APOL1 allelic variants are associated with lower age of dialysis initiation and thereby increased dialysis vintage in African and Hispanic Americans with non-diabetic end-stage kidney disease

Shay Tzur; Saharon Rosset; Karl Skorecki; Walter G. Wasser

doi:10.1093/ndt/gfr796

APOL1 allelic variants are associated with lower age of dialysis initiation and thereby increased dialysis vintage in African and Hispanic Americans with non-diabetic end-stage kidney disease

Shay Tzur
, Saharon Rosset
, Karl Skorecki
, Walter G. Wasser

Technion-Israel Institute of Technology
Tel Aviv University
Laboratory of Molecular Medicine
Hadassah University Medical Centre
Division of Nephrology

Research output: Contribution to journal › Article › peer-review

91 Scopus citations

Abstract

Background. The APOL1 G1 and G2 genetic variants make a major contribution to the African ancestry risk for a number of common forms of non-diabetic end-stage kidney disease (ESKD). We sought to clarify the relationship of APOL1 variants with age of dialysis initiation and dialysis vintage (defined by the time between dialysis initiation and sample collection) in African and Hispanic Americans, diabetic and non-diabetic ESKD. Methods. We examined APOL1 genotypes in 995 African and Hispanic American dialysis patients with diabetic and non-diabetic ESKD. Results. The mean age of dialysis initiation for non-diabetic African-American patients with two APOL1 risk alleles was 48.1 years, >9 years earlier than those without APOL1 risk alleles (t-test, P = 0.0003). Similar results were found in the non-diabetic Hispanic American cohort, but not in the diabetic cohorts. G1 heterozygotes showed a 5.3-year lower mean age of dialysis initiation (t-test, P = 0.0452), but G2 heterozygotes did not show such an effect. At the age of 70, 92% of individuals with two APOL1 risk alleles had already initiated dialysis, compared with 76% of the patients without APOL1 risk alleles. Although two APOL1 risk alleles are also associated with ∼2 years increased in dialysis vintage, further analysis showed that this increase is fully explained by earlier age of dialysis initiation. Conclusions.Two APOL1 risk alleles significantly predict lower age of dialysis initiation and thereby increased dialysis vintage in non-diabetic ESKD African and Hispanic Americans, but not in diabetic ESKD. A single APOL1 G1, but not G2, risk allele also lowers the age of dialysis initiation, apparently consistent with gain of injury or loss of function mechanisms. Hence, APOL1 mutations produce a distinct category of kidney disease that manifests at younger ages in African ancestry populations.

Original language	English
Pages (from-to)	1498-1505
Number of pages	8
Journal	Nephrology Dialysis Transplantation
Volume	27
Issue number	4
DOIs	https://doi.org/10.1093/ndt/gfr796
State	Published - Apr 2012
Externally published	Yes

Bibliographical note

Funding Information:
Acknowledgements. We thank all patients and health care professionals who participated in the study. We gratefully acknowledge Dr Revital Shemer, Mr Guennady Yudkovsky and Mr Eli Balshan for their helpful technical support and Ms. Beth Forrest from the United States Renal Data System for supplying additional epidemiological data. K.S. thanks the Arthur and Rosalinde Gilbert Foundation, the Eshagian Trust fund and the Sidney Kremer Kidney Disease Research Fund of the American and Canadian Technion Societies, the Slava Smolakovksy Fund of Rambam Medical Center as well as the Israel Science Foundation (grant no.3002/ 09). S.R. thanks the Israeli Science Foundation for grant 1227/09 and IBM for an Open Collaborative Research grant.

Funding

Acknowledgements. We thank all patients and health care professionals who participated in the study. We gratefully acknowledge Dr Revital Shemer, Mr Guennady Yudkovsky and Mr Eli Balshan for their helpful technical support and Ms. Beth Forrest from the United States Renal Data System for supplying additional epidemiological data. K.S. thanks the Arthur and Rosalinde Gilbert Foundation, the Eshagian Trust fund and the Sidney Kremer Kidney Disease Research Fund of the American and Canadian Technion Societies, the Slava Smolakovksy Fund of Rambam Medical Center as well as the Israel Science Foundation (grant no.3002/ 09). S.R. thanks the Israeli Science Foundation for grant 1227/09 and IBM for an Open Collaborative Research grant.

