Glomerular Hyperfiltration in Sickle Cell Disease

Abstract

Sickle cell disease (SCD) is a monogenetic, chronic anemia syndrome that is caused by a point mutation in the β-globin gene and affects approximately 100,000 individuals in the United States. Approximately 4 to 5% of these individuals have or will develop stage 5 chronic kidney disease (CKD), and 0.11% of patients who are on long-term maintenance renal replacement therapy have SCD-associated nephropathy (1–3). Homozygous hemoglobin S leads to severe, chronic, hemolytic anemia and the propensity for hemoglobin polymerization, and red blood cell (RBC) sickling causes small artery occlusions. SCD is a multiorgan syndrome with involvement of the central nervous system (infarcts, strokes), eyes, heart, lungs (pulmonary hypertension), spleen (infarcts), muscle, bone (avascular necrosis), and kidneys. Renal complications include chronic medullary injury and papillary necrosis and transient macrohematuria, which are thought to be caused by vasa recta occlusive disease as a result of RBC sickling. Medullary injury also causes reduced urine-concentrating ability and a mild form of (type IV) distal renal tubular acidosis. Glomerular abnormalities include micro- and macroalbuminuria and the nephrotic syndrome. Histologically, FSGS is the predominant glomerular lesion in patients with SCD and proteinuria (4). Of note, …