Sickle cell disease (SCD), first discovered in West Africa is an autosomal recessive hemoglobin disorder, predominantly affecting persons of African, Mediterranean, Indian, and Middle Eastern descent. It results from the replacement of glutamate for valine at the sixth amino acid of the beta-globin chain. The mutation results in hemoglobin S (HbS) tetramers that accumulate during tissue hypoxia, oxidative stress or dehydration. The accumulation leads to red blood cell sickling, early destruction of erythrocytes, and widespread vaso-occlusive episodes (VOC), subsequently resulting in multiorgan damage. Some of the renal complications, collectively known as sickle cell nephropathy (SCN), include hematuria, hyposthenuria, renal papillary necrosis, proteinuria, renal tubular disorders, acute and chronic kidney injury, sickle cell glomerulopathy, and renal medullary carcinoma. Clinically significant renal involvement occurs more frequently in sickle cell disease than in sickle cell trait or in combined hemoglobinopathies, except renal medullary carcinoma, which appears to be more common among sickle cell trait patients.
Natural history of SCD is highly variable with reduced life expectancy with multiorgan damage in symptomatic patients. In general, all patients have a reduced lifespan. Median survival in the United States and Jamaica is 45 to 55 years.
Natural history by age in SCD is as follows:
Newborn babies are asymptomatic for an initial couple of months, given fetal Hb (HbF) predominance.
Early childhood is characterized by episodes of dactylitis, acute chest syndrome (ACS), sepsis, splenic sequestration, and stroke. Human parvovirus B19 infection can lead to severe and sudden anemia in children and adolescents with SCD as the virus destroys precursors of the red blood cells.
After age 5: Classic painful vaso-occlusive crisis (VOC), which increases in frequency with age
Adolescence is associated with nocturnal enuresis, avascular necrosis of the hip, leg ulcerations, delayed puberty, and priapism.
After age 25 to 30, the frequency of VOC tends to reduce and is replaced with signs and symptoms of chronic organ damage, including heart failure, pulmonary hypertension, sickle hepatopathy, and sickle cell nephropathy (SCN).
The primary cause of death in younger patients is usually infection; whereas, in older patients, the primary cause of death is mostly irreversible organ damage.
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