A 41-year-old woman is being evaluated for peripheral edema. The patient has gained 6.8 kg (15 lb) over the past 8 weeks. Her urine is "frothy." She has no other medical problems and takes no medications. The patient does not use tobacco, alcohol, or illicit drugs. Blood pressure is 140/90 mm Hg and pulse is 80/min. Examination shows generalized edema. Heart sounds are normal. The abdomen is soft and nontender. Serum creatinine is 1.1 mg/dL. Urinalysis shows 4+ protein, 0-3 leukocytes/hpf, and oval fat bodies. Serum contains IgG4 antibodies to the phospholipase A2 receptor (PLA2R), a transmembrane protein abundant on podocytes. Which of the following is the most likely diagnosis?

Question

A 41-year-old woman is being evaluated for peripheral edema.  The patient has gained 6.8 kg (15 lb) over the past 8 weeks.  Her urine is "frothy."  She has no other medical problems and takes no medications.  The patient does not use tobacco, alcohol, or illicit drugs.  Blood pressure is 140/90 mm Hg and pulse is 80/min.  Examination shows generalized edema.  Heart sounds are normal.  The abdomen is soft and nontender.  Serum creatinine is 1.1 mg/dL.  Urinalysis shows 4+ protein, 0-3 leukocytes/hpf, and oval fat bodies.  Serum contains IgG4 antibodies to the phospholipase A2 receptor (PLA2R), a transmembrane protein abundant on podocytes.  Which of the following is the most likely diagnosis?

Quizplus · Accepted Answer

This patient with weight gain and edema with 4+ protein and oval fat bodies on urinalysis has nephrotic syndrome. The presence of phospholipase A2 receptor (PLA2R) antibodies suggests a diagnosis of membranous nephropathy. Antibodies against PLA2R, primarily IgG4, can lead to immune deposition in the glomerulus and are thought to be a major factor in the pathogenesis of primary (idiopathic) membranous nephropathy, a common cause of nephrotic syndrome in adults. Anti-PLA2R antibodies are highly specific for membranous nephropathy; positive titers effectively rule out other causes of nephrotic syndrome (eg, focal segmental glomerulosclerosis) and may eliminate the need for invasive renal biopsy. In addition, titers correlate with disease activity, and serial measurements can be used to determine the efficacy of immunosuppressive therapy. (Choice A) Focal segmental glomerulosclerosis causes nephrotic syndrome but is caused by direct (eg, cytotoxic drugs) or indirect (eg, glomerular hyperfiltration) podocyte injury. It is not associated with anti-PLA2R antibodies. (Choice C) Minimal change disease may be due to abnormal T-cell production of a glomerular permeability factor that affects the glomerular capillary wall, leading to fusion of the foot processes and marked proteinuria. There has been no association with anti-PLA2R antibodies. (Choice D) Mixed cryoglobulinemia is associated with IgM deposition in the glomerulus, leading to basement membrane thickening and cellular proliferation. Renal disease typically presents as membranoproliferative glomerulonephritis with hematuria and red blood cell casts. It is most common in patients with chronic hepatitis C infection. (Choice E) Renal disease in multiple myeloma is due to deposition of light chains (ie, cast nephropathy) and is not associated with anti-PLA2R antibodies. Educational objective: Primary (idiopathic) membranous nephropathy is associated with IgG4 antibodies to the phospholipase A2 receptor, which might play a role in development of the disease. Antibody titers are useful for diagnosis and correlate with disease activity. __________ References: M-type phospholipase A2 receptor as target antigen in idiopathic membranous nephropathy. (http://www.ncbi.nlm.nih.gov/pubmed/19571279)

A 41-Year-Old Woman Is Being Evaluated for Peripheral Edema