First drugs ever approved for lupus nephritis
Why does advanced chronic kidney disease (CKD) disproportionately affect individuals of African ancestry? Sethu Madhavan, MBBS, wants to uncover the molecular mechanisms underlying these racial disparities.
“While socioeconomic status, psychosocial factors and barriers to healthcare access are determinants of the increased burden of CKD in African Americans, genetic predisposition has long been suspected,” says Dr. Madhavan.
Over the last several years, evidence has come to light supporting this idea that genetic factors contribute to the excessive risk of nondiabetic CKD in African Americans. The evidence focuses on two genetic variants in the apolipoprotein L1 (APOL1) gene.
When APOL1 risk variants are present, we see:
- Increased risk of kidney disease associated with hypertension, HIV and glomerular processes
- Faster progression to end-stage kidney disease
- Dialysis initiation at a younger age
Donor kidneys with two copies of APOL1 variants have reduced survival.
With 14 percent of African Americans estimated to carry two copies of APOL1 risk variants, more than 5.5 million African Americans are at risk for CKD.
However, the molecular mechanisms by which APOL1 variants contribute to the development of CKD remain elusive. APOL1 is expressed in podocytes of the kidney and also circulates in blood as a component of HDL cholesterol.
Through research, Dr. Madhavan wants to understand the protein networks modulated by APOL1 risk variants. This information is vital to develop new treatments that reduce the racial disparities in kidney disease.
