Glomerular Disease & Pathology

Glomerular Anatomy

What is the glomerular filtration barrier?

Plasma water is filtered across capillary wall (GFB) into urinary space

Histological image of glomerular filtration barrier

If you see someone with an elevated creatinine and low protein, youd think of

tubulointerstitial or vascular disease

If you see someone with an elevated protein,

It is a major clue to glomerular disease

What are the clinical presentations of glomerular disease

• Asymptomatic urinary abnormalities

• Nephrotic syndrome

• Glomerulonephritis (nephritis)

What conditions do you see in glomerulonephtiris?

• Acute Kidney Injury (Acute Nephritis or RPGN)

• Chronic Kidney Disease (chronic glomerulonephritis)

Urinalysis abnormalities are common

What is the prevalence of albuminuria in the united states?

59y/o woman presents with two month history of swollen ankles. She had previously been well. No past history of heart disease, liver disease or diabetes

Examination

• BP 142/94

• P 72

• 3+ edema

• Chest clear

• No JVD

Investigations

• renal impairment: Screat 2.2mg/dl (creat clearance 34mls/min)

• urine protein 14.7g/24h (normal <0.1g/24h)

• Salb 1.8 g/dl

What does she have?

Nephrotic Syndrome

What are the clinical features of Nephrotic Syndrome?

• Proteinuria (>3.5g/24 hours)

• Hypoalbuminemia

• Edema

• Hyperlipidemia

• Lipidura

What are the complications of Nephrotic Syndrome?

• Clotting/Thrombosis- Liver is losing coagulating proteins

• Infection- You lose immunoglobulin in urine

• Cardiovascular disease- hyperlipidemia

Why do patients with nephrotic syndrome develop edema?

The kidneys are primarily holding onto kidneys itself because of low oncotic pressure this leads to interstitial shift. Primary sodium retention

Nephrotic syndrome is a disorder of

GLomerular Filtratration Barrier

What are some differential diagnoses of Nephrotic syndrome?

• Primary glomerular disease

  • Minimal change disease

  • FSGS

  • Membranous nephropathy

  • Membranoproliferative GN

• Systemic disease

  • Diabetes

  • Amyloid

  • Lupus

To make a differential diagnosis, you’d take a

Kidney biopsy

How does the kidney biopsy (pathology) assist in diagnosis?

Kidney biopsies are generally studies by

• light microscopy (LM)

• Immunofluorescence (IF)

• Electron microscopy (EM)

What type of microscopy evaluates which parts of the kidneys are affected?

Light microscopy

What type of microscopy evaluates Immune complexes?

Immunofluoresnece

What type of microscopy evaluates location of immune deposits?

Electron microscopy also looks at podocyte foot process integrity

Histological image of normal glomerulus

This slide is stained with Jones Methenamine Silver (JMS) which stains basement membranes and matrix in black- also note the normal tubules and small artery (at 8 o’clock to glomerulus)

What does a normal glomerulus look like in transmission electron microscopy?

What are podocyte foot process

Fine projections that come from neighboring cells

What is minimal change disease?

Characterized by little if any alterations by light or immunofluorescence microscopy

Instead of seeing a nice smooth pattern, you see

Diffuse effacement of podocyte foot processes by electron microscopy

Electron Micrograph showing normal podocyte foot processes

Minimal change disease histological image

Podocyte foot process effacement

What is Focal and Segmental Glomerulosclerosis (FSGS)?

Segmental scarring of capillary loops with attachments to Bowman’s capsule

What does a confident diagnosis of Focal and Segmental Glomerulosclerosis (FSGS) require?

The right clinical context and sufficient sampling (even one glomerulus with the right pattern of injury is enough to make the diagnosis!)

What is the mechanism of Focal and Segmental Glomerulosclerosis (FSGS)

Irreversible injury to podocyte —> destabilization of capillary segments scarring

What is the etiology of Focal and Segmental Glomerulosclerosis (FSGS)

• Circulating factor (anti-nephin antibiotics)

• Hyperfiltration injury

• Genetics

Focal and Segmental Glomerulosclerosis (FSGS) histological image

Another Focal and Segmental Glomerulosclerosis (FSGS) Histological image

Podocyte Foot Process Effacement seen in Focal and Segmental Glomerulosclerosis (FSGS)

What is membranous nephropathy?

Accumulation of immune deposits in the subepithelial space (below podocytes) that results in podocyte injury and proteinuria. It has a characteristic thickening of glomerular capillary loops with “spike” formation on silver stained sections