Clinical features and histology of apolipoprotein L1-associated nephropathy in the FSGS Clinical Trial

FSGS-CT Study Consortium

Research output: Contribution to journalArticle

58 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1443-1448
Number of pages6
JournalJournal of the American Society of Nephrology
Volume26
Issue number6
DOIs
StatePublished - Jun 1 2015

Fingerprint

Apolipoproteins
Histology
Clinical Trials
Genotype
African Americans
Mycophenolic Acid
Kidney
Proteinuria
Dexamethasone
Cyclosporine
Chronic Kidney Failure
Fibrosis
Alleles
Kidney Diseases
Atrophy
Young Adult

ASJC Scopus subject areas

  • Nephrology

Cite this

Clinical features and histology of apolipoprotein L1-associated nephropathy in the FSGS Clinical Trial. / FSGS-CT Study Consortium.

In: Journal of the American Society of Nephrology, Vol. 26, No. 6, 01.06.2015, p. 1443-1448.

Research output: Contribution to journalArticle

@article{58faaf9fb552419c972c8e4d1574cc1c,
title = "Clinical features and histology of apolipoprotein L1-associated nephropathy in the FSGS Clinical Trial",
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.",
author = "{FSGS-CT Study Consortium} and Kopp, {Jeffrey B.} and Winkler, {Cheryl A.} and Xiongce Zhao and Radeva, {Milena K.} and Gassman, {Jennifer J.} and D'Agati, {Vivette D.} and Nast, {Cynthia C.} and Changli Wei and Jochen Reiser and Guay-Woodford, {Lisa M.} and Pollak, {Martin R.} and Friedhelm Hildebrandt and Marva Moxey-Mims and Gipson, {Debbie S.} and Howard Trachtman and Friedman, {Aaron L.} and Kaskel, {Frederick J.}",
year = "2015",
month = "6",
day = "1",
doi = "10.1681/ASN.2013111242",
language = "English (US)",
volume = "26",
pages = "1443--1448",
journal = "Journal of the American Society of Nephrology : JASN",
issn = "1046-6673",
publisher = "American Society of Nephrology",
number = "6",

}

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.

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.

UR - http://www.scopus.com/inward/record.url?scp=84930447149&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84930447149&partnerID=8YFLogxK

U2 - 10.1681/ASN.2013111242

DO - 10.1681/ASN.2013111242

M3 - Article

C2 - 25573908

AN - SCOPUS:84930447149

VL - 26

SP - 1443

EP - 1448

JO - Journal of the American Society of Nephrology : JASN

JF - Journal of the American Society of Nephrology : JASN

SN - 1046-6673

IS - 6

ER -