A Quick & High-Yield Breakdown of Nephritic Syndrome

Hypertension
Hematuria, oliguria (symptoms you can see with your eyes)
Disruption/inflammation of glomeruli! If bad enough, can lead to glomerular basement membrane rupture and rapid loss of kidney function.
RBCs, WBCs, and RBC casts present on urine microscopy.
Proteinuria can be anywhere from sub-nephrotic proteinuria to nephrotic proteinuria.

Alport Syndrome (hereditary nephritis)

Caused by mutations in alpha 3, alpha 4, or alpha 5 type IV collagen
Typically X-linked dominant inheritance (COL4A5), and rarely can be autosomal recessive or dominant (COL4A3 or COL4A4).
“Can’t see, can’t pee, can’t hear a bee” (ocular disturbance, isolated hematuria, and sensorineural hearing loss)
Typically with isolated hematuria at a young age. However, progresses to proteinuria and kidney failure in adulthood.
On Kidney biopsy, the light microscopy can look normal at the early stages.
On EM, the GBM can look diffusely thin early in the disease. Later, the GBM has irregular appearance, alternating between thick and thin areas in a so-called “basket-weave” appearance.
No immune complexes are seen on IF.

IgA Nephropathy

GN caused by IgA deposition in the mesangial areas.
Can have a variable presentation and kidney biopsy: could present as isolated hematuria and mild mesangial expansion all they way to diffuse proliferative disease, glomerulosclerosis, and rarely cellular crescents.
Shares features with Henoch-Schonlein Purpura (hematuria, recent viral URI, purpuric rash, abdominal pain).

Post-infectious Glomerulonephritis, including Post-streptococcal Glomerulonephritis (PSGN)

Type III Hypersensitivity reaction (immune complex deposition of IgG or IgM in the glomerular membrane).
Decreased C3 due to consumption/activation of complement.
With PSGN, it occurs 2-3 weeks after Strep pyogenes (GAS) infection as cola colored urine, hypertension, and periorbital edema.
Can happen with many other infections; don’t think this is just a streptococcal thing!
Hypercellular, inflamed glomeruli on H&E.
“Lumpy-bumpy” Immune complex deposition under epithelial cells.
Granular IF and subepithelial ‘humps’ on EM.

Membranoproliferative Glomerulonephritis (MPGN)

This is the confusing one because it can present many ways: either microscopic hematuria with variable proteinuria (up to the nephrotic syndrome!), or gross hematuria/nephritis. In other words, it’s the disease that will have features of nephritic and nephrotic syndromes combined. (It can ‘do anything’).
It is typically secondary to other disease processes like Hepatitis B & Hepatitis C, Cryoglobulinemia, and some cancers like CLL.
Key word on the path: “Tram track appearance” on H&E, this means the process is slow enough that cells are laying down a new layer of GBM and mesangial cells can sometimes be seen squeezing between the two GBM layers.
There is immune complex deposition leading to a thick GBM.
On immunofluorescence there is Granular staining for IgG and Complement (C3).

Lupus Nephritis

Lupus can do lots of stuff in the kidney. If a patient has hematuria or proteinuria, you will always be correct to say “Lupus Nephritis” on the DDX.
Type III Hypersensitivity reaction
- Immune complex deposition of IgG, IgA, or IgM in the glomerulus.
  - These complexes can deposit in the mesangium or capillary loops.
Key word: “full house” of Immunofluorescence staining. In other words, everything is being deposited: polyclonal IgG, IgA, IgM, C3, and C1q.
Immune complexes activate complement, recruit inflammatory cells.
There is decreased C3 and C4 due to consumption/activation of complement.
On kidney biopsy, we can determine which class of Lupus nephritis is present:
- Class I: Only mesangial deposits, everything else normal.
- Class II: Mesangial deposits and mesangial hypercellularity.
- Class III: Inflammatory injury to <50% of the glomeruli, this could be cellular crescent formation, fibrinoid necrosis, or subendothelial immune deposits.
- Class IV: same as III but affecting >50% of the glomeruli.
- Class V: Features of Membranous Nephropathy (See the Nephrotic Syndrome post).
- Class VI: Advanced glomerulosclerosis. In other words, the ship has sailed and therapy is not likely to be effective.

Anti-GBM Disease

If isolated to the kidney, we call it Anti-GBM disease.
When it involves kidney AND lung, it is Goodpasture Syndrome.
Type II Hypersensitivity reaction (immune reaction against cellular antigens or extracellular matrix).
Anti-GBM antibodies are against Type IV collagen of basement membrane.
Linear IgG staining on immunofluorescence (looks like a continuous ribbon).

ANCA Vasculitis

Autoimmune disease where autoantibodies (anti-neutrophilic cytoplasmic antibodies) direct neutrophils to auto-activate and attack tissues.
The autoantibodies are directed against neutrophils, NOT the kidney. So, there will be no staining for immune complexes on kidney biopsy (“pauci-Immune”)
This category contains other diseases:
- Granulomatosis with polyangiitis
  - Involves the nasopharynx, lungs, and kidneys and has a positive c-ANCA.
- Microscopic Polyangiitis
  - Involves the skin, kidneys, lungs, nerves and has a positive p-ANCA.
When it only affects the kidney, we call it “Renal-limited ANCA vasculitis.”

Rapidly Progressive Glomerulonephritis (RPGN)

This is really just a generic term for any nephritic process that is acute and rapidly injuring the kidney.
Can be caused by many renal diseases: typically anti-GBM disease, ANCA vasculitis, Lupus Nephritis, or Post-infectious GN.
When it’s rapidly progressing, you’re more likely to see crescentic glomerulonephritis on biopsy (crescents comprised of fibrin and macrophages).

Check out NephSim for some practice cases!

Author:

Danae Olaso, MS2

The Kidney Zone