This patient with nephrotic syndrome, low serum C3 levels, and "tram-tracking" on kidney biopsy has type I membranoproliferative glomerulonephritis (MPGN). Chronic hepatitis C can result in type I MPGN.
MPGN is a nephrotic syndrome with two distinct forms. Type I is generally a slower disease secondary to systemic lupus erythematosus (SLE), chronic hepatitis C, or hepatitis B. Type II is a more aggressive disease caused by autoimmune activation of complement by nephritic factor, an autoantibody against C3. Both type I MPGN and type II MPGN share the laboratory findings of low serum C3; however only type II is associated with C3 nephritic factor. These two forms of MPGN can also be distinguished on biopsy. Type I shown "tram-tracking" (Figure 1), and type II shows intramembranous dense deposits. Treatment for MPGN is prednisone with or without plasmapheresis or interferion-alpha, and prognosis is poor.
In a review of management for chronic hepatitis C, Moyer et al. list type II cryoglobulinemia, MPGN, and porphryria cutanea tarda as the most common extra-hepatic ramifications of the disease. Curently, about 1.8% of the American population has been infected with hepatitis C.
In a 2013 review article regarding glomerulonephritis secondary to hepatitis C, Tang et al. remind readers that patients with hepatitis C-associated gromerulonephritis should be treated with pegylated interferon-alpha and ribavirin to address the underlying cause.
Figure A shows a a silver stained kidney biopsy from a patient with MPGN. Note the "tram-traking" (two separate layers of the basement membrane).
Illustration A shows a silver stained kidney biopsy of a patient with focal segmental glomerular sclerosis (FSGS). Note the focuses of sclerosis and hyalinosis.
Illustration B depicts a kidney biopsy from a patient with renal amyloidosis. Left: light microscopy showns congo red staining of amyloid. Right: polarized light causes amyloid to appear green ("apple green birefringence.")
Illustration C shows an electron microscopy (EM) view of a kidney biospy from a patient with membranous nephropathy. Note the "spike and dome" appearance caused by the formation of IgG and C3 sub-epithelial deposits.
Illustration D shows an H&E stained kidney biopsy is from a patient with diabetic nephropathy. Note the Kimmelstiel-Wilson lesions and glomerular sclerosis.
Answer 1: HIV is associated with focal segmental glomeruloscerolsis (FSGS). Pathology of FSGS is notable for discrete focuses of sclerosis and hyalinosis (Illustration A).
Answer 3: Chronic inflammatory disease such as RA are associated with renal amyloidosis. Biopsy is notable for positive staining with congo red and apple-green birefringence (Illustration B).
Answer 4: Syphilis is associated with membranous nephropathy. Biopsy would show "spike and dome" appearance on EM (Illustration C).
Answer 5: Uncontrolled diabetes is associated with diabetic nephropathy. Biopsy is notable for sclerosis and Kimmelstiel-Wilson lesions (Illustration D).
Moyer LA, Mast EE, Alter MJ. Hepatitis C: Part I. Routine serologic testing and diagnosis. Am Fam Physician. 1999 Jan 1;59(1):79-88, 91-2.
PMID:9917576 (Link to Abstract)
Tang SC, Lai KN. Hepatitis C virus-associated glomerulonephritis. Contrib Nephrol. 2013;181:194-206. doi: 10.1159/000348477. Epub 2013 May 8.
PMID:23689581 (Link to Abstract)