AMKD IS RAPIDLY PROGRESSIVE
APOL1-mediated kidney disease (AMKD) is a rapidly progressive form of proteinuric kidney disease.1,2 It is a genetic disease occurring in people with 2 variants of the APOL1 gene.3 Chronic kidney disease (CKD) patients of African ancestry with the APOL1 high-risk genotype progress to dialysis 9 to 12 years earlier than those who lack the high-risk genotype.2,4 AMKD is characterized by one or more of the following:
PROTEINURIA
Ranges from subnephrotic to nephrotic presentation1,5
RAPID PROGRESSION
Patients with AMKD have a higher annual rate of decline in estimated glomerular filtration rate (eGFR): 6.55 vs 3.63 mL/min/1.73m2/year2
LACK OF SYMPTOMS
Often, symptoms are not obvious to patients until the disease is advanced6-8
EARLY ONSET
Patients are often age 50 or younger. Some present when they are children9,10
OTHER FACTORS
Hypertension or a family history of kidney disease1
Among patients of African ancestry with diabetes, there is an increased risk of CKD and ESKD for those with the APOL1 high-risk genotype compared to those without.11
CLINICAL PRESENTATION
AMKD clinical presentations range from focal segmental glomerulosclerosis (FSGS) with edema and nephrotic-range proteinuria to hypertension-attributed kidney disease with no symptoms and subnephrotic proteinuria.1,3,5,12
In people of African ancestry, a significant proportion of various kidney disease diagnoses are in fact AMKD. In African Americans, AMKD accounts for approximately:
54%
to
73%
of FSGS9,10,13-16
62%
to
72%
of HIV-associated nephropathy17,18
23%
of hypertension-attributed CKD,19
47%
of hypertension-attributed ESKD13
39%
of nondiabetic ESKD4
17%
of lupus nephritis,20
25%
of lupus nephritis with ESKD21
14%
of membranous nephropathy22
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ESKD: end-stage kidney disease
References: 1. Freedman BI, Burke W, Divers J, et al. Diagnosis, education, and care of patients with APOL1-associated nephropathy: a Delphi consensus and systematic review. J Am Soc Nephrol. 2021;32(7):1765-1778. doi:10.1681/ASN.2020101399 2. Elliott MD, Marasa M, Cocchi E, et al. Clinical and genetic characteristics of CKD patients with high-risk APOL1 genotypes. J Am Soc Nephrol. 2023;34(5):909-919. doi:10.1681/ASN.0000000000000094 3. Friedman DJ, Pollak MR. APOL1 and kidney disease: from genetics to biology. Annu Rev Physiol. 2020;82:323-342. doi:10.1146/annurev-physiol-021119-034345 4. Tzur S, Rosset S, Skorecki K, Wasser WG. 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. Nephrol Dial Transplant. 2012;27(4):1498-1505. doi:10.1093/ndt/gfr796 5. Rosenberg AZ, Kopp JB. Focal segmental glomerulosclerosis. Clin J Am Soc Nephrol. 2017;12(3):502-517. doi:10.2215/CJN.05960616 6. Bellasi A, Di Lullo L, Di Iorio B. Chronic kidney disease: the silent epidemy. J Clin Med. 2019;8(11):1795. doi:10.3390/jcm8111795 7. KDIGO 2012 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease. Kidney Int Supp. 2013;3:1-150. 8. Understanding APOL1 kidney disease among black Americans. NephCure Kidney International. Accessed January 11, 2024. https://nephcure.org/understanding-apol1-kidney-disease-among-black-americans/ 9. Anyaegbu EI, Shaw AS, Hruska KA, Jain S. Clinical phenotype of APOL1 nephropathy in young relatives of patients with end-stage renal disease. Pediatr Nephrol. 2015;30(6):983-989. doi:10.1007/s00467-014-3031-0 10. Kopp JB, Nelson GW, Sampath K, et al. APOL1 genetic variants in focal segmental glomerulosclerosis and HIV-associated nephropathy. J Am Soc Nephrol. 2011;22(11):2129-2137. doi:10.1681/ASN.2011040388 11. Hung AM, Assimon VA, Chen HC, et al. Genetic inhibition of APOL1 pore-forming function prevents APOL1-mediated kidney disease. J Am Soc Nephrol. 2023;34(11):1889-1899. doi:10.1681/ASN.0000000000000219 12. U.S. Preventive Services Task Force. Screening for chronic kidney disease: recommendation statement. Am Fam Physician. 2014;89(4):290A-290B. Accessed January 11, 2024. https://www.aafp.org/pubs/afp/issues/2014/0215/od1.html 13. Genovese G, Friedman DJ, Ross MD, et al. Association of trypanolytic APOL1 variants with kidney disease in African Americans. Science. 2010;329(5993):841-845. doi:10.1126/science.1193032 14. Groopman EE, Marasa M, Cameron-Christie S, et al. Diagnostic utility of exome sequencing for kidney disease. N Engl J Med. 2019;380(2):142-151. doi:10.1056/NEJMoa1806891 15. Kallash M, Wang Y, Smith A, et al. Rapid progression of focal segmental glomerulosclerosis in patients with high-risk APOL1 genotypes. Clin J Am Soc Nephrol. 2023;18(3):344-355. doi:10.2215/CJN.0000000000000069 16. Kopp JB, Winkler CA, Zhao X, et al. Clinical features and histology of apolipoprotein L1-associated nephropathy in the FSGS clinical trial. J Am Soc Nephrol. 2015;26(6):1443-1448. doi:10.1681/ASN.2013111242 17. Atta MG, Estrella MM, Kuperman M, et al. HIV-associated nephropathy patients with and without apolipoprotein L1 gene variants have similar clinical and pathological characteristics. Kidney Int. 2012;82(3):338-343. doi:10.1038/ki.2012.111 18. Kopp JB, Heymann J, Winkler CA. APOL1 renal risk variants: fertile soil for HIV-associated nephropathy. Semin Nephrol. 2017;37(6):514-519. doi:10.1016/j.semnephrol.2017.07.004 19. Parsa A, Kao WHL, Xie D, et al. APOL1 risk variants, race, and progression of chronic kidney disease. N Engl J Med. 2013;369(23):2183-2196. doi:10.1056/NEJMoa1310345 20. Larsen CP, Beggs ML, Saeed M, Walker PD. Apolipoprotein L1 risk variants associate with systemic lupus erythematosus-associated collapsing glomerulopathy. J Am Soc Nephrol. 2013;24(5):722-725. doi:10.1681/ASN.2012121180 21. Freedman BI, Langefeld CD, Andringa KK, et al. End-stage renal disease in African Americans with lupus nephritis is associated with APOL1. Arthritis Rheumatol. 2014;66(2):390-396. doi:10.1002/art.38220 22. Chen DP, Henderson CD, Anguiano J, et al. Kidney disease progression in membranous nephropathy among black participants with high-risk APOL1 genotype. Clin J Am Soc Nephrol. 2023;18(3):337. doi:10.2215/CJN.0000000000000070