CRIC study, the primary outcomes were the slope in the estimated glomerular filtration rate (eGFR) and the composite of end-stage renal disease or a reduction of 50% in the eGFR from baseline.
Results:
In the AASK study, the primary outcome occurred in 58.1% of the patients in the APOL1 high-risk group and in 36.6% of those in the APOL1 low-risk group (hazard ratio in the high-risk group, 1.88; P<0.001). There was no interaction between APOL1 status and trial interventions or the presence of baseline proteinuria. In the CRIC study, black patients in the APOL1 high-risk group had a more rapid decline in the eGFR and a higher risk of the composite renal outcome than did white patients, among those with diabetes and those without diabetes (P<0.001 for all comparisons).
Conclusions:
Renal risk variants in APOL1 were associated with the higher rates of end-stage renal disease and progression of chronic kidney disease that were observed in black patients as compared with white patients, regardless of diabetes status. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others.).
Related Concept Videos
01:29Pharmacogenetic Phenotypes: Alterations in Pharmacokinetics, Drug Targets and Biologic Milieu
01:30Acute Kidney Injury IV: Diagnostic Studies and Prevention
01:25Chronic Kidney Disease I: Introduction
01:24Chronic Kidney Disease II: Clinical Manifestations
01:28Chronic Kidney Disease III: Interprofessional Care
01:28Diabetic Nephropathy