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Apolipoprotein L1 (APOL1) Coding Variants Are Associated With Creatinine Rise After Cardiac Surgery
Jamie R Privratsky1, Yi-Ju Li2, Carol Haynes3
1Department of Anesthesiology, Duke University Medical Center, Durham, NC.
Insights
African Americans undergoing cardiac surgery have a higher risk of acute kidney injury (AKI). Homozygous apolipoprotein L1 (APOL1) risk variants are linked to increased postoperative creatinine rise, suggesting they are independent AKI risk factors.
Area of Science:
- Nephrology
- Cardiovascular Surgery
- Genetics
Background:
- Acute kidney injury (AKI) is a significant complication following cardiac surgery, disproportionately affecting African Americans.
- While apolipoprotein L1 (APOL1) risk variants are known contributors to chronic kidney disease, their role in AKI post-cardiac surgery remains unclear.
Purpose of the Study:
- To investigate the association between homozygous APOL1 risk allele status and the incidence of AKI in African American patients after cardiac surgery.
- To determine if APOL1 coding variants are independent risk factors for AKI in this population.
Main Methods:
- Retrospective analysis of a single-center university hospital cohort.
- Genotyping of APOL1 alleles in African American patients from the CATHeterization GENetics study who underwent cardiac surgery with cardiopulmonary bypass.
- Assessment of AKI using peak serum creatinine rise (%ΔCr) and Kidney Disease: Improving Global Outcomes (KDIGO) criteria.
Main Results:
- The study included 125 African American patients (12 homozygous for APOL1 risk alleles, 113 controls).
- Patients with homozygous APOL1 risk alleles exhibited a significantly higher peak postoperative creatinine rise (%ΔCr 69.1% vs 29.6%; p=0.005 univariate, %ΔCr 88.5% vs 43.7%; p=0.006 multivariate).
- A trend towards KDIGO AKI development was observed in the APOL1 risk group, though not statistically significant.
Conclusions:
- Homozygous APOL1 chronic kidney disease risk variants are associated with a more than 2-fold increase in postoperative creatinine rise in African American cardiac surgery patients.
- These findings suggest that APOL1 risk alleles are independent risk factors for AKI following cardiac surgery.
Objective:
Acute kidney injury (AKI) is a complication of cardiac surgery that is considerably more common in African Americans (1.5-fold). Although homozygous status for apolipoprotein L1 (APOL1) risk alleles is associated with chronic kidney disease in individuals of African ancestry, whether these coding variants confer AKI risk is unknown. The present study examined whether APOL1 homozygous risk allele status was associated with AKI in African Americans after cardiac surgery.
Design:
Retrospective analysis of a cohort.
Setting:
Single-center university hospital.
Participants:
African American patients from the CATHeterization GENetics study cohort who underwent cardiac surgery with cardiopulmonary bypass.
Interventions:
Genotyping of APOL1 alleles.
Measurements And Main Results:
Data from 125 African American patients included 12 APOL1 risk (ie, homozygous for risk alleles) patients and 113 APOL1 control (ie, wildtype or heterozygous for risk alleles) patients. The primary outcome to reflect AKI was peak serum creatinine rise after surgery relative to the preoperative creatinine (%ΔCr). The secondary outcome was Kidney Disease: Improving Global Outcomes (KDIGO) AKI criteria. In the primary analysis, peak creatinine rise was higher in risk compared with control patients in both univariate (%ΔCr 69.1 v 29.6%; p = 0.005) and multivariate regression (%ΔCr 88.5 v 43.7%; p = 0.006) analyses. For the secondary outcome, a trend toward KDIGO AKI development was noted in APOL1 risk patients, but this was not statistically significant.
Conclusions:
African American cardiac surgery patients homozygous for APOL1 chronic kidney disease risk variants averaged a more than 2-fold higher postoperative creatinine rise even after adjustment for other risk factors, suggesting these alleles also are independent risk factors for AKI.
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