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N Engl J Med. 2013 Dec 5;369(23):2183-96. doi: 10.1056/NEJMoa1310345. Epub 2013 Nov 9.

APOL1 risk variants, race, and progression of chronic kidney disease.

Collaborators (320)

Wright JT Jr, Rahman M, Dancie R, Strauss L, Lea J, Wilkening B, Chapman A, Watkins D, Kopple JD, Miladinovich L, Choi J, Oleskie P, Secules C, Pogue V, Dowie D, Anderson H, Herbert L, Locko R, Nurse H, Cheng JT, Darkwa F, Dowdy V, Nicholas B, Randall O, Retta T, Xu S, Ketete M, Ordor D, Tilghman C, Miller E, Astor B, Diggs C, Charleston J, Harris C, Shields T, Appel L, Norris K, Martins D, Miller M, Howell H, Pitts L, Cheek D, Brooks D, Faulkner M, Adeyele O, Phillips K, Sanford G, Weaver C, Cleveland W, Chapman K, Smith W, Glover S, Phillips R, Lipkowitz M, Rafey M, Gabriel A, Condren E, Coke N, Hebert L, Shidham G, Hiremath L, Justice S, Bakris G, Lash J, Fondren L, Bagnuolo L, Cohan J, Frydrych A, Rostand S, Thornley-Brown D, Key B, Gabbai FB, O'Connor DT, Thomas B, Tisher C, Bichier G, Sarmiento C, Diaz A, Gordon C, Contreras G, Bourgoignie J, Florence-Green D, Junco J, Vassallo J, Jamerson K, Ojo A, Corbin T, Cornish-Zirker D, Graham T, Bloembergen W, Massry S, Smogorzewski M, Richardson A, Pitts L, Toto R, Peterson G, Saxena R, Lightfoot T, Blackstone SA, Loreto C, Lewis J, Schulman G, Sika M, McLeroy S, Agodoa LY, Briggs J, Kusek JW, Gassman J, Beck G, Greene T, Hu B, Brittain K, Sherer S, Tuason L, Kendrick C, Bi S, Litowitz H, Liu X, Wang X, Wiggins K, Tatum CA, Patterson N, Van Lente F, Waletzky J, O'Laughlin C, Burton L, McClellan W, Adams-Campbell L, Faber-Langendoen K, Kiberd B, Lee E, Meyer T, Nathan D, Stokes J, Taylor H, Wilson PW, deBacker T, Lansky A, Slack S, Feldman HI, Landis J, Anderson AH, Ballard S, Chai B, Dember LM, Dickson J, Durborow M, Girard C, Helker ES, Kanetsky PA, Kasner S, Kimmel SE, Kramlik S, Messe SR, Nessel L, Pan Q, Robinson N, Roy J, Tao KK, Whitehead K, Wolman M, Xie D, Yang WP, Zhang X, Townsend RR, Cohen D, Cuevas MM, Duckworth MJ, Ford V, Huan Y, Kallem RR, Leshner J, McDowell S, Mohler ER 3rd, Seamon WM, Sheridan A, Strelsin J, Teff K, VanderVeen S, Appel LJ, Anderson C, Bowers P, Chan T, Chang A, Charleston J, Crowley P, Harrison T, Jaar B, Jiggets D, Martin C, Miller EP, Ngoh P, Sozio S, Thomas L, Turban S, Fink J, Diamantidis C, Fink W, Lucas L, Page T, Parsa A, Scism B, Seliger S, Weir M, Rahman M, Dobre MA, Clark K, Corrigan V, Kisin G, Kanthety R, Strauss L, Wright JT Jr, Go AS, Choi A, Dorin P, Jensvold NG, Lo JC, Metzger L, Nasol EF, Ordonez JD, Perloff R, Sasso N, Thompson D, Yang J, Hsu CY, Chertow GM, Kusek JW, Narva AS, McClellan W, Fried L, Gilbertson DT, McCullough PA, Nathan D, O'Hare AM, Palevsky PM, Rich SS, Toto RD, Wei GS, Wilson PW, Ricardo A, He J, Hamm L, Alper B, Batuman V, Bazzano LA, Borja B, Chen J, Cooke C, Delafontaine P, DeSalvo KB, Dolan J, Hamm L, Lustigova E, Mahone E, Sansing L, Starcke C, Waight M, Schelling J, Horwitz E, Guillon L, O'Malley N, Schachere M, Sedor JR, Shella MA, Slaven A, Thornton J, Donovan M, Master S, Mifflin T, Morrell L, Navaneethan SD, Schreiber MJ, Taliercio J, Coleman M, Hopkins K, Markle T, Ramos M, Russo A, Slattery S, Stelmach K, Stephens V, Ojo A, Sundaram B, Briesmiester J, Cornish-Zirker D, Hill N, Jamerson K, Ringbloom M, Saran R, Smith D, Wilson J, Young E, Wright J, Steigerwalt SP, Bellovich K, DeLuca J, Makos G, Walls K, Flack JM, Sondheimer J, Mahn J, Maysura M, Migdal S, Mohanty M, Muzyk C, Zhuang Y, Lash JP, Brecklin C, Carmona E, Cohan J, Fischer M, Frydrych A, Lopez A, Lora C, Martinez M, Mercado A, Moreno B, Meslar P, Soliman EZ, Zhang ZM.

Author information

1
The authors' affiliations are listed in the Appendix.

Abstract

BACKGROUND:

Among patients in the United States with chronic kidney disease, black patients are at increased risk for end-stage renal disease, as compared with white patients.

METHODS:

In two studies, we examined the effects of variants in the gene encoding apolipoprotein L1 (APOL1) on the progression of chronic kidney disease. In the African American Study of Kidney Disease and Hypertension (AASK), we evaluated 693 black patients with chronic kidney disease attributed to hypertension. In the Chronic Renal Insufficiency Cohort (CRIC) study, we evaluated 2955 white patients and black patients with chronic kidney disease (46% of whom had diabetes) according to whether they had 2 copies of high-risk APOL1 variants (APOL1 high-risk group) or 0 or 1 copy (APOL1 low-risk group). In the AASK study, the primary outcome was a composite of end-stage renal disease or a doubling of the serum creatinine level. In the CRIC study, the primary outcomes were the slope in the estimated glomerular filtration rate (eGFR) and the composite of end-stage renal disease or a reduction of 50% in the eGFR from baseline.

RESULTS:

In the AASK study, the primary outcome occurred in 58.1% of the patients in the APOL1 high-risk group and in 36.6% of those in the APOL1 low-risk group (hazard ratio in the high-risk group, 1.88; P<0.001). There was no interaction between APOL1 status and trial interventions or the presence of baseline proteinuria. In the CRIC study, black patients in the APOL1 high-risk group had a more rapid decline in the eGFR and a higher risk of the composite renal outcome than did white patients, among those with diabetes and those without diabetes (P<0.001 for all comparisons).

CONCLUSIONS:

Renal risk variants in APOL1 were associated with the higher rates of end-stage renal disease and progression of chronic kidney disease that were observed in black patients as compared with white patients, regardless of diabetes status. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others.).

PMID:
24206458
PMCID:
PMC3969022
DOI:
10.1056/NEJMoa1310345
[Indexed for MEDLINE]
Free PMC Article

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