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MKSAP Quiz: 1-year history of lower extremity edema

This week's quiz asks readers to determine the most likely diagnosis for a 60-year-old man with a 30-year history of poorly controlled ankylosing spondylitis and intermittent uveitis who is evaluated for a 1-year history of lower extremity edema.


A 60-year-old man is evaluated for a 1-year history of lower extremity edema. He has a 30-year history of poorly controlled ankylosing spondylitis. He also has intermittent uveitis. His only medication is naproxen; he has been reluctant to initiate biologic agents.

On physical examination, blood pressure is 158/90 mm Hg. Other vital signs are normal. He has kyphosis with immobility of the cervical, thoracic, and lumbar spine. There is decreased range of motion of the shoulders and hips with 30-degree flexion contractures at both hips. There is 2+ bilateral swelling of the lower extremities.

Laboratory studies:

Albumin 2.5 g/dL (25 g/L)
C-reactive protein 6.3 mg/dL (63 mg/L)
Creatinine 1.8 mg/dL (159.1 μmol/L)
Urinalysis 3+ protein; no erythrocytes, leukocytes, casts, or eosinophils
Protein-creatinine ratio 5200 mg/g

Which of the following is the most likely diagnosis?

A. Analgesic nephropathy
B. IgA nephropathy
C. Interstitial nephritis
D. Renal amyloidosis

Reveal the Answer

MKSAP Answer and Critique

The correct answer is D. Renal amyloidosis. This content is available to MKSAP 19 subscribers as Question 72 in the Rheumatology section. More information about MKSAP is available online.

The most likely diagnosis is renal amyloidosis (Option D). Patients with long-standing, poorly controlled inflammatory diseases, such as ankylosing spondylitis (AS) or rheumatoid arthritis, can develop renal amyloidosis (AA amyloidosis). The prevalence of kidney disease in AS is 2% to 13%; in the past, AA amyloidosis was the leading cause of kidney disease (and remains a major cause) in patients with uncontrolled AS. With the advent of biologic therapy and subsequent control of inflammation in AS, the prevalence of AA amyloidosis has declined. AA amyloidosis most commonly affects the kidneys, manifesting as proteinuria and eventually end-stage kidney disease. It less commonly affects the gastrointestinal tract, heart, and peripheral nerves. In AS, AA amyloidosis is most often seen in men, patients with peripheral joint disease, and patients with a history of uveitis. Affected patients will usually manifest high levels of inflammatory markers, such as erythrocyte sedimentation rate and C-reactive protein, indicating insufficient control of disease-related inflammation. Treatment with effective medications, such as tumor necrosis factor inhibitors, may stabilize or improve the kidney manifestations of AA amyloidosis in patients with AS. When AA amyloidosis is suspected, Congo red staining of biopsy specimens from the kidney, rectum, or abdominal subcutaneous fat will reveal amyloid deposition.

Analgesic nephropathy (Option A) may develop after years of NSAID use and typically presents with abnormalities on routine urinalysis, including pyuria, proteinuria, and hematuria. Chronic kidney disease and end-stage kidney disease can develop in some patients. This patient's urine findings are not compatible with analgesic nephropathy.

IgA nephropathy (Option B) is seen in patients with AS but typically manifests as hematuria and proteinuria, not isolated proteinuria. IgA nephropathy in patients with AS tends to be milder, with less renal insufficiency, than in those with idiopathic IgA nephropathy. More aggressive treatment of AS does not seem to affect the clinical course of the AS-related IgA nephropathy.

Interstitial nephritis (Option C) can be caused by a variety of medications, including NSAIDs, antibiotics, and proton pump inhibitors. Symptoms may include fever, rash, and eosinophilia/eosinophiluria. All patients will have a rise in serum creatinine levels as well as pyuria, hematuria, and proteinuria. Leukocyte casts are typically seen on urinalysis. This patient lacks these laboratory findings.

Key Points

  • Patients with long-standing, poorly controlled ankylosing spondylitis can develop renal (AA) amyloidosis, the major cause of kidney disease in these patients.
  • AA amyloidosis most commonly affects the kidneys, manifesting as proteinuria and, eventually, renal insufficiency.