IM Board Review

Weight loss, fatigue, and renal failure

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A black 37-year-old man has gradually lost 100 lb (45 kg) over the past 2 years, and reports progressive fatigue and malaise as well. He has not noted swollen lymph nodes, fever, or night sweats. He denies dyspnea, cough, or chest pain. He has no skin rashes, and no dry or red eyes or visual changes. He reports no flank pain, dysuria, frank hematuria, foamy urine, decline in urine output, or difficulty voiding.

He has no history of significant medical conditions. He does not drink, smoke, or use recreational drugs. He is not taking any prescription medications and has not been using nonsteroidal anti-inflammatory drugs (NSAIDs) or combination analgesics. He does not have a family history of kidney disease.

Physical examination. He appears relaxed and comfortable. He does not have nasal polyps or signs of pharyngeal inflammation. He has no apparent lymphadenopathy. His breath sounds are normal without rales or wheezes. Cardiac examination reveals a regular rhythm, with no rub or murmurs. The abdomen is soft and nontender with no flank pain or groin tenderness. The skin is intact with no rash or nodules.

  • Temperature 98.4ºF (36.9ºC)
  • Blood pressure 125/70 mm Hg
  • Heart rate 102 beats per minute
  • Respiratory rate 19 per minute
  • Oxygen saturation 99% while breathing room air
  • Weight 194 lb (88 kg)
  • Body mass index 28 kg/m2.
Patient’s laboratory test results at presentation

Laboratory testing (Table 1) reveals severe renal insufficiency with anemia:

  • Serum creatinine 9 mg/dL (reference range 0.5–1.2)
  • Estimated glomerular filtration rate (eGFR) 8 mL/min/1.73m2 (using the Modification of Diet in Renal Disease Study equation).

His serum calcium level is normal, but his serum phosphorus is 5.3 mg/dL (reference range 2.5–4.6), and his parathyroid hormone level is 317 pg/mL (12–88), consistent with hyperparathyroidism secondary to chronic kidney disease. His 25-hydroxyvitamin D level is less than 13 ng/mL (30–80), and angiotensin-converting enzyme (ACE) is 129 U/L (9–67 U/L). His urinary calcium level is less than 3.0 mg/dL.

Urinalysis:

  • Urine protein 100 mg/dL (0–20)
  • No urine crystals
  • 3 to 5 coarse granular urine casts per high-power field
  • No hematuria or pyuria.
Renal biopsy study
Figure 1. Renal biopsy study demonstrated granulomatous interstitial nephritis (arrow) with nonnecrotizing granulomas identified within the interstitium (arrowhead) (periodic acid-Schiff, × 100).
Chest radiography shows normal lungs, heart size, and mediastinum.

Renal ultrasonography shows normal kidneys with no hydronephrosis.

Renal biopsy study demonstrates noncaseating granulomatous interstitial nephritis (Figure 1).

GRANULOMATOUS INTERSTITIAL NEPHRITIS

1. Based on the information above, what is the most likely cause of this patient’s kidney disease?

  • Medication
  • Granulomatosis with polyangiitis
  • Sarcoidosis
  • Infection

Granulomatous interstitial nephritis is a histologic diagnosis that is present in up to 1% of renal biopsies. It has been associated with medications, infections, sarcoidosis, crystal deposits, paraproteinemia, and granulomatosis with polyangiitis and also is seen in an idiopathic form.

Medicines implicated include anticonvulsants, antibiotics, NSAIDs, allopurinol, and diuretics.

Mycobacteria and fungi are the main infective causes and seem to be the main causative factor in cases of renal transplant.1 Granulomas are usually not found on kidney biopsy in granulomatosis with polyangiitis, and that diagnosis is usually made by the presence of antiproteinase 3 antibodies.2

Sarcoidosis is the most likely diagnosis in this patient after excluding implicated medications, infection, and vasculitis and confirming the presence of granulomatous interstitial nephritis on renal biopsy.

SARCOIDOSIS: A MULTISYSTEM DISEASE

Sarcoidosis is a multisystem inflammatory disease of unknown cause, characterized by noncaseating epithelioid granulomas. It can involve any organ but most commonly the thoracic and peripheral lymph nodes.3,4 Involvement of the eyes and skin is also relatively common.

Extrapulmonary involvement occurs in more than 30% of cases of sarcoidosis, almost always with concomitant thoracic involvement.5,6 Isolated extrathoracic sarcoidosis is unusual, found in only 2% of patients in a sarcoidosis case-control study.5

Current theory suggests that sarcoidosis develops from a cell-mediated immune response triggered by one or more unidentified antigens in people with a genetic predisposition.7

Sarcoidosis affects men and women of all ages, most often adults ages 20 to 40; but more recently, it has increased in US adults over age 55.8 The condition is more prevalent in Northern Europe and Japan, and in blacks in the United States.7

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