This document describes the standard techniques and terminology used in analyzing renal biopsy samples under light microscopy, immunofluorescence, and electron microscopy. It outlines the stains and antibody panels used to identify features in the glomeruli, tubules, interstitium, and blood vessels. Descriptive terms are provided for abnormalities in the glomerular structure, deposits, proliferation, and other patterns of injury. Common findings in tubulointerstitial and vascular components are also defined. Finally, the key components of native kidney and transplant biopsy reports are summarized.

1. Algorithmic Approach to the
Interpretation of Renal Biopsy

2. Basic stains required for LM
H&E PAS
• Glomerular: exudative lesions • Glomerular: GBM thickening, capillary
• Tubular: tubular epithelial damage wall collapse, Bowman’s capsule,
• Interstitial: edema, inflammation hyalinosis, sclerosis, mesangial
cellularity and matrix increase,
• Vascular: inflammation mesangiolysis, endo/extracapillary
proliferation
• Tubular: tubular protein droplets, TBM
thickening, tubulitis
• Vascular: hyaline arteriolosclerosis
Methanamine-silver (Jones stain) Masson trichrome
• Glomerular: GBM spikes, double • Glomerular: immune deposits, thrombi,
contours, breaks in GBM/Bowman’s fibrin, platelets
capsule • Tubular: tubular atrophy
• Tubular: tubulitis • Interstitial: fibrosis
• Interstitial: Fibrosis • Vascular: thrombi
• Vascular: internal elastic lamina

3. Routine antibody panel for IF
• IgG immune complex disease, Anti-GBM disease
• IgA IgA nephropathy, HSP, Liver disease, SLE
• IgM Waldenstrom’s macroglobulinemia, mixed cryoglobulinemia
• C1q C1q nephropathy, SLE
• C3 Dense deposit disease, C3 mesangial GN, resolving PIGN
• Fibrinogen Necrotizing lesion, thrombotic microangiopathy, crescents
• Kappa & Lambda Monoclonal Ig deposition disease, amyloidosis
• C4d (transplant) Humoral rejection

4. Descriptive terms and patterns of glomerular injury
Related to distribution
Focal Involving less than 50% of glomeruli by LM
Diffuse Involving 50% or more of glomeruli by LM
Segmental Involving a portion of the glomerular tuft
Global Involving the entire glomerular tuft

5. Descriptive terms and patterns of glomerular injury
Related to Structure
Obsolescence Total loss of normal glomerular architecture due to replacement by
sclerosis
Sclerosis Increased collagenous extracellular matrix expanding the mesangium,
occluding capillary lumina or forming adhesions to Bowman’s capsule
Fibrinoid necrosis Disruption of structure, with degeneration of local cells, extracellular matrix
and the basement membrane, often associated with fibrin deposition
Lobular Hypersegmentation of the normal lobular architecture of the normal
glomerular capillary tuft due to intracapillary hypercellularity or significant
mesangial expansions
Mesangiolysis Dissolution or attenuation of mesangial matrix and degeneration of
mesangial cells, often associated with glomerular capillary aneurysms
Mesangial interposition Extension of mesangial cells in the peripheral glomerular capillary
walls in the space located between endothelial cells and GMB
(subendothelial zone)

6. Descriptive terms and patterns of glomerular injury
Related to Structure
Hyalinosis Accumulation of glassy, refractile acellular material/plasmatic insudation
(PAS positive, methenamine-silver negative) which contains serum
proteins, other glycoproteins and lipids
Glomerular capillary collapse Retraction of glomerular tuft with closure of capillary lumina and
wrinkling and thickening of glomerular capillary walls
Glomerular capillary aneurysm Capillary lumen balloons out and appears ectatic due to
degeneration of mesangial cells and matrix (mesangiolysis)
Wire-loops Thickened glomerular capillary walls with a rigid appearance (wire-loop-like)
due to the presence of large and confluent subendothelial immune deposits
Tram-tracking/GBM reduplication Double contoured appearance of glomerular capillary walls
on PAS/silver stains due to the presence of deposits and
mesangial interposition between the endothelium and the
original GBM with creation of a new inner (subendothelial
side) basement-membrane-like material

7. Descriptive terms and patterns of glomerular injury
Related to Cell proliferation
Mesangial hypercellularity Presence of 3 or more mesangial and/or inflammatory cells per
mesangial area away from the vascular pole in a section that is
2-3 micron in thickness (WHO definition)
Endocapillary hypercellularity Increased cellularity within the confines of GMB composed of
endothelial cells, mesangial cells and /or inflammatory cells,
resulting in luminal narrowing or occlusion
Intracapillary hypercellularity Hypercellularity present in both mesangium and endocapillaries
Crescent The build-up of more than 2 layers of cells within Bowman’s
space caused by the proliferation of parietal cells, podocytes and
inflammatory cells, often with fibrin and collagen deposition.
Adhesion/synechia Localized narrow bridges of connective tissue between
glomerular tufts and Bowman’s capsule
Membranoproliferative Glomerular capillary wall thickening due to mesangial
interposition and duplication of GMB

8. Descriptive terms and patterns of glomerular injury
Related to Deposits
Intramembranous Within the GBM
Mesangial Within the mesangial matrix
Subendothelial Between the GBM and the endothelium
Subepithelial/epimembranous Between the GBM and podocytes
Humps Subepithelial electron-dense immune-type deposits with
a cigar-or dome-like appearance

