A 68-year-old African American man is evaluated for several weeks of progressive fatigue. His other complaints include abdominal discomfort, lower extremity edema, and chronic dry cough. He has not experienced fever, chills, or weight loss. He has a history of type 2 diabetes mellitus diagnosed 5 years ago, hypertension, and hyperlipidemia. Current medications include amlodipine, lisinopril, metformin, glyburide, and rosuvastatin.
His temperature is 37.1 C (98.8 F), blood pressure is 165/92 mm Hg, pulse is 84/min, and respirations are 16/min. Examination shows a 2/6 systolic ejection murmur along the left sternal border without radiation and 2+ pretibial edema bilaterally.
Laboratory results are as follows:

Chest X-ray shows mild cardiomegaly and small bilateral pleural effusions.
Which of the following is the most likely diagnosis?

Question

A 68-year-old African American man is evaluated for several weeks of progressive fatigue.  His other complaints include abdominal discomfort, lower extremity edema, and chronic dry cough.  He has not experienced fever, chills, or weight loss.  He has a history of type 2 diabetes mellitus diagnosed 5 years ago, hypertension, and hyperlipidemia.  Current medications include amlodipine, lisinopril, metformin, glyburide, and rosuvastatin.
His temperature is 37.1 C (98.8 F), blood pressure is 165/92 mm Hg, pulse is 84/min, and respirations are 16/min.  Examination shows a 2/6 systolic ejection murmur along the left sternal border without radiation and 2+ pretibial edema bilaterally.
Laboratory results are as follows:

Chest X-ray shows mild cardiomegaly and small bilateral pleural effusions.
Which of the following is the most likely diagnosis?

Quizplus · Accepted Answer

11ec193a_98f0_5f32_853d_6708734705f3_MD0002_00 This patient's clinical presentation is most consistent with multiple myeloma, given the hypercalcemia, anemia, renal insufficiency, and urinary protein discrepancy. The dipstick measurement for urinary protein detects only albumin, while the laboratory measurement for quantitative analysis detects all urinary proteins. When the amount of protein assessed by quantitative methods significantly exceeds the amount of protein detected by dipstick, it suggests the presence of non-albumin proteins (such as light chains). In this patient, urine dipstick +1 protein indicates a 30-100 mg/dL albumin excretion, whereas a urine total protein/creatinine ratio of 2.5 indicates approximately 2.5 g/d of total protein excretion. Approximately 40% of individuals with multiple myeloma have a serum creatinine concentration >1.5 mg/dL at presentation. This is associated with a significantly worse prognosis. Filtered light chains are directly toxic to renal tubular epithelial cells and can interact with Tamm Horsfall proteins (secreted into tubular fluid), causing extensive intratubular cast formation. Other factors contributing to renal disease include significant hypercalcemia, hyperuricemia, hyperviscosity, and renal plasma cell infiltration. (Choice A) Although this patient has few white blood cells present on urinalysis in addition to being exposed to several pharmacologic agents, acute interstitial nephritis is usually not associated with hypercalcemia. (Choice B) Diabetic nephropathy is not usually associated with a gap between the two methods of estimating proteinuria or hypercalcemia. (Choice C) Focal segmental glomerulosclerosis frequently presents with significant proteinuria and nephrotic syndrome, but not usually with either hypercalcemia or a discrepancy between the two methods of measuring proteinuria. (Choice E) Sarcoidosis is associated with hyperabsorptive hypercalcemia, granulomatous interstitial nephritis, several types of glomerular disorders, and hypercalciuria that can lead to kidney stones and obstructive uropathy. Sarcoidosis is not associated with differences in the dipstick and quantitative methods of measuring proteinuria. Educational objective: Multiple myeloma commonly presents with acute kidney injury, most commonly due to cast nephropathy. A discrepancy between the amounts of proteinuria detected by dipstick and by quantitative methods suggests non-albumin proteinuria and the presence of light chains, which are directly toxic to renal tubules or can combine with Tamm-Horsfall proteins to form casts. __________ References: Renal failure in multiple myeloma: presenting features and predictors of outcome in 94 patients from a single institution. (http://www.ncbi.nlm.nih.gov/pubmed/9759684) Improvement of cast nephropathy with plasma exchange depends on the diagnosis and on reduction of serum free light chains. (http://www.ncbi.nlm.nih.gov/pubmed/18385667) Criteria for the classification of monoclonal gammopathies, multiple myeloma and related disorders: a report of the International Myeloma Working Group. (http://www.ncbi.nlm.nih.gov/pubmed/12780789)

A 68-Year-Old African American Man Is Evaluated for Several Weeks