Funders	Funder number
American and Canadian Technion Societies
Eshagian Trust fund
Israeli Science Foundation	1227/09
Sidney Kremer Kidney Disease
Slava Smolakovksy Fund of Rambam Medical Center
International Business Machines Corporation
Rosalinde and Arthur Gilbert Foundation
Israel Science Foundation	3002/ 09

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

APOL1
African-Americans
Hispanic-Americans
dialysis
non-diabetic kidney disease

Access to Document

10.1093/ndt/gfr796

Cite this

@article{4dc6eedea358460eb8f6c1b5a1f2dcf7,

title = "APOL1 allelic variants are associated with lower age of dialysis initiation and thereby increased dialysis vintage in African and Hispanic Americans with non-diabetic end-stage kidney disease",

abstract = "Background. The APOL1 G1 and G2 genetic variants make a major contribution to the African ancestry risk for a number of common forms of non-diabetic end-stage kidney disease (ESKD). We sought to clarify the relationship of APOL1 variants with age of dialysis initiation and dialysis vintage (defined by the time between dialysis initiation and sample collection) in African and Hispanic Americans, diabetic and non-diabetic ESKD. Methods. We examined APOL1 genotypes in 995 African and Hispanic American dialysis patients with diabetic and non-diabetic ESKD. Results. The mean age of dialysis initiation for non-diabetic African-American patients with two APOL1 risk alleles was 48.1 years, >9 years earlier than those without APOL1 risk alleles (t-test, P = 0.0003). Similar results were found in the non-diabetic Hispanic American cohort, but not in the diabetic cohorts. G1 heterozygotes showed a 5.3-year lower mean age of dialysis initiation (t-test, P = 0.0452), but G2 heterozygotes did not show such an effect. At the age of 70, 92\% of individuals with two APOL1 risk alleles had already initiated dialysis, compared with 76\% of the patients without APOL1 risk alleles. Although two APOL1 risk alleles are also associated with ∼2 years increased in dialysis vintage, further analysis showed that this increase is fully explained by earlier age of dialysis initiation. Conclusions.Two APOL1 risk alleles significantly predict lower age of dialysis initiation and thereby increased dialysis vintage in non-diabetic ESKD African and Hispanic Americans, but not in diabetic ESKD. A single APOL1 G1, but not G2, risk allele also lowers the age of dialysis initiation, apparently consistent with gain of injury or loss of function mechanisms. Hence, APOL1 mutations produce a distinct category of kidney disease that manifests at younger ages in African ancestry populations.",

keywords = "APOL1, African-Americans, Hispanic-Americans, dialysis, non-diabetic kidney disease",

author = "Shay Tzur and Saharon Rosset and Karl Skorecki and Wasser, \{Walter G.\}",

note = "Funding Information: Acknowledgements. We thank all patients and health care professionals who participated in the study. We gratefully acknowledge Dr Revital Shemer, Mr Guennady Yudkovsky and Mr Eli Balshan for their helpful technical support and Ms. Beth Forrest from the United States Renal Data System for supplying additional epidemiological data. K.S. thanks the Arthur and Rosalinde Gilbert Foundation, the Eshagian Trust fund and the Sidney Kremer Kidney Disease Research Fund of the American and Canadian Technion Societies, the Slava Smolakovksy Fund of Rambam Medical Center as well as the Israel Science Foundation (grant no.3002/ 09). S.R. thanks the Israeli Science Foundation for grant 1227/09 and IBM for an Open Collaborative Research grant.",

year = "2012",

month = apr,

doi = "10.1093/ndt/gfr796",

language = "אנגלית",

volume = "27",

pages = "1498--1505",

journal = "Nephrology Dialysis Transplantation",

issn = "0931-0509",

publisher = "Oxford University Press",

number = "4",

}

APOL1 allelic variants are associated with lower age of dialysis initiation and thereby increased dialysis vintage in African and Hispanic Americans with non-diabetic end-stage kidney disease. / Tzur, Shay; Rosset, Saharon; Skorecki, Karl et al.
In: Nephrology Dialysis Transplantation, Vol. 27, No. 4, 04.2012, p. 1498-1505.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - APOL1 allelic variants are associated with lower age of dialysis initiation and thereby increased dialysis vintage in African and Hispanic Americans with non-diabetic end-stage kidney disease

AU - Tzur, Shay

AU - Rosset, Saharon

AU - Skorecki, Karl

AU - Wasser, Walter G.

N1 - Funding Information: Acknowledgements. We thank all patients and health care professionals who participated in the study. We gratefully acknowledge Dr Revital Shemer, Mr Guennady Yudkovsky and Mr Eli Balshan for their helpful technical support and Ms. Beth Forrest from the United States Renal Data System for supplying additional epidemiological data. K.S. thanks the Arthur and Rosalinde Gilbert Foundation, the Eshagian Trust fund and the Sidney Kremer Kidney Disease Research Fund of the American and Canadian Technion Societies, the Slava Smolakovksy Fund of Rambam Medical Center as well as the Israel Science Foundation (grant no.3002/ 09). S.R. thanks the Israeli Science Foundation for grant 1227/09 and IBM for an Open Collaborative Research grant.

