MKSAP Quiz: 4-week history of dyspnea on exertion
A 54-year-old woman is evaluated for a 4-week history of dyspnea on exertion, malaise, fatigue, and anorexia. History is significant for hypertension, gout, and osteoarthritis. Following a physical exam, lab studies, and chest radiograph, what is the most likely diagnosis?
A 54-year-old woman is evaluated for a 4-week history of dyspnea on exertion, malaise, fatigue, and anorexia. History is significant for hypertension, gout, and osteoarthritis. Medications are losartan, hydrochlorothiazide, allopurinol, naproxen, and aspirin.
On physical examination, blood pressure is 148/84 mm Hg, and pulse rate is 98/min; other vital signs are normal. Conjunctivae are pale. There is 2+ edema of the ankles.
Laboratory studies:
| Hemoglobin | 8.0 g/dL (80 g/L) |
| Albumin | 3.0 g/dL (30 g/L) |
| Calcium | 9.8 mg/dL (2.5 mmol/L) |
| Creatinine | 2.2 mg/dL (194.5 µmol/L); 3 weeks ago: 1.2 mg/dL (106.1 µmol/L) |
| Total protein | 8.4 g/dL (84 g/L) |
| Urate | 7.0 g/dL (0.41 mmol/L) |
| Urinalysis | 1+ protein; 2-5 granular casts/hpf; 1-2 erythrocytes/hpf |
| Urine protein-creatinine ratio | 6100 mg/g |
Chest radiograph is normal.
Which of the following is the most likely diagnosis?
A. Light chain cast nephropathy
B. NSAID-induced acute tubular injury
C. Renal sarcoidosis
D. Uric acid nephropathy
MKSAP Answer and Critique
The correct answer is A. Light chain cast nephropathy. This content is available to MKSAP 18 subscribers as Question 91 in the Nephrology section. More information about MKSAP is available online.
The most likely diagnosis is light chain cast nephropathy in this patient with multiple myeloma. In multiple myeloma, acute kidney injury from light chain cast nephropathy is the most common type of kidney disease. Cast nephropathy is characterized by intratubular obstruction with light chain casts that can result in acute tubular injury. A clinical clue to the diagnosis is the presence of an elevated urine protein-creatinine ratio, with minimal proteinuria detected by dipstick urinalysis (dipstick urinalysis detects albumin but not light chains). Other supporting findings are the presence of anemia and hypercalcemia (when calcium measurement is corrected for albumin).
Exposure to NSAIDs can cause tubular injury. However, NSAIDs do not cause a discrepancy in proteinuria between urinalysis and urine protein-creatinine ratio.
Renal sarcoidosis can result in tubulointerstitial dysfunction. Other kidney manifestations include direct ureteral involvement, retroperitoneal fibrosis, and, more commonly, hypercalcemia, hypercalciuria, nephrolithiasis, and nephrocalcinosis via excessive production of 1,25-dihydroxyvitamin D in granulomas. However, renal sarcoidosis is rare in patients without thoracic sarcoidosis and cannot account for the discrepancy in proteinuria between urinalysis and urine protein-creatinine ratio.
Uric acid nephropathy is unlikely given the modest elevation in the serum urate level. Furthermore, an elevated urine protein-creatinine ratio is not consistent with uric acid nephropathy.
Key Point
- Clinical clues to the diagnosis of light chain cast nephropathy from multiple myeloma include an elevated urine protein-creatinine ratio with minimal proteinuria by urine dipstick, anemia, and hypercalcemia.