What are the underlying pathogenesis of chronic kidney disease (CKD) and risk factors associated with CKD progression in patients with SCN?
• Pathogenesis of CKD: Although glomerular filtration is increased in younger patients with SCD, it progressively declines after the age of 30. The development of CKD is thought to be due to early glomerular hypertrophy and hyperfiltration; tubular hyperfunctioning; endothelial injury with repeated sickling and vasoocclusive episodes; hemolysis and iron-induced proinflammatory and profibrotic changes in endothelial cells; and glomerular mesangium and tubulointerstitium.
• Risk factors for CKD progression: underlying hypertension, nephrotic range proteinuria, severe anemia, vasoocclusive crisis, acute chest syndrome, stroke, β S -gene haplotype, genetic variants of MYH9 and APOL1 , pulmonary hypertension, and infection with parvovirus B19. Of note, although studies have provided statistical evidence implicating APOL1 variation in nondiabetic nephropathies, MYH9 risk variants are still associated with CKD in non–African American populations and in SCD nephropathy. It has been hypothesized that MYH9 and APOL1 may be coregulated and interact under anemic stress to induce nephropathy risk.
• Protective factors: coinheritance with α-thalassemia, higher fetal hemoglobin.
