Target Organ Damage in African American Hypertension: Role of APOL1

Overview

Journal Curr Hypertens Rep

Specialty Cardiology & Vascular Diseases

Date 2011 Nov 10

PMID 22068337

Citations 30

Authors

Barry I Freedman

Mariana Murea

Affiliations

Soon will be listed here.

Abstract

Apolipoprotein L1 (APOL1) gene association studies and results of the African American Study of Kidney Disease and Hypertension are disproving the longstanding concept that mild to moderate essential hypertension contributes substantially to end-stage renal disease susceptibility in African Americans. APOL1 coding variants underlie a spectrum of kidney diseases, including that attributed to hypertension (labeled arteriolar or hypertensive nephrosclerosis), focal segmental glomerulosclerosis, and HIV-associated nephropathy. APOL1 nephropathy risk variants persist because of protection afforded from the parasite that causes African sleeping sickness. This breakthrough will lead to novel treatments for hypertensive African Americans with low-level proteinuria, for whom effective therapies are lacking. Furthermore, APOL1 nephropathy risk variants contribute to racially variable allograft survival rates after kidney transplantation and assist in detecting nondiabetic forms of nephropathy in African Americans with diabetes. Discovery of APOL1-associated nephropathy was a major success of the genetics revolution, demonstrating that secondary hypertension is typically present in nondiabetic African Americans with nephropathy.

Citing Articles

Differing sensitivities to angiotensin converting enzyme inhibition of kidney disease mediated by APOL1 high-risk variants G1 and G2.

Sula Karreci E, Jacas S, Donovan O, Pintye D, Wiley N, Zsengeller Z Kidney Int. 2024; 106(6):1072-1085.

PMID: 39181397 PMC: 11585418. DOI: 10.1016/j.kint.2024.07.026.

Management of Type 2 Diabetes Mellitus and Kidney Failure in People with HIV-Infection in Africa: Current Status and a Call to Action.

Wearne N, Davidson B, Blockman M, Jones J, Ross I, Dave J HIV AIDS (Auckl). 2023; 15:519-535.

PMID: 37700755 PMC: 10493098. DOI: 10.2147/HIV.S396949.

Effects of Testing and Disclosing Ancestry-Specific Genetic Risk for Kidney Failure on Patients and Health Care Professionals: A Randomized Clinical Trial.

Nadkarni G, Fei K, Ramos M, Hauser D, Bagiella E, Ellis S JAMA Netw Open. 2022; 5(3):e221048.

PMID: 35244702 PMC: 8897752. DOI: 10.1001/jamanetworkopen.2022.1048.

Replication of European hypertension associations in a case-control study of 9,534 African Americans.

Kaur H, Crawford D, Liang J, Benchek P, Zhu X, Kallianpur A PLoS One. 2021; 16(11):e0259962.

PMID: 34793544 PMC: 8601554. DOI: 10.1371/journal.pone.0259962.

Outcomes of Hypertensive Kidney Donors Using Current and Past Hypertension Definitions.

Ibrahim H, Hebert S, Murad D, Adrogue H, Nguyen D, Graviss E Kidney Int Rep. 2021; 6(5):1242-1253.

PMID: 34013102 PMC: 8116910. DOI: 10.1016/j.ekir.2021.02.034.

References

Genovese G, Friedman D, Ross M, Lecordier L, Uzureau P, Freedman B . Association of trypanolytic ApoL1 variants with kidney disease in African Americans. Science. 2010; 329(5993):841-5. PMC: 2980843. DOI: 10.1126/science.1193032. View

Swanson S, Hypolite I, Agodoa L, Batty Jr D, Hshieh P, Cruess D . Effect of donor factors on early graft survival in adult cadaveric renal transplantation. Am J Transplant. 2002; 2(1):68-75. DOI: 10.1034/j.1600-6143.2002.020112.x. View

Marcantoni C, Ma L, Federspiel C, Fogo A . Hypertensive nephrosclerosis in African Americans versus Caucasians. Kidney Int. 2002; 62(1):172-80. DOI: 10.1046/j.1523-1755.2002.00420.x. View

Callender C, Cherikh W, Traverso P, Hernandez A, Oyetunji T, Chang D . Effect of donor ethnicity on kidney survival in different recipient pairs: an analysis of the OPTN/UNOS database. Transplant Proc. 2009; 41(10):4125-30. PMC: 2826243. DOI: 10.1016/j.transproceed.2009.06.182. View

Freedman B . Susceptibility genes for hypertension and renal failure. J Am Soc Nephrol. 2003; 14(7 Suppl 2):S192-4. DOI: 10.1097/01.asn.0000070075.89996.4a. View

