A 64-year-old man comes to the office due to persistent back pain, constipation, and easy fatigability for the last several months. Blood pressure is 115/75 mm Hg and pulse is 88/min. The patient has dry mucous membranes. Laboratory results are as follows:
| Hemoglobin | 8.6 g/dL |
| Mean corpuscular volume | 92 fL |
| Blood urea nitrogen | 68 mg/dL |
| Creatinine | 3.8 mg/dL |
| Total protein | 8.9 g/dL |
| Albumin | 3.5 g/dL |
Renal biopsy is performed and light microscopy shows atrophic tubules, many of which contain large, obstructing, waxy casts that stain intensely with eosin. Which of the following is the most likely diagnosis in this patient?
Multiple myeloma | |
Pathophysiology |
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Manifestations |
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Laboratory |
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Radiology |
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This patient with back pain, fatigue, normocytic anemia, renal failure, and a gamma gap (serum total protein minus serum albumin ≥4 g/dL) likely has multiple myeloma (MM). MM is a lymphoproliferative disorder characterized by monoclonal plasma cell proliferation and production of monoclonal immunoglobulins. It should be suspected in elderly patients with any combination of hypercalcemia (causes constipation), normocytic anemia (causes fatigue), bone pain (often in the back and ribs due to lytic lesions), elevated gamma gap (due to the presence of large amounts of monoclonal proteins), or renal failure.
Renal failure in MM is often caused by light chain cast nephropathy. Free light chains (Bence Jones proteins) are filtered by the glomerulus in small amounts and then reabsorbed in the tubules. When levels exceed reabsorptive capacity, light chains precipitate with Tamm-Horsfall protein and form casts that cause tubular obstruction and epithelial injury, leading to impaired renal function. On light microscopy, numerous large, glassy eosinophilic casts are seen. Deposition of light chain fragments in the glomerular mesangium and capillary loops can also cause renal failure in MM (amyloid light-chain amyloidosis).
(Choice A) Acute pyelonephritis presents acutely with fever, flank pain, and pyuria. White blood cell casts may be present.
(Choices B and D) Both nephrotoxins (eg, aminoglycosides) and ischemia cause acute tubular necrosis, which classically presents with muddy brown, granular epithelial cell casts and tubular epithelial cells in the urine.
(Choice C) Hypersensitivity interstitial nephritis is often associated with initiation of a new medication. Eosinophilia and eosinophiluria with white cell casts containing eosinophils may be seen; however, waxy eosinophilic casts are not present.
(Choice E) Chronic lead intoxication produces chronic tubulointerstitial nephritis (interstitial fibrosis and tubular atrophy seen on light microscopy); casts are unexpected.
(Choices G and H) Nonsteroidal anti-inflammatory drugs (NSAIDs) may cause chronic interstitial nephritis or acute papillary necrosis; urinalysis may show clear, hyaline casts. Excessive NSAID use is often associated with a microcytic (from gastrointestinal bleeding) rather than normocytic anemia, and a gamma gap would not be expected.
(Choice I) Chronic hyperuricemia leads to urate nephropathy due to precipitation of urate crystals. On light microscopy, needle-shaped crystals are seen in the interstitium and tubular lumen.
Educational objective:
Multiple myeloma should be suspected in elderly patients with any combination of hypercalcemia, normocytic anemia, bone pain, elevated gamma gap, or renal failure. Renal failure is commonly caused by light chain cast nephropathy; large, waxy, eosinophilic casts composed of Bence Jones proteins are seen in the tubular lumen.