Prevalence of kidney health genetic variants in adults with sickle cell nephropathy

The pathophysiology and genetic risk for sickle cell disease (SCD)-related chronic kidney disease (CKD) are not well understood. In 70 adults with SCD-related CKD and without APOL1 inherited in a high-risk pattern, 24 (34%) had pathogenic variants in candidate genes using KidneySeq (TM). A moderate impact INF2 variant was observed in 20 (29%) patients and those with 3 versus 0-2 pathogenic or moderate impact glomerular genetic variants had higher albuminuria and lower estimated glomerular filtration rate (adjusted p <= 0.015). Using a panel of preselected genes implicated in kidney health, we observed several variants in people with sickle cell nephropathy. The pathophysiology of sickle cell nephropathy is complex with damage to the vasculature, glomerulus, and tubules implicated in sickle cell disease-related chronic kidney disease. Using a panel of pre-selected genes linked to kidney health, we observed variants in 34% (24/70) of adults with sickle cell nephropathy and without APOL1 G1 and G2 variants inherited in a high-risk pattern. The presence of three or more gene variants impacting glomerular function was associated with lower estimated glomerular filtration rate (eGFR) and higher urine albumin-to-creatinine ratios.image