Test your medicine knowledge with the MKSAP challenge, in partnership with the American College of Physicians.

A 53-year-old woman is evaluated for a 3-month history of swelling of the face, hands, and feet. She has untreated hepatitis C virus infection. She takes lithium for bipolar disorder. She has no additional symptoms.

On physical examination, temperature is normal, blood pressure is 134/93 mm Hg, pulse rate is 71/min, and respiration rate is 18/min. Bilateral periorbital edema and swelling of the hands and legs are noted. The remainder of the examination is unremarkable.

Laboratory studies:

Complete blood count	Normal
Albumin	1.6 g/dL (16 g/L)
Blood urea nitrogen	28 mg/dL (10 mmol/L)
Complement (C3 and C4)	Normal
Serum creatinine	1.5 mg/dL (133 µmol/L)
Cryoglobulin	Negative
Serum protein electrophoresis	Normal
Rheumatoid factor	Negative
Hepatitis B surface antigen	Negative
Hepatitis C virus antibodies	Positive with low RNA titer
HIV antibodies	Negative
Antinuclear antibodies	Negative
Urinalysis	4+ protein; 4-7 erythrocytes/hpf; 4-7 leukocytes/hpf
24-Hour urine collection of protein	14 g/24 h

Ultrasound shows normal-sized kidneys.

Percutaneous kidney biopsy results show glomeruli of normal size and cellularity, with patent capillary lumina. Diffuse fusion of podocyte foot processes is noted on electron microscopy. Immunofluorescence studies show no immune deposits.

Which of the following is the most likely cause of this patient’s nephrotic syndrome?

A: Hepatitis C virus–associated glomerulonephritis
B: Lupus nephritis
C: Membranous glomerulopathy
D: Minimal change glomerulopathy

MKSAP Answer and Critique

The correct answer is D: Minimal change glomerulopathy.

Minimal change glomerulopathy (MCG) associated with lithium use is the cause of the nephrotic syndrome in this patient. MCG is usually idiopathic, but it also can be associated with atopic diseases; infections such as mononucleosis; malignancies such as Hodgkin lymphoma or carcinomas; and the use of NSAIDs, lithium, or rifampin. MCG usually presents as the nephrotic syndrome and may be accompanied by acute kidney injury, hematuria, and hypertension. Diagnosis is confirmed with kidney biopsy that reveals diffuse fusion and effacement of podocyte foot processes on electron microscopy with normal glomeruli by light and immunofluorescence microscopies. Lithium potentiates tumor necrosis factor– and interleukin-1–induced cytokines and cytokine receptor expression in T-cell hybridomas. It also accelerates interleukin-2 production in human T cells. These effects may have a role in podocyte toxicity and may explain why some patients develop massive proteinuria.

Lupus nephritis is unlikely in the absence of other findings associated with systemic lupus erythematosus and a negative antinuclear antibody titer.

Hepatitis C virus–associated glomerulonephritis, lupus nephritis, and membranous glomerulopathy always exhibit immune complex deposition on immunofluorescence microscopy.

Key Point

• Minimal change glomerulopathy is usually idiopathic, but it also can be associated with atopic diseases; infections such as mononucleosis; malignancies such as Hodgkin lymphoma or carcinomas; and the use of NSAIDs, lithium, or rifampin.

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