The renal circulation is complex and is characterized by a highly perfused arteriolar network, reaching cortical glomerular structures adjacent to lower-flow vasa recta that descend into medullary segments. Disorders of the larger vessels, including renal artery stenosis and atheroembolic disease, are discussed elsewhere (Chap. 322). This chapter examines primary disorders of the renal microvessels, many of which are associated with thrombosis and hemolysis.
Thrombotic microangiopathy (TMA) is a pathologic lesion characterized by endothelial cell injury in the terminal arterioles and capillaries. Platelet and hyaline thrombi causing partial or complete occlusion are integral to the histopathology of TMA. TMA is usually accompanied by microangiopathic hemolytic anemia (MAHA) with its typical features of thrombocytopenia and schistocytes, but not always. In the kidney, TMA is characterized by swollen endocapillary cells (endotheliosis), fibrin thrombi, platelet plugs, arterial intimal fibrosis, and a membranoproliferative pattern in the glomerulus. Fibrin thrombi may extend into the arteriolar vascular pole, producing glomerular collapse and at times cortical necrosis. In kidneys that recover from acute TMA, secondary focal segmental glomerulosclerosis may develop. Diseases associated with this lesion include thrombotic thrombocytopenic purpura (TTP), hemolytic-uremic syndrome (HUS), malignant hypertension, scleroderma renal crisis, antiphospholipid syndrome, preeclampsia/HELLP (hemolysis, elevated liver enzymes, low platelet count) syndrome, HIV infection, and radiation nephropathy. TMA can also be seen in myeloproliferative neoplasm (MPN)-related glomerulopathy and POEMS (polyneuropathy, endocrinopathy, organomegaly, monoclonal gammopathy and skin changes) syndrome which are not associated with MAHA.
HEMOLYTIC-UREMIC SYNDROME/THROMBOTIC THROMBOCYTOPENIC PURPURA
HUS and TTP are the prototypes for MAHA. Historically, HUS and TTP were distinguished mainly by their clinical and epidemiologic differences. TTP develops more commonly in adults and was thought to have more neurologic complications while HUS occurs more frequently in children, particularly when associated with hemorrhagic diarrhea. However, atypical HUS (aHUS) can have its first appearance in adulthood, and better testing has revealed that neurologic involvement is as common in HUS as in TTP. Currently, HUS and TTP can be differentiated etiologically and treated according to their specific pathophysiologic features.
HUS is loosely defined by the presence of MAHA and renal impairment. At least four variants are recognized. The most common is Shiga toxin–producing Escherichia coli (STEC) HUS, which is also known as D+ (diarrhea-associated) HUS or enterohemorrhagic E. coli (EHEC) HUS. Most cases involve children <5 years of age, but adults also are susceptible, as evidenced by a 2011 outbreak in northern Europe. Diarrhea, often bloody, precedes MAHA within 1 week in >80% of cases. Abdominal pain, cramping, and vomiting are frequent, whereas fever is typically absent. Neurologic symptoms, including dysphasia, hyperreflexia, blurred vision, memory deficits, encephalopathy, perseveration, and agraphia, often develop, especially in adults. Seizures and cerebral infarction can occur in severe cases. STEC HUS is caused by the Shiga toxins (Stx1 and Stx2), which are also referred to as verotoxins. These toxins are produced ...