Vasculature and kidney complications in sickle cell disease

Abstract

Recent developments in sickle cell disease include the concept of a vasculopathic state and the classification of sickle cell disease into a hemolysis-endothelial dysfunction phenotype or a viscosity-vasoocclusion phenotype. The hemolysis-endothelial dysfunction phenotype largely reflects deficiency of or resistance to nitric oxide. In addition to discussing these areas, we suggest that the hemolysis-endothelial dysfunction phenotype also reflects the instability of sickle hemoglobin, the release of heme, and the induction of heme oxygenase-1. From these perspectives the renal complications of sickle cell disease are discussed and classified.

Figure 1.

Modified hemolysis-endothelial dysfunction phenotype and proposed renal pathophysiology in human SCD. Hemolysis in human SCD leads to NO scavenging by plasma hemoglobin (HbSS) and increased amounts of heme because of the instability of sickle hemoglobin. Heme is cytotoxic, thereby injuring glomerular cells and causing proteinuria and CKD. Induction of heme oxygenase-1, through the generation of carbon monoxide and other actions, induces vasodilation, and thus promotes hyperfiltration. The minus sign signifies that induction of heme oxygenase-1 can mitigate the adverse effects of heme by degrading heme and other cytoprotective effects of heme oxygenase-1.