APOL1Risk Alleles are Associated with More Severe Arteriosclerosis in Renal Resistance Vessels with Aging and Hypertension.
The increased risk of end-stage kidney disease (ESKD) among hypertensive African Americans is partly related toAPOL1allele variants. Hypertension-associated arterionephrosclerosis consists of arteriosclerosis, glomerulosclerosis, and cortical fibrosis. The initial glomerulosclerosis, attributed to preglomerular arteriosclerosis and ischemia, consists of focal global glomerulosclerosis (FGGS), but in biopsy studies, focal segmental glomerulosclerosis (FSGS) is found with progression to ESKD, particularly in African Americans. This is a study of arterionephrosclerosis in successfullyAPOL1genotyped autopsy kidney tissue of 159 African Americans (61 no risk alleles, 68 one risk allele, 30 two risk alleles) and 135 whites aged 18-89 years from a general population with no clinical renal disease. Glomerulosclerosis was nearly exclusively FGGS with only three subjects having FSGS-like lesions that were unrelated toAPOL1risk status. For both races, in multivariable analysis, the dependent variables of arteriosclerosis, glomerulosclerosis, and cortical fibrosis were all significantly related to the independent variables of older age (P < 0.001) and hypertension (P < 0.001). A relationship betweenAPOL1genotype and arteriosclerosis was apparent only after 35 years of age when, for any level of elevated blood pressure, more severe arteriosclerosis was found in the interlobular arteries of 14 subjects with twoAPOL1risk alleles when compared to African Americans with none (n = 37, P = 0.02) or one risk alleles (n = 35, P = 0.02). With the limitation of the small number of subjects contributing to the positive results, the findings imply thatAPOL1risk alleles recessively augment small vessel arteriosclerosis in conjunction with age and hypertension. FSGS was not a significant finding, indicating that in the early stages of arterionephrosclerosis, the primary pathologic influence ofAPOL1genotype is vascular rather than glomerular.
Department of Pathology, University of Mississippi Medical Center, Jackson, Mississippi.
Michael D
MD
Hughson
Centre for Chronic Disease, The University of Queensland, Brisbane, Queensland, Australia.
Wendy E
WE
Hoy
Centre for Chronic Disease, The University of Queensland, Brisbane, Queensland, Australia.
Susan A
SA
Mott
Cardiovascular Program Biomedicine Discovery Institute and Department of Anatomy and Developmental Biology, School of Biomedical Sciences, Monash University, Melbourne, Victoria, Australia.
Victor G
VG
Puelles
Cardiovascular Program Biomedicine Discovery Institute and Department of Anatomy and Developmental Biology, School of Biomedical Sciences, Monash University, Melbourne, Victoria, Australia.
John F
JF
Bertram
Basic Research Laboratory, Center for Cancer Research, National Cancer Institute, Lidos Biomedical Inc., Frederick National Laboratory, Frederick, Maryland.
Cheryl L
CL
Winkler
Kidney Disease Section, National Institute of Diabetes and Digestive and Kidney Disease, National Institutes of Health, Bethesda, Maryland.
Jeffrey B
JB
Kopp