Sickle Cell Disease and CKD: An Update

Abstract

Background: Sickle cell disease is an inherited red blood cell disorder that affects approximately 100,000 people in the U.S. and 25 million people worldwide. Vaso-occlusion and chronic hemolysis lead to dysfunction to vital organ systems, with the kidneys being among the most commonly affected organs. Summary: Early renal manifestations include medullary ischemia with loss of urine concentrating ability and hyperfiltration. This can be followed by progressive damage characterized by persistent albuminuria and a decline in the estimated glomerular filtration rate. The risk of sickle nephropathy is greater in those with the APOL1 G1 and G2 kidney risk variants and variants in HMOX1 and lower in those that co-inherit α-thalassemia. Therapies to treat sickle cell disease-related kidney damage focus on sickle cell disease modifying therapies (e.g. hydroxyurea) or those adopted from the non-sickle cell disease kidney literature (e.g. renin-angiotensin-aldosterone system inhibitors), although data on their clinical efficacy are limited to small studies with short follow up periods. Kidney transplantation for end-stage kidney disease improves survival compared to hemodialysis but is underutilized in this patient population. Key Messages: Kidney disease is a major contributor to early mortality and more research is needed to understand the pathophysiology and to develop targeted therapies to improve kidney health in sickle cell disease.