AJKD

QUIZ PAGE ANSWERS JULY 2004

A 79-year-old Caucasian man presented with acute renal failure. A review of systems was positive for anorexia, nausea, and vomiting, but was otherwise negative. His blood pressure was 156/88 mm Hg, and urine output over 24 hours was 1.7 L. His medical history was remarkable for hypertension and possible upper respiratory infection about 2 weeks prior to admission, with cutaneous rash after antibiotic use. His serum creatinine level was 10 mg/dL (884 mol/L); blood urea nitrogen, 57 mg/dL (20.3 mmol/L); sodium, 135 mEq/L (mmol/L); potassium, 4.6 mEq/L (mmol/L); chloride, 95 mEq/L (mmol/L); bicarbonate, 27 mEq/L (mmol/L); calcium, 9.2 mg/dL (2.30 mmol/L); phosphorus, 5.9 mg/dL (1.91 mmol/L); and albumin, 3.2 g/dL (32 g/L). He was anemic with a hematocrit value of 27.9% and hemoglobin level of 9.7 g/dL (97 g/L); white blood cell and platelet counts were 12,200 103/L (109/L) and 157,000 103/L (109/L), respectively. Antinuclear antibodies were positive at 1:40, antineutrophil cytoplasmic antibodies were negative, and C3 was 127 mg/dL. Urinalysis showed specic gravity of 1.006, pH of 7.5, no protein, and 4 white blood cells and 1 red blood cell per high-power eld.

What is your clinical differential diagnosis?

The clinical differential diagnosis included drug-induced acute interstitial nephritis.

Figures 29A and 29B.

What do you see by light microscopy? (Glomeruli [not shown] were unremarkable.)

There is a marked interstitial inltrate containing numerous eosinophils with focal granulomatous reaction (Fig 29A; Jones silver stain, original magnication 200). Some tubular proles contained eosinophils within the tubular epithelium (Fig 29B; Jones silver stain, original magnication 1,000).

Figures 29C and 29D.

What additional features do you observe by light microscopy?

Other tubules contain casts with sharply delineated borders with surrounding syncytial giant cell formation (Fig 29C; Jones silver stain, original magnication 400). Silver positive spicules protrude from the border of one of these casts with surrounding inammatory cell reaction (Fig 29D; Jones silver stain, original magnication 1,000). Interestingly, Congo red stain was positive in this area, but not elsewhere.

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Figure 29E.

QUIZ PAGE ANSWERS

(continued)

What do you see by immunouorescence microscopy?

By immunouorescence, there is 3 staining for light chain in the casts with only trace staining for . There is no staining in the glomerular or tubular basement membranes (Fig 29E; anti- antibody, original magnication 200). Immunoglobulin G (IgG), IgA, IgM, C3, and C1q staining were negative.

What is your diagnosis, and what additional laboratory test(s) do you think would be useful in this setting?
These light microscopic and immunouorescence ndings are diagnostic of light chain cast nephropathy. Although no amyloid deposits were detected in glomeruli, vessels, or interstitium, the patient may develop amyloid in the future because the monoclonal light chain in this patient may also have amyloidogenic properties as shown by the amyloid staining present in the cast. Light microscopy also showed numerous eosinophils in the interstitium with granulomatous reaction and eosinophils detected also within the tubular epithelium. Although eosinophils can be seen in light chain cast nephropathy as part of the inammatory response, in this patient with history of cutaneous rash after antibiotic administration, the eosinophils and the granulomatous reaction may represent morphologic ndings of a superimposed drug-induced hypersensitivity reaction. Additional useful tests would include serum protein electrophoresis and urine protein electrophoresis (with immunoxation if needed to detect the underlying monoclonal protein) and bone marrow biopsy. In this patient, a bone marrow biopsy was within normal limits, but serum and urine immunoxation revealed monoclonal light chain.

Final Diagnosis: Light chain cast nephropathy.

Case provided by Agnes B. Fogo, MD, Michele Rossini, MD, Vanderbilt University Medical Center, Nashville, TN; and Andrew Lazin, MD, Gulf Coast Kidney Associates, Venice, FL. If you have an interesting case you would like to submit for consideration, please go to http://ajkd.edmgr.com to do so.