Sickle Cell Nephropathy

Excerpt

Sickle cell disease refers to a group of disorders in which the sickle mutation is coinherited with a pathogenic variant at the other beta-globin allele that reduces or abolishes normal beta-globin production. These disorders include sickle cell anemia (homozygous sickle mutation [Hb SS]), sickle-beta thalassemia, hemoglobin SC disease, and other variants. A common feature of all types of sickle cell disease is that hemoglobin S (Hb S) constitutes over 50% of total hemoglobin and is the predominant form. Sickle cell disease is an autosomal recessive hemoglobinopathy caused by the substitution of valine for glutamate at the sixth position of the beta-globin chain. This mutation promotes hemoglobin S tetramer formation during oxidative stress, dehydration, or hypoxia, resulting in red blood cell (RBC) sickling, premature erythrocyte destruction, and widespread vaso-occlusive episodes, leading to multiorgan damage.

Renal manifestations, collectively referred to as sickle cell nephropathy, are common and include hematuria, hyposthenuria, renal papillary necrosis, proteinuria, renal tubular acidosis, acute and chronic kidney injury, sickle cell glomerulopathy, and renal medullary carcinoma. Notably, significant renal involvement occurs more frequently in sickle cell disease than in sickle cell trait or other combined hemoglobinopathies, although renal medullary carcinoma is more common in sickle cell trait.

Patients with sickle cell disease face a high risk of morbidity and mortality due to nephropathy. Kidney involvement is particularly concerning due to its early onset and devastating progression. Approximately 10% to 20% of all deaths in patients with sickle cell anemia are due to renal disease, and 30% of deaths in patients with sickle cell anemia are due to irreversible organ failure are complicated by kidney failure. Several challenges compound this burden:

1. Patients with sickle cell disease tend to develop renal failure at a younger age.

2. These patients face a higher mortality following end-stage kidney disease compared to Black patients without sickle cell disease.

3. Historically, outcomes after renal transplantation have been poor, leading many transplant centers to avoid putting these patients on the transplant list, despite recent improvements in post-transplant survival rates.