Sickle Cell Disease and CKD: An Update

Abstract

<b><i>Background:</i></b> Sickle cell disease is an inherited red blood cell disorder that affects approximately 100,000 people in the USA and 25 million people worldwide. Vaso-occlusion and chronic hemolysis lead to dysfunction of vital organ systems, with the kidneys being among the most commonly affected organs. <b><i>Summary:</i></b> Early renal manifestations include medullary ischemia with the 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 <i>APOL1</i> G1 and G2 kidney risk variants and variants in <i>HMOX1</i> and lower in those that coinherit 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 nonsickle 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. <b><i>Key Messages:</i></b> Kidney disease is a major contributor to early mortality, and more research is needed to understand the pathophysiology and develop targeted therapies to improve kidney health in sickle cell disease.