title: Patterns of Kidney Function Decline Associated with APOL1 Genotypes: Results from AASK.
abstract: 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.
  
  
  
  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.
  
  
  
  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).
  
  
  
  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.
authors.affiliation: 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.
authors.forename: Adrienne
authors.initials: A
authors.lastname: Tin
authors.affiliation: Division of Nephrology, Johns Hopkins School of Medicine, Baltimore, Maryland.
authors.forename: Morgan E
authors.initials: ME
authors.lastname: Grams
authors.affiliation: Division of Nephrology, Johns Hopkins School of Medicine, Baltimore, Maryland.
authors.forename: Michelle
authors.initials: M
authors.lastname: Estrella
authors.affiliation: Division of Nephrology and Hypertension, Department of Medicine, Georgetown University Medical Center, Washington, DC.
authors.forename: Michael
authors.initials: M
authors.lastname: Lipkowitz
authors.affiliation: Division of Biostatistics, University of Utah, Salt Lake City, Utah; and.
authors.forename: Tom H
authors.initials: TH
authors.lastname: Greene
authors.affiliation: Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
authors.forename: Wen Hong Linda
authors.initials: WHL
authors.lastname: Kao
authors.affiliation: Department of Biostatistics, University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Liang
authors.initials: L
authors.lastname: Li
authors.affiliation: 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.
authors.forename: Lawrence J
authors.initials: LJ
authors.lastname: Appel
mesh_terms: D000328:Adult; D001741:Black or African American; D000368:Aged; D000483:Alleles; D000075944:Apolipoprotein L1 / Q000235:genetics*; D003404:Creatinine / Q000652:urine; D018450:Disease Progression; D005260:Female; D005838:Genotype; D005919:Glomerular Filtration Rate / Q000235:genetics*; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011507:Proteinuria / Q000209:etiology / Q000652:urine; D051436:Renal Insufficiency, Chronic / Q000235:genetics* / Q000503:physiopathology*; D012307:Risk Factors
chemical_list: C108666:APOL1 protein, human; D000075944:Apolipoprotein L1; D003404:Creatinine
keywords: AASK (African American Study of Kidney Disease and Hypertension); African Americans; Alleles; Epidemiology and outcomes; Follow-Up Studies; Genotype; Humans; Kidney Diseases; chronic kidney disease; genetic renal disease; glomerular filtration rate; hypertension