title: APOL1 risk variants, race, and progression of chronic kidney disease.
abstract: BACKGROUND
  Among patients in the United States with chronic kidney disease, black patients are at increased risk for end-stage renal disease, as compared with white patients.
  
  
  METHODS
  In two studies, we examined the effects of variants in the gene encoding apolipoprotein L1 (APOL1) on the progression of chronic kidney disease. In the African American Study of Kidney Disease and Hypertension (AASK), we evaluated 693 black patients with chronic kidney disease attributed to hypertension. In the Chronic Renal Insufficiency Cohort (CRIC) study, we evaluated 2955 white patients and black patients with chronic kidney disease (46% of whom had diabetes) according to whether they had 2 copies of high-risk APOL1 variants (APOL1 high-risk group) or 0 or 1 copy (APOL1 low-risk group). In the AASK study, the primary outcome was a composite of end-stage renal disease or a doubling of the serum creatinine level. In the CRIC study, the primary outcomes were the slope in the estimated glomerular filtration rate (eGFR) and the composite of end-stage renal disease or a reduction of 50% in the eGFR from baseline.
  
  
  RESULTS
  In the AASK study, the primary outcome occurred in 58.1% of the patients in the APOL1 high-risk group and in 36.6% of those in the APOL1 low-risk group (hazard ratio in the high-risk group, 1.88; P<0.001). There was no interaction between APOL1 status and trial interventions or the presence of baseline proteinuria. In the CRIC study, black patients in the APOL1 high-risk group had a more rapid decline in the eGFR and a higher risk of the composite renal outcome than did white patients, among those with diabetes and those without diabetes (P<0.001 for all comparisons).
  
  
  CONCLUSIONS
  Renal risk variants in APOL1 were associated with the higher rates of end-stage renal disease and progression of chronic kidney disease that were observed in black patients as compared with white patients, regardless of diabetes status. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others.).
authors.affiliation: The authors' affiliations are listed in the Appendix.
authors.forename: Afshin
authors.initials: A
authors.lastname: Parsa
authors.forename: W H Linda
authors.initials: WH
authors.lastname: Kao
authors.forename: Dawei
authors.initials: D
authors.lastname: Xie
authors.forename: Brad C
authors.initials: BC
authors.lastname: Astor
authors.forename: Man
authors.initials: M
authors.lastname: Li
authors.forename: Chi-yuan
authors.initials: CY
authors.lastname: Hsu
authors.forename: Harold I
authors.initials: HI
authors.lastname: Feldman
authors.forename: Rulan S
authors.initials: RS
authors.lastname: Parekh
authors.forename: John W
authors.initials: JW
authors.lastname: Kusek
authors.forename: Tom H
authors.initials: TH
authors.lastname: Greene
authors.forename: Jeffrey C
authors.initials: JC
authors.lastname: Fink
authors.forename: Amanda H
authors.initials: AH
authors.lastname: Anderson
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Choi
authors.forename: Jackson T
authors.initials: JT
authors.lastname: Wright
authors.forename: James P
authors.initials: JP
authors.lastname: Lash
authors.forename: Barry I
authors.initials: BI
authors.lastname: Freedman
authors.forename: Akinlolu
authors.initials: A
authors.lastname: Ojo
authors.forename: Cheryl A
authors.initials: CA
authors.lastname: Winkler
authors.forename: Dominic S
authors.initials: DS
authors.lastname: Raj
authors.forename: Jeffrey B
authors.initials: JB
authors.lastname: Kopp
authors.forename: Jiang
authors.initials: J
authors.lastname: He
authors.forename: Nancy G
authors.initials: NG
authors.lastname: Jensvold
authors.forename: Kaixiang
authors.initials: K
authors.lastname: Tao
authors.forename: Michael S
authors.initials: MS
authors.lastname: Lipkowitz
authors.forename: Lawrence J
authors.initials: LJ
authors.lastname: Appel
mesh_terms: D000328:Adult; D001741:Black or African American / Q000235:genetics*; D000368:Aged; D000075944:Apolipoprotein L1; D001053:Apolipoproteins / Q000235:genetics*; D003404:Creatinine / Q000097:blood; D048909:Diabetes Complications / Q000235:genetics; D018450:Disease Progression; D005260:Female; D020022:Genetic Predisposition to Disease; D005919:Glomerular Filtration Rate; D006801:Humans; D006973:Hypertension / Q000150:complications; D007676:Kidney Failure, Chronic / Q000208:ethnology / Q000235:genetics; D008075:Lipoproteins, HDL / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D020641:Polymorphism, Single Nucleotide; D011507:Proteinuria; D051436:Renal Insufficiency, Chronic / Q000208:ethnology* / Q000235:genetics*; D044465:White People / Q000235:genetics
chemical_list: C108666:APOL1 protein, human; D000075944:Apolipoprotein L1; D001053:Apolipoproteins; D008075:Lipoproteins, HDL; D003404:Creatinine