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J Am Soc Nephrol. 2015 Jun;26(6):1443-8. doi: 10.1681/ASN.2013111242. Epub 2015 Jan 8.

Clinical Features and Histology of Apolipoprotein L1-Associated Nephropathy in the FSGS Clinical Trial.

Author information

1
Kidney Disease Section, jbkopp@nih.gov.
2
Basic Research Laboratory, Center for Cancer Research, National Cancer Institute, Leidos Biomedical Research, Inc., Frederick National Laboratory, Frederick, Maryland;
3
Biostatistics Core, and.
4
Department of Quantitative Heath Sciences, Cleveland Clinic, Cleveland, Ohio;
5
Department of Pathology, Columbia University Medical Center, New York, New York;
6
Department of Pathology, Cedars-Sinai Medical Center, Los Angeles, California;
7
Department of Medicine, Rush University Medical Center, Chicago, Illinois;
8
Center for Translational Science, Children's National Health System, Washington, DC;
9
Beth Israel Deaconess Medical Center and.
10
Children's Hospital Boston, Harvard Medical School, Boston, Massachusetts;
11
Division of Kidney, Urology and Hematology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland;
12
Department of Pediatrics and Communicable Disease, University of Michigan, Ann Arbor, Michigan;
13
Department of Pediatrics, New York University School of Medicine, New York, New York;
14
Department of Pediatrics, University of Minnesota Medical School, Minneapolis, Minnesota; and.
15
Children's Hospital at Montefiore, Albert Einstein College of Medicine, Bronx, New York.

Abstract

Genetic variants in apolipoprotein L1 (APOL1) confer risk for kidney disease. We sought to better define the phenotype of APOL1-associated nephropathy. The FSGS Clinical Trial involved 138 children and young adults who were randomized to cyclosporin or mycophenolate mofetil plus pulse oral dexamethasone with a primary outcome of proteinuria remission. DNA was available from 94 subjects who were genotyped for APOL1 renal risk variants, with two risk alleles comprising the risk genotype. Two APOL1 risk alleles were present in 27 subjects, of whom four subjects did not self-identify as African American, and 23 of 32 (72%) self-identified African Americans. Individuals with the APOL1 risk genotype tended to present at an older age and had significantly lower baseline eGFR, more segmental glomerulosclerosis and total glomerulosclerosis, and more tubular atrophy/interstitial fibrosis. There were differences in renal histology, particularly more collapsing variants in those with the risk genotype (P=0.02), although this association was confounded by age. APOL1 risk genotype did not affect response to either treatment regimen. Individuals with the risk genotype were more likely to progress to ESRD (P<0.01). In conclusion, APOL1 risk genotypes are common in African-American subjects with primary FSGS and may also be present in individuals who do not self-identify as African American. APOL1 risk status is associated with lower kidney function, more glomerulosclerosis and interstitial fibrosis, and greater propensity to progress to ESRD. The APOL1 risk genotype did not influence proteinuria responses to cyclosporin or mycophenolate mofetil/dexamethasone.

KEYWORDS:

FSGS; cyclosporin; genetic renal disease

PMID:
25573908
PMCID:
PMC4446865
DOI:
10.1681/ASN.2013111242
[Indexed for MEDLINE]
Free PMC Article

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