PY - 2012/4

Y1 - 2012/4

N2 - Background. The APOL1 G1 and G2 genetic variants make a major contribution to the African ancestry risk for a number of common forms of non-diabetic end-stage kidney disease (ESKD). We sought to clarify the relationship of APOL1 variants with age of dialysis initiation and dialysis vintage (defined by the time between dialysis initiation and sample collection) in African and Hispanic Americans, diabetic and non-diabetic ESKD. Methods. We examined APOL1 genotypes in 995 African and Hispanic American dialysis patients with diabetic and non-diabetic ESKD. Results. The mean age of dialysis initiation for non-diabetic African-American patients with two APOL1 risk alleles was 48.1 years, >9 years earlier than those without APOL1 risk alleles (t-test, P = 0.0003). Similar results were found in the non-diabetic Hispanic American cohort, but not in the diabetic cohorts. G1 heterozygotes showed a 5.3-year lower mean age of dialysis initiation (t-test, P = 0.0452), but G2 heterozygotes did not show such an effect. At the age of 70, 92% of individuals with two APOL1 risk alleles had already initiated dialysis, compared with 76% of the patients without APOL1 risk alleles. Although two APOL1 risk alleles are also associated with ∼2 years increased in dialysis vintage, further analysis showed that this increase is fully explained by earlier age of dialysis initiation. Conclusions.Two APOL1 risk alleles significantly predict lower age of dialysis initiation and thereby increased dialysis vintage in non-diabetic ESKD African and Hispanic Americans, but not in diabetic ESKD. A single APOL1 G1, but not G2, risk allele also lowers the age of dialysis initiation, apparently consistent with gain of injury or loss of function mechanisms. Hence, APOL1 mutations produce a distinct category of kidney disease that manifests at younger ages in African ancestry populations.

AB - Background. The APOL1 G1 and G2 genetic variants make a major contribution to the African ancestry risk for a number of common forms of non-diabetic end-stage kidney disease (ESKD). We sought to clarify the relationship of APOL1 variants with age of dialysis initiation and dialysis vintage (defined by the time between dialysis initiation and sample collection) in African and Hispanic Americans, diabetic and non-diabetic ESKD. Methods. We examined APOL1 genotypes in 995 African and Hispanic American dialysis patients with diabetic and non-diabetic ESKD. Results. The mean age of dialysis initiation for non-diabetic African-American patients with two APOL1 risk alleles was 48.1 years, >9 years earlier than those without APOL1 risk alleles (t-test, P = 0.0003). Similar results were found in the non-diabetic Hispanic American cohort, but not in the diabetic cohorts. G1 heterozygotes showed a 5.3-year lower mean age of dialysis initiation (t-test, P = 0.0452), but G2 heterozygotes did not show such an effect. At the age of 70, 92% of individuals with two APOL1 risk alleles had already initiated dialysis, compared with 76% of the patients without APOL1 risk alleles. Although two APOL1 risk alleles are also associated with ∼2 years increased in dialysis vintage, further analysis showed that this increase is fully explained by earlier age of dialysis initiation. Conclusions.Two APOL1 risk alleles significantly predict lower age of dialysis initiation and thereby increased dialysis vintage in non-diabetic ESKD African and Hispanic Americans, but not in diabetic ESKD. A single APOL1 G1, but not G2, risk allele also lowers the age of dialysis initiation, apparently consistent with gain of injury or loss of function mechanisms. Hence, APOL1 mutations produce a distinct category of kidney disease that manifests at younger ages in African ancestry populations.

KW - APOL1

KW - African-Americans

KW - Hispanic-Americans

KW - dialysis

KW - non-diabetic kidney disease

UR - https://www.scopus.com/pages/publications/84859338200

U2 - 10.1093/ndt/gfr796

DO - 10.1093/ndt/gfr796

M3 - ???researchoutput.researchoutputtypes.contributiontojournal.article???

C2 - 22357707

AN - SCOPUS:84859338200

SN - 0931-0509

VL - 27

SP - 1498

EP - 1505

JO - Nephrology Dialysis Transplantation

JF - Nephrology Dialysis Transplantation

IS - 4

ER -

APOL1 allelic variants are associated with lower age of dialysis initiation and thereby increased dialysis vintage in African and Hispanic Americans with non-diabetic end-stage kidney disease

Abstract

Bibliographical note

Funding

UN SDGs

Keywords

Access to Document

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