Kidney damage in individuals with sickle cell disease begins in infancy and can progress to kidney failure, which has a high mortality rate. Urinary albumin excretion (albuminuria) is a sensitive marker of early kidney damage in individuals with sickle cell disease. While guidelines from the National Heart, Lung and Blood Institute (NHLBI) recommend screening for albuminuria beginning at 10 years of age for all sickle cell patients, genetic testing may allow earlier identification of individuals at risk for kidney disease.
Two variants, G1 (rs73885319/rs60910145) and G2 (rs71785313), in the apolipoprotein L-1 (APOL1) gene confer an increased risk of kidney failure to African Americans without sickle cell disease (PMID: 24206458) and of albuminuria and chronic kidney disease (CKD) in individuals with sickle cell disease (PMID: 21910715).
We used whole genome sequencing in a longitudinal cohort of children and young adults with sickle cell disease to more closely examine the association of these variants to the age of onset of albuminuria. We identified that young individuals with a combination of risk alleles of two of the APOL1 variants (G1/G1, G1/G2, or G1/G2) were more likely to develop albuminuria earlier in childhood.
Kaplan-Meier curves showing an earlier age of albuminuria diagnosis for sickle cell patients with the high-risk APOL1 genetic model compared to sickle cell patients without the high-risk genetic model. The high-risk genetic model is defined as either (1) containing one risk allele for rs73885319 /rs60910145 and one risk allele for rs71785313 OR (2) having two copies of the risk allele of either the rs73885319/rs60910145 variant or the rs71785313 variant.