In recent years new information clarified our ideas on the pathophysiology of the nephropathy in sickle cell anemia (SCA). Whereas the medullary vascular pathology with its subsequent disturbances in renal concentrating and acidifying capacity are well documented [1–4], in recent years more attention has been given to the changes in cortical functions. Not only did renal blood flow and glomerular filtration rate (GFR) appear to be elevated, but proximal tubular activity, both reabsorptive and secretory, also were found to be increased. Arguments suggest that this hyperfiltration with increased proximal tubular activity is secondary to the medullary changes and mediated by abnormalities in renal vasoactive substances.

Sickle cell nephropathy thus is no longer confined to the medullary changes per se; it extends to a more complex entity with changes in cortical functions which compensate for a defective water and sodium conservation in the medulla.

In this work we will first briefly review the well known medullary abnormalities, both anatomical and functional, and focus thereafter on the changes in renal hemodynamics and proximal tubular functions, particularly with respect to their pathophysiology. Finally, we will discuss the role of renal vasoactive hormones in this entity.