9. Descriptive terms and patterns of tubulointerstitial and vascular injury
Tubules
Tubulitis Lymphocytes or other inflammatory cells infiltrating tubular epithelium
Tubular atrophy Tubular involution/obsolescence due to ischemia, obstruction, toxic or
inflammatory injury with different LM appearances including classic
atrophy, endocrine and thyroidization changes
Tubular casts Various coagulated proteins and other elements in tubular lumens usually
but not exclusively seen in distal nephron
Hydropic degeneration/ Fine regular cytoplasmic vacuolization of the proximal tubules
Osmotic nephrosis

10. Descriptive terms and patterns of tubulointerstitial and vascular injury
Tubules
Hyaline droplet PAS/silver-positive protein reabsorption droplets because of increased
protein loss by glomeruli
Fatty change Finely vacuolated cytoplasm with clear vacuoles in the cytoplasm of tubular
epithelium in which the lipid has been dissolved out during preparation of
paraffin sections
Hypokalemic change Large irregular sized coarse clear vacuoles in the cytoplasm of tubular
epithelial cells, especially the distal tubular cells
Intranuclear inclusions Seen in nuclei with various morphology depending on etiology, often
associated with viral infections (CMV, BK polyomavirus and adenovirus),
can be observed in tubular epithelial cell regeneration and lead
nephropathy

11. Descriptive terms and patterns of tubulointerstitial and vascular injury
Interstitium
Edema Increased extracellular fluid in the interstitium resulting in increased spacing
between tubules
Interstitial foam cells Macrophages with cytoplasm lipid-containing vacuoles
Inflammation Infiltration of lymphocytes, plasma cells, and often eosinophils and
neutrophils with associated tubular injury
Fibrosis Interstitial expansion by collagen
Granuloma Collection of epithelioid histiocytes with/with out surrounding multinucleated
giant cells and lymphocytes

12. Descriptive terms and patterns of tubulointerstitial and vascular injury
Vessels
Intimal thickening Fibrous thickening of the intimal layer, usually in a concentric configuration
and associated with varying degrees of luminal stenosis
Hyaline sclerosis Accumulation of PAS-positive/silver-negative material in the intima and /or
media resulting in a characteristic “glassy” acellular refractile change in
small arteries and arterioles
Endothelialitis/endarteritis Infiltration of mononuclear cells under arterial and arteriolar
endothelium
Arteritis Necrosis, fibrinoid degeneration and inflammation of arteries with
leukocytoclasia and disruption of internal elastic lamina
Vasculitis Necrosis, fibrinoid degeneration and leukocytoclastic inflammation of
arteries, arterioles and veins

25. Components of Native Kidney Biopsy Pathology Report
Light microscopy
• Presence and relative proportion of renal capsule, cortex, medulla, pelvic
urothelial lining and others (i.e., skeletal muscle, liver, intestine)
• Total number of glomeruli and the number/percentage of globally sclerotic
glomeruli if any
• Description of diagnostic morphology lesions/changes/patterns in glomeruli,
tubules, interstitium and vessels
• Description of important or relevant negative findings

26. Components of Native Kidney Biopsy Pathology Report
Immunofluorescence microscopy
• Total number of glomeruli and the number of globally sclerotic glomeruli if
present
• Description of positive or negative results for each Ig and complement
components in glomeruli
• Description of the location, stain pattern and intensity of the deposits in
glomeruli
• Description of immunoreactants in tubulointerstitial compartment and
vessels if present

27. Components of Native Kidney Biopsy Pathology Report
Electron microscopy
• Total number of glomeruli and the number of globally sclerotic glomeruli if
present
• Description of glomerular abnormalities/changes
• Description of the location, number, size, appearance/substructure of
electron dense deposits if present
• Description of degree of foot process effacement
• Description of relative changes in tubulointerstitial and vascular component

28. Components of Native Kidney Biopsy Pathology Report
Diagnosis
• Including morphologic pattern plus a particular pathogenic or
clinicopathologic category of the disease
Comment
• Clinicopathologic correlation
• List of differential diagnoses if necessary
• Pertinent histologic prognostic indicators
• Activity/chronicity indices of lupus nephritis

29. Components of Renal Transplant Biopsy Pathology Report
Light microscopy
• Glomeruli: glomerulitis, fibrin thrombosis, double contours, and other
glomerular lesions
• Tubules: tubular injury, inflammation (tubulitis), nuclear atypia/inclusions
• Interstitium: nature and degree of cellular infiltrate (i.e., edema, activated
mononuclear cell, malignant cells, leukocytes in peritubular capillaries)
• Vessels: endarteritis, myocyte necrosis, thrombi, nodular hyaline, intimal
elastosis

30. Components of Renal Transplant Biopsy Pathology Report
Immunofluorescence microscopy
• C4d staining in peritubular capillaries

31. Components of Renal Transplant Biopsy Pathology Report
Electron microscopy
• Glomerular abnormalities
• Viral particles
• Peritubular capillary basement membrane multilayering

32. Components of Renal Transplant Biopsy Pathology Report
Diagnosis
• Including a particular patholonic or clinicopathologic category of the disease
(Banff Classification for Renal Transplant Pathology)
Comment
• Clinicopathologic correlation
• List of differential diagnoses if necessary
• Pertinent histologic prognostic indicators