TY - JOUR
T1 - Clinical features and histology of apolipoprotein L1-associated nephropathy in the FSGS Clinical Trial
AU - FSGS-CT Study Consortium
AU - Kopp, Jeffrey B.
AU - Winkler, Cheryl A.
AU - Zhao, Xiongce
AU - Radeva, Milena K.
AU - Gassman, Jennifer J.
AU - D'Agati, Vivette D.
AU - Nast, Cynthia C.
AU - Wei, Changli
AU - Reiser, Jochen
AU - Guay-Woodford, Lisa M.
AU - Pollak, Martin R.
AU - Hildebrandt, Friedhelm
AU - Moxey-Mims, Marva
AU - Gipson, Debbie S.
AU - Trachtman, Howard
AU - Friedman, Aaron L.
AU - Kaskel, Frederick J.
N1 - Publisher Copyright:
Copyright © 2015 by the American Society of Nephrology.
PY - 2015/6/1
Y1 - 2015/6/1
N2 - 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.
AB - 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.
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U2 - 10.1681/ASN.2013111242
DO - 10.1681/ASN.2013111242
M3 - Article
C2 - 25573908
AN - SCOPUS:84930447149
SN - 1046-6673
VL - 26
SP - 1443
EP - 1448
JO - Journal of the American Society of Nephrology
JF - Journal of the American Society of Nephrology
IS - 6
ER -