Abstract: FR-PO106
Apolipoprotein L1 Is Associated with Larger HDL Particles in CKD
Session Information
- Molecular Mechanisms of CKD - II
October 26, 2018 | Location: Exhibit Hall, San Diego Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: CKD (Non-Dialysis)
- 1903 CKD (Non-Dialysis): Mechanisms
Authors
- Hoofnagle, Andrew N., University of Washington, Seattle, Washington, United States
- Andrews, Michael L., Centers for Disease Control and Prevention, Atlanta, Georgia, United States
- Kuklenyik, Zsuzsanna, Centers for Disease Control and Prevention, Atlanta, Georgia, United States
- de Boer, Ian H., University of Washington, Seattle, Washington, United States
- Kestenbaum, Bryan R., University of Washington, Seattle, Washington, United States
Background
Apolipoprotein L1 (ApoL1) is a potential mediator of inflammatory kidney injury and disease progression. Two polymorphisms in the APOL1 gene (G1 and G2) increase the risk of chronic kidney disease (CKD) in Blacks. The mechanism of injury may involve ApoL1 expressed within the kidney (e.g., in podocytes) and/or ApoL1 secreted by the liver (i.e., in plasma). We have previously demonstrated that ApoL1 is depleted from the HDL2/3 fraction of plasma in patients with lower eGFR. In this study, we aimed to quantify the distribution of ApoL1 within plasma to help clarify the biochemistry of ApoL1.
Methods
We determined ApoL1 phenotype and plasma concentrations using targeted mass spectrometry (MS) among 424 participants from the Seattle Kidney Study, a racially diverse, well-characterized cohort of patients with CKD. For 20 participants, we used asymmetric flow field-flow fractionation (AF4) to fractionate plasma into 40 fractions, which were each analyzed using MS to determine relative concentrations of ApoL1.
Results
Plasma concentration of ApoL1 was associated with age, race, and ApoL1 phenotype (Table 1). In addition, both plasma concentration of ApoL1 and the ratio of the amount of ApoL1 in HDL to total plasma ApoL1 were directly correlated with eGFR. However, only the ratio of ApoL1 in HDL to total ApoL1 was significantly associated with eGFR, after controlling for age, race, and phenotype, which suggested that ApoL1 is located in a different fraction of plasma in CKD. We then used AF4 and MS to determine that ApoL1 is associated with larger particles (similar to HDL1 particles containing ApoE) in participants with lower eGFR, after controlling for race and genotype (p<0.01).
Conclusion
These results demonstrate that plasma ApoL1 is biochemically different in patients with reduced eGFR, which may be related to the role ApoL1 plays in the progression of CKD.
| Total ApoL1 in plasma | Ratio of ApoL1 in HDL to total plasma ApoL1 | |||
| Independent variable | % Change | p-value | % Change | p-value |
| Age (per year) | 0.57% lower | <0.001 | 0.12% higher | 0.73 |
| Race (Black) 1 | 40% higher | <0.001 | 63% lower | <0.001 |
| 1 ApoL1 risk allele 1 | 34% higher | <0.001 | 66% lower | <0.001 |
| 2 ApoL1 risk alleles 1 | 15% higher | 0.045 | 66% lower | <0.001 |
| eGFR (per loss of 10 ml/min/1.73m2 ) | 1.7% lower | 0.024 | 11% lower | <0.001 |
| eGFR (per loss of 10 ml/min/1.73m2 ) 2 | <0.01% lower | 0.89 | 12% lower | <0.001 |
1White or G0/G0 individuals as comparator. 2Model with age, race, number of risk alleles, and eGFR included.
Funding
- NIDDK Support