A Pregnant Woman with New Proteinuria - Renal and Urology News

A Pregnant Woman with New Proteinuria

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A Hispanic woman in her 20s is referred to nephrology for evaluation of recently discovered proteinuria. She is 16 weeks into her first pregnancy. She has no significant medical history and no specific knowledge of proteinuria. The woman has had lower extremity edema and foamy urine for about the past two weeks. She denies any fevers or recent illness. She further denies any headaches, dyspnea, chest pain, abdominal pain, liver disease, gross hematuria, rash, or arthralgias. Her blood pressure is 115/65 and she has 2+ leg edema on exam.

Her serum creatinine is 0.4 mg/dL. Glucose is normal. Urinalysis reveals SG 1.029, 600 protein and 8 RBCs. A 24 hour urine protein measures 6.3 grams protein, total cholesterol is 294 mg/dL, serum albumin is 1.7 g/dL. ANA and anti DS DNA assays are negative. C3 level is within normal limits. SPEP is normal. Hepatitis and HIV serology are also negative. Imaging of kidneys revealed normal-sized organs.

Representative micrographs of light and EM specimens are shown. Immunofluorescence (not shown) revealed 2+ kappa and lambda granular glomerular basement membrane (GBM) staining. C3 stained 1+ in the GBM. IgG4 stained 4+ in the GBM. C4 and C1q stains were negative.

Immunohistochemical stain for IgG4.This patient had an uncomplicated biopsy at 18 weeks into her pregnancy. The biopsy was performed to determine the cause of her proteinuria and thus to assist in choosing best treatment options in a high risk pregnancy. ...

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Immunohistochemical stain for IgG4.

This patient had an uncomplicated biopsy at 18 weeks into her pregnancy. The biopsy was performed to determine the cause of her proteinuria and thus to assist in choosing best treatment options in a high risk pregnancy. 

The renal biopsy for this patient was consistent with idiopathic membranous nephropathy. In the Jones silver and trichome stained images, there are subtle beaded, spiked appearing bumps on the epithelial side of the glomerular basement membranes. The electron micrograph confirms subepithelial deposits of varying size. Immunologic staining for IgG4 was strongly positive.

Membranous nephropathy is a common cause of nephrotic syndrome in non-diabetic patients. It can be divided into idiopathic/primary versus secondary variants. Recent advances have suggested that a majority of cases of idiopathic membranous nephropathy may involve production of autoantibodies to the phospholipase A2 receptor (PLA2R).  IgG subclass staining on idiopathic membranous biopsies reveal high rates of selective IgG subclass 4 positivity. 

Secondary causes of membranous nephropathy include systemic lupus erythematosus (SLE), histologically classified as WHO class V lupus nephritis. Malignancies such as lung, breast, and colon cancers can also lead to membranous nephropathy. Secondary membranous biopsies tend to have a more non-specific IgG subclass staining (IgG1, IgG2, or IgG3) with less IgG4 positivity. Other secondary causes of membranous nephropathy include drugs such as gold, NSAIDs, and penicillamine.  Infectious etiologies include hepatitis B, and less commonly, hepatitis C.

Answer:Idiopathic membranous nephropathy

This case was prepared by Kevin T. Harley, MD, Assistant Clinical Professor of Medicine and Philip Carpenter, MD, Professor of Clinical Pathology, at the University of California in Irvine.

References

  1. Haas M, IgG subclass deposits in glomeruli of lupus and nonlupus membranous nephropathies. Am J Kidney Dis. 1994;23:358-364.
  2. Ohtani H, Wakui H, Komatsuda A, et al, Distribution of glomerular IgG subclass deposits in malignancy-associated membranous nephropathy. Nephrol Dial Transplant 2004;19:574-579.
  3. Qu Z, Liu G, Li J, et al, Absence of glomerular IgG4 deposition in patients with membranous nephropathy may indicate malignancy Nephrol Dial Transplant 2012;27:1931-1937.
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