Approach to the Renal Biopsy

by Dr. Agnes Fogo of Vanderbilt University

Dr Fogo first starts with some normal histology. Normally, there about 3 mesangial cells in the mesangium. Capillary loops are all open. She shows a silver stain that clearly highlights open capillary loops with thin basement membranes. A normal EM showing the homogenous basement membrane and well defined structures.

Fogo will focus mostly on the glomerulus such as podocyte and GBM injury. We start with a thick GBM with proteinuria. She shows a light microscopic slide with a thick non-smooth GBM on silver stain. Spicules are evident on the silver stain, which are considered deposits. on IF, the entire glomerulus lights up with a granular pattern. EM shows subepithelial deposits. Diagnosis = membranous nephropathy.

Now we have a patient with irregularly thickened GBM. Silver stain shows irregular feathery extrusions. EM shows fibrils, randomly arranged. Congo red stain shows bright green. Diagnosis = amyloid (not specified as primary or secondary).

Another thick GBM on a PAS (appears as a pink area that is thick, drawn with a felt-tip pen rather than a fine point pen). The arterials show hyalinosis (both afferent and efferent) and the mesangium is expanded. The EM shows a thick GBM w/o deposits. Diagnosis = diabetic nephropathy.

Now we have a patient with proteinuria and hematuria and segmental sclerosis. This is seen in FSGS of various subtypes (which are clinically important) but not always. Fogo shows an IF with mesangial pattern of positivity: diagnosis = IgA nephropathy.

Fogo now talks about crescents. Crescents can occur in almost any disease. Crescents have a half-moon shape that occur because of a reaction to a rupture of the glomerulus. Crescents are almost always secondary, so be sure to look for the underlying renal disease that led to their formation. Crescents are divided into cellular, fibrocellular, and fibrous. The former are acute, the latter are chronic changes

Now onto the double contour basement membrane. The EM clearly shows cells interposed between the true and false basement membranes.