A 46-year-old previously healthy woman comes to the emergency department due to 4 days of intermittent fever, abdominal pain, and vomiting. For the past 2 days she has also had decreased urine output, skin rash, and progressive lethargy. Her temperature is 38.3 C (101 F), blood pressure is 130/80 mm Hg, and pulse is 100/min. There is a scattered petechial rash, facial puffiness, and 1+ bilateral pedal edema on physical examination. Laboratory studies show hemoglobin of 8.9 g/dL with elevated reticulocyte count and a platelet count of 26,000/mm³. Bleeding time is prolonged; prothrombin time and activated partial thromboplastin time are normal. The peripheral blood smear shows schistocytes and reduced platelets with presence of giant forms. Blood urea nitrogen is 46 mg/dL and serum creatinine is 2.3 mg/dL. Urinalysis is positive for proteinuria and hematuria. Which of the following is most likely to be seen on renal biopsy?

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This patient has the pentad of fever, neurologic symptoms (progressive lethargy), renal failure, anemia, and thrombocytopenia in the setting of a gastrointestinal illness. She most likely has thrombocytopenic thrombotic purpura-hemolytic uremic syndrome (TTP-HUS), one of the thrombotic microangiopathy (TMA) syndromes. These share common clinical and pathologic features, including: Unlike disseminated intravascular coagulation, in which coagulation cascade activation leads to prolongation of coagulation studies (prothrombin time [PT] and activated partial thromboplastin time [aPTT]), TTP is almost always characterized by normal PT and aPTT. The pentad of symptoms described in this patient is classic for TTP. (Choice A) Focal segmental glomerulosclerosis, including its collapsing variant, commonly manifests as heavy proteinuria. (Choice B) Crescentic or rapidly progressive glomerulonephritis (RPGN) typically presents with macroscopic hematuria, hypertension, and progressive renal failure. It is classified as anti-glomerular basement membrane (with hemoptysis in Goodpasture syndrome), immune-complex mediated (eg, systemic lupus erythematous), or pauci-immune (with pulmonary, upper respiratory, and kidney involvement in granulomatosis with polyangiitis). (Choice C) Poststreptococcal glomerulonephritis is typically a childhood disease that can follow streptococcal pharyngitis and lead to increased Coca-Cola-colored urine output and periorbital edema. (Choice D) Henoch-Schönlein purpura is typically a childhood disease with nonthrombocytopenic palpable purpura and arthritis; IgA nephropathy commonly presents with recurrent hematuria and low-grade proteinuria following an upper respiratory tract infection. Both diseases have similar histopathologic findings with IgA deposition in the mesangium. (Choice E) Acute tubular necrosis due to ischemia (eg, prolonged hypotension), nephrotoxins (eg, antibiotics), or pigment deposition (eg, myoglobinuria) generally presents with rising creatinine and muddy brown granular casts on urinalysis. Educational objective: Primary thrombotic microangiopathy (TMA) syndromes share common clinical and pathologic features and result in platelet activation and diffuse microthrombosis in arterioles and capillaries. TMA syndromes present with hemolytic anemia with schistocytes, thrombocytopenia, and organ injury (eg, brain, kidneys, heart). __________ References: Thrombotic microangiopathy and associated renal disorders. (http://www.ncbi.nlm.nih.gov/pubmed/22802583) Pathogenesis of thrombotic microangiopathies. (http://www.ncbi.nlm.nih.gov/pubmed/18215115) Thrombotic microangiopathies. (http://www.ncbi.nlm.nih.gov/pubmed/22888446)

A 46-Year-Old Previously Healthy Woman Comes to the Emergency Department