Sickle Cell Nephropathy

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: 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.