A 63-year-old man comes to the emergency department due to abdominal pain. Physical examination shows abdominal tenderness without guarding or rebound. His laboratory test results are as follows: On further investigation, magnetic resonance angiography of the abdomen reveals mesenteric vein thrombosis. Flow cytometry shows absence of CD55 on the surface of red blood cells. Which of the following is the most likely pathologic renal finding in this patient?

Question

A 63-year-old man comes to the emergency department due to abdominal pain.  Physical examination shows abdominal tenderness without guarding or rebound.  His laboratory test results are as follows:  On further investigation, magnetic resonance angiography of the abdomen reveals mesenteric vein thrombosis.  Flow cytometry shows absence of CD55 on the surface of red blood cells.  Which of the following is the most likely pathologic renal finding in this patient?

Quizplus · Accepted Answer

This patient's presentation is consistent with paroxysmal nocturnal hemoglobinuria (PNH), a disorder due to complement-mediated hemolysis. PNH is usually due to a mutated phosphatidylinositol glycan class A (PIGA) gene, which helps synthesize the glycosylphosphatidylinositol (GPI) anchor protein. This protein helps attach several cell surface proteins (eg, CD55 decay accelerating factor, CD59 MAC inhibitory protein) that inactivate complement. Absence of these proteins leads to uncontrolled complement-mediated hemolysis. Manifestations of PNH include the following: Chronic hemolysis with breakdown of iron-containing erythrocytes can also lead to iron deposition in the kidney (hemosiderosis), which can interfere with proximal tubule function and cause interstitial scarring and cortical infarcts. The hemosiderosis combined with microvascular thrombosis can increase the risk of chronic kidney disease. (Choices A and C) Cast nephropathy is usually seen in multiple myeloma and is due to large amounts of monoclonal free chain deposition in the kidney. Interstitial nephritis (inflammation in the area surrounding the renal tubules) is most commonly due to drugs (eg, analgesics, antibiotics), recent infection, or systemic conditions (eg, sarcoidosis). (Choices D and E) Membranous glomerulonephritis can be associated with systemic lupus erythematosus, drugs (eg, nonsteroidal anti-inflammatory drugs [NSAIDs]), hepatitis B and C, or solid tumor malignancies (eg, lung, prostate, gastrointestinal). Minimal change disease can be associated with drugs (eg, NSAIDs), hematologic malignancies (eg, lymphoma, leukemia), or allergens (eg, fungi). Educational objective: Paroxysmal nocturnal hemoglobinuria is due to a gene defect that leads to uncontrolled complement-mediated hemolysis. The classic triad includes hemolytic anemia (hemoglobinuria), pancytopenia, and thrombosis at atypical sites. Chronic hemolysis can cause iron deposition in the kidney (hemosiderosis). __________ References: Paroxysmal nocturnal hemoglobinuria (http://www.ncbi.nlm.nih.gov/pubmed/25237200) Fanconi syndrome and CKD in a patient with paroxysmal nocturnal hemoglobinuria and hemosiderosis. (http://www.ncbi.nlm.nih.gov/pubmed/19833423) Renal involvement in paroxysmal nocturnal hemoglobinuria (http://www.ncbi.nlm.nih.gov/pubmed/23752125)

A 63-Year-Old Man Comes to the Emergency Department Due to Abdominal