Cherikh W, Young C, Kramer B, Taranto S, Randall H, Fan P . Ethnic and gender related differences in the risk of end-stage renal disease after living kidney donation. Am J Transplant. 2011; 11(8):1650-5. DOI: 10.1111/j.1600-6143.2011.03609.x. View

Candiano G, Musante L, Carraro M, Faccini L, Campanacci L, Zennaro C . Apolipoproteins prevent glomerular albumin permeability induced in vitro by serum from patients with focal segmental glomerulosclerosis. J Am Soc Nephrol. 2001; 12(1):143-150. DOI: 10.1681/ASN.V121143. View

Freedman B, Hicks P, Bostrom M, Cunningham M, Liu Y, Divers J . Polymorphisms in the non-muscle myosin heavy chain 9 gene (MYH9) are strongly associated with end-stage renal disease historically attributed to hypertension in African Americans. Kidney Int. 2009; 75(7):736-45. PMC: 2698223. DOI: 10.1038/ki.2008.701. View

Kuller L, Grandits G, Cohen J, Neaton J, Prineas R . Lipoprotein particles, insulin, adiponectin, C-reactive protein and risk of coronary heart disease among men with metabolic syndrome. Atherosclerosis. 2006; 195(1):122-8. PMC: 2098784. DOI: 10.1016/j.atherosclerosis.2006.09.001. View

10.

Perneger T, Whelton P, Klag M, Rossiter K . Diagnosis of hypertensive end-stage renal disease: effect of patient's race. Am J Epidemiol. 1995; 141(1):10-5. DOI: 10.1093/oxfordjournals.aje.a117338. View

11.

Gordon S, Hofmann S, Askew D, Davidson W . High density lipoprotein: it's not just about lipid transport anymore. Trends Endocrinol Metab. 2010; 22(1):9-15. PMC: 3036841. DOI: 10.1016/j.tem.2010.10.001. View

12.

Freedman B . Renal microvascular susceptibility in African American pedigrees. Transplant Proc. 1993; 25(4):2423-5. View

13.

Tzur S, Rosset S, Shemer R, Yudkovsky G, Selig S, Tarekegn A . Missense mutations in the APOL1 gene are highly associated with end stage kidney disease risk previously attributed to the MYH9 gene. Hum Genet. 2010; 128(3):345-50. PMC: 2921485. DOI: 10.1007/s00439-010-0861-0. View

14.

Steiner R . 'Normal for now' or 'at future risk': a double standard for selecting young and older living kidney donors. Am J Transplant. 2010; 10(4):737-741. DOI: 10.1111/j.1600-6143.2010.03023.x. View

15.

Vanhamme L, Paturiaux-Hanocq F, Poelvoorde P, Nolan D, Lins L, Van Den Abbeele J . Apolipoprotein L-I is the trypanosome lytic factor of human serum. Nature. 2003; 422(6927):83-7. DOI: 10.1038/nature01461. View

16.

Fung M, Salem R, Lipkowitz M, Bhatnagar V, Pandey B, Schork N . Methylenetetrahydrofolate reductase (MTHFR) polymorphism A1298C (Glu429Ala) predicts decline in renal function over time in the African-American Study of Kidney Disease and Hypertension (AASK) Trial and Veterans Affairs Hypertension Cohort (VAHC). Nephrol Dial Transplant. 2011; 27(1):197-205. PMC: 3350339. DOI: 10.1093/ndt/gfr257. View

17.

Gopalakrishnan I, Iskandar S, Daeihagh P, Divers J, Langefeld C, Bowden D . Coincident idiopathic focal segmental glomerulosclerosis collapsing variant and diabetic nephropathy in an African American homozygous for MYH9 risk variants. Hum Pathol. 2010; 42(2):291-4. PMC: 3022108. DOI: 10.1016/j.humpath.2010.07.016. View

18.

Freedman B . End-stage renal failure in African Americans: insights in kidney disease susceptibility. Nephrol Dial Transplant. 2002; 17(2):198-200. DOI: 10.1093/ndt/17.2.198. View

19.

OSeaghdha C, Parekh R, Hwang S, Li M, Kottgen A, Coresh J . The MYH9/APOL1 region and chronic kidney disease in European-Americans. Hum Mol Genet. 2011; 20(12):2450-6. PMC: 3098737. DOI: 10.1093/hmg/ddr118. View

20.

Freedman B, Iskandar S, Appel R . The link between hypertension and nephrosclerosis. Am J Kidney Dis. 1995; 25(2):207-21. DOI: 10.1016/0272-6386(95)90001-2. View