People of African or Afro-Caribbean ancestry are estimated to be 3-5 more likely to develop CKD and in the UK people of ‘black’ ethnicity represent 7.8% of UK patients requiring renal replacement therapy (UK RR 21st Report) compared with 3.0% people of ‘black’ ethnicity living in the UK (UK 2011 Census data). Furthermore, the median age of incident renal replacement therapy (RRT) patients is significantly lower in the UK in people of black ethnicity (White 65.8 years, South Asian 61.1 years and Black 56.5 years) (UK RR 21st Report). These data highlight the substantial health inequalities in CKD in the UK for people of African or Afro-Caribbean ancestry, but current understanding of contributing genetic factors are limited.

There are several studies, predominantly from the USA, which report new genetic variants (e.g. Apolipoprotein 1, Sickle cell trait, MYH9) which increase CKD risk in people of African ancestry but their contribution to CKD development and progression in the UK is unknown. Similarly established risk factors with genetic influences (e.g. hypertension) are recognised to cause and accelerate progression of CKD in African American studies but the contribution of these factors in first, second and third generation people of African ancestry living in the UK has not been explored.

Social factors including access to health services and lack of trust in health care professionals have also been proposed to be associated with CKD progression in African Americans, but these important factors have not been studied in the UK with universal health care provision.

Unfortunately, current UK CKD studies have poor representation of people of African / Afro-Caribbean ancestry. Cohorts enriched with people of Black, Asian and Minority Ethnicities or exclusively of African ancestry are needed to study both genetic and biopsychosocial factors which contribute to disease onset and progression in people of African ancestry living in the UK and RaDaR provides the ideal platform to support this work.

People of African or Afro-Caribbean ancestry with CKD (KDIGO definition), >18 years and one or more of the following:

• Sickle Cell Nephropathy: Known Sickle Cell disease with reduced kidney function, and/or blood or protein in urine with no other cause for kidney disease identified.

• Suspected or confirmed APOL1 disease including: Focal segmental glomerulosclerosis (primary or secondary) on renal biopsy; Non-diabetic and non-immunological kidney disease with no other confirmed cause

• Suspected or confirmed hypertensive kidney disease

• End stage kidney disease of unknown cause

There are new trials being developed to reduce progression of CKD in people with APOL1 high risk alleles and Sickle Cell Nephropathy. Please contact RDG group for further details.

RDG Research Plans

• Prevalence of high-risk genotypes (e.g. APOL1 and sickle trait) in UK population compared to African countries
• Study of novel genetic and epigenetic risk factors to predict progression of CKD in people of African or Afro-Caribbean ancestry
• Mechanisms of disease progression in proteinuric and non-proteinuric CKD in people of African or Afro-Caribbean ancestry
• Exploration of impact of low birth weight, poor maternal nutrition, history of childhood illness first/second generation of African or Afro-Caribbean ancestry on development of genetic causes of CKD
• Qualitative work to enhance recruitment to research in people of African or Afro-Caribbean ancestry
• Exploration of novel research design including telemedicine and digital monitoring to improve participation in research

References

1 S. Limou, G. W. Nelson, J. B. Kopp, and C. A. Winkler, “APOL1 kidney risk alleles: population genetics and disease associations,” Advances in Chronic Kidney Disease, vol. 21, no. 5, 2014 pp. 426–433

2 Sumaili EK, Shemer R, Kruzel-Davila E, Cohen EP, Mutantu PN, Bukabau JB, Makulo JR, Mokoli VM, Luse JL, Pakasa NM, Cavalier E. G1 is the major APOL1 risk allele for hypertension-attributed nephropathy in Central Africa. Clinical kidney journal. 2019 Apr;12(2):188-95.

3 Caskey F, Dreyer G, Evans K, Methven S, Scott J, Brettle A, Castledine C, Chapman F, Fraser S, Hounkpatin H, Hughes J. Kidney Health Inequalities in the United Kingdom: Reflecting on the past, reducing in the future

4 Umeukeje EM, Young BA. Genetics and ESKD Disparities in African Americans. American Journal of Kidney Diseases. 2019 Dec 1;74(6):811-21

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