Basic renal pathology

How to approach a renal biopsy

Professor Peter Furness

University Hospitals of Leicester
pnf1@le.ac.uk
Initial approach
 Clinical information?
 Cortex / medulla?
 Glomeruli (How many?)
 Tubules

 Interstitium

 Blood vessels
Glomerular disease nomenclature

Normal Segmental Global

Focal Diffuse
Glomerular disease nomenclature:
When is a diagnosis not a diagnosis?
Descriptive Focal segmental proliferative glomerulonephritis

Focal segmental glomerulosclerosis

Mesangiocapillary glomerulonephritis

Membranous glomerulonephritis

Specific Alport syndrome

Normal H&E
Normal H&E
Normal Silver
ASSESSMENT OF GLOMERULAR DAMAGE

Cell proliferation
 Which cells? Location? Segmental/global?
Extent? Age?
Cytoplasm or matrix?
Sclerosis
 Pattern and extent of sclerosis (tuft adhesions, tip,
hilar, random, global, grouped, periglomerular)
Crescents
 Number? Extent? Cellular? Fibrous? WHY?
Mesangial hypercellularity (mild)
Mesangial hypercellularity
Glomerular tuft adhesion?
Glomerular tuft adhesion
Focal segmental proliferation - PAS
Segmental necrosis
Segmental sclerosis
Segmental necrosis – Methenamine silver
Segmental sclerosis- Methenamine silver
Crescents – how old?
‘Spikes’ in membranous nephropathy
Very early membranous nephropathy
‘Double contours’
Minimal change nephropathy
Minimal change nephropathy
ASSESSMENT OF GLOMERULAR DAMAGE

 Immunocytochemistry

 Mesangial, loop or both?

 Granular or linear?

 Which IGs?

 Is it artefactual?
Mesangial positivity in IgA nephropathy
Capillary loop positivity. Linear or granular?
The perils of peroxidase - Insufficient Trypsin
The perils of peroxidase – Too much trypsin
ASSESSMENT OF GLOMERULAR DAMAGE

 Electron Microscopy
 Electron dense deposits?
Mesangial? Subendothelial? Subepithelial? Linear?

 Basement membrane structure/thickness?

 Foot process effacement?
 Amyloid? Odd inclusions etc.?
 Anything else?
Normal filtration barrier
Minimal change – foot process effacement
Electron dense deposits. Where are they???
Navigating a glomerulus…
Sometimes one image is diagnostic…
Normal tubules and interstitium
Normal cortex and interstitium
Tubules and interstitium PAS
Tubular vacuolation – cause?
Tubular atrophy
Tubular atrophy - silver
ATN – morphology and function are poorly correlated
ATN - regeneration
‘Interstitial nephritis’
Myeloma
Artery – H&E
Artery – EVG – normal?
Artery – EVG
Renal Biopsies – Diagnostic process
information – what is possible?
 Clinical
 Morphology
 Glomeruli, tubules, interstitium, blood vessels…
 Morphological ‘diagnosis’
 Further investigations?
 E. M., immuno, incorporate clinical information…
 Disease process diagnosis
 Differential diagnosis – order of probability?
 ‘Grade’ and ‘stage’?
 Clinico-pathological correlation – preferably with video camera
 Refine probabilities. Does it make sense? Don’t be dogmatic.