62-year-old woman with edema and proteinuria
A 62-year-old woman with a 3-year history of stable IgG kappa monoclonal gammopathy presents for follow-up. For the past 3 months, she has experienced progressive fatigue, dyspnea on exertion, and bilateral lower extremity edema. She is a part-time librarian and finds it difficult to shelve books on high shelves. Her medical history is also notable for hypertension. Her temperature is 37.0°C (98.6°F), blood pressure is 108/78 mmHg, pulse is 86/min, and respirations are 16/min. Jugular venous pressure is 10 cm. Lungs are clear. There is 2+ symmetric pitting edema to the knees. Laboratory studies show a creatinine of 1.5 mg/dL (baseline 0.9 mg/dL) and an albumin of 2.9 g/dL. A spot urine protein-to-creatinine ratio is 5.5 g/g. An ECG shows low limb lead voltage and a pseudoinfarct pattern. Which of the following is the most appropriate next diagnostic test?
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A
Explanation
Clinical Pearl:
In a patient with a monoclonal gammopathy who develops new end-organ damage such as nephrotic-range proteinuria or restrictive cardiomyopathy, systemic AL amyloidosis should be suspected. The diagnosis requires tissue confirmation, for which an abdominal fat pad aspirate is a high-yield, low-risk initial test.
Explanation:
This patient with a known IgG kappa monoclonal gammopathy presents with new-onset nephrotic-range proteinuria, worsening renal function, and clinical and ECG findings suggestive of restrictive cardiomyopathy (elevated JVP, low limb lead voltage). This constellation is highly concerning for systemic light chain (AL) amyloidosis. The most appropriate next step is to obtain tissue for pathologic confirmation. An abdominal fat pad aspirate with Congo red staining is the recommended initial test due to its high diagnostic yield (around 85%) and low procedural risk. A bone marrow biopsy is often performed in the workup of plasma cell dyscrasias, but its sensitivity for detecting amyloid deposits is lower than that of a fat pad aspirate. While an echocardiogram would likely show characteristic findings like ventricular thickening, it would not provide a definitive tissue diagnosis, which is required. Repeating serum protein electrophoresis is low yield as a stable monoclonal gammopathy is already known; this test would not confirm tissue deposition. A renal biopsy is an invasive procedure that should be reserved for cases where less invasive testing, such as a fat pad aspirate, is non-diagnostic.
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