Malignant vascular disease of the kidney: nature of the lesions, mediators of disease progression, and the case for bilateral nephrectomy.

A case of thrombotic microangiopathy presenting as a hemolytic uremic syndrome complicated by untreatable hypertension and ultimately requiring bilateral nephrectomy is discussed. Severe hypertension and renal failure may complicate the course of vascular diseases of the kidney, including thrombotic microangiopathy, chronic hypertension, and scleroderma. Toxins, pressure stress, and immune material may trigger the initial injury to vascular endothelium. The malignant course of these renal vascular diseases seems linked to the severity of vascular injury. Endothelial injury manifests with swelling and detachment of endothelial cells from the basement membrane, expansion of the subendothelial space, and newly formed basement membrane-like material. In arterioles, endothelial injury precedes myointimal swelling and proliferation, leading to vascular lumina narrowing or obliteration and secondary glomerular ischemia, with glomerular tuft collapse and garland-like wrinkling and thickening of the capillary wall. Endothelial cell injury is very likely the common determinant of a cascade of events that lead to irreversible renal failure. When the initial insult (toxins, mechanical stress, antibodies) is promptly removed, lesions are self-limiting and the patient usually recovers. However, a severe insult persisting for some time can lead to chronic and irreversible vascular lesions that, through renal ischemia, trigger maximal activation of the renin angiotensin system with a brisk elevation in arterial blood pressure that may combine to further vascular injury and renal ischemia. Moreover, enhanced shear stress in the severely narrowed microcirculation, through abnormal von Willebrand factor processing, can also favor endothelial injury and platelet aggregation, which may further worsen the vascular lesions and sustain the microangiopathic process. Plasma manipulation, arteriolar vasodilators, and angiotensin-converting enzyme inhibitors normally control the vicious circle, but in few severe cases bilateral nephrectomy remains the last chance to save the patient's life.