Fig. 2.

Salient pathogenic processes in the development of sickle cell nephropathy. Sickle cell nephropathy largely reflects an underlying functional vasculopathy. This vasculopathy leads to a perfusion paradox, wherein medullary hypoperfusion occurs in conjunction with kidney and/or cortical hyperperfusion. The renal vasculopathy also leads to aberrant renal vascular responses to stress that occur systemically or in distant organs and tissues. This response is characterized by enhanced renal vasoconstriction and resultant vasoocclusion. Recurrent cycles of ischemia and ischemia–reperfusion injury thus occur, thereby leading to subclinical and clinical acute kidney injury. These processes summate in the initiation and progression of sickle cell nephropathy. ^[131]Adapted from Nath et al. Nat Rev Nephrol. 2015;11 : 161–171.