4 - Glomerular Disease

Nephrotic syndrome

1. Proteinuria of > 3.5g/d

2. Hypoalbuminemia of <3mg/dL

3. Edema

4. Hyperlipidemia/lipiduria

Types of diseases causing nephrotic syndrome

1. Membranous nephropathy

2. Focal and Segmental Glomeruloscelrosis

3. Minimal Change Disease

Membranous nephropathy

• What is it

• Demographic

• What can we find

• A disease where immune complexes against podocyte antigens(PLA2R) bind to podocytes and attack them via the complement system, which leads to inflammation and thickening of the basement membrane

• Found in adults

• Visible thick GBM on light microscopy, IgG found on immunofluorescence and deposits visible on electron microscopy

MCD

• What is it

• Demographic

• What can we find

• Treatment

• A T-cell attack against podocytes which leads to foot process effacement and damage to the slit diaphragm, resulting in increased permeability

• Children 1-7

• Nothing on LM and IF, but foot process effacement on electron microscopy

• Responds well to steroids

FSGS

• What is it

• Demographic

• What can we find

• Treatments

• Damage to some podocytes often due to a trigger or chronic overwork causes sclerosis(scarring) of some podocytes, meaning that some glomeruli will be damaged

• Adults

• Segmental sclerosis in LM, nothing on IF, and foot process effacement on EM, but can present with hypertension and microscopic hematuria

• Doesn’t respond too well to steroids, can often progress to end stage kidney disease

Nephritic Syndrome

1. Hematuria w dysmorphic RBC/RBC casts

2. Oliguria + azotemia

3. Hypertension

APIGN

• What is it

• Demographic and onset

• What can we find

• Treatment

• Antibodies form against antigens of bacteria like streptococcus and form complexes that get stuck in the glomerulus and activate complement, causing damage and recruiting inflammatory cells

• Young children, 1-4 weeks

• Hypercellularity, IgG and complement positive on IF, subepithelial humps on EM, decreased complement amount and found antibodies for an earlier sickness like strep

• Self-resolving

IgA nephropathy

• What is it

• Demographic and onset

• What can we find

• A condition where the body has dysfunctionally structured IgA, so when a infection happens, our body makes antibodies against our own IgA, which forms complexes and deposits in the mesangium, causing proliferation and damage can go from asymptomatic to rapidly progressing glomerularnephritis

• Common in young adults but can be any age, and this condition happens very fast, sometimes even during the sickness itself

• Asymptomatic to RPGN, increased mesangial cells in LM, IgA found in mesangium in IF, and deposits in EM

Alport Syndrome

• What is it

• Demographic and onset

• What can we find

• A genetic condition where the type IV collagen that forms the basement membrane is faulty, which leads to easier leaking

• Starts with hematuria episodes since birth and progresses to chronic kidney disease

• Basket-weave appearance on EM, often presents with sensorineural hearing loss and eye abnormalities

RPGN

• What is it

• Types and their differences

• Rapidly Progressing Glomerular Nephritis

• Anti-GBM(Antibodies against the GBM, IF forms a linear pattern following the GBM outline), Immune-complex mediated(IgA nephropathy, APIGN, etc., IF is granular due to complexes), Pauci-immune(ANCA antibodies attack neutrophils, this damages blood vessels all over the body including the glomerular capillaries)

What is SLE, and what is lupus nephritis?

SLE is a condition where the body creates antibodies against itself, and lupus nephritis is a version where these antibody antigen complexes form in the kidney and cause complement activation

What are the 6 types of lupus nephritis?

• Class 1: Minimal mesangial, damage just at mesangial level and so small it’s asymptomatic and not seen in LM

• Class 2: Mesangial proliferative, damage at mesangial level still but noticeable on LM now

• Class 3: Focal, spread now to subendothelial level at the capillary, in less than 50% of glomeruli

• Class 4: Diffuse, also subendothelial but in over 50% of glomeruli

• Class 5: Membranous, happens at the subepithelial level, similar to MN, can cause nephrotic syndrome symptoms

• Class 6: Sclerotic stage, 90% scarring and presents as CKD

What is the antibody we should be finding every time in lupus nephritis?

IgG

How does DM affect the glomerulus?

Diabetes leads to glycation of proteins, causing the basement membrane to thicken, and causing the mesangium to grow, while also raising pressure inside the glomerulus

How does amyloidosis affect the glomerulus?

Amyloidosis is accumulation of misfolded proteins, with the main types being AA amyloidosis and AL amyloidosis, from chronic inflammation raising serum amyloid A and from light chain production respectively, which physically impairs glomerulus activity

How do we see amyloidosis on staining?

Green apple bifringerence on Congo red stain

Wireloop lesions are indicative of what?

Subendothelial deposits in the glomerulus, which are often found in class III or IV lupus nephritis