Adrienne Tin1, Morgan E Grams2, Michelle Estrella2, Michael Lipkowitz3, Tom H Greene4, Wen Hong Linda Kao5, Liang Li6, Lawrence J Appel7. 1. Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland; Welch Center for Prevention, Epidemiology and Clinical Research, Johns Hopkins Medical Institutions, Baltimore, Maryland; atin1@jhu.edu. 2. Division of Nephrology, Johns Hopkins School of Medicine, Baltimore, Maryland; 3. Division of Nephrology and Hypertension, Department of Medicine, Georgetown University Medical Center, Washington, DC; 4. Division of Biostatistics, University of Utah, Salt Lake City, Utah; and. 5. Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland; 6. Department of Biostatistics, University of Texas MD Anderson Cancer Center, Houston, Texas. 7. Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland; Welch Center for Prevention, Epidemiology and Clinical Research, Johns Hopkins Medical Institutions, Baltimore, Maryland;
Abstract
BACKGROUND AND OBJECTIVES: Trajectories of eGFR in patients with CKD are highly variable. Only a subset of patients with CKD experiences a steady decline in eGFR. The objective of our study was to investigate whether eGFR trajectory patterns differ by APOL1 risk status. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Our study was a longitudinal observational study of 622 participants in the African American Study of Kidney Disease and Hypertension with APOL1 genotyping and sufficient follow-up for estimating GFR trajectories. The predictor was APOL1 high-risk status (having two copies of the G1 or G2 risk alleles) versus low-risk status (zero or one copy of the risk alleles), and the outcome was four eGFR trajectory patterns on the basis of the joint probabilities of linearity and progression: steady decline, unsteady decline, steady stable, and unsteady stable. RESULTS: Over a median follow-up of 9 years, 24.0% of participants experienced steady eGFR decline, 25.9% had an unsteady decline, 25.6% were steady and stable, and 24.6% were unsteady but stable. Those experiencing steady decline had lower eGFR and higher urine protein-to-creatinine ratio at baseline than participants with the other eGFR trajectory patterns. The APOL1 high-risk group was associated with a greater odds for the steady decline pattern than the APOL1 low-risk group (unadjusted odds ratio, 2.45; 95% confidence interval, 1.62 to 3.69). This association remained significant after adjusting for demographic factors, baseline eGFR, urine protein-to-creatinine ratio, treatment assignment, and follow-up time (adjusted odds ratio, 1.59; 95% confidence interval, 1.00 to 2.52). CONCLUSIONS: Among patients with CKD attributed to hypertension, those with the APOL1 high-risk genotype were more likely to experience a steady decline trajectory in eGFR than those without the APOL1 high-risk genotype. These findings suggest a persistent underlying pathophysiologic process in those patients with the APOL1 high-risk genotype.
BACKGROUND AND OBJECTIVES: Trajectories of eGFR in patients with CKD are highly variable. Only a subset of patients with CKD experiences a steady decline in eGFR. The objective of our study was to investigate whether eGFR trajectory patterns differ by APOL1 risk status. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Our study was a longitudinal observational study of 622 participants in the African American Study of Kidney Disease and Hypertension with APOL1 genotyping and sufficient follow-up for estimating GFR trajectories. The predictor was APOL1 high-risk status (having two copies of the G1 or G2 risk alleles) versus low-risk status (zero or one copy of the risk alleles), and the outcome was four eGFR trajectory patterns on the basis of the joint probabilities of linearity and progression: steady decline, unsteady decline, steady stable, and unsteady stable. RESULTS: Over a median follow-up of 9 years, 24.0% of participants experienced steady eGFR decline, 25.9% had an unsteady decline, 25.6% were steady and stable, and 24.6% were unsteady but stable. Those experiencing steady decline had lower eGFR and higher urine protein-to-creatinine ratio at baseline than participants with the other eGFR trajectory patterns. The APOL1 high-risk group was associated with a greater odds for the steady decline pattern than the APOL1 low-risk group (unadjusted odds ratio, 2.45; 95% confidence interval, 1.62 to 3.69). This association remained significant after adjusting for demographic factors, baseline eGFR, urine protein-to-creatinine ratio, treatment assignment, and follow-up time (adjusted odds ratio, 1.59; 95% confidence interval, 1.00 to 2.52). CONCLUSIONS: Among patients with CKD attributed to hypertension, those with the APOL1 high-risk genotype were more likely to experience a steady decline trajectory in eGFR than those without the APOL1 high-risk genotype. These findings suggest a persistent underlying pathophysiologic process in those patients with the APOL1 high-risk genotype.
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