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PubMed ID:
36479469
Public Release Type:
Journal
Publication Year: 2022
Affiliation: 1. University of Southern California Viterbi School of Engineering, Daniel J. Epstein Department of Industrial and Systems Engineering, Los Angeles, CA
2. Leonard D. Schaeffer Center for Health Policy & Economics, University of Southern California, Los Angeles, CA
2. University of Southern California Keck School of Medicine, Department of Medicine, Los Angeles, CA
DOI:
https://doi.org/10.1016/j.xkme.2022.100563
Authors:
Nguyen A,
Suen S,
Lin E
Request IDs:
22088
,
22550
Studies:
African American Study of Kidney Disease and Hypertension Cohort Study
,
African American Study of Kidney Disease and Hypertension Study (Clinical Trial)
,
Chronic Renal Insufficiency Cohort Study
Rationale and Objective Patients with a high-risk Apolipoprotein L1 (APOL1) genotype are more likely to develop chronic kidney disease and end-state kidney disease (ESKD). However, it is unclear whether this increased risk is entirely due to the eventual development of proteinuria. Study Design Retrospective observational study of the AASK and CRIC cohorts. Exposures and Predictors Self-identified race (Black/non-Black) and presence of high-risk APOL1 genotype. The primary model was adjusted for age, gender, estimated glomerular filtration rate, and urine protein to creatinine ratio. Outcomes Time to ESKD defined as years to dialysis or transplantation. Analytical Approach We used Cox proportional hazard models to study how proteinuria mediates the association between APOL1 and ESKD. We modeled proteinuria at baseline and as a time varying covariate. Results A high-risk APOL1 genotype was associated with a significantly higher risk of ESKD, even for patients with minimal proteinuria (HR: 1.87; 95% CI [1.23. 2.84]). The association was not significant among patients with high proteinuria (HR: 1.22, 95% CI [0.93, 1.61]). When modeling proteinuria as a time varying covariate, a high-risk APOL1 genotype was associated with higher ESKD risk even among patients who never developed proteinuria (HR: 2.04, 95% CI: [1.10, 3.77]). Compared to non-Black patients, Black patients without the high-risk genotype did not have higher risk of ESKD (HR: 0.96, 95% CI: [0.85, 1.10]). Limitations Two datasets were combined to increase statistical power. Limited generalizability beyond the study cohorts. Residual confounding common to observational studies. Conclusions A high-risk APOL1 genotype is significantly associated with increased ESKD risk, especially among patients without baseline proteinuria. Although our results suggest that the risk is partially mediated through proteinuria, higher ESKD risk was present even among patients who never developed proteinuria. Providers should consider screening for the high-risk APOL1 genotype, especially among Black patients without proteinuria in populations with CKD.
